CN101979394A - A method to inhibit ethylene responses in plants - Google Patents

A method to inhibit ethylene responses in plants Download PDF

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Publication number
CN101979394A
CN101979394A CN2010101281818A CN201010128181A CN101979394A CN 101979394 A CN101979394 A CN 101979394A CN 2010101281818 A CN2010101281818 A CN 2010101281818A CN 201010128181 A CN201010128181 A CN 201010128181A CN 101979394 A CN101979394 A CN 101979394A
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base
phenyl
ethyl
methyl
oxygen base
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CN101979394B (en
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R·M·雅格布森
M·J·凯利
F·L·维迈耶
K·A·埃文斯
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Rohm and Haas Co
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Rohm and Haas Co
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    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
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Abstract

The present invention generally relates to methods of inhibiting ethylene responses in plants and plant materials, and particularly relates to methods of inhibiting various ethylene responses including plant maturation and degradation, by exposing plants to cyclopropene derivatives and compositions thereof wherein: 1) at least one substituent on the cyclopropene ring contains a carbocyclic or heterocyclic ring, or 2) a substituent contains silicon, sulfur, phosphorous, or boron, or 3) least one substituent contains from one to four non-hydrogen atoms and at least one substituent contains more than four non-hydrogen atoms.

Description

A kind of method that suppresses ethylene reaction in the plant
Patent application of the present invention is that international application no is PCT/US02/06339, international filing date is on February 25th, 2002, and the application number that enters the China national stage is 02801969.5, denomination of invention is divided an application for the application for a patent for invention of " a kind of method that suppresses ethylene reaction in the plant ".
Technical field
The present invention relates generally to suppress the method for ethylene reaction in plant and the vegetable material, more specifically to by in the composition that plant is exposed to cyclopropene derivatives and they with the method for the various ethylene reactions that suppress to comprise that plant is ripe and wear out, wherein at least one substituting group on the cyclopropylene ring comprises carbocyclic ring or heterocycle.
Background technology
Well-known ethene can cause plant or plant part for example to comprise, flower, leaf, the precocious death of fruit and vegetables.Ethene also quickens leaf flavescence and cessation of growth cessation and makes fruit early-maturing, flower and leaf drop.This activity be understood that be by with plant in specific ethylene receptor interact and realize.Many is not that the compound of ethene is influential to these acceptors: the effect of some compound imitation ethene; Other compound can hinder the combination of ethene and offset its effect thus.In order to determine these ethene inductive effects, very active subject is obstruction or reduces the research of ethene to the deleterious effect of plant at present.
Be disclosed in people's such as Sisler United States Patent (USP) U.S.5 with the method for ethene effect in diazacyclo pentadiene and derivative thereof the opposing plant, in 100,462.People's such as Sisler United States Patent (USP) U.S.5 in 518,988, discloses cyclopropylene and derivative thereof, comprises the 1-methylcyclopropene, as the purposes of the effective blocker of ethene bonded.Yet, be that they are typically unsettled gas with the subject matter of these compounds, the danger of blast will be arranged when being compressed.
Although these effort are arranged, still there are demand in ripe and aged compound and composition to the may command plant in this area.Preferably, new compound can be avoided the explosion hazard of 1-methylcyclopropene, in addition, can provide other the mode that for example transmits by the liquid or solid formulation.
Summary of the invention
We have found to provide the new cyclopropene derivatives of a class of above-mentioned many advantages.These compounds and their composition provide a kind of method that suppresses the ethene effect in the plant, comprise the cyclopropene derivatives of the following formula of using ethene suppressing effect significant quantity or the step of its composition and plant contact:
Figure GSA00000039172900021
Wherein:
A) R 1And R 3One of be H, and R 2, R 4With R 1And R 3In another be independently selected from the group of H and following formula:
-(L) n-Z
Wherein:
I) n is 1 to 12 integer;
Ii) L is selected from group D1 independently of one another, D2, and among E or the J one, wherein:
D1 is the group of following formula:
Figure GSA00000039172900022
D2 is the group of following formula:
Figure GSA00000039172900023
E is the group of following formula:
Figure GSA00000039172900032
And
J is the group of following formula:
Figure GSA00000039172900033
Wherein:
A) X and Y are the group of following formula independently of one another:
-(L) m-Z；
And
B) m is 0 to 8 integer; With
C) two D2 or E group are adjacent one another are at the most, and do not have the J group adjacent one another are;
Iii) Z is selected from independently of one another:
A) hydrogen, halogen, cyano group, nitro, nitroso-group, azido-, chlorate anions, bromate, iodate, isocyanato-, isocyanide, isothiocyanato, five fluorine sulfenyls, or
B) group G, wherein G is unsubstituted or replaces; Undersaturated, fractional saturation or saturated; Monocycle, dicyclo, three ring or condensed; 4 to 14 yuan of carbocyclic rings or heterocyclic systems, wherein:
1) when ring system comprises 4 yuan of heterocycles, heterocycle comprises 1 heteroatoms;
2) when ring system comprised 5 yuan or multicomponent heterocycle or encircles heterocycle more, heterocyclic or polycyclic heterocycle comprised 1 to 4 heteroatoms;
3) each heteroatoms is independently selected from N, O and S;
4) substituent number is 0 to 5, and each substituting group is independently selected from X;
B) non-hydrogen atom in each compound adds up to 50 or still less; And
C)-(L) nHeteroatomic among the-Z adds up to 0 to 4; And
D) one of following any condition:
I) R 1Or R 3Comprise at least one group G; Or
Ii) at least one L group is the E group; Or
Iii) at least one R 1, R 2, R 3, and R 4Comprise one to four non-hydrogen atom and at least one R 1, R 2, R 3, and R 4Comprise and surpass four non-hydrogen atoms;
And enantiomorph, steric isomer, salt and their mixture.
For purpose of the present invention, each key table opened in the structure of various L groups shows one to another L group, the key of Z group or cyclopropylene part.For example, structure
Figure DEST_PATH_GSB00000400069600011
Represent that a Sauerstoffatom has the key of two other atoms; It does not represent the dme part.
Typical R 1, R 2, R 3And R 4Group comprises, for example: alkenyl, alkyl, alkynyl, kharophen alkenyl, kharophen alkyl, the kharophen alkynyl, alkenyloxy, alkoxyl group, alkynyloxy group, alkoxy alkoxy alkyl, alkoxy alkenyl, alkoxyalkyl, alkoxyl group alkynyl, alkoxy carbonyl alkenyl, alkoxy carbonyl alkyl, alkoxy carbonyl alkynyl, alkyl-carbonyl, alkyl-carbonyl oxygen base alkyl, alkyl (Alkoximino) alkyl, carboxyl alkenyl, carboxyalkyl, carboxyl alkynyl, dialkyl amido, the halogenated alkoxy alkenyl, halogenated alkoxy alkyl, halogenated alkoxy alkynyl, halogenated alkenyl, haloalkyl, halo alkynyl, hydroxyl alkenyl, hydroxyalkyl, the hydroxyl alkynyl, trialkylsilkl alkenyl, trialkylsilkl alkyl, the trialkylsilkl alkynyl, the dialkyl phosphine acid group closes (phosphonato), and the dialkyl group phosphate radical closes (phosphato), and two alkylthio phosphate radicals close, dialkyl aminoalkyl, the alkyl sulphonyl alkyl, alkylthio alkenyl, alkylthio alkyl, the alkylthio alkynyl, dialkyl amino sulfonyl, halogenated alkylthio alkenyl, halogenated alkylthio alkyl, the halogenated alkylthio alkynyl, alkoxy-carbonyl oxy; Cycloalkenyl, cycloalkyl, cycloalkynyl radical, the kharophen cycloalkenyl, kharophen cycloalkyl, kharophen cycloalkynyl radical, cycloalkenoxy, cycloalkyloxy, ring alkynyloxy group, alkoxyl group alkoxyl group cycloalkyl, alkoxyl group cycloalkenyl, alkoxyl group cycloalkyl, the alkoxyl group cycloalkynyl radical, alkoxy carbonyl cycloalkenyl, alkoxy carbonyl cycloalkyl, the alkoxy carbonyl cycloalkynyl radical, naphthene base carbonyl, alkyl-carbonyl oxygen basic ring alkyl, carboxyl cycloalkenyl, the carboxyl cycloalkyl, the carboxyl cycloalkynyl radical, bicyclic alkyl amino, halo cycloalkyloxy cycloalkenyl, halo cycloalkyloxy cycloalkyl, halo cycloalkyloxy cycloalkynyl radical, halo cycloalkenyl, halogenated cycloalkyl, the halo cycloalkynyl radical, the hydroxyl cycloalkenyl, hydroxyl cycloalkyl, hydroxyl cycloalkynyl radical, the trialkylsilkl cycloalkenyl, dialkyl group silyl cycloalkyl, trialkylsilkl cycloalkynyl radical, dialkyl amido cycloalkyl, the alkyl sulphonyl cycloalkyl, naphthene base carbonyl oxygen base alkyl, naphthene sulfamide base alkyl, alkylthio cycloalkenyl, the alkylthio cycloalkyl, the alkylthio cycloalkynyl radical, bicyclic alkyl amino alkylsulfonyl, halogenated alkylthio cycloalkenyl, the halogenated alkylthio cycloalkyl, the halogenated alkylthio cycloalkynyl radical; Aryl, alkenyl aryl, alkylaryl, alkynyl aryl, the kharophen aryl, aryloxy, alkoxyl group alkoxy aryl, alkoxy aryl, the alkoxy carbonyl aryl, aryl carbonyl, alkyl-carbonyl oxygen Ji Fangji, carboxyl aryl, ammonia diaryl base, halogenated alkoxy aryl, halogenated aryl, hydroxyaryl, the trialkylsilkl aryl, dialkyl amido aryl, alkyl sulphonyl aryl, aryl sulfonyl alkyl, the alkylthio aryl, artyl sulfo alkyl, ammonia diaryl base alkylsulfonyl, halogenated alkylthio aryl; Heteroaryl, alkenyl heteroaryl, miscellaneous alkyl aryl, the alkynyl heteroaryl, kharophen heteroaryl, heteroaryl oxygen base, alkoxyl group alkoxyl group heteroaryl, alkoxyl group heteroaryl, alkoxy carbonyl heteroaryl, the heteroaryl carbonyl, alkyl-carbonyl oxygen base heteroaryl, carboxyl heteroaryl, two heteroaryl aminos, the halogenated alkoxy heteroaryl, halo heteroaryl, hydroxyl heteroaryl, the trialkylsilkl heteroaryl, the dialkyl amido heteroaryl, alkyl sulphonyl heteroaryl, heteroarylsulfonyl alkyl, the alkylthio heteroaryl, heteroaryl sulfenyl alkyl, two heteroaryl amino alkylsulfonyls, halogenated alkylthio heteroaryl; Heterocyclic radical, alkenyl heterocyclic radical (heteroycycyl), alkyl heterocyclic (heteroycycyl), alkynyl heterocyclic radical (heteroycycyl), kharophen heterocyclic radical, heterocyclyloxy base, alkoxyl group alkoxyl group heterocycle, alkoxyl group heterocyclic radical, alkoxy carbonyl heterocyclic radical, the heterocyclic radical carbonyl, alkyl-carbonyl oxygen base heterocyclic radical, carboxyl heterocyclic radical, two heterocyclic radical amino, the halogenated alkoxy heterocyclic radical, the halogenated heterocyclic base, hydroxyl heterocyclic radical, trialkylsilkl heterocyclic radical, the dialkyl amido heterocyclic radical, the alkyl sulphonyl heterocyclic radical, alkylthio heterocyclic radical, heterocyclic radical sulfenyl alkyl, two heterocyclic radical amino-sulfonyls, the halogenated alkylthio heterocyclic radical; Hydrogen, fluorine, chlorine, bromine, iodine, cyano group, nitro, nitroso-group, azido-, chlorate anions close (chlorato), and bromate closes (bromato), and iodate closes (iodato), isocyanato-, isocyanide, isothiocyanato, five fluorine sulfenyls; Acetoxyl group, the carbonyl oxyethyl group, cyanate radical closes, nitroxyl, oxynitroso, the perchlorate closes, the propadiene base; The butyl sulfydryl, diethyl phosphoric acid
Figure GSA00000039172900061
The 3,5-dimethylphenyl silyl, isoquinolyl, sulfydryl, naphthyl, phenoxy group, phenyl, piperidyl, pyridyl, quinolyl, triethylsilyl, trimethyl silyl; And the analogue that replaces.
Typically the G group comprises, for example: saturated or undersaturated cycloalkyl, dicyclo, trinucleated, polycyclic, saturated or undersaturated heterocyclic radical, the not phenyl that replaces or replace, naphthyl, or the heteroaryl ring system is for example, cyclopropyl, cyclobutyl, ring penta-3-alkene-1-base, 3-methoxyl group hexamethylene-1-base, phenyl, 4-chloro-phenyl-, 4-fluorophenyl, the 4-bromophenyl, 3-nitrophenyl, 2-p-methoxy-phenyl, the 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, the 4-ethylphenyl, 2-methyl-3-p-methoxy-phenyl, 2, the 4-dibromo phenyl, 3, the 5-difluorophenyl, 3,5-3,5-dimethylphenyl, 2,4,6-trichlorophenyl, 4-p-methoxy-phenyl, naphthyl, 2-chloronaphthyl, methylnaphthyl, 2, the 4-Dimethoxyphenyl, 4-(trifluoromethyl) phenyl, 2-iodo-4-aminomethyl phenyl, pyridine-2-base, pyridin-3-yl, pyridin-4-yl, pyrazinyl, pyrimidine-2-base, pyrimidine-4-base, pyrimidine-5-base, pyridazinyl, triazol-1-yl, imidazoles-1-base, thiophene-2-base, thiene-3-yl-, furans-2-base, furans-3-base, pyrryl oxazolyl ， isoxazolyl, thiazolyl, isothiazolyl, 4-oxadiazole base, thia di azoly, quinolyl, isoquinolyl, tetrahydrofuran base, pyrrolidyl, piperidyl, THP trtrahydropyranyl, morpholinyl, piperazinyl, dioxolane base alkyl dioxin, indolinyl and 5-methyl-6-chromanyl, adamantyl, norcamphyl and their replacement analogue be for example: 3-butyl-pyridine-2-base, 4-bromo-pyridine-2-base, 5-carbonyl oxyethyl group-pyridine-2-base, 6-methoxy ethoxy-pyridine-2-base
Preferred R 1, R 2, R 3And R 4In two be hydrogen.More preferably R 1And R 2Be hydrogen or R 3And R 4Be hydrogen.Even more preferably R 2, R 3, and R 4Be hydrogen or R 1, R 2And R 3Be hydrogen.R most preferably 2, R 3And R 4Be hydrogen.
Preferred n is 0 to 8.Most preferably n is 1 to 7.Preferred m is 0 to 4.Most preferably m is 0 to 2.
Preferably, D1 is-CXY-,-CO-, or-CS-.More preferably D1 is-CXY-.Preferably, D2 be-O-or-NX-.Preferably E is-S-,-SiXY-, or-SO 2-.Preferably, X and Y are H independently, halogen, OH, SH ,-C (O) (C 1-C 4) alkyl-,-C (O) O (C 1-C 4) alkyl-,-O-(C 1-C 4) alkyl ,-S-(C 1-C 4) alkyl, or replacement or unsubstituted (C 1-C 4) alkyl.Preferably, Z is H, halogen, or G.More preferably, Z is H or G.
Preferably, G is replacement or unsubstituted independently of one another; Five, six or seven yuan; Aryl, heteroaryl, heterocyclic radical, or cycloalkyl ring.More preferably, G is independently of one another for replacing or unsubstituted phenyl pyridyl, cyclohexyl, cyclopentyl, suberyl, pyrryl, furyl, thiophenyl, triazolyl, pyrazolyl, 1,3-dioxolanyl, or morpholinyl.More preferably, G is the phenyl that does not replace or replace, cyclopentyl, suberyl, or cyclohexyl.Most preferably, G is a cyclopentyl, suberyl, and cyclohexyl, phenyl, or the phenyl that replaces, wherein substituting group is independently selected from 1 to 3 methyl, methoxyl group, and halogen.
Another aspect of the present invention is a kind of by cyclopropene derivatives from ethylene receptor blocking-up significant quantity to plant that use or the method that its composition is blocked ethylene receptor in the plant.
Also disclose the inhibition plant and come off naturally, prolonged the survival time of flower arrangement, and suppressed the fruit of harvesting or the sophisticated method of vegetables, comprised the cyclopropene derivatives from significant quantity to plant or its composition that apply.
Method described here can be carried out with various approach, for example by plant is contacted with cyclopropene derivatives or their composition, or with solid, liquid, or with the form of gas; Or the fruit by making plant, flower arrangement, harvesting or the vegetables of harvesting are exposed in the atmosphere of filling with cyclopropene derivatives or their composition.These and other suitable method of application will at length be discussed following.For realizing purpose of the present invention, " contact " is to instigate cyclopropylene and close the interosculating so that the ethylene receptor of sufficient amount is subjected to the influence of cyclopropylene of plant.
The Pestcidal compositions that comprises compound of the present invention also is included among the present invention.Preferred composition comprises 0.005% to 99%, weight; Preferred 1% to 95%, weight; More preferably 2% to 90%, weight; More preferably 3% to 80%, weight; Or most preferably 4% to 70%, weight, active compound of the present invention.These compositions can comprise one or more auxiliary agent, for example, and carrier, extender, tackiness agent (binder), lubricant, tensio-active agent and/or dispersion agent, wetting agent, spreading agent, dispersion agent, tackiness agent, tackiness agent
Figure GSA00000039172900081
Defoamer, thickening material, and emulsifying agent.Common employed such auxiliary agent can find hereinafter in this area: John W.McCutcheon, Inc.publication Detergents andEmulsifiers, Annual, Allured Publishing Company, Ridgewood, New Jersey, U.S.A.
All percentage ratios are weight percentage as used herein, and all umbers are parts by weight, unless otherwise mentioned, and be comprise end value with combinative.All proportions is a weight ratio, and all proportions scope be comprise end value with combinative.All molar range be comprise end value with combinative.
Can use the carrier of numerous organic solvents as active compound of the present invention, for example, hydrocarbon is hexane for example, benzene, toluene, dimethylbenzene, kerosene, diesel oil, oil fuel and petroleum naphtha, ketone is acetone for example, methyl ethyl ketone and pimelinketone, and chlorinated hydrocarbon is tetracol phenixin for example, and ester is ethyl acetate for example, amyl acetate-n and butylacetate, ether, for example, ethylene glycol monomethyl ether and methyl carbitol, alcohol for example, ethanol, methyl alcohol, Virahol, amylalcohol, ethylene glycol, propylene glycol, acetate butyl card must ester and glycerine.
The mixture of water and organic solvent perhaps with solution or with emulsion, also can be used as the inert support of active compound.
Can prepare solid by various ordinary methods, the liquids and gases preparation.Therefore active ingredient, if the solid words are with finely divided form, can be with finely divided solid carrier lift-over.Perhaps, the active ingredient of liquid form comprises their mixture, solution, and dispersion, emulsion and suspension can mix with the solid carrier with finely divided form.In addition, the active ingredient of solid-state form can be mixed with liquid vehicle, forms mixture, solution, dispersion, emulsion and suspension or the like.
Active compound of the present invention can be applied to plant by various suitable methods.For example, active compound can be separately with gas, liquid, or solid form is by using compound with wanting processed plant contact.In addition, active compound can be changed into the form of salt, then is applied in plant.Perhaps, can form the composition that comprises one or more active compound of the present invention.Composition can be with gas, liquid, or solid form is by using composition with wanting processed plant contact.Such composition can comprise inert support.Similarly, when with the form of gas, compound can be dispersed in the inert gas carrier so that a kind of gas solution to be provided.Also active compound can be suspended in the liquor that can be used as inert support, for example in the organic solvent or the aqueous solution.The solution that comprises active compound can be heterogenetic or homogeneous, and can be various forms, comprises mixture, dispersion, emulsion, suspension or the like.
Also cyclopropylene can be encapsulated in the molecule encapsulants.Preferred encapsulation agent comprises cyclodextrin, crown ether, polysiloxane and zeolite.Preferred encapsulation agent comprises alpha-cylodextrin, beta-cyclodextrin, and γ-Huan Hujing.Most preferred encapsulation agent will change according to the substituent size of R.Yet, will understand fully as those skilled in the art, can also use the mixture of any cyclodextrin or cyclodextrin according to the present invention, the cyclodextrin of cyclodextrin and modification.Cyclodextrin can be from Wacker Biochem Inc., Adrian, and MI or Cerestar USA, Hammond, IN, and other supplier obtains.When encapsulated, because the capacity limitation of molecule encapsulation agent, the enriched material of preferred cyclopropylene will typically be less than other composition.
The composition of active compound and they can also be used with aerosol, for example, by their are for example used pressurized gas, nitrogen, carbonic acid gas, Refrigerant 12, trichlorofluoromethane or other halon and be dispersed in the air.
The amount of the cyclopropylene that the ethene suppressing effect is required will be according to the type of specific cyclopropylene, the vegetable material that provides and quantity, employed cyclopropene compositions and the capacity that will handle and is different.Usually, in processing tank the gas processing of cyclopropylene (mensuration volume/volume) concentration be about 1,000,000,000/(" ppb ") 0.1 part to 1,000,000/(" ppm ") 1000 parts enough ethene restraining effect can be provided.Similarly, the spraying of cyclopropylene handle application concentration (gravimetry/weight) for about 1,000,000,000/(" ppb ") 0.01 part to 1,000,000/(" ppm ") 1000 parts enough ethene restraining effect can be provided.
Use with general meaning at this term " plant ", and comprise that for example, xylophyta is tree and shrubs for example; Herbaceous plant; Vegetables, fruit and farm crop; And ornamental plant.Comprise any part of complete stool plant and they by the processed plant of method described herein, field crop for example, potted plant, seed, flower arrangement (stem and flower), and the fruit and the vegetables of results.
With the compound and the plant of handling, preferably handle with the active compound of non-plant toxicity quantity by method of the present invention.
Can use the present invention to regulate various ethene effect, for example flower, fruit and vegetables is ripe and/or old and feeble; Coming off of leaf, flower and fruit; Ornamental plant is the shortening in the survival life-span of the seedling of potted plant, flower arrangement, shrub, seed and dormancy for example; In certain plants (for example, pea) effect of inhibition growth, the effect of stimulating growth (for example paddy rice), the growth hormone activity, the restraining effect of terminal growth, the control of apical dominance, branched increase, increase is tillered, and changes the form of plant, adjusting is to the phytopathogen susceptibility of fungi for example, change the biochemical composition (for example increasing leaf area) of plant, the termination or the restraining effect of flower and seed development, lodging effect with respect to the stem area, the hormesis of seed germination and breaking dormancy, and hormone or epinasty effect.
Active compound of the present invention has been proved to be beyond thought effective inhibitor of the ethylene action of plant, fruit and vegetables, even when using with lower concentration also is.What wherein need to illustrate a bit is, compound of the present invention is compared with the compound in the prior art and can be caused insensitive to long term of ethene.Even the insensitive of this long term to ethene also may appear when using with the concentration lower than previous compound.
Another embodiment of the present invention relates to newfound cyclopropene member's compound.These compounds comprise the compound of following formula:
Wherein:
A) R 1And R 3One of be H, and R 2, R 4With R 1And R 3In another be independently selected from the group of H and following formula:
-(L) n-Z
Wherein:
I) n is 1 to 12 integer;
Ii) L is selected from group D1 independently of one another, D2, and among E or the J one, wherein:
D1 is the group of following formula:
D2 is the group of following formula
Figure GSA00000039172900112
E is the group of following formula:
And
J is the group of following formula:
Figure GSA00000039172900121
Wherein:
A) X and Y are the group of following formula independently of one another:
-(L) m-Z；
And
B) m is 0 to 8 integer; With
C) two D2 or E group are adjacent one another are at the most, and do not have the J group adjacent one another are;
Iii) Z is selected from independently of one another:
A) hydrogen, halogen, cyano group, nitro, nitroso-group, azido-, chlorate anions, bromate, iodate, isocyanato-, isocyanide, isothiocyanato, five fluorine sulfenyls, or
B) group G, wherein G is unsubstituted or replaces; Undersaturated, fractional saturation or saturated; Monocycle, dicyclo, three ring or condensed; 4 to 14 yuan of carbocyclic rings or heterocyclic systems, wherein:
1) when ring system comprises 4 yuan of heterocycles, heterocycle comprises 1 heteroatoms;
2) when ring system comprised 5 yuan or multicomponent heterocycle or encircles heterocycle more, heterocyclic or polycyclic heterocycle comprised 1 to 4 heteroatoms;
3) each heteroatoms is independently selected from N, O and S;
4) substituent number is 0 to 5, and each substituting group is independently selected from X;
B) non-hydrogen atom in each compound adds up to 50 or still less; And
C)-(L) nHeteroatomic among the-Z adds up to 0 to 4; And
D) one of following any condition:
I) R 1Or R 3Comprise at least one group G; Or
Ii) at least one L group is the E group; Or
Iii) at least one R 1, R 2, R 3, and R 4Comprise one to four non-hydrogen atom and at least one R 1, R 2, R 3, and R 4Comprise and surpass four non-hydrogen atoms;
And enantiomorph, steric isomer, salt and their mixture;
Or their composition.
Condition is:
A)-(L) n-Z is not a trimethyl silyl, trimethyl silyl alkylsulfonyl or mercaptan; With
B) R 1Not benzenesulfonyl, phenyl sulphur ethyl, phenylbenzene hydroxymethyl, benzo [g] quinoline-7-alcohol-1-methyl, malonic ester derivative, the amino cyclonene of the 3-of replacement, dialkoxy benzylamino carbonyl; With
C) R 3Not 2-phenyl-vinyl, thiophenyl, (4-bromo-2-aminomethyl phenyl) carboxylamine N-carbonyl, (4-bromo-2-aminomethyl phenyl) urethanum N-carbonyl, malonic ester derivative, aryloxy, or dialkoxy benzylamino carbonyl.
Compound of the present invention can be by many method preparations.General reference is seen: Closs, G.L.Advan.Alicyclic Chem.1966,1,53-127 and AlDulayymi, A.R.; Al Dulayymi, J.R; Baird, M.S.; And Koza, G.Russian Journal of Organic Chemistry 1997,33,798-816.
Bromo alkene and dibromo carbene reaction obtain three bromo cyclopropane, can be with it with lithium methide or the as directed cyclopropylene that changes into of other organolithium compound.(see Baird, M.S.; Hussain, H.H.; Nethercott, W.J Chem.Soc.Perkin Trans.11986,1845-1854 and Baird, M.S.; Fitton, H.L.; Clegg, W; McCamley, A.J Chem.Soc.Perkin Trans.1 1993,321-326).If use lithium methide or other lithium alkylide of monovalent, will obtain the cyclopropylene of single bromo.With two equivalents or how normal lithium alkylide, (lithiated) cyclopropylene of lithiumation will be formed.Can be with its water cancellation, the cyclopropylene shown in obtaining (E=H).Alternatively, the cyclopropenyl radical lithium can react with electrophilic reagent, obtains the deutero-cyclopropylene.The example of such electrophilic reagent comprises alkylating agent, trisubstituted chlorosilane, borate, dialkyl group or diaryl disulphide, ketone, aldehyde, ester, acid amides and nitrile.
Figure GSA00000039172900141
Bromo alkene can prepare by standard method.Available chloro-alkenes substitutes bromo alkene.
Can also with the cyclopropane of three bromos with reductive agent for example diethyl phosphite change the cyclopropane of single bromo into.Can use other reductive agent.
Figure GSA00000039172900142
1, the dibasic alkene of 1-can also with the dibromo carbene reaction, obtain dibromizated intermediate.It is reduced to the cyclopropane of single bromo by zinc.The elimination of carrying out bromine with alkali obtains cyclopropylene (referring to Binger, P.Synthesis 1974,190).
Figure GSA00000039172900151
Can be with cyclopropylene with for example sodium amide deprotonation in liquefied ammonia of highly basic, and with haloalkane or the reaction of other electrophilic reagent, the cyclopropylene that obtains replacing (reference: Schipperijn, A.J.; Smael, P., Recl.Trav.Chim.Pays-Bas, 1973,92,1159).Can be with the cyclopropylene alkyl lithium reagents deprotonation that replaces, and react with electrophilic reagent.
Figure GSA00000039172900152
Can three bromo cyclopropane of alcohol or the derivative that cyclopropylene changes a kind of good leavings group (for example sulphonate) into will be comprised.Can replace leavings group to obtain the cyclopropylene of other replacement with nucleophilic reagent.
Figure GSA00000039172900153
Can use 1-trialkylsilkl-2-hydroxyl cyclopropane of producing by vinyl trialkyl silane precursor compound (Mizojiri, R. as cyclopropylene; Urabe, H.; Sato, F.J.Org Chem.2000,65,6217).
Figure GSA00000039172900161
Also 1-trialkylsilkl-2-halo cyclopropane can be eliminated by fluoridizing catalysis, be obtained cyclopropylene (Billups, W.E.; Lee, C-A; Arney, B.E.; Whitmire, K.H.J Am.Chem.Soc., 1991,113,7980. and Banwell, M.C.; Corbett, M.; Gulbis, J.; Mackay, M.F.; Reum, M.E.J.Chem.Soc.Perkin Trans.1,1993,945).
With diazonium compound and acetylene addition is another kind of method (Mueller, the P. that can be used for synthetic cyclopropylene; Cranisher, C, Helv Chim Acta 1993,76,521).
Figure GSA00000039172900162
Ester can be hydrolyzed to carboxylic acid.
Similarly, dihalo-Cabbeen and acetylene addition can be obtained 1-alkyl-3,3-dihalo cyclopropylene (Bessard, Y.; Schlosser, M.; Tetrahedron, 1991,47,7323).
Compound of the present invention can also be by the preparation as follows of malonic ester derivative.
Figure GSA00000039172900171
Other method that produces cyclopropylene can find in the reference below: Duerr, H., Angew.Chem.1967,24,1104; People such as Closs, J.Am.Chem.1963,85,3796; Baird, M.S.; Dale, C.M.; Al Dulayymi, J.R.J Chem.Soc.Perkin Trans.1,1993,1373-1374; Koster, people such as R., Liebigs Annalen Chem.1973,1219-1235; Closs, G.L.; Closs, L.E., J.Am.Chem.Soc., 1961,83,1003-1004; Stoll, A.T.; Negishi, E., Tetrahedron Lett.1985,26,5671-5674.
Embodiment
Embodiment:
General reaction: all cyclopropylene are stored down at-80 ℃.Total overall reaction is carried out under nitrogen atmosphere.The sudden strain of a muscle formula chromatography of cyclopropylene carries out under nitrogen atmosphere.The target complete compound purity is 80% or higher unless otherwise mentioned.The cyclopropylene that 1-is replaced never heats, and should notice that these compounds time at room temperature will taper to minimum level.
The preparation of embodiment 1:1-chloro-4-ring third-1-thiazolinyl methyl-benzene (compound 1)
A.1-(2-bromo allyl group)-4-chlorinated benzene
By means of using refractory pebbles valve 8 milliliters of (0.0622mol) 2 that under nitrogen atmosphere, pack into, 50 milliliters of diethyl ether solutions of 3-propylene bromide.Refrigerative adds the diethyl ether solution of 62 milliliters of (0.062mol) 1M 4-chlorophenyl magnesium bromides simultaneously at leisure by feed hopper in ice-water bath.Stir be warmed up to room temperature simultaneously in 2 hours after, will be reflected in the ice bath cooling again, add 50 milliliters of 1N hydrochloric acid by means of syringe then.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Solvent is removed from filtrate in a vacuum.Resistates with cold pentane development, is obtained 12.0 gram 1-(2-bromo allyl group)-4-chlorinated benzene, be oily, it is used without further purifying.
B.2-(4-chlorophenyl methyl)-1,1,2-three bromo cyclopropane
In 20 milliliters of methenyl bromide solution of 11.4 gram (0.0494 mole) 1-(2-bromo allyl group)-4-chlorinated benzene, add 0.686 gram (0.00213 mole) Tetrabutyl amonium bromide.Be heated to 58.5 ℃ after one hour, add 10.7 milliliters of (0.0494 mole) 50% aqueous sodium hydroxide solutions.This step was repeated in two days seven times.Behind the cool to room temperature, add hexane and water.With mixture by the gravity filtration of qualitative corrugation filter paper.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Solvent is removed from filtrate in a vacuum.Resistates with hexane column chromatography purifying, is obtained 2.3 gram 2-(4-chlorophenyl methyl)-1,1,2-three bromo cyclopropane.
C.1-(4-chlorophenyl methyl)-cyclopropylene
By means of using refractory pebbles valve 1.20 gram (0.00298mol) 2-(4-chlorophenyl methyl)-1,1 that under nitrogen atmosphere, pack into, 6 milliliters of diethyl ether solutions of 2-three bromo cyclopropane.Refrigerative adds 6.38 milliliters of (0.00893mol) 1, the ether solution of 4M lithium methide at leisure by syringe simultaneously in ice-water bath.After 15 minutes, add 2 ml waters by means of syringe.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Desolvate in bathing from filtrate, to remove under warm 20 ℃ in a vacuum, obtain 0.430 gram 1-(4-chlorophenyl methyl)-cyclopropylene, be oil.
The preparation of embodiment 2:1-(2-thienyl) methyl-cyclopropylene (compound 2)
The Grignard reagent of preparation 2-bromothiophene, and by changing it into 1-(2-thienyl) methyl-cyclopropylene with the employed identical reaction sequence of the preparation of compound 1.
The preparation of embodiment 3:2-(3-ring third-1-thiazolinyl-propyl group)-[1,3] dioxane (compound 3)
Preparation 2-(2-brooethyl)-1, the Grignard reagent of 3-dioxane, and change it into 2-(3-ring third-1-thiazolinyl-propyl group)-[1,3] dioxane by the reaction sequence identical with being used to prepare compound 1.
The preparation of embodiment 4:1-(6-(phenyl dimetylsilyl)-hexyl)-cyclopropylene (compound 4)
A.2-bromo-8-(phenyl dimetylsilyl)-Xin-1-alkene
(37 milliliters, the THF solution of 0.5M 18.5mmol) cools off in ice bath with commercially availabie pentamethylene two (magnesium bromide).Add the solution of 3.16 gram (18.5mmol) phenyl dimethylchlorosilanes in 7 milliliters of THF roughly.Reaction mixture was stirred 15 minutes down at 5 ℃, at room temperature stirred then 35 minutes, then be cooled to 5 ℃ again.Will be in 5 milliliters of THF roughly 2, (3.7 grams 18.5mmol) join in the reaction mixture 3-propylene bromide, and it is continued 5 minutes down at 5 ℃, are warmed up to room temperature then and stir and spend the night.With the cancellation of reaction mixture water.Add ether and a small amount of 1NHCl.Separate each phase,, use the magnesium chloride drying, then stripping organic phase water and salt water washing.The column chromatography purifying obtains 1.47 gram 2-bromo-8-(phenyl dimetylsilyl)-Xin-1-alkene, water white oil.
B.N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and N, N '-dibenzyl-N, N, N ', N '-tetraethyl-ethylene ammonium dibromide (phase-transfer catalyst)
To 16.5 gram (142mmol) N that stir, N, N ' adds 50.1 gram (292mmol) cylites in the 60 gram acetonitrile solutions of N '-Tetramethyl Ethylene Diamine.Mixture self heats up, and stirs 2.5 hours, and observing has a large amount of precipitations on it.Slurry is diluted with ether, filter,, obtain the N that 61.8g wants, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide, white solid, fusing point 230-232 ℃ with ether washing and dry.
With similar method, use N, N, N ', N '-tetraethyl-ethylene diamine obtains N, N '-dibenzyl-N, N, N ', N '-tetraethyl-ethylene ammonium dibromide, white solid, decomposes by fusing point 190-193 ℃.
C.2-(6-(phenyl dimetylsilyl)-hexyl)-1,1,2-three bromo cyclopropane
With 1.4 gram (4.3mmol) 2-bromo-8-(phenyl dimetylsilyl)-Xin-1-alkene, 3.2 restrain 45% potassium hydroxide aqueous solution (25.6mmol), 0.2 gram N, N '-dibenzyl-N, N, N ', the mixture of N '-tetraethyl-ethylene ammonium dibromide and 7.5 milliliters of methylene dichloride is handled with 1.1 milliliters of methenyl bromides (12.6mmol).Well-beaten reaction mixture is at room temperature continued to spend the night.Add entry and methylene dichloride, separate each phase.With methylene dichloride with dried over mgso and stripping.During stripping, add a little amount of heptane to help to remove remaining methenyl bromide.The column chromatography purifying obtains 1.02 gram 2-(6-(phenyl dimetylsilyl)-hexyl)-1,1,2-three bromo cyclopropane, colourless liquid.
D.1-(6-(phenyl dimetylsilyl)-hexyl)-cyclopropylene
With 0.95 gram (1.9mmol) 2-(6-(phenyl dimetylsilyl)-hexyl)-1,1, the diethyl ether solution of 2-three bromo cyclopropane is cooled to-78 ℃.(1.4M, 5.7mmol), placed reaction mixture 30 minutes water cancellation then by 4.1 milliliters in ice bath to add excessive lithium methide.Separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, 200 milligrams of 1-(6-(phenyl dimetylsilyl)-hexyl)-cyclopropylene obtained, colourless liquid.
The preparation of embodiment 5:1-(α, α-Er Jiajibianji)-cyclopropylene (compound 5)
A. α, α-Er Jiajibianji cyanogen
In having 1000 milliliter of 3 neck flask of mechanical stirring, outside water-bath, internal thermometer, condenser and feed hopper, add 250 gram methyl-sulphoxides, 59 gram (504mmol) Bian Jiqings and 160 gram (1127mmol) methyl iodide.Internal temperature is risen to+45 ℃, then the speed with 0.7 per second adds the 8350%NaOH aqueous solution.Reinforced finishing after two hours.With dense slurry cooling, with 1000 ml waters and 500 milliliters of ether and 500 milliliters of hexane dilutions.Tell organic layer and concentrated.It comprises single and dimethylated compound.Further add 250 gram methyl-sulphoxides in this enriched material as previously discussed, the 60 gram methyl iodide and the 37 gram 50%NaOH aqueous solution add two hours.After the cooling, use 1000 ml waters, 500 milliliters of ether and 500 milliliters of hexanes dilutions obtain organic layer, and it is washed with 500 ml waters, use anhydrous magnesium sulfate drying, and evaporate to dryness in a vacuum, obtain 69 and restrain α, alpha-alpha-dimethyl phenyl cyanide.
H. α, the α-Er Jiajibianji methyl ketone
In having magnetic agitation, reflux exchanger and membranous 500 milliliters of round-bottomed flasks, under the dry nitrogen atmosphere, add 30 gram (207mmol) α, α-Er Jiajibianji cyanogen and 200 milliliters of ether.By means of intubate in three minutes, be added in lithium methide in the ether (1.4M, 160 milliliters, 224mmol).Exothermic heat of reaction is warming up to gentle reflux between charge period.Stir after 20 minutes, will react 100 milliliters of water-reducible concentrated hydrochloric acid aqueous solution quenchers of 45 milliliters of usefulness of adding of passing through slowly.Stir after one hour, separate organic layer, use anhydrous magnesium sulfate drying, and evaporate to dryness in a vacuum, obtain 32 and restrain α, α-Er Jiajibianji methyl ketone.
C.1-(α, α-Er Jiajibianji)-1-vinylchlorid
In 250 milliliters of round-bottomed flasks of magnetic agitation and reflux exchanger are housed, pack into 15 the gram (98mmol) POCl3,30 the gram (145mmol) PC15 and 19.9 the gram (123mmol) α, the α-Er Jiajibianji methyl ketone.In oil bath, reaction is heated to 110 ℃.-hour after gas evolution stop.To react cooling also is poured on ice and the ammonium hydroxide aqueous solution carefully.Handle extract with ether, obtain 1-(α, α-Er Jiajibianji)-1-vinylchlorid and 1-(α, α-Er Jiajibianji)-1, the mixture of 1-ethylene dichloride.Vacuum distilling obtains 1-(α, the α-Er Jiajibianji)-1-vinylchlorid of purifying, 110-120 ℃ of boiling point (23 torr).
D.1-(α, α-Er Jiajibianji) 1-chloro-2,2-dibromo cyclopropane
Magnetic agitation adds 4.5 gram (25mmol) 1-(α in 100 milliliters of round-bottomed flask dresses of magnetic agitation are housed, α-Er Jiajibianji)-1-vinylchlorid, 25 gram (100mmol) methenyl bromides, 27 gram methylene dichloride, 0.37 gram N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and 12.4 gram (100mmol) 45%KOH aqueous solution.Stir the cyclopropane that spends the night and obtain wanting, transformation efficiency 20% fast.Wash water layer with water, handle again with fresh methenyl bromide, catalyzer and KOH and spend the night, cause further conversion.Provide enough transformation efficiencys after handling for the third time.With the organic layer evaporate to dryness of solution washing, use hexane solution chromatographic separation on silica gel of 2% ether in a vacuum, obtain 4.2 gram 1-(α, α-Er Jiajibianji)-1-chloro-2,2-dibromo cyclopropane.
E.1-(α, α-Er Jiajibianji)-cyclopropylene
In having stirring rod and membranous 50 ml flasks, under the dry nitrogen atmosphere, add 1.73 gram (4.9mmol) 1-(α, α-Er Jiajibianji)-1-chloro-2,2-dibromo cyclopropane and 12 milliliters of ether.Cooling added the ether solution of 9.0 milliliters of (12.6mmol) 1.4M lithium methides after 10 minutes by syringe in ice bath.Form precipitation at once.Stir after 10 minutes, will react with 3 ml water cancellation.Remove water layer,, bathe evaporate to dryness under the temperature at+25 ℃ in a vacuum, obtain 0.94 gram 1-(α, α-Er Jiajibianji)-cyclopropylene the organic layer anhydrous magnesium sulfate drying.
The preparation of embodiment 6:3-methyl-3-benzyl ring propylene (compound 6)
A.2,2-two bromo-1-methyl isophthalic acid-benzyl ring propane
In 30.4 milliliters of (0.348 mole) methenyl bromide solution of 12.5 milliliters of (0.0963 mole) alpha-methyl styrenes and 1.34 gram (0.00416 mole) Tetrabutyl amonium bromides, add 20.9 milliliters of (0.400 mole) 50% aqueous sodium hydroxide solutions at leisure by means of feed hopper.Be heated to 55 ℃ after one hour, add 20.9 milliliters of (0.400 mole) 50% aqueous sodium hydroxide solutions.After heating 2 hours in addition, cooling is reacted to room temperature when adding hexane and water.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Solvent is removed from filtrate in a vacuum.The vacuum distilling separated product obtains 24.1 grams 2, and 2-two bromo-1-methyl isophthalic acid-benzyl ring propane are oil.
B.2-bromo-1-methyl isophthalic acid-benzyl ring propane
To 6.40 gram (0.0221 moles) 2, add 2.16 gram (0.0360 mole) Glacial acetic acid and 2.11 gram (0.0323 mole) zinc powders in the 22 gram methanol solutions of 2-two bromo-1-methyl isophthalic acid-benzyl ring propane.After at room temperature stirring 4 hours, remove in a vacuum and desolvate.In the resistates that produces, add hexane and water.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Vacuum is removed the solvent in the filtrate, obtains 3.24 gram 2-bromo-1-methyl isophthalic acid-benzyl ring propane, is oil, and it can use without further purifying.
C.3-methyl-3-benzyl ring propylene
In 5 milliliters of dimethyl sulfoxide solutions of 1.56 gram (0.00739 mole) 2-bromo-1-methyl isophthalic acid-benzyl ring propane, add 1.429 gram (0.0127 mole) potassium tert.-butoxides.Reaction is heated to 72 ℃ after 4 hours, adds ether and water.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Vacuum is removed the solvent in the filtrate, obtains the pure 3-methyl-3-benzyl ring propylene of 0.88g 70%, is oil.Main by product (roughly 20%) is 1-methyl isophthalic acid-benzyl ring propane.
The preparation of embodiment 7:3-methyl-3-phenoxymethyl ring third-2-alkene (compound 7)
Can the methylallyl phenyl ether be converted into 3-methyl-3-phenoxymethyl ring third-2-alkene of purity 90% by being similar to the mode that alpha-methyl styrene is converted into 3-methyl-3-benzyl ring propylene (embodiment 6).
The preparation of embodiment 8:1-methyl-2-benzyl rings propylene (compound 8)
In stirring rod and membranous 50 ml flasks are housed, under the dry nitrogen atmosphere, add 1 milligram 1,10-phenanthroline, 1.34 gram (11.5mmol) N, N, N ', N '-Tetramethyl Ethylene Diamine and 25 milliliters of tetrahydrofuran (THF)s.Mixture is cooled to-30 ℃, adds 1.5 milliliters of (22mmol) 1-methylcyclopropenes by syringe.(by 3-chloro-2-methyl-propylene production; See Hopf, H.; Wachholz, G.; Walsh, R.Chem.Ber.1985,118,3579, and Koster, people such as R, Liebigs Annalen Chem.1973,1219-1235).For preparing the hexane liquid that a kind of dark ferrugineous solution need add 1.0 milliliters of 1.6M butyllithiums.Add 6.0 milliliters of 1.6M butyl lithium solutions (9.6mmol) further, stirred 15 minutes down, obtain the 1-methylcyclopropene solution of lithiumation at-30 ℃.Add 1.64 gram cylites, being warmed to slowly in 20 minutes+5 ℃, the color that obtains shoaling.To react with 0.5 ml methanol cancellation, promptly bathe temperature evaporates to dryness down in+25 ℃ in a vacuum, between ether and diluted hydrochloric acid aqueous solution, distribute, use anhydrous magnesium sulfate drying, and evaporate to dryness more in a vacuum, obtain 1.3 and restrain 1-methyl-2-benzyl rings propylene.
Embodiment 9:1-(2-(4-chloro-phenyl-sulphur) ethyl) cyclopropylene (compound 9)
A.2-bromo-4-(1-ethoxy ethoxy)-but-1-ene
With 10.38 gram (0.0687 mole) 3-bromo-3-butene-1-20 milliliters of diethyl ether solutions of alcohol and the refrigerative in ice-water bath of 50 milligrams of (0.000263 mole) tosic acid monohydrates whiles, drip to add 19 milliliters of (0.199 mole) ethyl vinyl ethers at leisure, keep internal temperature＜10 ℃.At 0 ℃ after following 1 hour, add several triethylamines.Reaction mixture is poured on waterborne.Change the mixture that obtains over to separating funnel, separate each phase.With the organic layer of telling salt water washing, the dry and filtration with salt of wormwood then.Remove the solvent in the filtrate in a vacuum, obtain 14.04 gram 2-bromo-4-(1-ethoxy ethoxy)-but-1-enes, be oil.
B.1,1,2-three bromo-2-[2-(1-ethoxy ethoxy)-ethyl]-cyclopropane
In 108 milliliters of dichloromethane solutions and 0.5-0.9 milliliter 45% potassium hydroxide aqueous solution of 14.02 gram (0.0628 mole) 2-bromo-4-(1-ethoxy ethoxy)-but-1-enes, add 16.4 milliliters of (0.118 mole) methenyl bromides and 2.88 gram (0.00628 mole) N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and 28 milliliters of (0.314 mole) 45% potassium hydroxide aqueous solutions.After 3 days reaction mixture is poured on waterborne.Change the mixture that obtains over to separating funnel, separate each phase.In isolating organic layer, add 2.88 gram (0.00628mol) N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and 28 milliliters of (0.314mol) 45% potassium hydroxide aqueous solutions.After 24 hours, add hexane and water.With mixture by the gravity filtration of qualitative corrugation filter paper.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Remove the solvent in the filtrate in a vacuum, obtain 17.0 grams 1,1,2-three bromo-2-[2-(1-ethoxy ethoxy)-ethyl]-cyclopropane, be oil.
C.1,1,2-three bromo-2-(2-hydroxyethyl) cyclopropane
To 16.5 gram (0.0418 moles) 1,1,2-three bromo-2-[2-(1-ethoxy ethoxy)-ethyl]-slurry of cyclopropane in 145 ml methanol and 40 ml waters in, add 0.306 gram (0.00161 mole) tosic acid monohydrate and 145 milliliters of 6M hydrochloric acid.After at room temperature stirring 1 hour, in a vacuum solvent is removed from reaction mixture.In resistates, add ethyl acetate and water.Change the mixture that obtains over to separating funnel, separate each phase.With the organic layer of telling salt water washing, use MgSO then 4Dry also filtration.In a vacuum solvent is removed from filtrate, obtained 11.9 grams 1,1,2-three bromo-2-(2-hydroxyethyl) cyclopropane is oil.
D.1,1,2-three bromo-2-(2-phenylsulfonyloxy ethyl) cyclopropane
With 3.00 gram (0.00929 moles) 1,1, the dichloromethane solution of 2-three bromo-2-(2-hydroxyethyl) cyclopropane and 0.901 milliliter (0.0111 mole) drip 1.18 milliliters of (0.00929 mole) benzene sulfonyl chlorides of adding by valinche when pyridine solution is cooled to 0 ℃.Be warming up to room temperature.After 3 days, add entry.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.In a vacuum solvent is removed from filtrate, it is pure 1,1 to obtain 3.10 grams 80%, and 2-three bromo-2-(2-phenylsulfonyloxy ethyl) cyclopropane is oil.
E.2-(2-(4-chloro-phenyl-sulphur) ethyl)-1,1,2-three bromo cyclopropane
The methanol solution that in 3 ml methanol solution of 0.234 gram (0.162 mole) 4-chlorine phenylmercaptan, adds 0.371 milliliter of (0.00162 mole) 25% sodium methylate.At room temperature stir about removed in a vacuum and desolvates after 1 hour.In resistates, add 0.750 gram (0.00151 mole) 1,1, the anhydrous N of 2-three bromo-2-(2-phenylsulfonyloxy ethyl)-cyclopropane, dinethylformamide solution.At room temperature stir for after 24 hours, reaction mixture is poured on waterborne, use ethyl acetate extraction then.With organic layer MgSO 4Dry also filtration.In a vacuum solvent is removed from filtrate, obtained 0.750 gram oil, it then with 0.5% to 1% ether/hexane column chromatography purifying, is obtained 0.500 gram 2-(2-(4-chloro-phenyl--sulphur) ethyl)-1,1,2-three bromo cyclopropane are oil.
F.1-(2-(4-chloro-phenyl-sulphur) ethyl) cyclopropylene
By means of using refractory pebbles valve 0.500 gram (0.0011mol) 2-(2-(4-chloro-phenyl-sulphur) ethyl)-1,1 that under nitrogen atmosphere, packs into, 6 milliliters of diethyl ether solutions of 2-three bromo cyclopropane.Refrigerative adds the ether solution of 2.38 milliliters of (0.00334mol) 1.4M lithium methides simultaneously at leisure by syringe in ice-water bath.After 15 minutes, add 2 ml waters by means of syringe.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Desolvate in bathing from filtrate, to remove under warm 20 ℃ in a vacuum, obtain 0.100 gram 1-(2-(4-chloro-phenyl-sulphur) ethyl) cyclopropylene, be oil.
Embodiment 10:2-(2-phenylsulfonyloxy ethyl)-cyclopropylene (compound 10)
By means of using refractory pebbles valve 0.745 gram (0.00150mol) 1,1 that under nitrogen atmosphere, pack into, 4 milliliters of diethyl ether solutions of 2-three bromo-2-(2-phenylsulfonyloxy ethyl)-cyclopropane.In dry ice/acetone batch, be cooled in-78 ℃, add the ether solution of 23.45m1 (0.00450mol) 1.4M lithium methide by syringe at leisure.In ice-water bath, be warming to 0 ℃ after 15 minutes, be cooled to then-78 ℃ about 30 minutes, then add 2 ml waters by syringe.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Bathe under the temperature at 20 ℃ and in a vacuum solvent to be removed from filtrate, obtain＞0.155 gram has been infected with 70% pure 2-(2-phenylsulfonyloxy ethyl)-cyclopropylene of 30%1-(2-hydroxyethyl) cyclopropylene, has been oil.
The preparation of embodiment 11:2-(1-(4-bromine pyrazoles))-1-ethyl cyclopropylene (compound 11)
A.2-hydroxyl-1-ethyl cyclopropylene
With 1.15 gram (3.6mmol) 1,1,40 milliliters of diethyl ether solutions of 2-three bromo-2-(2-hydroxyethyl) cyclopropane (preparation as mentioned above) are cooled to-78 ℃.The adding lithium methide (1.4M, 10.3 milliliters, 14.4mmol).Reaction mixture is warmed to 5 ℃, and kept 1/2nd hours.To react the water cancellation, separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, thick product is used for next step reaction at once.
B.2-methyl sulphonyl-1-ethyl cyclopropylene
The thick product of above-mentioned reaction is dissolved in 5 milliliters of ether, and in ice bath, cools off.Add triethylamine (1 milliliter), add 0.49 gram methylsulfonyl chloride (4.3mmol) then.Reaction mixture was stirred 1 hour.Add entry with other ether and separate each phase.Wash ether with water twice mutually, use the salt water washing, use dried over mgso, and stripping, obtain the light yellow liquid of 380 milligrams of 2-methyl sulphonyls-1-ethyl cyclopropylene.
C.2-(1-(4-bromine pyrazoles))-1-ethyl cyclopropylene
(0.13g 3.3mmol) adds 0.51 gram 4-bromine pyrazoles (3.5mmol) in the suspension of 5 milliliters of DMF to 60% sodium hydride.To react and at room temperature stir 15 minutes, in ice bath, cool off then.Adding 2-methyl sulphonyl-1-ethyl cyclopropylene (280 milligrams, 1.7mmol).Remove ice bath, will react and at room temperature stir 2 hours.In reaction mixture, add ether and water, and separate each phase.With water with other ether extraction.The ether that merges is washed with water three times mutually, use the salt water washing, use dried over mgso, and stripping.The chromatographic separation product obtains 30 milligram of 72% pure 2-(1-(4-bromine pyrazoles))-1-ethyl cyclopropylene.
The preparation of embodiment 12:7-(1-imidazoles)-1-heptyl cyclopropylene (compound 12)
A.1-(1-ethoxy ethoxy)-6-bromohexane
In 40 milliliters of diethyl ether solutions of 80 milligrams of toluenesulphonic acidss of refrigerative, inject 20 gram (110mmol) 6-bromine hexanol and 40 milliliters of ethyl vinyl ethers simultaneously by the funnel that adds that separates.During 1 hour that injects, the temperature of maintenance reaction mixture is at 7 ℃ or be lower than 7 ℃ temperature.The reaction mixture stirring was longer than 20 minutes, is added roughly 1 milliliter of triethylamine then.With reaction mixture water and salt water washing, use the salt of wormwood drying, filter and stripping, obtain the light yellow liquid of 25.7 grams, it can be used without purifying further.
B.9-(1-ethoxy ethoxy)-2-bromine ninth of the ten Heavenly Stems-1-alkene
Handle the slurry of 5.6 gram magnesium smear metals (230mmol) in 100 milliliters of THF with a small amount of glycol dibromide.(38.5 grams, 152mmol), holding temperature is at 40-50 ℃ to inject 1-(1-ethoxy ethoxy)-6-bromohexane in reaction mixture at leisure.After adding end, reaction mixture was deposited 20 minutes, under 0 ℃, transferred to 33.4 gram (167mmol) 2 then, in 25 milliliters of THF solution of 3-propylene bromide by intubate.Reaction mixture was stirred 15 minutes down at 0 ℃, at room temperature stirred water cancellation then then 15 minutes.Reaction mixture is transferred in the separating funnel.Add a small amount of 1NHCl, separate each phase,, use dried over mgso then, filter and stripping, obtain the yellow liquid of 33.63 grams, it can be used without purifying further ether phase water and salt water washing.
C.1,1,2-three bromo-2-(7-hydroxyl heptyl) cyclopropane
With 9-(1-ethoxy ethoxy)-2-bromine ninth of the ten Heavenly Stems-1-alkene (33.63g, 115mmol), 4.1 gram N, N '-dibenzyl-N, N, N ', N '-tetraethyl-ethylene ammonium dibromide, 42 gram 45% potassium hydroxide (337mmol), the mixture of 93 gram methenyl bromides (368mmol) and 280 gram methylene dichloride at room temperature promptly stirred two days.When reaction stopped, reaction mixture changed separating funnel over to, washed with water.Methylene dichloride is changed in the flask mutually, as above handle, then restir 3 days at room temperature with the phase-transfer catalyst and 45% potassium hydroxide of equal amts.Reaction mixture is washed with water, with dried over mgso methylene dichloride phase, then stripping.Product was at room temperature handled 1 hour with 320 ml methanol and 40 milliliters of 1NHCl.Stripped methanol adds ethyl acetate.With organic phase water and salt water washing, use 200 milliliters of silica gel treatment then.Filter, then stripping obtains 38 gram black products.With its chromatographic separation on silica gel, obtain 19.0 grams 1,1,2-three bromo-2-(7-hydroxyl heptyl) cyclopropane, light yellow liquid.
D.1-(7-hydroxyl heptyl)-cyclopropylene
(1.4M 10mmol) handles 1.0 grams 1,1,25 milliliters of diethyl ether solutions of 2-three bromo-2-(7-hydroxyl heptyl) cyclopropane (2.5mmol) with 7.2 milliliters of lithium methides down at-78 ℃.After 5 minutes, reaction mixture is warmed to 0 ℃, and deposits in this temperature.To react and use the saturated ammonium chloride cancellation.With reaction mixture water and salt water washing, use dried over mgso, filter and stripping, obtain 240 milligrams of 1-(7-hydroxyl heptyl)-cyclopropylene.
E.1-(7-mesyloxy heptyl)-cyclopropylene
50 milliliters of diethyl ether solutions of 3.8mmol1-(7-hydroxyl heptyl)-cyclopropylene are cooled off in ice bath.(4.2mmol stirs reaction mixture 2.5 hours down at 0 ℃ to add triethylamine (1 milliliter) and 0.48 gram methylsulfonyl chloride.With reaction mixture water and salt water washing, use dried over mgso, filter and stripping, obtain 1-(7-mesyloxy heptyl)-cyclopropylene, it can use without further purifying.
F.7-(1-imidazoles)-1-heptyl cyclopropylene
(0.08g 2mmol) adds 0.14 gram imidazoles (2mmol) in the suspension of 5 milliliters of DMF to 60% sodium hydride in ice bath.To react and stir 15 minutes, add 3 milliliters of DMF liquid of 0.3 gram (1.3mmol) 1-(7-mesyloxy heptyl)-cyclopropylene then.Reaction mixture was stirred 10 minutes, remove ice bath then, at room temperature stirring reaction is 1 hour.In reaction mixture, add ether and water, and separate each phase.With water with other ether extraction.The ether that merges is washed with water three times mutually, use the salt water washing, use dried over mgso, and stripping.The chromatographic separation product obtains 80 milligrams of 7-(1-imidazoles)-1-heptyl cyclopropylene.
The preparation of embodiment 13:7-(diphenyl amino)-1-heptyl cyclopropylene (compound 13)
(0.42g 2.5mmol) is cooled to-78 ℃ in 10 milliliters of THF, with 1.6 milliliters of (1.4m, 2.2mmol) lithium methide processing with pentanoic.Add 1-(7-mesyloxy heptyl)-cyclopropylene, remove cryostat, and reaction mixture is warming up to room temperature.To react and place water cancellation then 5.5 hours.In reaction mixture, add ether and water, and separate each phase.Wash ether with water twice mutually, use the salt water washing, use dried over mgso, and stripping.The chromatographic separation product obtains 80 milligrams of 7-(diphenyl amino)-1-heptyl cyclopropylene, is colourless liquid.
The preparation of embodiment 14:1-cyclohexyl ring propylene (compound 14)
By cyclohexane carboxylic acid methyl esters and vinyl trimethyl silyl such as Mizojiri, R.; Urabe, H.; Sato, F.J.Org Chem.2000, preparation 1-cyclohexyl-2-(trimethyl silyl) ring propyl alcohol described in 65,6217.Change this material into cyclopropylene with the similar method described in same reference.
The preparation of embodiment 15:1-((2-carboxy-N-morpholinyl) ethyl)-cyclopropylene
A.2-(2-bromo-allyl group)-diethyl malonate
By using hexane wash, remove in 21.70 gram (0.542 mole) 60% sodium hydride oil solutions, be oil.In being suspended in 200 milliliters of resistatess in the tetrahydrofuran (THF), add 84.38 milliliters of (0.556 mole) diethyl malonates at leisure by feed hopper.When reaction being cooled to-35 to-10 ℃, add 100 gram (0.400 moles) 2,3-propylene bromide at leisure by feed hopper.Be heated to and refluxed back 1 hour, will react cool to room temperature, and vacuum concentration.In resistates, add hexane and water, change the mixture that obtains over to separating funnel, and separate each phase.With the organic layer of telling 1N salt acid elution, then with dried over mgso and filtration.In a vacuum solvent is removed from filtrate, obtained 154 gram 2-(2-bromo-allyl group)-diethyl malonates, be oil.
B.2-(2-bromo-allyl group)-propanedioic acid
The mixture of 10.5 gram (0.0376 mole) 2-(2-bromo-allyl group)-diethyl malonates and 37.6 milliliters of (0.470 mole) 50% aqueous sodium hydroxide solutions was at room temperature stirred 4 days.With the reaction mixture ether extraction.By the isolating water layer of adding concentrated hydrochloric acid acidifying, and add ether.Change the mixture that obtains over to separating funnel, separate each phase.The organic layer of telling is also filtered with dried over mgso.In a vacuum solvent is removed from filtrate, obtained the solid of 5.3 gram 2-(2-bromo-allyl group)-propanedioic acid, can continue without purification.
C.4-bromo-penta-obtusilic acid
5.3g (0.0238 mole) is clean, and unpurified 2-(2-bromo-allyl group)-propanedioic acid is heated to 125-130 ℃, keeps 8 hours, obtains 3.73 gram 4-bromo-, penta-obtusilic acid, can continue without purification.
D.4-bromo-penta-obtusilic acid ethyl ester
1 N that has to 3.73 gram (0.0208 mole) unpurified 4-bromo-penta-obtusilic acids adds 1.18 milliliters of (0.0162 mole) thionyl chloride in 3 milliliters of chloroformic solutions of dinethylformamide.After this mixture heating up to 60 ℃ kept 30 minutes, it is joined in the solution of 2.46 milliliters of (0.0436 mole) ethanol and 1.97 milliliters of (0.024 mole) pyridines and 13 milliliters of methylene dichloride.Stir after 30 minutes, with the reaction mixture vacuum concentration.In resistates, add ether and water.Change the mixture that obtains over to separating funnel, separate each phase.The organic layer of telling is also filtered with dried over mgso.In a vacuum solvent is removed from filtrate, is obtained 3.5 gram 4-bromo-, penta-obtusilic acid ethyl ester, be oil, with it by the vacuum distilling purifying.
E.1,1,2-three bromo-2-((3-carbonyl oxyethyl group) ethyl)-cyclopropane
To be similar to the mode of the preparation corresponding intermediates described in the embodiment 9, preparation 1,1,2-three bromo-2-((3-carbonyl oxyethyl group) ethyl-cyclopropyl alkane.
The resistates that obtains is passed through the column chromatography purifying with ether/hexane.
F.1,1,2-three bromo-2-((2-carboxyl) ethyl)-cyclopropane
With 10.2 gram (0.0269 moles) 1,1,2-three bromo-2-((the 3-carbonyl oxyethyl group) ethyl) solution of cyclopropane in 40 milliliters of (0.736 mole) 48% Hydrogen bromides and 40 ml waters is heated to backflow, keeps 8 hours, with its cool to room temperature, then passes through Shark The filter paper vacuum filtration.Before adding ether, wash isolated solid with water.Solution is changed in the separating funnel, with the saturated sodium bicarbonate aqueous solution washing, with its separation, and by adding the 1N hcl acidifying.Again change the aqueous solution over to separating funnel, and use ether extraction.The organic layer of telling is also filtered with dried over mgso.In a vacuum solvent is removed from filtrate, obtained 5.9 grams 1,1, the solid of 2-three bromo-2-((2-carboxyl))-ethyl cyclopropane, it can directly use.
G.1,1,2-three bromo-2-((2-carboxy-N-morpholinyl) ethyl)-cyclopropane
To 0.97 gram (0.00276 mole) 1,1,2-three bromo-2-((2-carboxyl))-ethyl-cyclopropyl alkane adds 1 N in the slurry of 2 milliliters of chloroforms, dinethylformamide and 0.434 milliliter of (0.00596 mole) thionyl chloride.After the reflux 15 minutes, with the reaction mixture vacuum concentration.2 milliliters of dichloromethane solutions of resistates are joined in 1 milliliter of dichloromethane solution of 0.486 milliliter of (0.00552 mole) morpholine, it is cooled to-20 ℃.After 30 minutes, with the reaction mixture vacuum concentration.Extract from the 1N hydrochloric acid of minimum with ethyl acetate and to obtain resistates.With organic layer MgSO 4Dry also filtration.In a vacuum solvent is removed from filtrate, obtained 1.08 grams 1,1,2-three bromo-2-((2-carboxyl N-morpholinyl) ethyl)-cyclopropane are oil.
H.1-((2-carboxy-N-morpholinyl) ethyl)-cyclopropylene
Prepare 0.460 in the mode that is similar to compound 1 and restrain 60% pure 1-((2-carboxy-N-morpholinyl) ethyl)-cyclopropylene.
3-hydroxyl carbonyl methyl isophthalic acid, 2,3-triphenyl cyclopropylene (compound 40) is commercially availabie.
The preparation of embodiment 16:1-(7-(N-piperidyl imino-heptyl))-cyclopropylene (compound 36)
A.1-(7-(enanthaldehyde))-cyclopropylene
1-(7-hydroxyl heptyl)-cyclopropylene (by implementing 12 preparations) is passed through Arrowood, T.L. with the Swem oxygenizement; Kass, S.R.Telrahedrom, 1999,55, the method for describing among the 6739-48 is oxidized to 1-(7-(enanthaldehyde))-cyclopropylene.
B.1-(7-N-piperidyl imino--heptyl))-cyclopropylene
In the ethanolic soln of 100 milligrams of 1-(7-(enanthaldehyde))-cyclopropylene (0.66mmol), add 70 milligrams of (0.70mmol) N-amino piperidines.Reaction mixture was stirred 2 hours, add ether then, water and several acetate.Isolate water,, use dried over mgso then, and filter ether phase water and salt water washing.The stripping solvent obtains 70 milligrams of 1-(7-N-piperidyl imino--heptyl))-cyclopropylene.
The preparation of embodiment 17:1-(3-4-trifluoromethylphenopendant methyl)-2-ethyl cyclopropylene (compound 37)
A.1,1,2-three bromo-2-ethyl cyclopropane
By preparing 1,1 by 2-bromo-1-butylene, 2-three bromo-2-ethyl cyclopropane with the used identical method of embodiment 4c.
B.1-(methylol)-2-ethyl cyclopropylene
With 3.0 gram (10mmol) 1,1,50 milliliters of diethyl ether solutions of 2-three bromo-2-ethyl cyclopropane are cooled to-78 ℃.The adding lithium methide (1.4M, 21.4 milliliters, 30mmol).Reaction mixture is warmed to 5 ℃.(1.20 grams 40mmol), stir reaction mixture 1 hour down at 5 ℃, allow to be warming up to room temperature then, restir one hour to add solid polyformaldehyde.To react the water cancellation, separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, obtain 900 milligrams of 1-(methylol)-2-ethyl cyclopropylene, be yellow oil.
C.1-(mesyloxy methyl)-2-ethyl cyclopropylene
In ice bath to 0.70g (7.13mmol) 1-(methylol)-2-ethyl cyclopropylene (compound 3) and 2 milliliters of triethylamines in the solution of 15 milliliters of ether, add 0.86 gram (7.5mmol) methylsulfonyl chloride.Reaction mixture was placed 1.5 hours water cancellation then.Separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, obtain 840 milligrams of 1-(mesyloxy methyl)-2-ethyl cyclopropylene, be yellow oil.
D.1-(3-4-trifluoromethylphenopendant methyl)-2-ethyl cyclopropylene
At room temperature (0.41 gram 2.5mmol) joins 0.07g sodium hydride (1.8mmol) in the suspension of 3 milliliters of DMF with the 3-trifloro methyl phenol.After 15 minutes, add 2 milliliters of DMF solution of 0.3 gram (1.7mmol) 1-(mesyloxy methyl)-2-ethyl cyclopropylene, then reaction mixture was stirred 2 hours.Add ethyl acetate and water.Separate each phase, ethyl acetate is used 1N aqueous sodium hydroxide solution and salt water washing mutually, use dried over mgso then, filter and stripping, obtain 160 milligrams of 1-(3-4-trifluoromethylphenopendant methyl)-2-ethyl cyclopropylene, be tawny liquid.
Embodiment 18:2-octyl group-1-(preparation of 2-(2-boron-1,3-dioxetane))-cyclopropylene (compound 38)
A.2-octyl group-1-(boric acid)-cyclopropylene
Will with and embodiment 1 described in 1.30 gram (3.3mmol) 2-octyl groups-1,1 of same method preparation, the ethereal solution of 2-three bromo cyclopropane is cooled to-78 ℃.The adding lithium methide (1.4M, 5.9 milliliters, 8.3mmol), reaction mixture was stirred 10 minutes, put into ice bath then, placed 30 minutes, and then be cooled to-78 ℃.Add triisopropyl boric acid ester (0.9 milliliter 3.9mmol), with reaction mixture stirring 15 minutes, is warming to 0 ℃ then.Add entry, the ether and the 1NHCl aqueous solution (abundance makes solution be acid).Separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, product is dissolved in the ether again, extract three times with the 1N aqueous sodium hydroxide solution.Extract with the acidifying of 6N aqueous hydrochloric acid, is used ether extraction three times.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, obtain 2-octyl group-1-(the boric acid)-cyclopropylene of 400 milligrams of light yellow solids.
B.2-octyl group-1-(2-(2-boron-1,3-dioxy butane (dioxetane)))-cyclopropylene
At room temperature use 0.3 milliliter 1, the 3-dihydroxypropane is handled the mixture of 10 milliliters of pentanes of 270 milligrams of 2-octyl group-1-(boric acid)-cyclopropylene (1.4mmol).1.5 after hour, change reaction mixture over to separating funnel.With pentane solution water and salt water washing, use dried over mgso, filter and stripping, obtain 90 milligram of 50% pure 2-octyl group-1-(2-(2-boron-1,3dioxetane))-cyclopropylene.
The NMR prediction: 0.88 (t, 3H), 0.98 (s, 2H), 1.1-1.3 (m, 10H), 1.55 (m, 2H), 1.9 (m, 2H), 2.5 (m, 2H), 4.1-4.4 (m, 4H)
The preparation of embodiment 19:1-methyl-2-(hydroxyl-(3-p-methoxy-phenyl) methyl) cyclopropylene (compound 39)
Under nitrogen keep to bathe temperature under-40 ℃ to about 2 milligram 1, in the mixture of 10-phenanthroline in 50 milliliters of diethyl ether, add (2.5 milliliters of Diisopropylamines successively by syringe, 17.9mmol), diethyl ether (3 milliliters), 1-methylcyclopropene (1.1 grams, 20.4mmol; By 3-chloro-2-methyl-propylene production, see Hopf, people such as H. Chem.Ber.1985,118,3579 and Koster, people such as R. Liebigs Annalen Chem.1973,1219-1235.).Add 1.0 milliliters of N-butyllithiums (1.6M hexane solution) then, remain brown up to solution.After this then add the same butyllithium (10.0 milliliters, 16 mmol) of another part.After stirring 15 minutes under-40 ℃, reaction is cooled to-70 ℃, adding 3-methoxybenzaldehyde (1.9 milliliters, 15.6mmol).After 3 minutes, will react quencher by adding 3 ml waters.After being warming up to room temperature, separate each layer.Organic phase is also dry in a vacuum with dried over mgso.Resistates is dissolved in diethyl ether,, washs with saturated sodium bicarbonate aqueous solution at last with 1M hydrochloric acid, salt water washing.Separate each layer.Organic phase with dried over mgso and dry in a vacuum, is obtained 1.0 gram 1-methyl-2-(hydroxyl (3-p-methoxy-phenyl) methyl) cyclopropylene.
Embodiment 20:1-phenyl-2.3,3-trichlorine cyclopropylene (compound 41)
By Eicher, theophil; Huch, Volker; Schneider, Volker; Veith, Michael.Synthesis, 1989,5, the method for describing among the 367-72 prepares 1-phenyl-2,3,3-trichlorine cyclopropylene.
Embodiment 21:1-(4-aminomethyl phenyl ketonic oxygen Ji Dingji)-cyclopropylene (compound 44)
A.5,6-two bromo-oneself-1-alcohol
(11.23g, in about 20 milliliters of dichloromethane solutions 112.3mmol), (5.80 milliliters add 12, about 20 milliliters of dichloromethane solutions 112.3+mmol) to add bromine to ice bath refrigerative 5-hexen-1-ol.Behind reinforced the finishing, mixture is dry in a vacuum, obtain 29.1 grams 5,6-two bromo-oneself-1-alcohol.
B.5-bromo-oneself-5-alkene-1-alcohol
To ice bath refrigerative 5,6-two bromo-oneself-(29.1 grams add tetrahydrofuran (THF) (62.4g, 112mmol) liquid of 20% potassium tert.-butoxide to 1-alcohol in about 59 milliliters of tetrahydrofuran solutions 112mmol).Behind reinforced the finishing, reaction mixture is warmed up to room temperature, stir about 30 minutes.Add ether and separate each phase then with water.With the organic layer dried over mgso of telling, dry in a vacuum then.Resistates is used 5 orifice plate post vacuum distilling purifying, obtain 23.16 grams, 87% pure 5-bromo-oneself-5-alkene-1-alcohol.
C.4-methyl-phenylformic acid 5-bromo-oneself-the 5-alkenyl esters
To the 5-bromo-oneself-5-alkene-1-alcohol (4.39 grams, add in 10.6 gram dichloromethane solutions 24.5mmol) 4-toluene acyl chlorides (3.95 grams, 25.6mmol) and triethylamine (3.3 restrain, 33mmol).At room temperature stir about diluted mixture after 2 hours with diethyl ether, then used the salt water washing with 1N hydrochloric acid then.Separate each phase, the organic layer dried over mgso is dry in a vacuum then, obtain 7.3 gram 4-methyl-phenylformic acid 5-bromo-oneself-the 5-alkenyl esters.
D.4-methyl-phenylformic acid 4-(1,2,2-three bromo-cyclopropyl)-butyl ester
In round-bottomed flask, drop into 4-methyl-phenylformic acid 5-bromo-oneself-the 5-alkenyl esters (7.3 grams, 24.6mmol), N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide (0.30 gram, 0.66mmol), methylene dichloride (25 gram), (25 grams are 98.9mmol) with 45% potassium hydroxide aqueous solution (11.5 grams for methenyl bromide, 92mmol), at room temperature stir 4 days.After adding entry, separate each layer.In the organic layer of telling, add N, N '-dibenzyl-N, N, N ', (0.30 gram, 0.66mmol), (27 grams, 107mmol) (12 restrain methenyl bromide N '-Tetramethyl Ethylene Diamine dibromide, 96mmol) with 45% potassium hydroxide aqueous solution.At room temperature restir added hexane and water after one day.With mixture gravity filtration, and separate each layer by qualitative filter paper.With the organic layer dried over mgso of telling, dry in a vacuum then.Use ethyl acetate/hexane by the column chromatography purifying resistates that obtains, obtain 4.9 and restrain 61% pure 4-methyl-phenylformic acid 4-(1,2,2-three bromo-cyclopropyl)-butyl ester.
E.4-(1,2,2-three bromo-cyclopropyl)-Ding-1-alcohol
(45.5 grams, (30 grams are 107mmol) with 30 gram water to add 50% wet chemical in 250 gram methanol solutions 97mmol) to 4-methyl-phenylformic acid 4-(1,2,2-three bromo-cyclopropyl)-butyl ester.With reaction be heated to 60 ℃ about 2 hours, cool to room temperature then.After about 15 hours, (30 grams 107mmol) with 30 gram water, are heated to 60 ℃ with reaction and kept about 2 hours, then cool to room temperature to add 50% aqueous solution salt of wormwood.With the reaction mixture vacuum concentration, the resistates that obtains with ether extraction then.Organic layer is washed with alkalization water (pH10).Separate each phase, organic phase is for using dried over mgso, dry in a vacuum then.Use ether/hexane to pass through the column chromatography purifying resistates, obtain 14.5 and restrain 74% pure 4-(1,2,2-three bromo-cyclopropyl)-Ding-1-alcohol.
F.1-(4-hydroxybutyl)-cyclopropylene
Under nitrogen atmosphere, add 4-(1,2,2-three bromo-cyclopropyl)-Ding-1-alcohol (5.11 grams, 4 milliliters of diethyl ether solutions 14.5mmol), and be cooled to 0 ℃.Use syringe, add the 1.4M lithium methide diethyl ether (41.6 milliliters, 58.2mmol).After 15 minutes, will react quencher by adding about 2 ml waters.Separate each phase.With the organic layer dried over mgso of telling, and dry in a vacuum, obtain 2.51 gram 1-(4-hydroxybutyl)-cyclopropylene, be oil.
G.1-(4-aminomethyl phenyl ketonic oxygen Ji Dingji)-cyclopropylene
(810 milligrams, 5-10 milliliter dichloromethane solution 7.23mmol) is cooled to 0 ℃ with 1-(4-hydroxybutyl)-cyclopropylene.To wherein add triethylamine (0.895 milliliter, 7.88mmol), then add 4-toluene acyl chlorides (0.794 milliliter, 7.30mmol).About 10 ℃ down stir 1 hour after, reaction is cooled to 0 ℃, and add triethylamine (0.895 milliliter, 7.88mmol), then add 4-toluene acyl chlorides (0.794 milliliter, 7.30mmol).At room temperature stir about-hour after, with the reaction mixture vacuum concentration.In resistates, add diethyl ether and water.Separate each phase.With the organic layer of telling 1N salt acid elution, use dried over mgso then, and dry in a vacuum, obtain 2.05 oil.Use ethyl acetate/hexane at silica gel upper prop chromatogram purification it, obtain 470 milligram of 50% pure 1-(4-aminomethyl phenyl ketonic oxygen Ji Dingji)-cyclopropylene, have remaining right-toluic acid.
Embodiment 22:1-benzyl-2-bromine cyclopropylene (compound 45)
A.1-benzyl-1,2,2-three bromo cyclopropane
Prepare 1-benzyl-1,2 by method shown in the embodiment 1b by 1-(2-bromo-allyl group)-benzene, 2-three bromo cyclopropane.
B.1-benzyl-2-bromine cyclopropylene
With 1-benzyl-1,2,2-three bromo cyclopropane (1.21 grams, 3.27mmol) and diethyl phosphite (1.69 milliliters, 13.1mmol) and triethylamine (0.455 milliliter 3.26mmol) is at room temperature mixed 24 hours.In reaction mixture, add hexane, it is used 1N salt acid elution.Separate each phase.Water layer is extracted with diethyl ether, and separate each phase.Use diethyl ether/hexane at silica gel upper prop chromatogram purification the organic layer that merges, obtain 300 milligrams of 1-benzyls-2-bromine cyclopropylene, be oil.
Embodiment 23:1-benzyl-2-chlorine cyclopropylene (compound 46)
A.1-(2-bromo-allyl group)-benzene
By 2,3-propylene bromide and phenyl-magnesium-bromide prepare 1-(2-bromo-allyl group)-benzene by method shown in the embodiment 1a.
B.1-benzyl-1-bromo-2,2-two Cyclopropanoyl Chlorides
To 1-(2-bromo-allyl group)-benzene (6.80 grams, chloroform 34.5mmol) (39.4 milliliters 493mmol) add 45% potassium hydroxide aqueous solution (16.2ml in the solution, 189mmol) and N, N '-dibenzyl-N, N, N ', and N '-Tetramethyl Ethylene Diamine dibromide (790 milligrams, 1.72mmol).After at room temperature stirring 3 days, add chloroform (2 milliliters) and 45% potassium hydroxide aqueous solution (16.2ml, 189mmol) and N, N ' dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide (790 milligrams, 1.72mmol).At room temperature restir added hexane and water after one day.Separate each phase.With the organic layer dried over mgso of telling, and dry in a vacuum, obtaining 6.7 gram 1-benzyl-1-bromo-2,2-two Cyclopropanoyl Chlorides are oil.
C.1-benzyl-2-chlorine cyclopropylene
With 1-benzyl-1-bromo-2, (1.45 grams, about 4 milliliters of diethyl ether solutions 5.18mmol) are cooled to 0 ℃ to 2-two Cyclopropanoyl Chlorides, and are placed under the nitrogen atmosphere.To the ether that wherein adds the 1.4M lithium methide (3.70 milliliters, 5.18mmol) liquid.After 15 minutes, will react quencher by adding 2 ml waters.Separate each phase.With the organic layer dried over mgso of telling, and dry in a vacuum, obtain 720 milligrams of 1-benzyls-2-chlorine cyclopropylene, be oil.
Embodiment 24:1-(the preparation of 2-(furans-2-base ketonic oxygen base ethyl)-cyclopropylene (compound 47)
A.2-bromo-4-(1-ethoxy ethoxy)-but-1-ene
With 20 milliliters of diethyl ether solutions and 50 milligrams of (0.000263 mole) tosic acid-hydrate refrigerative whiles in ice-water bath of 10.38 gram (0.0687 mole) commercially available 3-bromo-3-butene-1-alcohol, drip to add 19 milliliters of (0.199 mole) ethyl vinyl ethers at leisure, keep internal temperature＜10 ℃.At 0 ℃ after following 1 hour, add several triethylamines.Reaction mixture is poured on waterborne.Change the mixture that obtains over to separating funnel, separate each phase.With the organic layer of telling salt water washing, the dry and filtration with salt of wormwood then.Remove the solvent in the filtrate in a vacuum, obtain 14.04 gram 2-bromo-4-(1-ethoxy ethoxy)-but-1-enes, be oil.
B.1,1,2-tribromo 2-[2-(1-ethoxy ethoxy)-ethyl]-cyclopropane
In 108 milliliters of dichloromethane solutions and 0.5-0.9 milliliter 45% potassium hydroxide aqueous solution of 14.02 gram (0.0628 mole) 2-bromo-4-(1-ethoxy ethoxy)-but-1-enes, add 16.4 milliliters of (0.118 mole) methenyl bromides and 2.88 gram (0.00628 mole) N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and 28 milliliters of (0.314 mole) 45% potassium hydroxide aqueous solutions.After 3 days reaction mixture is poured on waterborne.Change the mixture that obtains over to separating funnel, separate each phase.In isolating organic layer, add 2.88 gram (0.00628mol) N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and 28 milliliters of (0.314mol) 45% potassium hydroxide aqueous solutions.After 24 hours, to wherein adding hexane and water.With mixture by the gravity filtration of qualitative corrugation filter paper.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Remove the solvent in the filtrate in a vacuum, obtain 17.0 grams 1,1,2-three bromo-2-[2-(1-ethoxy ethoxy)-ethyl]-cyclopropane, be oil.
C.2-(2-hydroxyethyl)-1,1,2-three bromo cyclopropane
To 16.5 gram (0.0418 moles) 1,1,2-three bromo-2-[2-(1-ethoxy ethoxy)-ethyl]-slurry of cyclopropane in 145 ml methanol and 40 ml waters in, add 0.306 gram (0.00161 mole) tosic acid monohydrate and 145 milliliters of 6M hydrochloric acid.After at room temperature stirring 1 hour, in a vacuum solvent is removed from reaction mixture.In resistates, add ethyl acetate and water.Change the mixture that obtains over to separating funnel, separate each phase.With the organic layer of telling salt water washing, use MgSO then 4Dry also filtration.In a vacuum solvent is removed from filtrate, obtained 11.9 gram 2-(2-hydroxyethyl)-1,1,2-three bromo cyclopropane are oil.
D.1-(2-hydroxyethyl)-cyclopropylene
With 1.15 gram (3.6mmol) 2-(2-hydroxyethyl)-1,1,40 milliliters of diethyl ether solutions of 2-three bromo cyclopropane (preparation as mentioned above) are cooled to-78 ℃.The adding lithium methide (1.4M, 10.3 milliliters, 14.4mmol).Reaction mixture is warmed to 5 ℃, and kept 1/2nd hours.To react the water cancellation, separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, thick product is used for next step reaction at once.
E) 1-(2-(furans-2-base ketonic oxygen base ethyl)-cyclopropylene
To 0 ℃ 1-(2-hydroxyethyl)-cyclopropylene (300 milligrams, add in about 10 milliliters of dichloromethane solutions 3.56mmol) triethylamine (0.540 milliliter, 3.88mmol) and furans-2-carbonyl chloride (0.356 milliliter, 3.60mmol).At room temperature stir about is after 2 hours, with the reaction mixture vacuum concentration.In resistates, add diethyl ether and water.Separate each phase.With organic layer 1N salt acid elution.Separate each mutually after, with the organic layer dried over mgso, and drying in a vacuum, obtain 430 milligrams of oil.Use diethyl ether/hexane at silica gel upper prop chromatogram purification it, (2-(furans-2-base ketonic oxygen base ethyl)-cyclopropylene is oil to obtain 20 milligrams of 1-.
The preparation of embodiment 25:1-(7-(4-mesyloxy phenyl)-ketonic oxygen base heptyl)-cyclopropylene (compound 53)
A.1-(1-ethoxy ethoxy)-6-bromohexane
In 40 milliliters of diethyl ether solutions of 80 milligrams of toluenesulphonic acidss of refrigerative, inject 20 gram (110mmol) 6-bromine hexanol and 40 milliliters of ethyl vinyl ethers simultaneously by the funnel that adds that separates.During 1 hour that injects, the temperature of maintenance reaction mixture is at 7 ℃ or be lower than 7 ℃ temperature.The reaction mixture stirring was longer than 20 minutes, is added roughly 1 milliliter of triethylamine then.With reaction mixture water and salt water washing, use the salt of wormwood drying, filter and stripping, obtain the light yellow liquid of 25.7 grams, it can be used without purifying further.
B.9-(1-ethoxy ethoxy)-2-bromine ninth of the ten Heavenly Stems-1-alkene
Handle the slurry of 5.6 gram magnesium smear metals (230mmol) in 100 milliliters of THF with a small amount of glycol dibromide.(38.5 grams, 152mmol), holding temperature is at 40-50 ℃ to inject 1-(1-ethoxy ethoxy)-6-bromohexane in reaction mixture at leisure.After adding end, reaction mixture was deposited 20 minutes, under 0 ℃, transferred to 33.4 gram (167mmol) 2 then, in 25 milliliters of THF solution of 3-propylene bromide by intubate.Reaction mixture was stirred 15 minutes down at 0 ℃, at room temperature stirred water cancellation then then 15 minutes.Reaction mixture is transferred in the separating funnel.Add a small amount of 1NHCl, separate each phase,, use dried over mgso then, filter and stripping, obtain the yellow liquid of 33.63 grams, it can be used without purifying further ether phase water and salt water washing.
C.1,1,2-three bromo-2-(7-hydroxyl heptyl) cyclopropane
With 9-(1-ethoxy ethoxy)-2-bromine ninth of the ten Heavenly Stems-1-alkene (33.63g, 115mmol), 4.1 gram N, N '-dibenzyl-N, N, N ', N '-tetraethyl-ethylene ammonium dibromide, 42 gram 45% potassium hydroxide (337mmol), the mixture of 93 gram methenyl bromides (368mmol) and 280 gram methylene dichloride at room temperature promptly stirred two days.When reaction stopped, reaction mixture changed separating funnel over to, washed with water.Methylene dichloride is changed in the flask mutually, handle as previously mentioned, then restir 3 days at room temperature with the phase-transfer catalyst and 45% potassium hydroxide of equal amts.Reaction mixture is washed with water, with dried over mgso methylene dichloride phase, then stripping.Product was at room temperature handled 1 hour with 320 ml methanol and 40 milliliters of 1NHCl.Stripped methanol adds ethyl acetate.With organic phase water and salt water washing, use 200 milliliters of silica gel treatment then.Filter, then stripping obtains 38 gram black products.With its chromatographic separation on silica gel, obtain 19.0 grams 1,1,2-three bromo-2-(7-hydroxyl heptyl) cyclopropane, light yellow liquid.
D.1-(7-hydroxyl heptyl)-cyclopropylene
(1.4M 10mmol) handles 1.0 grams 1,1,25 milliliters of diethyl ether solutions of 2-three bromo-2-(7-hydroxyl heptyl) cyclopropane (2.5mmol) with 7.2 milliliters of lithium methides down at-78 ℃.After 5 minutes, reaction mixture is warmed to 0 ℃, and deposits in this temperature.To react and use the saturated ammonium chloride cancellation.With reaction mixture water and salt water washing, use dried over mgso, filter and stripping, obtain 240 milligrams of 1-(7-hydroxyl heptyl)-cyclopropylene.
E.1-(7-(4-mesyloxy phenyl) ketonic oxygen base heptyl)-cyclopropylene
To (537 milligrams of 15 ℃ 1-(7-hydroxyl heptyl)-cyclopropylene; 3.47mmol), (764 milligrams of 4-sulfonyloxy methyl yl benzoic acids; 3.82mmol), N; (42.1 milligrams of N-dimethyl aminopyridines; 0.347mmol) and (33.0 milligrams of tosic acid monohydrates; 0.173mmol) about 30 milliliters of dichloromethane solutions in add N, N '-dicyclohexylcarbodiimide (85.8 milligrams, about 10 milliliters of dichloromethane solutions 4.16mmol).At room temperature stir about is after 90 minutes, by very easily moist filter paper with the reaction mixture vacuum filtration.In filtrate, add entry, and with mixture stir about 30 minutes.Separate each mutually after, with the organic layer dried over mgso, and dry in a vacuum, obtain 1.5 and restrain 70% pure 1-(7-(4-mesyloxy phenyl) ketonic oxygen base heptyl)-cyclopropylene.
Embodiment 26:1-(2-pyridyl sulfur phenenyl)-cyclopropylene (compound 55)
A.4-bromine penta-obtusilic acid ethyl ester
By Mori, M.; Deng the people at Journal of Organic Chemistry, 1983,48, the method for describing among the 4058-4067 prepares 4-bromine penta-obtusilic acid ethyl ester.
B.3-(1,2,2-three bromo-cyclopropyl)-ethyl propionate
To 4-bromine penta-obtusilic acid ethyl ester (24.24 grams, 11.7mmol) 148 milliliters of dichloromethane solutions in add (35.3 milliliters of methenyl bromides, 35.1mmol), N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide (4.40 the gram, 1.17mmol) and 45% potassium hydroxide aqueous solution (54.2 milliliters, 58.5mmol).After at room temperature stirring 3 days, add entry, separate each layer.In the organic layer of telling, add methenyl bromide (35.3 milliliters, 35.1 mmol), N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide (4.40 the gram, 1.17mmol) and 45% potassium hydroxide aqueous solution (54.2 milliliters, 58.5mmol).At room temperature restir added hexane and water after 3 days.With mixture gravity filtration, and separate each layer by qualitative filter paper.With the organic layer dried over mgso of telling, dry in a vacuum then.Use ether/hexane at silica gel upper prop chromatogram purification resistates, obtain 20.5 gram 3-(1,2,2-three bromo-cyclopropyl)-ethyl propionates, be oil.
C.3-(1,2,2-three bromo-cyclopropyl)-propionic acid
(20.5 grams, 54.0mmol) solution in about 80 ml waters and 80 milliliters of Hydrogen bromides is heated to backflow with 3-(1,2,2-three bromo-cyclopropyl)-ethyl propionate.After about 4 hours, cooling is reacted to room temperature, and adds ether.Separate each phase.The organic layer of telling is washed with dilute sodium hydroxide aqueous solution, make it pass through the pH test paper and measure enough alkalescence of demonstration.Separate each phase, and by adding dilute hydrochloric acid acidifying water layer.Add ether to water layer.Separate each phase.With the organic layer told with dried over mgso and vacuum concentration.Resistates is made the hexane development,, obtain 3.23 gram 3-(1,2,2-three bromo-cyclopropyl)-propionic acid solids then with the ether development.
D.1-(3-hydroxypropyl)-1,2,2-three bromo cyclopropane
(850 milligrams, about 1 milliliter of tetrahydrofuran solution 2.42mmol) is cooled to-10 ℃ with 3-(1,2,2-three bromo-cyclopropyl)-propionic acid.To the tetrahydrofuran (THF) liquid that wherein drip to add the 1M borane at leisure (1.97 milliliters, 1.96mmol).After at room temperature stirring is spent the night, add the mixture of 1 milliliter of one to one Glacial acetic acid and water.With the mixture vacuum concentration.The resistates that obtains is poured in 10 milliliters of saturated sodium bicarbonate aqueous solutions on ice.Add ethyl acetate and separate each phase, this step is repeated.With the organic layer dried over mgso of telling, vacuum concentration then.Resistates is dissolved in ether, uses the saturated sodium bicarbonate aqueous solution washed twice.Separate each phase, and with the organic layer dried over mgso of telling, vacuum concentration obtains 540 milligrams of 1-(3-hydroxypropyl)-1,2 then, 2-three bromo cyclopropane are oil.
E.1-(3-phenyl sulfonyloxy propyl group)-1,2,2-three bromo-cyclopropane
To 0 ℃ 1-(3-hydroxypropyl)-1,2,2-three bromo cyclopropane (540 milligrams, add in the cooling solution of about 3 milliliters of methylene dichloride 1.60mmol) pyridine (0.155 milliliter, 1.92mmol) and benzene sulfonyl chlorination thing (0.203 milliliter, 1.60mmol).After at room temperature stirring 3 days, add entry and separate each phase.With the organic layer told with dried over mgso and vacuum concentration.Resistates is dissolved in ether, with 1N salt acid elution.Separate each phase, with the organic layer dried over mgso of telling, and vacuum concentration, obtaining 500 milligrams of 1-(3-phenyl sulfonyloxy propyl group)-1,2,2-three bromo-cyclopropane are oil.
F.1-(2-pyridyl thiopropyl)-1,2,2-three bromo-cyclopropane
To the 2-mercaptopyridine (0.117 gram, add in about 3 ml methanol solution 1.04mmol) 25% sodium methylate methanol solution (0.239 milliliter, 1.04mmol).After at room temperature stirring one hour, with the reaction mixture vacuum concentration.To being dissolved in 3 milliliters of N, add 1-(3-phenyl sulfonyloxy propyl group)-1,2 in the resistates of dinethylformamide, 2-three bromo-cyclopropane (500 milligrams, 3 milliliters of N 1.04mmol), dinethylformamide solution.After at room temperature stirring 16 hours, add entry with ether and separate each phase.With the organic layer told with dried over mgso and vacuum concentration.Use ethyl acetate/hexane at silica gel upper prop chromatogram purification resistates, obtain 200 milligrams of 1-(2-pyridyl thiopropyl)-1,2,2-three bromo-cyclopropane are oil.
G.1-(2-pyridyl thiopropyl)-cyclopropylene
With 1-(2-pyridyl thiopropyl)-1,2, (200 milligrams, 2 milliliters of diethyl ether solutions 0.465mmol) are cooled to 0 ℃ to 2-three bromo-cyclopropane, and place under the nitrogen atmosphere.Adding 1.4M lithium methide in this solution (1.00 milliliters, 1.39mmol).After 15 minutes, will react quencher by adding 1 ml water.Separate each phase, with the organic layer dried over mgso of telling, then vacuum concentration obtains 50 milligrams of 1-(2-pyridyl thiopropyl)-cyclopropylene, is oil.
Embodiment 27:1-(8-phenylsulfonyloxy octyl group)-cyclopropylene (compound 56)
A.9,10-two bromo-last of the ten Heavenly stems-1-alcohol
The about 20 milliliters of dichloromethane solutions that in about 70 milliliters of dichloromethane solutions of ice/brine bath refrigerative last of the ten Heavenly stems-9-alkene-1-alcohol (40.34 grams, 0.258 mole), add bromine (13.3 milliliters, 0.258 mole).At room temperature stir about with the reactant vacuum concentration, obtained 9 after 15 minutes, and the oil of 10-two bromo-last of the ten Heavenly stems-1-alcohol can use without further purifying.
B.9-bromo-last of the ten Heavenly stems-9-alkene-1-alcohol
To ice bath refrigerative 9, in about 140 milliliters of tetrahydrofuran solutions in 10-two bromo-last of the ten Heavenly stems-1-alcohol (81.7 grams, 0.258 mole), add tetrahydrofuran (THF) (24.8 grams, the 0.258 mole) solution of 20% potassium tert.-butoxide.At about 5 ℃ of following stir abouts 10 minutes and stir about after 15 minutes, at room temperature with the reaction mixture vacuum concentration.In resistates, add entry and ether.Separate each phase.With the magnesium drying that the organic layer of telling is used, then vacuum concentration obtains 66.1 gram oil.It by the vacuum distilling purifying, is obtained 35.3 grams about 66% pure 9-bromo-last of the ten Heavenly stems-9-alkene-1-alcohol, be oil.
C.2-bromo-10-(1-ethoxy ethoxy)-last of the ten Heavenly stems-1-alkene
(11.75 grams add about 37 milligrams of tosic acid monohydrates in about 15 milliliters of diethyl ether solutions 50.0mmol) to 9-bromo-last of the ten Heavenly stems-9-alkene-1-alcohol.After solution is cooled to approximately-10 ℃, add ethyl vinyl ether (13.8 milliliters, 144 moles) at leisure with the speed that keeps internal temperature to be lower than 10 ℃.After adding several triethylamines, solution with water is then used the salt water washing.With the organic layer of telling salt of wormwood drying, vacuum concentration then, obtain the pure 2-bromo-10-(1-ethoxy ethoxy) of 16.2 grams about 72%-last of the ten Heavenly stems-1-alkene, be oil.
D.1,1,2-three bromo-2-[8-(1-ethoxy ethoxy)-octyl group]-cyclopropane
To 2-bromo-10-(1-ethoxy ethoxy)-last of the ten Heavenly stems-1-alkene (16.2 the gram, 52.7mmol) 90.9 milliliters of dichloromethane solutions in add (13.2 milliliters of methenyl bromides, 158mmol), N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide (2.41 the gram, 5.27mmol) and 45% potassium hydroxide aqueous solution (22.6 milliliters, 263mmol).After at room temperature stirring 2 days, add entry, separate each layer.In the organic layer of telling, add N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide (2.41 the gram, 5.27mmol) and 45% potassium hydroxide aqueous solution (22.6 milliliters, 263mmol).At room temperature restir added hexane and water after 2 days.With mixture gravity filtration, and separate each layer by qualitative filter paper.With the organic layer dried over mgso of telling, dry in a vacuum then, obtain 24.7 grams 1,1,2-three bromo-2-[8-(1-ethoxy ethoxy)-octyl group]-oil of cyclopropane, can use without further purifying.
E.1-(8-hydroxyethyl)-1,2,2-three bromo-cyclopropane
To 1,1,2-three bromo-2-[8-(1-ethoxy ethoxy)-octyl group]-(24.7 grams add about 44 ml waters, about 337 milligrams of tosic acid monohydrates and about 160 milliliters of 6M hydrochloric acid to cyclopropane in about 160 ml methanol solution 51.5mmol).At room temperature stir about is after 1 hour, with the reaction mixture vacuum concentration.With resistates vacuum distilling purifying, obtain 15.6 and restrain 65% pure 1-(8-hydroxyethyl)-1,2, the oil of 2-three bromo-cyclopropane can directly use.
F.1-(8-phenylsulfonyloxy octyl group)-1,2,2-three bromo-cyclopropane
To 1-(8-hydroxyethyl)-1,2,2-three bromo-cyclopropane (15.6 grams, and about 50 milliliters of dichloromethane solutions adding pyridine 38.3mmol) (3.72 milliliters, 45.9mmol).In acetone/the dry ice bath, solution is cooled to-20 ℃, add simultaneously benzene sulfonyl chloride (4.89 milliliters, 38.3mmol).After at room temperature stirring 16 hours, add pyridine (3.72 milliliters, 45.9mmol) and benzene sulfonyl chloride (4.89 milliliters, 38.3mmol).After at room temperature stirring 5 hours, add pyridine (3.72 milliliters, 45.9mmol) and benzene sulfonyl chloride (4.89 milliliters, 38.3mmol).After at room temperature stirring 16 hours, add entry and separate each phase then.With the organic layer told with dried over mgso and vacuum concentration.Resistates is dissolved in ether, washs with saturated sodium bicarbonate aqueous solution then.Separate each phase, with the organic layer dried over mgso of telling, and vacuum concentration, obtaining 14.5 gram 1-(8-phenylsulfonyloxy octyl group)-1,2,2-three bromo-cyclopropane are oil.
G.1-(phenylsulfonyloxy octyl group)-cyclopropylene
With 1-(phenylsulfonyloxy octyl group)-1,2, about 8 milliliters of diethyl ether solutions of 2-three bromo-cyclopropane (2.7 gram, 4.94 moles) are cooled to 0 ℃ and place under the nitrogen atmosphere.The ether solution of adding 1.4M lithium methide in this solution (10.6 milliliters, 14.8mmol).After 15 minutes, will react quencher by adding about 4 ml waters.Separate each phase, with the organic layer dried over mgso of telling, and vacuum concentration, obtain 1.2 gram 1-(phenylsulfonyloxy octyl group)-cyclopropylene, be oil.
Embodiment 28:1-(4-aminomethyl phenyl sulphur octyl group)-cyclopropylene (compound 57)
A.1-(phenylsulfonyloxy octyl group)-cyclopropylene
By 1-(phenylsulfonyloxy octyl group)-1,2,2-three bromo-cyclopropane prepare 1-(phenylsulfonyloxy octyl group)-cyclopropylene by method shown in the embodiment 27.
B.1-(4-aminomethyl phenyl sulphur octyl group)-cyclopropylene
To sodium hydride (60% oil solution, 73.2 milligrams, N 1.83mmol), add in dinethylformamide (2 milliliters) suspension right-thiocresol (189 milligrams, N 1.52mmol), dinethylformamide (2 milliliters) solution.At room temperature stir after 15 minutes when bubbling stops, at N, add in the dinethylformamide (2 milliliters) 1-(phenylsulfonyloxy octyl group)-cyclopropylene (470 milligrams, 1.52mmol).Behind the stir about 2 hours, add entry and ethyl acetate, separate each phase then.Wash the organic layer of telling with water twice, use dried over mgso, and vacuum concentration, obtain 200 milligrams of 1-(4-aminomethyl phenyl sulphur octyl group)-cyclopropylene, be oil.
Embodiment 29:1-(1H-1,2.4-triazole-2-base sulphur octyl group)-cyclopropylene (compound 58)
A.1-(phenylsulfonyloxy octyl group)-cyclopropylene
By 1-(phenylsulfonyloxy octyl group)-1,2,2-three bromo-cyclopropane prepare 1-(phenylsulfonyloxy octyl group)-cyclopropylene by method shown in the embodiment 27.
B.1-(1H-1,2,4-triazole-2-base sulphur octyl group)-cyclopropylene
To 1-(phenylsulfonyloxy octyl group)-cyclopropylene (480 milligrams, about 2 milliliters of N 1.55mmol), (19.8% at tetrahydrofuran (THF) to add potassium tert.-butoxide in the dinethylformamide solution, 734 milligrams, 1.55mmol) and 1H-1,2,4-triazole-3-mercaptan (172 rags, 1.71mmol).At room temperature stir about is after 2 hours, add sodium iodide (87.7 milligrams, 775mmol).Reaction is heated to about 50 ℃ after about 2 hours, adds entry and ethyl acetate, separate each phase then.Wash the organic layer of telling with water twice, use dried over mgso, and vacuum concentration.Use hexane/ethyl acetate at silica gel upper prop chromatogram purification resistates, obtain 30 and restrain 70% pure 1-(1H-1,2,4-triazole-2-base sulphur octyl group)-cyclopropylene, be oil.
Embodiment 30:1-(1-methyl-2-pyrrolylcarbonyl oxygen base propyl group)-cyclopropylene (compound 59)
A.1-(3-hydroxypropyl)-1,2,2-three bromo cyclopropane
Prepare 1 (3-hydroxypropyl)-1,2,2-three bromo cyclopropane by the described method of embodiment 26d by 3-(1,2,2-three bromo-cyclopropyl)-propionic acid.
B.1-(3-hydroxypropyl)-cyclopropylene
With 1-(3-hydroxypropyl)-1,2, (750 milligrams, about 4 milliliters of diethyl ether solutions 2.22mmol) are cooled to 0 ℃ to 2-three bromo cyclopropane, and place under the nitrogen atmosphere.By syringe add the 1.4M lithium methide (6.36 milliliters, 8.90mmol).After 15 minutes, add about 2 ml waters and separate each phase then.With the organic layer dried over mgso of telling, vacuum concentration obtains 1-(3-hydroxypropyl)-cyclopropylene then, can directly use.
C.1-(1-methyl-2-pyrrolylcarbonyl oxygen base propyl group)-cyclopropylene
To (221 milligrams of 1-(3-hydroxypropyl)-cyclopropylene, 2.22mmol) about 15 milliliters of dichloromethane solutions in, add (306 milligrams of 1-methyl-2-pyrroles's carboxylic acid acid, 2.42mmol), (27.0 milligrams of 4-dimethylaminopyridines, 0.222mmol) and the tosic acid monohydrate (21.2 milligrams, 0.111mmol).After mixture is cooled to about 15 ℃, add N at leisure in batches, and N '-dicyclohexylcarbodiimide (550 milligrams, about 10 milliliters of dichloromethane solutions 2.66mmol).At room temperature stir about is after 2 hours, by very easily moist filter paper with the reaction mixture vacuum filtration.Add entry and separate each phase then.With the organic layer dried over mgso of telling, vacuum concentration then.Use hexane/ethyl acetate at silica gel upper prop chromatogram purification resistates, obtain 15 milligrams of 1-(1-methyl-2-pyrrolylcarbonyl oxygen base propyl group)-cyclopropylene, be oil.
Embodiment 31:1-ethyl-2-(3-(4-chloro-phenyl-)-rattle away-6-ketone-1-yl)-cyclopropylene (compound 60)
A.3-(4-chloro-phenyl-)-rattle away-6-ketone
Can prepare 3-(4-chloro-phenyl-)-rattle away-6-ketone as the method for the DE 2435244 (1976) described in the embodiment 3.
B.1-(mesyloxy methyl)-2-ethyl cyclopropylene
Prepare 1-(mesyloxy methyl) 2-ethyl cyclopropylene by method shown in the embodiment 17c.
C.1-ethyl-2-(3-(4-chloro-phenyl-)-rattle away-6-ketone-1-yl)-cyclopropylene
Sodium hydride in ice bath (60% oil solution, 0.08g, N 2mmol), ((0.41 restrains 4-chloro-phenyl--rattle away-6-ketone, 2mmol) to add 3-in dinethylformamide (4 milliliters) suspension.Stir after 15 minutes, (0.35 restrains, 2mmol) to add 1-(mesyloxy methyl)-2-ethyl cyclopropylene.After at room temperature stirring 45 minutes, add entry and ethyl acetate.Separate each phase.With organic layer water and the salt water washing of telling successively, use dried over mgso then, dry in a vacuum at last.Use hexane/ethyl acetate at silica gel upper prop chromatogram purification resistates, obtain 340 milligrams of 1-ethyl-2-(3-(4-chloro-phenyl-)-rattle away-6-ketone-1-yl)-cyclopropylene, the off-white color solid.
The preparation of embodiment 32:1-triethylsilyl methylcyclopropene (compound 63)
A.3-Trichloromonosilane base-2-bromopropylene
As Hollingworth, G.J.; Lee, T.V.Sweeney, J.B.Synthetic Commun.1996, this compound of preparation described in 26,1117.Product is mixed with hexane and filter.With the filtrate stripping, and need not further purify and use (need not distill).
B.3-triethylsilyl-2-bromopropylene
Add 7 milliliters of (3.0m, 21mmol) ethylmagnesium bromide in 20 milliliters of THF solution of 1.3 gram 3-Trichloromonosilane base-2-bromopropylenes (5mmol) in ice bath.Reaction is warmed to room temperature, and stirs and spend the night water cancellation then.Add ether, and reaction mixture is transferred in the separating funnel.Add a small amount of 1NHCl, separate each phase,, use dried over mgso then, filter and stripping ether phase water and salt water washing.Chromatographic separation obtains 300 milligrams of 3-triethylsilyl-2-bromopropylenes.
C.N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and N, N '-dibenzyl-N, N, N ', N '-tetraethyl-ethylene ammonium dibromide (phase-transfer catalyst)
To 16.5 gram (142mmol) N that stir, N, N ' adds 50.1 gram (292mmol) cylites in the 60 gram acetonitrile solutions of N '-Tetramethyl Ethylene Diamine.Mixture self heats up, and stirs 2.5 hours, and observing has a large amount of precipitations on it.Slurry is diluted with ether, filter,, obtain the N that 61.8g wants, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide, white solid, fusing point 230-232 ℃ with ether washing and dry.
With similar method, use N, N, N ', N '-tetraethyl-ethylene diamine obtains N, N '-dibenzyl-N, N, N ', N '-tetraethyl-ethylene ammonium dibromide, white solid, decomposes by fusing point 190-193 ℃.
D) 2-triethylsilyl methyl isophthalic acid, 1,2-three bromo cyclopropane
With 300 milligrams of (1.27mmol) 3-triethylsilyl-2-bromopropylenes, 0.47 restrain 45% potassium hydroxide aqueous solution (3.8mmol), 75 milligrams of N, N '-dibenzyl-N, N, N ', the mixture of N '-tetraethyl-ethylene ammonium dibromide and 3 milliliters of methylene dichloride is handled with 0.33 milliliter of methenyl bromide (3.8mmol).Well-beaten reaction mixture was at room temperature deposited 5.5 hours.Add entry and methylene dichloride, separate each phase.Methylene dichloride is placed reaction flask mutually, and restrain 45% potassium hydroxide aqueous solution (3.8mmol) and 75 milligrams of N, N '-dibenzyl-N, N, N ', N '-tetraethyl-ethylene ammonium dibromide processing with other 0.47.The reaction mixture stirring is spent the night, add entry and other methylene dichloride then, and separate each phase.With methylene dichloride with dried over mgso and stripping.During stripping, add a little amount of heptane to help to remove remaining methenyl bromide.The column chromatography purifying obtains 390 milligrams of 2-triethylsilyl methyl isophthalic acids, and 1,2-three bromo cyclopropane, colourless liquid.
E) 1-triethylsilyl methylcyclopropene
With 0.36 gram (0.9mmol) 2-triethylsilyl methyl isophthalic acid, 1,5 milliliters of diethyl ether solutions of 2-three bromo cyclopropane are cooled to-78 ℃.(1.4M, 2.8mmol), placed reaction mixture 5 minutes, then sampling by 2.0 milliliters in ice bath to add excessive lithium methide.Between sampling date, make the reaction mixture cooling get back to-78 ℃.The small amount of methanol cancellation is used in reaction, and is warming to room temperature.Add other ether and water.Separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, 100 milligrams of 1-triethylsilyl methylcyclopropenes obtained, colourless liquid.
The preparation of embodiment 33:1-trimethyl silyl methylcyclopropene (compound 64)
Change commercially available 3-trimethyl silyl-2-bromopropylene into 1-trimethyl silyl methylcyclopropene to be similar to embodiment 1 described mode.
The preparation of embodiment 34:6-(trimethyl silyl)-hexyl ring third-2-alkene (compound 65)
A.2-bromo-8-(trimethyl silyl)-Xin-1-alkene
(50 milliliters, the THF solution of 0.5M 25mmol) cools off in ice bath with commercially availabie pentamethylene two (magnesium bromide).10 milliliters of THF solution that add 2.72 gram (25mmol) trimethylchlorosilanes.Reaction mixture was stirred 30 minutes down at 5 ℃, at room temperature stirred then 1 hour, then be cooled to 5 ℃ again.Will be in 6 milliliters of THF 2, (5.0 grams 25mmol) join in the reaction mixture 3-propylene bromide, it is warmed up to room temperature and stirred two hours.With the cancellation of reaction mixture water.Add ether and a small amount of 1NHCl.Separate each phase,, use the magnesium chloride drying, then stripping organic phase water and salt water washing.The column chromatography purifying obtains 1.62 gram 2-bromo-8-(trimethyl silyl)-Xin-1-alkene, water white oil.
B.2-(6-(trimethyl silyl)-hexyl)-1,1,2-three bromo cyclopropane
With 1.52 gram (5.8mmol) 2-bromo-8-(trimethyl silyl)-Xin-1-alkene, 4.3 restrain 45% potassium hydroxide aqueous solution (34mmol), 0.2 gram N, N '-dibenzyl-N, N, N ', the mixture of N '-tetraethyl-ethylene ammonium dibromide and 10 milliliters of methylene dichloride is handled with 1.5 milliliters of methenyl bromides (17.4mmol).Well-beaten reaction mixture is at room temperature continued to spend the night.Add other 4 grams, 45% potassium hydroxide aqueous solution, and will react and at room temperature stir again one hour.Add entry and methylene dichloride, separate each phase.With methylene dichloride with dried over mgso and stripping.During stripping, add a little amount of heptane to help to remove remaining methenyl bromide.The column chromatography purifying obtains 1.13 gram 2-(6-(trimethyl silyl)-hexyl)-1,1,2-three bromo cyclopropane, water white oil.
C.6-(trimethyl silyl)-hexyl ring third-2-alkene
With 0.96 gram (2.2mmol) 2-(6-(trimethyl silyl)-hexyl)-1,1,10 milliliters of diethyl ether solutions of 2-three bromo cyclopropane are cooled to-78 ℃.(1.4M, 7.1mmol), placed reaction mixture 30 minutes water cancellation then by 5.1 milliliters in ice bath to add excessive lithium methide.Separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, 370 milligrams of 6-(trimethyl silyl)-hexyl ring third-2-alkene obtained, colourless liquid.
The preparation of embodiment 35.2-(trimethyl silyl)-ethyl ring third-2-alkene (compound 66)
A.2-bromo-4-(trimethyl silyl)-but-1-ene
To ice bath refrigerative 5.0 gram (50mmol) 2, and 30 milliliters of commercially available trimethyl silyl methylmagnesium-chlorides of adding in 20 milliliters of diethyl ether solutions of 3-propylene bromide (1M, 30mmol).Reaction mixture was stirred 30 minutes down at 0 ℃, be warmed up to room temperature then.Add THF (10 milliliters), and the reaction mixture stirring is spent the night.The water cancellation.Reaction mixture is transferred in the separating funnel.Add a small amount of 1NHCl, separate each phase,, use dried over mgso then, filter and stripping, obtain 4.5 gram 2-bromo-4-(trimethyl silyl)-but-1-enes, can use without further purifying with ether phase water and salt water washing.
B.2-(trimethyl silyl)-ethyl ring third-2-alkene
To be similar to the mode that 2-bromo-8-(trimethyl silyl)-Xin-1-alkene is converted into 6-(trimethyl silyl)-hexyl ring third-2-alkene (embodiment 3) 2-bromo-4-(trimethyl silyl)-but-1-ene is converted into 2-(trimethyl silyl)-ethyl ring third-2-alkene.
The preparation of embodiment 36:2-octyl group-1-trimethyl silyl cyclopropylene (compound 67)
A.2-bromine last of the ten Heavenly stems-1-alkene
In being housed, 500 milliliter of 3 neck flask of magnetic agitation, feed hopper and reflux exchanger add 17 gram (700mmol) magnesium smear metals.Cover with 20 milliliters of ether with dried nitrogen exchange atmospheric atmosphere and with the magnesium smear metal.Add 2 gram glycol dibromides, have reaction thereon by bubbling and muddy proof.After 5 minutes, add 200 milliliters of ether, and cause mixture to reflux.Slowly add 100 milliliters of ether solutions of 90 gram (503mmol) 1-heptyl bromides with the speed of enough keeping backflow, spend 50 minutes.To react further and reflux 30 minutes, obtain heptyl magnesium bromide solution.
In being housed, 1000 milliliter of 3 neck flask of magnetic agitation, barrier film and reflux exchanger under nitrogen atmosphere, add 75 gram (375mmol) 2,200 milliliters of ether solutions of 3-propylene bromide.In reaction, shift heptyl magnesium bromide solution by intubate with the speed that control refluxes.After refluxing again 60 minutes, reaction is at room temperature stirred spend the night.To react and use the aqueous hydrochloric acid cancellation, use the salt water washing, anhydrous magnesium sulfate drying, rotary evaporation, and distill under 12 torrs by 5 column plate porous sheet-piles and to obtain 52 gram 2-bromines last of the ten Heavenly stems-1-alkene, 105-115 ℃ of boiling point (12 torr).
B.2-octyl group-1,1,2-three bromo cyclopropane
In 125 milliliters that have magnetic agitation single neck flasks, add 20 gram (91mmol) 2-bromines last of the ten Heavenly stems-1-alkene, 75 gram (297mmol) methenyl bromides, 200 gram methylene dichloride, 2.2 gram N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and 20 gram (161mmol) 45% potassium hydroxide aqueous solutions.Mixture was stirred 3 days, add 100 ml waters thereon, separate organic layer, with 30 gram methenyl bromides, 2.0 gram N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and 25 grams, 45% potassium hydroxide aqueous solution are handled again.Restir washes reaction with water two days later, drying, and rotary evaporation also separates with the hexane elution chromatography on silica gel.Obtain 41 gram 2-octyl groups-1,1,2-three bromo cyclopropane.
C.2-octyl group-1-trimethyl silyl cyclopropylene
With 0.98 gram (2.5mmol) 2-octyl group-1,1,10 milliliters of diethyl ether solutions of 2-three bromo cyclopropane are cooled to-78 ℃.The adding lithium methide (1.4M, 5.35 milliliters, 7.5mmol), reaction mixture was stirred 30 minutes, place ice bath then, placed 30 minutes.(0.81g, 7.5mmol), and reaction mixture is placed water cancellation then in 45 minutes to add the trimethylammonium silicon chlorides.Add other ether and separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, 370 milligrams of 2-octyl groups-1-trimethyl silyl cyclopropylene obtained, yellow liquid.
The preparation of embodiment 37:1 (2-mesyloxy ethyl)-cyclopropylene (compound 68)
A.2-bromo-4-(1-ethoxy ethoxy)-but-1-ene
With 20 milliliters of diethyl ether solutions and 50 milligrams of (0.000263 mole) tosic acid monohydrate refrigerative whiles in ice-water bath of 10.38 gram (0.0687 mole) commercially available 3-bromo-3-butene-1-alcohol, drip to add 19 milliliters of (0.199 mole) ethyl vinyl ethers at leisure, keep internal temperature＜10 ℃.At 0 ℃ after following 1 hour, add several triethylamines.Reaction mixture is poured on waterborne.Change the mixture that obtains over to separating funnel, separate each phase.With the organic layer of telling salt water washing, the dry and filtration with salt of wormwood then.In a vacuum solvent is removed from filtrate, obtained 14.04 gram 2-bromo-4-(1-ethoxy ethoxy)-but-1-enes, be oil.
B.1,1,2-tribromo 2-[2-(1-ethoxy ethoxy)-ethyl]-cyclopropane
In 108 milliliters of dichloromethane solutions and 0.5-0.9 milliliter 45% potassium hydroxide aqueous solution of 14.02 gram (0.0628 mole) 2-bromo-4-(1-ethoxy ethoxy)-but-1-enes, add 16.4 milliliters of (0.118 mole) methenyl bromides and 2.88 gram (0.00628 mole) N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and 28 milliliters of (0.314 mole) 45% potassium hydroxide aqueous solutions.After 3 days reaction mixture is poured on waterborne.Change the mixture that obtains over to separating funnel, separate each phase.In isolating organic layer, add 2.88 gram (0.00628mol) N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and 28 milliliters of (0.314mol) 45% potassium hydroxide aqueous solutions.After 24 hours, to wherein adding hexane and water.With mixture by the gravity filtration of qualitative corrugation filter paper.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.In a vacuum solvent is removed from filtrate, is obtained 17.0 grams 1,1,2-three bromo-2-[2-(1-ethoxy ethoxy)-ethyl]-cyclopropane, be oil.
C.2-(2-hydroxyethyl)-1,1,2-three bromo cyclopropane
To 16.5 gram (0.0418 moles) 1,1,2-three bromo-2-[2-(1-ethoxy ethoxy)-ethyl]-slurry of cyclopropane in 145 ml methanol and 40 ml waters in, add 0.306 gram (0.00161 mole) tosic acid monohydrate and 145 milliliters of 6M hydrochloric acid.After at room temperature stirring 1 hour, in a vacuum solvent is removed from reaction mixture.In resistates, add ethyl acetate and water.Change the mixture that obtains over to separating funnel, separate each phase.With the organic layer of telling salt water washing, use MgSO then 4Dry also filtration.In a vacuum solvent is removed from filtrate, obtained 11.9 gram 2-(2-hydroxyethyl)-1,1,2-three bromo cyclopropane are oil.
C.1-(2-hydroxyethyl)-cyclopropylene
With 1.15 gram (3.6mmol) 2-(2-hydroxyethyl)-1,1,40 milliliters of diethyl ether solutions of 2-three bromo cyclopropane (preparation as mentioned above) are cooled to-78 ℃.The adding lithium methide (1.4M, 10.3 milliliters, 14.4mmol).Reaction mixture is warmed to 5 ℃, and kept 1/2nd hours.To react the water cancellation, separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping.Thick product is used for next step reaction at once.
E) 1-(2-mesyloxy ethyl)-cyclopropylene
The thick product of above-mentioned reaction is dissolved in 5 milliliters of ether, and in ice bath, cools off.Add triethylamine (1 milliliter), add 0.49 gram methylsulfonyl chloride (4.3mmol) then.Reaction mixture was stirred 1 hour.Add entry with other ether and separate each phase.Wash ether with water twice mutually, use the salt water washing, use dried over mgso, and stripping, obtain the light yellow liquid of 380 milligrams of 1-(2-mesyloxy ethyl)-cyclopropylene.
The preparation of embodiment 38:1-(7-mesyloxy heptyl)-cyclopropylene (compound 69)
A.1-(1-ethoxy ethoxy)-6-bromohexane
In 40 milliliters of diethyl ether solutions of 80 milligrams of toluenesulphonic acidss of refrigerative, inject 20 gram (110mmol) 6-bromine hexanol and 40 milliliters of ethyl vinyl ethers simultaneously by the funnel that adds that separates.During 1 hour that injects, the temperature of maintenance reaction mixture is at 7 ℃ or be lower than 7 ℃ temperature.The reaction mixture stirring was longer than 20 minutes, is added roughly 1 milliliter of triethylamine then.With reaction mixture water and salt water washing, use the salt of wormwood drying, filter and stripping, obtain the light yellow liquid of 25.7 grams, it can be used without purifying further.
B.9-(1-ethoxy ethoxy)-2-bromine ninth of the ten Heavenly Stems-1-alkene
Handle the slurry of 5.6 gram magnesium smear metals (230mmol) in 100 milliliters of THF with a small amount of glycol dibromide.(38.5 grams, 152mmol), holding temperature is at 40-50 ℃ to inject 1-(1-ethoxy ethoxy)-6-bromohexane in reaction mixture at leisure.After adding end, reaction mixture was deposited 20 minutes, under 0 ℃, transferred to 33.4 gram (167mmol) 2 then, in 25 milliliters of THF solution of 3-propylene bromide by intubate.Reaction mixture was stirred 15 minutes down at 0 ℃, at room temperature stirred water cancellation then then 15 minutes.Reaction mixture is transferred in the separating funnel.Add a small amount of 1NHCl, separate each phase,, use dried over mgso then, filter and stripping, obtain the yellow liquid of 33.63 grams, it can be used without purifying further ether phase water and salt water washing.
C.1,1,2-three bromo-2-(7-hydroxyl heptyl) cyclopropane
With 9-(1-ethoxy ethoxy)-2-bromine ninth of the ten Heavenly Stems-1-alkene (33.63g, 115mmol), 4.1 gram N, N '-dibenzyl-N, N, N ', N '-tetraethyl-ethylene ammonium dibromide, 42 gram 45% potassium hydroxide (337mmol), the mixture of 93 gram methenyl bromides (368mmol) and 280 gram methylene dichloride at room temperature promptly stirred two days.When reaction stopped, reaction mixture changed separating funnel over to, washed with water.Methylene dichloride is changed in the flask mutually, handle as previously mentioned, then restir 3 days at room temperature with the phase-transfer catalyst and 45% potassium hydroxide of equal amts.Reaction mixture is washed with water, with dried over mgso methylene dichloride phase, then stripping.Product was at room temperature handled 1 hour with 320 ml methanol and 40 milliliters of 1NHCl.Stripped methanol adds ethyl acetate.With organic phase water and salt water washing, use 200 milliliters of silica gel treatment then.Filter, then stripping obtains 38 gram black products.With its chromatographic separation on silica gel, obtain 19.0 grams 1,1,2-three bromo-2-(7-hydroxyl heptyl) cyclopropane, light yellow liquid.
D.1-(7-hydroxyl heptyl)-cyclopropylene
(1.4M 10mmol) handles 1.0 grams 1,1,25 milliliters of diethyl ether solutions of 2-three bromo-2-(7-hydroxyl heptyl) cyclopropane (2.5mmol) with 7.2 milliliters of lithium methides down at-78 ℃.After 5 minutes, reaction mixture is warmed to 0 ℃, and deposits in this temperature.To react and use the saturated ammonium chloride cancellation.With reaction mixture water and salt water washing, use dried over mgso, filter and stripping, obtain 240 milligrams of 1-(7-hydroxyl heptyl)-cyclopropylene.
E.1-(7-mesyloxy heptyl)-cyclopropylene
50 milliliters of diethyl ether solutions of 4.3mmol1-(7-hydroxyl heptyl)-cyclopropylene are cooled off in ice bath.Add triethylamine (1 milliliter) and 0.54 gram methylsulfonyl chloride (4.7mmol), reaction mixture was stirred 2.5 hours down at 0 ℃.With reaction mixture water and salt water washing, use dried over mgso, filter and stripping, obtain 0.83 milligram of 1-(7-mesyloxy heptyl)-cyclopropylene.
The preparation of embodiment 39:1-(7-second sulphur heptyl)-cyclopropylene (compound 70)
0.35 gram (1.5mmol) 1-(7-mesyloxy heptyl)-cyclopropylene and 0.36 mixture that restrains the DMF liquid of 80% sulfur alcohol sodium (4.5mmol) were at room temperature stirred one hour.The adding ether is with water and separate each phase.Organic phase with 1N sodium hydroxide solution, water (secondary) and salt water washing, is used dried over mgso, filter and stripping.Chromatographic separation obtains the colourless liquid of 140 milligrams of 1-(7-second sulphur heptyl)-cyclopropylene.
The preparation of embodiment 40:1-bromo-2-octyl group-cyclopropylene (compound 71)
A.2-bromine last of the ten Heavenly stems-1-alkene
In being housed, 500 milliliter of 3 neck flask of magnetic agitation, feed hopper and reflux exchanger add 17 gram (700mmol) magnesium smear metals.Cover with 20 milliliters of ether with dried nitrogen exchange atmospheric atmosphere and with the magnesium smear metal.Add 2 gram glycol dibromides, have reaction thereon by bubbling and muddy proof.After 5 minutes, add 200 milliliters of ether, and cause mixture to reflux.Slowly add 100 milliliters of ether solutions of 90 gram (503mmol) 1-heptyl bromides with the speed of enough keeping backflow, spend 50 minutes.To react further and reflux 30 minutes, obtain heptyl magnesium bromide solution.
In being housed, 1000 milliliter of 3 neck flask of magnetic agitation, barrier film and reflux exchanger under nitrogen atmosphere, add 75 gram (375mmol) 2,200 milliliters of ether solutions of 3-propylene bromide.In reaction, shift heptyl magnesium bromide solution by intubate with the speed that control refluxes.After refluxing again 60 minutes, reaction is at room temperature stirred spend the night.To react and use the aqueous hydrochloric acid cancellation, use the salt water washing, anhydrous magnesium sulfate drying, rotary evaporation, and distill under 12 torrs by 5 column plate porous sheet-piles and to obtain 52 gram 2-bromines last of the ten Heavenly stems-1-alkene, 105-115 ℃ of boiling point (12 torr).
B.N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide (phase-transfer catalyst)
To 16.5 gram (142mmol) N that stir, N, N ' adds 50.1 gram (292mmol) cylites in the 60 gram acetonitrile solutions of N '-Tetramethyl Ethylene Diamine.Mixture self heats up, and stirs 2.5 hours, and observing has a large amount of precipitations on it.Slurry is diluted with ether, filter,, obtain the N that 61.8g wants, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide, white solid, fusing point 230-232 ℃ with ether washing and dry.
C.2-octyl group-1,1,2-three bromo cyclopropane
In 125 milliliters that have magnetic agitation single neck flasks, add 20 gram (91mmol) 2-bromines last of the ten Heavenly stems-1-alkene, 75 gram (297mmol) methenyl bromides, 200 gram methylene dichloride, 2.2 gram N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and 20 gram (161mmol) 45% potassium hydroxide aqueous solutions.Mixture was stirred 3 days, add 100 ml waters thereon, separate organic layer, with 30 gram methenyl bromides, 2.0 gram N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide and 25 grams, 45% potassium hydroxide aqueous solution are handled again.Restir washes reaction with water two days later, drying, and rotary evaporation also separates with the hexane elution chromatography on silica gel.Obtain 41 gram 2-octyl groups-1,1,2-three bromo cyclopropane.
D.1-bromo-2-octyl group-cyclopropylene
By means of make by the refractory pebbles valve under nitrogen atmosphere, pack into 3.18 the gram (0.00813mol) 1,1,2-three bromo-2-octyl groups--6 milliliters of diethyl ether solutions of cyclopropane.Refrigerative adds the ether solution of 5.81 milliliters of (0.00813mol) 1.4M lithium methides simultaneously at leisure by syringe in ice-water bath.After 15 minutes, add 2 ml waters by means of syringe.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Desolvate in bathing from filtrate, to remove under warm 20 ℃ in a vacuum, obtain 1.43 gram 1-bromo-2-octyl group-cyclopropylene, be oil.
The preparation of embodiment 41:3-methyl-3-amyl group-cyclopropylene (compound 72)
A.1,1-two bromo-2-methyl-2-amyl group-cyclopropane
In 14.4 milliliters of (0.162 mole) methenyl bromide solution of 7.01 milliliters of (0.0446 mole) 2-methyl-heptan-1-alkene, add 0.635 gram (0.00193 mole) Tetrabutyl amonium bromide and 15.1 milliliters (0.185 mole), 50% aqueous sodium hydroxide solution.After being heated to 55 ℃ 1 hour, will react cool to room temperature, and add hexane and water.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Solvent is removed from filtrate in a vacuum.Vacuum distilling purifying resistates obtains 10.9 grams 1, and 1-two bromo-2-methyl-2-amyl group-cyclopropane are oil.
B.2-bromo-1-methyl-1-pentene base-cyclopropane
To 6.59 gram (0.0232 moles) 1, add 1.47 milliliters of (0.0255 mole) Glacial acetic acid and 1.49 gram (0.0227 mole) zinc powders in about 20 ml methanol solution of 1-two bromo-2-methyl-2-amyl group-cyclopropane.Stir after 1 hour, in reaction mixture, add 1.47 milliliters of (0.0255 mole) Glacial acetic acid and 1.49 gram (0.0227 mole) zinc powders.Behind the stir about 2 hours, with the reaction mixture vacuum concentration.After adding hexane and water, change the mixture that obtains over to separating funnel, and separate each phase.With organic layer MgSO 4Dry also filtration.In a vacuum solvent is removed from filtrate, it is pure to obtain 2.2 gram 2-bromo-1-methyl-1-pentene base-cyclopropane 95%, is oil.
C.3-methyl-3-amyl group-cyclopropylene
In 5 milliliters of dimethyl sulfoxide solutions of 1.03 gram (0.502 mole) 2-bromo-1-amyl group-cyclopropane, add 0.563 gram (0.502 mole) potassium tert.-butoxide.Be heated to 85 ℃ after 2 hours, add 0.075 other gram (0.00516 mole) potassium tert.-butoxide.Reaction is heated to 85 ℃ after 1 hour, adds ether and water.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.Solvent is removed from filtrate in a vacuum.Resistates is absorbed in 4 milliliters of methyl-sulphoxides, to wherein adding 0.6 gram (0.536 mole) potassium tert.-butoxide.To react 90 ℃ of heating after 7 hours, add entry and ethyl acetate, and the mixture that obtains be changed over to separate each phase in the separating funnel then.With organic layer MgSO 4Dry also filtration.In a vacuum solvent is removed from filtrate, obtained the mixture of the 180 milligrams of 50%3-methyl-3-amyl group-cyclopropylene and the trimethyl carbinol.
The preparation of embodiment 42:3-methyl-3-nonyl-cyclopropylene (compound 73)
Can prepare this compound by the mode that is similar to compound 2.Obtain 40%3-methyl-3 nonyls-cyclopropylene, the mixture of 30%1-methyl isophthalic acid nonyl-cyclopropane and 20%1-methyl isophthalic acid-nonyl-2-bromine cyclopropane.
The preparation of embodiment 43:1-heptyl-2-methyl-cyclopropylene (compound 74)
10-phenanthroline, the solution of 1.74 milliliters of Tetramethyl Ethylene Diamines and 20 milliliters of tetrahydrofuran (THF)s under nitrogen atmosphere, pack 1 milligram 1 into by means of using the refractory pebbles valve.Be cooled in-30 ℃, adding 1.5 milliliters of 1-methylcyclopropenes by plastic injector.(by 3-chloro-2-methyl-propylene production; See Hopf, H.; Wachholz, G.; Walsh, R.Chem.Ber.1985,118,3579, and Koster, people such as R, Liebigs Annalen Chem.1973,1219-1235).Refrigerative adds the hexane liquid of 8 milliliters of (11.5mmol) 1.6M n-Butyl Lithiums simultaneously at leisure by syringe in-40 ℃ of baths.-30 ℃ following 15 minutes, drip to add 1.90 milliliters of (11.5mmol) 1-indoles heptane by syringe.In natural warming to 5 ℃, stir after 30 minutes, reaction mixture vacuum-drying under 20 ℃ bath temperature.After adding ether and 1N hydrochloric acid, change the mixture that obtains over to separating funnel, and separate each phase.With organic layer MgSO 4Dry also filtration.Under 20 ℃ of bath temperature, in a vacuum solvent is removed from filtrate.Resistates with hexane column chromatography purifying, is obtained 0.700 gram 1-heptyl-2-methyl-cyclopropylene, be oil.
The embodiment 44:1-bromo-2-(preparation of 2-(carbonyl (acetoxy-methyl)) ethyl-cyclopropyl alkene (compound 75)
A.2-(2-bromo-allyl group)-diethyl malonate
By using hexane wash, remove in 21.70 gram (0.542 mole) 60% sodium hydride oil solutions, be oil.In being suspended in 200 milliliters of resistatess in the tetrahydrofuran (THF), add 84.38 milliliters of (0.556 mole) diethyl malonates at leisure by feed hopper.When reaction being cooled to-35 to-10 ℃, add 100 gram (0.400 moles) 2,3-propylene bromide at leisure by feed hopper.Be heated to and refluxed back 1 hour, will react cool to room temperature, and vacuum concentration.In resistates, add hexane and water, change the mixture that obtains over to separating funnel, and separate each phase.With the organic layer of telling 1N salt acid elution, then with dried over mgso and filtration.In a vacuum solvent is removed from filtrate, obtained 154 gram 2-(2-bromo-allyl group)-diethyl malonates, be oil.
B.2-(2-bromo-allyl group)-propanedioic acid
The mixture of 10.5 gram (0.0376 mole) 2-(2-bromo-allyl group)-diethyl malonates and 37.6 milliliters of (0.470 mole) 50% aqueous sodium hydroxide solutions was at room temperature stirred 4 days.With the reaction mixture ether extraction.By the isolating water layer of adding concentrated hydrochloric acid acidifying, and add ether.Change the mixture that obtains over to separating funnel, separate each phase.The organic layer of telling is also filtered with dried over mgso.In a vacuum solvent is removed from filtrate, obtained the solid of 5.3 gram 2-(2-bromo-allyl group)-propanedioic acid, can continue without purification.
C.4-bromo-penta-obtusilic acid
5.3g (0.0238 mole) is clean, and unpurified 2-(2-bromo-allyl group)-propanedioic acid is heated to 125-130 ℃, keeps 8 hours, obtains 3.73 gram 4-bromo-, penta-obtusilic acid, can continue without purification.
D.4-bromo-penta-obtusilic acid ethyl ester
1 N that has to 3.73 gram (0.0208 mole) unpurified 4-bromo-penta-obtusilic acids adds 1.18 milliliters of (0.0162 mole) thionyl chloride in 3 milliliters of chloroformic solutions of dinethylformamide.After this mixture heating up to 60 ℃ kept 30 minutes, it is joined in the solution of 2.46 milliliters of (0.0436 mole) ethanol and 1.97 milliliters of (0.024 mole) pyridines and 13 milliliters of methylene dichloride.Stir after 30 minutes, with the reaction mixture vacuum concentration.In resistates, add ether and water.Change the mixture that obtains over to separating funnel, separate each phase.The organic layer of telling is also filtered with dried over mgso.In a vacuum solvent is removed from filtrate, is obtained the oil of 3.5 gram 4-bromo-, penta-obtusilic acid ethyl ester, with it by the vacuum distilling purifying.
E.1,1,2-three bromo-2-(2-(carbonyl oxyethyl group)) ethyl-cyclopropyl alkene
To be similar to preparation 2-octyl group-1,1, the mode of 2-three bromo cyclopropane (embodiment 1) prepares 1,1,2-three bromo-2-(2-(carbonyl oxyethyl group)) ethyl-cyclopropyl alkene.
F.1,1,2-three bromo-2-(2-(carboxyl)) ethyl-cyclopropyl alkene
With 10.2 gram (0.0269 moles) 1,1, ((3-carbonyl oxyethyl group) ethyl-cyclopropyl alkene is heated to backflow to 2-three bromo-2-in the solution of 40 milliliters of (0.736 mole) 48% Hydrogen bromides and 40 ml waters, kept 8 hours, with its cool to room temperature, then passes through Shark The filter paper vacuum filtration.Before adding ether, wash isolated solid with water.Solution is changed in the separating funnel, with the saturated sodium bicarbonate aqueous solution washing, with its separation, and by adding the 1N hcl acidifying.Again change the aqueous solution over to separating funnel, and use ether extraction.The organic layer of telling is also filtered with dried over mgso.In a vacuum solvent is removed from filtrate, obtained 5.9 grams 1,1, the solid of 2-three bromo-2-((2-carboxyl)) ethyl-cyclopropyl alkene can directly use without further purifying.
G.1,1,2-three bromo-2-(2-(carbonyl (acetoxy-methyl)) ethyl-cyclopropyl alkene
To 0.800 gram (0.00228 mole) 3-1,1, about 2 milliliters of anhydrous N of 2-three bromo-2-(2-(carboxyl)) ethyl-cyclopropyl alkene add 0.224 milliliter of (0.00228 mole) bromomethyl acetate in the dinethylformamide solution, add 0.396 milliliter of (0.00228 mole) diisopropylethylamine then.Reaction is heated to 60 ℃ after 2 hours, adds entry and ether.Change the mixture that obtains over to separating funnel, separate each phase.With the water layer ethyl acetate extraction.With organic phase water and the salt water washing successively that merges.With organic layer MgSO 4Dry also filtration.In a vacuum solvent is removed from filtrate, obtained 0.900 gram 1,1,2-three bromo-2-(2-(carbonyl (acetoxy-methyl)) ethyl-cyclopropyl alkene.
H.1-bromo-2-(2-(carbonyl (acetoxy-methyl))-ethyl-cyclopropyl alkene
To 0.800 gram (0.00202 mole) 1,1,2-three bromo-2-(add 0.281 milliliter of (0.00202 mole) triethylamine in 1.04 milliliters of (0.00808 mole) diethyl phosphorous acid ester solution of 2-(carbonyl (acetoxy-methyl)) ethyl-cyclopropyl alkene.At room temperature stir about was absorbed in reaction mixture in the hexane after 16 hours, with 1N salt acid elution.Then with the water layer ether extraction.The organic phase that merges is washed with the 3N aqueous sodium carbonate.With organic layer MgSO 4Dry also filtration.Under 20 ℃ of bath temperature, in a vacuum solvent is removed from filtrate.Resistates is placed under the above reaction conditions again, and subsequently with the same manner aftertreatment.Use ether/hexane to pass through the column chromatography purifying resistates, (2-(carbonyl (acetoxy-methyl))-ethyl-cyclopropyl alkene is oil to obtain 180 milligrams of 1-bromo-2-.
The embodiment 45:1-bromo-2-(preparation of 2-(carbonyl oxyethyl group)-ethyl-cyclopropyl alkene (compound 76)
To be similar to by 1,1,2-three bromo-2-(2-(carbonyl (acetoxy-methyl))-ethyl-cyclopropyl alkene (embodiment 5) the preparation 1-bromo-2-(mode of 2-(carbonyl (acetoxy-methyl))-ethyl-cyclopropyl alkene, by 1,1, (2-(carbonyl oxyethyl group)-ethyl-cyclopropyl alkene prepares 1-bromo-2-(2-(carbonyl oxyethyl group)-ethyl-cyclopropyl alkene to 2-three bromo-2-.
The embodiment 46:1-bromo-2-(preparation of 2-(carboxyl)-ethyl-cyclopropyl alkene (compound 77)
(add 0.0768 gram (1.37mmol) potassium hydroxide in 2 milliliters of absolute ethanol solution of 2-(carbonyl oxyethyl group)-ethyl-cyclopropyl alkene to 200 milligrams of (0.913mmol) 1-bromo-2-.Stir after 1 hour, add ether and water.Change the mixture that obtains over to separating funnel, separate each phase.After adding the isolating water layer of 1N concentrated hydrochloric acid acidifying, add ether.Change the mixture that obtains over to separating funnel, separate each phase.With organic layer MgSO 4Dry also filtration.In a vacuum solvent is removed from filtrate under 20 ℃ of bath temperature, (2-(carboxyl)-ethyl-cyclopropyl alkene,＞70% is pure, is oil to obtain 160 milligrams of 1-bromo-2-.
The preparation of embodiment 47:1-octyl group-3-carboxyl-cyclopropylene (compound 78)
A.1-octyl group-3-(carbonyl oxygen base oxethyl)-cyclopropylene
Pass through Mueller, P. by 1-decine and ethyl diazoacetate; Pautex, N.; The method of Helv.Chirn Acta 1990,73,1233 prepares 1-octyl group-3-(carbonyl oxygen base oxethyl)-cyclopropylene.
B.1-octyl group-3-carboxyl-cyclopropylene
(1.12g 5mmol) at room temperature stirs a week with 100 milliliters of 0.2N potassium hydroxide with 1-octyl group-3-(carbonyl oxygen base oxethyl)-cyclopropylene.Add ether and separate each phase.With aqueous phase as acidified and use dichloromethane extraction.Organic phase with dried over mgso and stripping, is obtained 0.8 gram 1-octyl group-3-carboxyl-cyclopropylene.
Embodiment 48:1-trimethyl silyl-2,3, the preparation of 3-trimethylammonium cyclopropylene (compound 79)
By preparing compound 5 employed identical methods by 2-bromine last of the ten Heavenly stems-1-alkene, prepare compound 79 by 2-bromo-3-methyl-2-butene, be 36% diethyl ether solution.
The preparation of embodiment 49:1-(butyl dimetylsilyl)-2-methylcyclopropene (compound 80)
By preparing compound 5 employed identical methods, prepare compound 80 by the 2-bromopropylene by 2-bromine last of the ten Heavenly stems-1-alkene.
The preparation of embodiment 50:1-triethylsilyl-2-methylcyclopropene (compound 81)
By preparing compound 5 employed identical methods, prepare compound 81 by the 2-bromopropylene by 2-bromine last of the ten Heavenly stems-1-alkene.
The preparation of embodiment 51:1-(7-t-butyldimethylsilyl oxygen base heptyl)-cyclopropylene (compound 82)
A.1-(7-hydroxyl heptyl)-cyclopropylene
Prepare 1-(7-hydroxyl heptyl)-cyclopropylene with the identical method described in the embodiment 7.
B.1-(7-tertiary butyl methyl-silicane base oxygen base heptyl)-cyclopropylene
To 1-(7-hydroxyl heptyl)-cyclopropylene (1.07g, 3.47mmol) 19.4 milliliters of dichloromethane solutions in, add tert-butyldimethylsilyl chloride thing (.562 gram, 3.75mmol) and N, N-dimethyl aminopyridine (.213g, 1.74mmol) and triethylamine (.368ml, 2.64mmol.).After reaction mixture at room temperature stirred 2 hours, add N, the N-dimethyl aminopyridine (.213g, 1.74mmol) and triethylamine (.368ml, 2.64mmol).After in addition 45 minutes, will react quencher by adding about 3 milliliters of saturated aqueous ammonium chlorides.Separate each phase.The organic layer of telling is used salt solution, saturated sodium bicarbonate aqueous solution and water washing successively.To tell organic layer once more, use dried over mgso, and vacuum concentration, 1.2 grams obtained.Resistates with 5% ethyl acetate/hexane column chromatography purifying, is obtained 440 milligrams of (theoretical 47%) 1-(7-t-butyldimethylsilyl oxygen base heptyl)-cyclopropylene, be oil. The preparation of embodiment 52:1-(mesyloxy methyl)-2-ethyl cyclopropylene (compound 83)
A.1,1,2-three bromo-2-ethyl cyclopropane
By preparing 1,1 by 2-bromo-1-butylene, 2-three bromo-2-ethyl cyclopropane with embodiment 5 used identical methods.
B.1-(methylol)-2-ethyl cyclopropylene
With 3.0 gram (10mmol) 1,1,50 milliliters of diethyl ether solutions of 2-three bromo-2-ethyl cyclopropane are cooled to-78 ℃.The adding lithium methide (1.4M, 21.4 milliliters, 30mmol).Reaction mixture is warmed to 5 ℃.(1.20 grams 40mmol), stir reaction mixture 1 hour down at 5 ℃, allow to be warming up to room temperature then, restir one hour to add solid polyformaldehyde.To react the water cancellation, separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, obtain the yellow oil of 900 milligrams of 1-(methylol)-2-ethyl cyclopropylene.
A.1-(mesyloxy methyl)-2-ethyl cyclopropylene
In ice bath to 0.70g (7.13mmol) 1-(methylol)-2-ethyl cyclopropylene (compound 3) and 2 milliliters of triethylamines in the solution of 15 milliliters of ether, add 0.86 gram (7.5mmol) methylsulfonyl chloride.Reaction mixture was placed 1.5 hours water cancellation then.Separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, obtain the yellow oil of 840 milligrams of 1-(mesyloxy methyl)-2-ethyl cyclopropylene.
The preparation of embodiment 53:1-(diethoxy-sulfenyl phosphoryl sulfenyl methyl)-2-ethyl cyclopropylene (compound 84)
A.1-(mesyloxy methyl)-2-ethyl cyclopropylene
By preparing 1-(mesyloxy methyl) 2-ethyl cyclopropylene by 1-(methylol)-2-ethyl cyclopropylene with embodiment 13 employed identical methods.
B.1-(diethoxy-sulfenyl phosphoryl sulfenyl methyl)-2-ethyl cyclopropylene
With 1-(mesyloxy methyl)-2-ethyl cyclopropylene (.66 gram, 3.75mmol) and disulfide group phosphoric acid 0,0 '-diethyl ester, (.84g 3.75mmol) mixes with 4.4 milliliters of dimethyl formamides sylvite.The reaction mixture stirring after 4 hours, is then added entry and ether.Separate each phase.Ether is washed with water more than twice mutually, with using dried over mgso then, and stripping, obtain 510 milligrams of (theoretical 51%) 1-(diethoxy-sulfenyl phosphoryl sulfenyl methyl)-2-ethyl cyclopropylene, be oil.
The preparation of embodiment 54:1-(4-mesyloxy butyl)-cyclopropylene (compound 85)
A.5,6-two bromo-oneself-1-alcohol
(11.23g, in about 20 milliliters of dichloromethane solutions 112.3mmol), (5.80 milliliters add 12, about 20 milliliters of dichloromethane solutions 112.3+mmol) to add bromine to ice bath refrigerative 5-hexen-1-ol.Behind reinforced the finishing,, obtain 29.1 grams 5 with mixture vacuum-drying, 6-two bromo-oneself-1-alcohol.
B.5-bromo-oneself-5-alkene-1-alcohol
To ice bath refrigerative 5,6-two bromo-oneself-(29.1 grams add tetrahydrofuran (THF) (62.4g, 112mmol) liquid of 20% potassium tert.-butoxide to 1-alcohol in about 59 milliliters of tetrahydrofuran solutions 112mmol).Behind reinforced the finishing, reaction mixture is warmed up to room temperature, stir about 30 minutes.Add ether and separate each phase then with water.With the organic layer dried over mgso of telling, dry in a vacuum then.Resistates is used 5 orifice plate post vacuum distilling purifying, obtain 23.16 grams, 87% pure 5-bromo-oneself-5-alkene-1-alcohol.
C.4-methyl-phenylformic acid 5-bromo-oneself-the 5-alkenyl esters
To the 5-bromo-oneself-5-alkene-1-alcohol (4.39 grams, add in 10.6 gram dichloromethane solutions 24.5mmol) 4-toluene acyl chlorides (3.95 grams, 25.6mmol) and triethylamine (3.3 restrain, 33mmol).At room temperature stir about diluted mixture after 2 hours with diethyl ether, then used the salt water washing with 1N hydrochloric acid then.Separate each phase, the organic layer dried over mgso is dry in a vacuum then, obtain 7.3 gram 4-methyl-phenylformic acid 5-bromo-oneself-the 5-alkenyl esters.
D.4-methyl-phenylformic acid 4-(1,2,2-three bromo-cyclopropyl)-butyl ester
In round-bottomed flask, drop into 4-methyl-phenylformic acid 5-bromo-oneself-the 5-alkenyl esters (7.3 grams, 24.6mmol), N, N '-dibenzyl-N, N, N ', N '-Tetramethyl Ethylene Diamine dibromide (0.30 gram, 0.66mmol), methylene dichloride (25 gram), (25 grams are 98.9mmol) with 45% aqueous solution potassium hydroxide (11.5 grams for methenyl bromide, 92mmol), at room temperature stir 4 days.After adding entry, separate each layer.In the organic layer of telling, add N, N '-dibenzyl-N, N, N ', (0.30 gram, 0.66mmol), (27 grams, 107mmol) (12 restrain methenyl bromide N '-Tetramethyl Ethylene Diamine dibromide, 96mmol) with 45% aqueous solution potassium hydroxide.At room temperature restir added hexane and water after one day.With mixture gravity filtration, and separate each layer by qualitative filter paper.With the organic layer dried over mgso of telling, dry in a vacuum then.Use ethyl acetate/hexane by the column chromatography purifying resistates that obtains, obtain 4.9 and restrain 61% pure 4-methyl-phenylformic acid 4-(1,2,2-three bromo-cyclopropyl)-butyl ester.
E.4-(1,2,2-three bromo-cyclopropyl)-Ding-1-alcohol
(45.5 grams, (30 grams are 107mmol) with 30 gram water to add 50% wet chemical in 250 gram methanol solutions 97mmol) to 4-methyl-phenylformic acid 4-(1,2,2-three bromo-cyclopropyl)-butyl ester.With reaction be heated to 60 ℃ about 2 hours, cool to room temperature then.After about 15 hours, (30 grams 107mmol) with 30 gram water, are heated to 60 ℃ with reaction and kept about 2 hours, then cool to room temperature to add 50% aqueous solution salt of wormwood.With the reaction mixture vacuum concentration, the resistates that obtains with ether extraction then.Organic layer is washed with alkalization water (pH10).Separate each phase, organic phase is for using dried over mgso, dry in a vacuum then.Use ether/hexane to pass through the column chromatography purifying resistates, obtain 14.5 and restrain 74% pure 4-(1,2,2-three bromo-cyclopropyl)-Ding-1-alcohol.
F.1-(4-hydroxybutyl)-cyclopropylene
Under nitrogen atmosphere, add 4-(1,2,2-three bromo-cyclopropyl)-Ding-1-alcohol (5.11 grams, 4 milliliters of diethyl ether solutions 14.5mmol), and be cooled to 0 ℃.Use syringe, add the 1.4M lithium methide diethyl ether (41.6 milliliters, 58.2mmol).After 15 minutes, will react quencher by adding about 2 ml waters.Separate each phase.With the organic layer dried over mgso of telling, and vacuum-drying, obtain 2.51 gram 1-(4-hydroxybutyl)-cyclopropylene, be oil.
G.1-(4-mesyloxy butyl)-cyclopropylene
(2.43 grams, about 10 milliliters of dichloromethane solutions 21.6mmol) cool off in-20 ℃ of baths with 1-(4-hydroxybutyl)-cyclopropylene.In mixture, add triethylamine (3.32 milliliters, 23.7mmol) and methylsulfonyl chloride (1.67 milliliters, 21.6mmol).After about one hour, in reaction, add entry and separate each phase then.With the organic layer dried over mgso of telling, and vacuum-drying.In resistates, add about 8 milliliters of methylene dichloride, triethylamine (1.39 milliliters, 10mmol) and methylsulfonyl chloride (0.701 milliliter, 9.1mmol).After about one hour, in reaction, add entry and separate each phase then.With the organic layer dried over mgso of telling, and vacuum-drying, obtain the pure 1-of 2.9g70% (4-mesyloxy butyl)-cyclopropylene, be oil.
The preparation of embodiment 55:2-octyl group-1-(boric acid)-cyclopropylene (compound 86)
With 1.30 gram (3.3mmol) 2-octyl groups-1,1,20 milliliters of diethyl ether solutions of 2-three bromo cyclopropane (embodiment 5) are cooled to-78 ℃.The adding lithium methide (1.4M, 5.9 milliliters, 8.3mmol), reaction mixture was stirred 10 minutes, put into ice bath then, placed 30 minutes, and then be cooled to-78 ℃.Add triisopropyl boric acid ester (0.9 milliliter 3.9mmol), with reaction mixture stirring 15 minutes, is warming to 0 ℃ then.Add entry, the ether and the 1NHCl aqueous solution (enough making solution show acid).Separate each phase.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, product is dissolved in the ether again, extract three times with the 1N aqueous sodium hydroxide solution.Extract with the acidifying of 6N aqueous hydrochloric acid, is used ether extraction three times.Ether is washed with water mutually, use the salt water washing, use dried over mgso, and stripping, obtain 2-octyl group-1-(the boric acid)-cyclopropylene of 400 milligrams of light yellow solids.
The preparation of embodiment 56:2-methyl isophthalic acid-(boric acid, single isopropyl esters)-cyclopropylene (compound 87)
With about 2 milligram 1, about 50 milliliters of diethyl ether solutions of 10-phenanthroline are cooled to-40 ℃, and place under the nitrogen atmosphere.To wherein by syringe add diisopropylamine (3.33 milliliters, 23.8mmol) and the 1-methylcyclopropene (1.90 milliliters, 27.8mmol; By 3-chloro-2-methyl-propylene production; See Hopf, H.; Wachholz, C.; Walsh, R.Chem.Ber.1985,118,3579, and Koster, people Liebigs Annalen Chem.1973 such as R., 1219-1235).Add 1.7 milliliters of N-butyllithiums (1.6M hexane solution) then, remain brown up to solution.After this then add the same butyllithium of another part (14.9 milliliters, 23.8mmol).After stirring 15 minutes under-40 ℃, and adding triisopropyl boric acid ester (4.60 milliliters, 19.8mmol).After about 10 minutes, add 12 milliliters of 6N hydrochloric acid.After stirring 15 minutes under-10 ℃, separate each phase.With the organic layer dried over mgso of telling, vacuum concentration obtains 3.5 gram 2-methyl isophthalic acid-(boric acid, single isopropyl esters)-cyclopropylene then, is oil.
Can prepare following compound in a similar manner:
Table 1: other compound
Figure GSA00000039172900631
Compound number R 1 R 2 R 3 R 4 Purity % Note
16? H? H? 4-methoxyl group-phenoxy group-methyl CH 3 30? 30%1-(4-methoxyl group phenoxymethyl)-1-methyl cyclopropane
17? Benzyl H? H? H? ? ?
18? Styroyl H? H? H? ? ?
19? H? H? Styroyl CH 3 55? 36%1-styroyl-1-methyl cyclopropane
20? H? H? Benzyl CH 3 50? 24%1-benzyl-1-methyl cyclopropane
21? 2-cyclohexyl-ethyl H? H? H? ? ?
22? Suberyl-methyl H? H? H? ? ?
23? Cyclohexyl-methyl H? H? H? ? ?
24? The 4-methyl-benzyl H? H? H? ? ?
25? The 3-phenyl propyl H? H? H? ? ?
26? 2-methoxyl group-benzyl H? H? H? ? ?
27? The 4-phenyl butyl H? H? H? ? ?
28? 2-(4-oxygen phenyl) ethyl H? H? H? 72? ?
29? The 3-methyl-benzyl H? H? H? ? ?
30? 2,4,6-trimethylammonium-benzyl H? H? H? 40? 49%3-(2,4, the 6-trimethylphenyl)-2-bromopropylene
31? Cyclopentyl-methyl H? H? H? ? ?
32? 7-(1-pyrroles)-heptyl H? H? H? ? ?
33? 3-(2-(1, the 3-dioxolane))-propyl group H? H? H? 75? The precursor of 10% tribromo cyclopropane
34? 7-(1-(1,2, the 4-triazole))-heptyl H? H? H? ? ?
35? 2-(2 pyridyl sulfenyl)-ethyl H? H? H? ? ?
42? 2-(4,6-dimethyl pyrimidine-2-yl)-ethyl H? H? H? ? ?
43? 2-(4-pyridine sulfenyl)-ethyl H? H? H? 50? 50% ethyl acetate
48? 2-(3-furyl acyloxy)-ethyl H? H? H? ? ?
49? 2-(cumarone-2-base carbonyl oxygen base) ethyl H? H? H? ? ?
50? 2-(5,6-dichloropyridine-3-base carbonyl oxygen base)-ethyl H? H? H? ? ?
51? 2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base carbonyl oxygen base)-ethyl H? H? H? ? ?
52? 2-(the basic ketonic oxygen base of N-t-BOC-isothiazolidine-4)-ethyl H? H? H? ? ?
54? 7-(2-tetrachloro furyl carbonyl oxygen base)-heptyl H? H? H? ? ?
61? 3-(pyrazine-2-base ketonic oxygen base)-propyl group H? H? H? 50％? 50% solvent
62? 2-(4-(1H-pyrroles-1-base phenyl) ketonic oxygen base)-ethyl H? H? H? ? ?
Use various light splitting technologies qualitative to compound.The NMR data of compound 1-35 provide in table 2.For the compound that comprises impurity, do not report the chemical shift of impurity, adjust integration so that only consider the contribution of target compound.
Table 2:NMR data
Compound # NMR?
1? (CDCl3)：1.0(d，2H)，3.8(s，2H)，6.6(m，1H)，7.2(d，2H)，7.25(d，2H)?
2? (CDCl3)：1.0(d，2H)，4.0(s，2H)，6.6(m，1H)，6.95(d，1H)，7.0(m，1H)，7.2(d，1H)?
3? (CDCl3)：0.88(d，2H)，1.3(d，2H)，1.5-1.8(m，2H)，2.0-2.2(m，2H)，2.5(m，2H)，3.7- 3.9(m，2H)，4.1-4.2(m，2H)，4.55(m，1H)，6.5(m，1H)?
4? (CDCl3)：0.25(s，6H)，0.7-0.8(m，2H)，0.87(d，2H)，1.2-1.4(m，6H)，1，5-1.7(m， 2H)，2.45(t，2H)，6.45(bs，1H)，7.3-7.45(m，3H)，7.45-7.6(m，2H)?
5? (CDCl3)：1.05(s，2H)，1.53(s，6H)，6.5(s，1H)，7.1-7.5(m，5H).
6? (d6?Acetone)：1.6(s，3H)，7.1-7.3(m，5H)，7.45(s，2H)?
7? (CDCl3)：1.3(s，3H)，3.9(s，2H)，6.8-7.0(m，3H)，7.25(m，2H)，7.35(s，2H)?
8? (CDCl3)：0.89(2H，s)，2.03(3H，s)，3.75(2H，s)，7.1-7.4(5H，m)?
9? (CDCl3)：0.94(d，2H)，2.8(t，2H)，3.1(t，2H)，6.6(m，1H)，7.3(m，4H)?
10? (CDCl3)：0.85(d，2H)，2.8(t，2H)，4.3(t，2H)，6.6(m，1H)，7.6(m，2H)，7.7(m，1H)， 7.9(m，2H)?
11? (CDCl3)：0.92(d，2H)，1.58(s，4H)，3.05(t，2H)，4.55(t，2H)，6.6(bs，1H)，7.39(s， 1H)，7.47(s，1H)?
12? (CDCl3)：0.87(d，2H)，1.2-1.4(m，6H)，1.57(m，2H)，1.79(m，2H)，2.47(td，2H)， 3.92(t，2H)，6.44(m，1H)，6.90(bs，1H)，7.06(bs，1H)，7.46(bs，1H)?
13? (CDCl3)：0.87(d，2H)，1.2-1.4(m，6H)，1.5-1.8(m，4H)，2.47(t，2H)，3.67(t，2H)， 6.42(bs，1H)，6.9-7.1(m，6H)，7.2-7.4(m，4H)?
14? (CDCl3)：0.88(d，2H)，1.2-1.5(m，5H)，1.55-2.0(m，5H)，2.4-2.6(m，2H)，6.40 (t，1H)?
15? (CDCl3)：0.90(d，2H)，2.6-2.9(m，4H)，3.6-3.8(m，8H)，6.5(m，1H)?
16? (CDCl3)：1.2(s，3H)，3.8(s，3H)，3.9(s，2H)，6.8(m，4H)，7.35(s，2H)?
17? (CDCl3)：1.1(d，2H)，3.8(s，2H)，6.5(m，1H)，7.2-7.35(m，5H)
18? (CDCl3)：0.92(d，2H)，2.8(t，2H)，2.9(t，2H)，6.45(m，1H)，7.15-7.3(m，5H)?
19? (CDCl3)：1.18(s，3H)，1.78(m，2H)，2.42(m，2H)，7.1-7.2(m，3H)，7.2-7.3(m，2H)， 7.3(s，2H)?
20? (CDCl3)：1.17(s，3H)，2.76(s，2H)，7.1(m，2H)，7.15-7.3(m，3H)，7.35(s，2H)?
21? (CDCl3)：0.89(d，2H)，0.88-1.0，(m，1H)，1.1-1.35(m.4H)，1.47(q，2H)，1.6- 1.85(m，4H)，2.48(td，2H)，6.42(t，1H)?
22? (CDCl3)：0.87(d，2H)，1.15-1.3，(m，2H)，1.35-1.9(m，11H)，2.40(dd，2H)，6.43 (t，1H)?
23? (CDCl3)：0.87(d，2H)，0.9-1.05，(m，2H)，1.1-1.35(m，3H)，1.4-1.8(m，6H)，2.37 (dd，2H)，6.40(t，1H)?
24? (CDCl3)：1.0(d，2H)，2.3(s，3H)，3.8(s，2H)，6.56(m，1H)，7.1(m，4H)?
25? (CDCl3)：0.9(d，2H)，1.9(m，2H)，2.45(t，2H)，2.6(t，2H)，6.5(m，1H)，7.1-7.3(m，5H)?
26? (CDCl3)：1.0(d，2H)，3.8(s，3H)，6.55(m，1H)，6.9(m，2H)，7.2(m，2H)?
27? (CDCl3)：0.88(d，2H)，1.6-1.75(m，4H)，2.55(t，2H)，2.65(t，2H)，6.4(m，1H)， 7.15(m，3H)，7.25(m，2H)?
28? (CDCl3)：0.9(d，2H)，2.7-2.8(m，2H)，2.8-2，9(m，2H)，6.5(m，1H)，7.15(d，2H)， 7.3(d，2H)?
29? (CDCl3)：1.0(d，2H)，2.3(s，3H)，3.8(s，2H)，6.58(m，1H)，7.1(m，3H)，7.2(m，1H)?
30? (CDCl3)：0.9(d，2H)，2.25(m，9H)，3.75(s，2H)，6.45(m，1H)，6.85(s，1H)?
31? (CDCl3)：0.89(d，2H)，1.1-1.3(m，2H)，1.45-1.65(m，4H)，1.65-1.85(m，2H)， 2.15(m，1H)，2.45(d，2H)，6.44(m，1H)?
32? (CDCl3)：0.87(d，2H)，1.2-1.4(m，6H)，1.56(pentet，2H)，1.87(pentet，2H)，2.46 (td，2H)，4.12(t，2H)，6.23(t，1H)，6.42(t，1H)，7.36(d，1H)，7.50(d，1H)?
33? (CDCl3)：0.89(d，2H)，1.7(m，4H)，2.5(m，2H)，3.8-4.0(m，4H)，4.9(m，1H)， 6.47(m，1H)?
34? (CDCl3)：0.87(d，2H)，1.2-1.4(m，6H)，1.57(m，2H)，1.88(m，2H)，2.47(t，2H)， 4.17(t，2H)，6.43(bs，1H)，7.94(s，1H)，8.04(s，1H)?
35? (CDCl3)：0.97(d，2H)，2.9(t，2H)，3.4(t，2H)，6.6(m，1H)，6.98(m，1)，7.16(m，1H)， 7.49m，1H)，8.4(m，1H)?
36? (CDCl3)：0.9(d，2H)，1.2-1.9(m，H)，2.25(m，2H)，2.45(m，2H)，2.9(t，4H)，6.45 (m，1H)，6.95(m，1H)?
37? (CDCl3)：0.8-1.2(m，5H)，2.3(q，2H)，5.1(s，3H)，7.0-7.5(m，4H)?
38? (CDCl3)：0.9(m，5H)，1.2-1.8(m，14H)，2.6(t，2H)，4.0-4.2(m，4H)?
39? (CDCl3)：1.04(d，2H)，2.10(s，3H)，2.2(d，1H)，3.8(s，3H)，5.65(bs，1H)，6.85(d， 1H)，6.9(m，2H)，7.3(d，1H)?
41? (CDCl3)：7.5(m，3H)，7.7(m，2H)?
42? (CDCl3)：0.97(d，2H)，2.4(s，6H)，2.95(t，2H)，3.4(t，2H)，6.55(m，1H)，6.7(s， 1H)?
43? (CDCl3)：0.9(d，2H)，2.9(t，2H)，3.3(t，2H)，6.65(m，1H)，7.15(m，2H)，8.45(m， 2H)?
44? (CDCl3)：0.9(d，2H)，1.55-1.9(m，6H)，2.4(s，3H)，4.3(t，2H)，6.5(m，1H)，7.2 (d，2H)，7.9(d，2H)?
45? (CDCl3)：1.6(s，2H)，3.81(s，2H)，7.2-7.4(m，5H)?
46? (CDCl3)：1.6(s，2H)，3.8(s，2H)，7.2-7..(m，5H)?
47? (CDCl3)：0.9(d，2H)，2.95(t，2H)，4.7(d，2H)，6.5(m，1H)，6.6(m，1H)，7.2(m， 1H)，7.6(M，1H)?
48? (CDCl3)：0.95(d，2H)，2.9(t，2H)，4.5(t，2H)，6.6(m，1H)，6.7(d，1H)，7.4(d， 1H)，8.0(s，1H)?
49? (CDCl3)：0.99(d，2H)，3.05(t，2H)，4.65(t，2H)，6.7(m，1H)，7.3-7.8(m，5H)?
50? (CDCl3)：0.9(d，2H)，2.98(t，2H)，4.61(t，2H)，6.7(m，1H)，8.35(s，1H)，8.9(s， 1H)?
51? (CDCl3)：0.9(d，2H)，3.0(m，5H)，4.6(t，2H)，6.7(m，1H)?
52? (CDCl3)：0.9(d，2H)，1.4(d，9H)，2.8(t，2H)，3.2-3.5(m，2H)，4.7-4.9(m，5H)，6.6 (m，1H)?
53? (CDCl3)：0.88(d，2H)，1.2-1.9(m，10H)，2.48(t，2H)，3.08(s，3H)，4.36(t，2H)， 6.45(m，1H)，8.03(d，2H)，8.23(d，2H)?
54? (CDCl3)：0.95(d，2H)，1.2-1.4(m，6H)，1.5-1.7(m，4H)，1.8-2.1(m，4H)，2.5(t， 2H)，3.9-4.2(m，4H)，4.5(m，1H)，6.45(m，1H)?
55? (CDCl3)：0.9(d，2H)，2.05(m，2H)，2.7(m，2H)，3.2(m，2H)，6.5(m，1H)，7.0(t， 1H)，7.2(d，1H)，7.5(t，1H)，8.4(d，1H)?
56? (CDCl3)：0.9(d，2H)，1.3-1.75(m，8H)，2.4-2.55(m，4H)，3.6(m，2H)，4.1(t， 2H)，6.45(m，1H)，7.5-7.7(m，3H)，7.9(m，2H)?
57? (CDCl3)：0.9(d，2H)，1.3-1.7(m，14H)，2.0(s，3H)，3.65(t，2H)，6.45(m，1H)，7.1 (d，2H)，7.25(d，2H)?
58? (CDCl3)：0.9(d，2H)，1.3-1.8(m，12H)，2.4(m，2H)，3.2(t，2H)，6.45(m，1H)， 7.25(s，1H)，8.15(s，1H)?
59? (CDCl3)：0.9(d，2H)，1.3(m，2H)，2.6(t，2H)，3.95(s，3H)，4.3(t，2H)，6.1(m， 1H)，6.5(m，1H)，6.8(m，1H)，6.95(m，1H)?
60? (CDCl3)：0.97(t，3H)，1.1(s，2H)，2.4(m，2H)，5.2(s，2H)，7.05(d，1H)，7.45(d， 2H)，7.7(d，1H)，7.74(d，2H)?
61? (CDCl3)：0.95(d，2H)，2.1(m，2H)，2.7(t，2H)，4.5(t，2H)，6.55(m，1H)，8.7(d， 2H)，9.32(s，1H)?
62? (CDCl3)：0.9(d，2H)，2.9(t，2H)，4.55(t，2H)，6.35(m，2H)，6.65(m，1H)，7.15 (m，2H)，7.45(d，2H)，8.1(d，2H)?
63? (CDCl3)：0.55(q，6H)，0.88(d，2H)，0.94(t，9H)，1.99(s，2H)，6.25(bs，1H).?
64? (CDCl3)：0(s，9H)，0.82(d，2H)，1.91(s，2H)，6.22(bs，1H).?
65? (CDCl3)：0(s，9H)，0.45-0.65(m，2H)，0.91(d，2H)，1.25-1.5(m，6H)，1.60 (pentet.2H)，2.50(t?d，2H)，6.45(t，1H).?
66? (CDCl3)：0(s，9H)，0.79(m，2H)，0.90(d，2H)，2.48(td，2H)，6.37(t，1H).?
67? (CDCl3)：0.09(s，9H)，0.65(s，2H)，0.82(t，3H)，1.2-1.4(m，10H)，1.55(pentet， 2H)，2.47(t，2H).?
68? (CDCl3)：0.98(d，2H)，2.96(tdq，2H)，3.04(s，3H)，4.47(t，2H)，6.75(bs，1H).?
69? (CDCl3)：0.88(d，2H)，1.2-1.45(m，6H)，1.6(pentet，2H)，1.75(pentet，2H)，2.45 (td，2H)，3.00(s，3H)，4.23(t，2H)，6.4(t，1H).?
70? (CDCl3)：0.88(d，2H)，1.25(t，3H)，1.25-1.45(m，6H)，1.5-1.75(m，4H)，2.4- 2.65(m，6H)，6.43(t，1H).?
71? (CDCl3)：0.88(t，3H)，1.2-1.4(m，10H)，1.5(s，2H)，1.6(m，2H)，2.4(t，2H)?
72? (CDCl3)：0.9(t，3H)，1.15(s，3H)，1.15-1.5(m，6H)，1.7(m，2H)，7.35(s，2H)?
73? (CDCl3)：0.9(t，3H)，1.1(s，3H)，1.15-1.5(m，16H)，7.34(s，2H)?
74? (CDCl3)：0.77(s，2H)，0.9(t，3H)，1.15-1.4(m，8H)，1.55(m，2H)，2(t，3H)， 2.35(m，2H)?
75? (CDCl3)：1.55(s，2H)，2.1(s，3H)，2.75(m，2H)，2.8(m，2H)，5.77(s，2H)?
76? (CDCl3)：1.3(t，3H)，1.55(s，2H)，2.6(t，2H)，2.8(t，2H)，4.1(q，2H)?
77? (CDCl3)：1.56(s，2H)，2.65(t，2H)，2.8(t，2H)?
78? (CDCl3)：0.88(t，3H)，1.1-1.5(m，10H)，1.6(pentet，2H)，2.13(d，2H)，2.51(t， 2H)，6.33(bs，1H).?
79? (CDCl3)：0(s，9H)，0.95(s，6H)，1.96(s，3H).?
80? (CDCl3)：0.16(8，6H)，0.67(t，2H)，0.75(s，2H)，0.91(t，3H)，1.25-1.45 (m，2H)，2.25(s，3H).?
81? (CDCl3)：0.64(q，6H)，0.74(s，2H)，0.95(t，9H)，2.24(s，3H).?
82? (CDCl3)：0(s，6H)，0.84(m，11H)，1.2-1.6(m.10H)，2.45(t，2H)，3.55(t， 2H)，6.45(m，1H)?
83? (CDCl3)：1.12(s，2H)，1.20(t，3H)，2.53(q，2H)，3.05(s，3H)，5.18(s， 2H).?
84? (CDCl3)：0.9(s，2H)，1.3(t，3H)，1.4(t，6H)，2.5(m，2H)，3.9(d，2H)，4.1- 4.4(m，4H)?
85? (CDCl3)：0.9(d，2H)，1.7-1.9(m，4H)，2.6(t，2H)，3.0(s，3H)，4.3(t.2H)，?
? 6.5(m，1H)?
86? (CDCl3)：0.88(s，2H，and?t，3H)，1.2-1.4(m，8H)，1.5-1.7(m，4H)，2.61 (t，2H)，4.53(br，s，2H).?
87? (d6DMSO)：0.7(d，2H)，1.1(d，6H)，2.2(d，3H)，3.8(m，1H)，8.05(br.s， 1H)?
Biological activity:
The check of tomato epinasty
Purpose: this test method is used for measuring when experimental compound is used with the composition of volatile gases or spray solution, the ability of ethene inductive epinasty growth response in the experimental compound blocking-up tomato.
Processing tank has the size suitable to test plant, and is air-locked.Each processing tank is equipped with reusable barrier film to be used for the injection of ethene.Test plant is a Patio kind tomato seedling, and per three inches square plastic basins are planted two strains.
Volatile gases is handled need be contained in 4.8L capacity polystyrene processing tank with two basin Patio var. tomatoes, has 50X9mm to comprise the plastics Petri dish of Gelman filter bed half (top or lower part) in the case.The experimental compound that will be dissolved in 1.0 milliliters of proper amies in the acetone is pipetted on the filter bed, and processing tank is sealed at once.The ethylene gas that after four hours final concn is equaled 10ppm v/v is injected in the encapsulation process case.After 16 hours processing tank is opened in extraction hood; allow blowing air, plant is engraved the visible vestige, to represent and to compare with undressed control group through the ethene processing; come protective plant in case the degree of ethene inductive epinasty was represented with 0 to 10 minute by giving with experimental compound.Expression in 10 fens protection fully.Expression in 0 fen is to not protection of ethylene action.Gas processing concentration is volume/volume.
Processing is used in sprinkling need use the DeVilbiss atomizer, with whole leaves and the stem with two basin Patio var. tomatoes, covers fully with the experimental compound that is dissolved in 10% acetone/90% water and has an appropriate amount of 0.05%SilwettL-77 tensio-active agent.With plant dry air four hours in drying hood, change over to then in the airtight 4.8L polystyrene processing tank.
The ethylene gas that final concn is equaled 10ppm v/v is injected in the encapsulation process case.After 16 hours processing tank is opened in extraction hood; allow blowing air; plant is engraved the visible vestige; to represent and to compare with undressed control group through the ethene processing; come protective plant to hinder the degree of ethene inductive epinasty, with expression in 0 to 10 fen by giving with experimental compound.Expression in 10 fens protection fully.Expression in 0 fen is to not protection of ethylene action.
When using with gas or sprays, the activity of compound of the present invention in the test of tomato epinasty provides in table 3.
Table 3: the activity of compound of the present invention in the test of tomato epinasty
Compound # Qi Ti @1000ppm Qi Ti @10ppm Pen Wuji @10ppm
1? NT? 10? 10?
2? NT? 10? 7?
3? NT? 8? 0?
4? NT? 4? 10?
5? NT? 5? 2?
6? 7? 2.5? 1?
7? 10? 4? 2?
8? 10? 0? 0?
9? NT? 10? 10?
10? NT? 10? 10?
11? 8 a 2? 0?
12? 10 b 5.5? 3.5?
13? NT? 0? 10?
14? NT? NT? NT?
15? NT? 10? 0?
16? 10 c 3.75? 4.5?
17? NT? 9? 2?
18? NT? 10? 6?
19? 7.5? 2? 2?
20? 7? 0? 0?
21? NT? 10? 10?
22? NT? 9? 10?
23? NT? 10? 10?
24? NT? 10? 10?
25? NT? 10? 10?
26? NT? 10? 5?
27? NT? 10? 10?
28? NT? 9.5? 8?
29? NT? 10? 10?
30? 8? 3? 0?
31? NT? 9? 7.5?
32? 10? 3? 10?
33? NT? 8? 0?
34? 10? 4.5? 9?
35? NT? 10? 9?
36? 10 c 5? 3?
37? 2? 0? 0?
38? 10(@850ppm)? 3? 0?
39? 10? 2? 0?
40? NT? 7? 0?
41? 2? 0? 0?
42? 3(@343.4ppm)? NT? 2?
43? NT? 10? 0?
44? 7? 0? 0?
45? 10? 5? 0?
46? 10? 5? 0?
47? 10(@551ppm)? 0? 0?
48? NT? 10? NT?
49? 9(@343.4ppm)? 0? 0?
50? 9? 0? 0?
51? 3? 0? 0(8@1000ppm)?
52? 3? 0? 2(10@1000ppm)?
53? 10? 0? 0?
54? 2? 0? 0?
55? 10(@800ppm)? NT? 3?
56? NT? 5? 10?
57? 10? 0? 2?
58? NT? 3? 0?
59? NT? 3? 4?
60? 0? 4? 0?
61? 10(@438ppm)? 0? 0?
62? 10(@509ppm)? 0? 0?
63? NT? 10? 10?
64? NT? 10? 9?
65? NT? 10? 6?
66? NT? 10? 10?
67? NT? 6? 3?
68? 10? 3? 5?
69? 8? 0? 0?
70? NT? 2? 10?
aUnder 600ppm, measure
bUnder 850ppm, measure
cUnder 500ppm, measure
NT represents not have mensuration.
Compound # Gas @1000? ppm Gas @500 ppm Gas @10? ppm Sprays @10? ppm
71? ?10? NT? ?1? ?3?
72? 9? NT? 0? 2?
73? 8? NT? 0? 0?
74? 10? NT? 0? 0?
75? NT? NT? 10? 0?
76? NT? NT? 10? 0?
77? NT? NT? 8? 2?
78? 5? 10? 0? 0?
NT represents not have mensuration.
Compound # Qi Ti @1000ppm Qi Ti @10ppm Pen Wuji @10ppm
79? NT? 10? NT?
80? 7? 0? 0?
81? 10? 0? 0?
82? 10? 3? 0?
83? 10? 4? 2?
84? 10? 0? 0?
85? 10? 0? 0?
86? NT? 10? 0?
NT represents not have mensuration.

Claims (5)

1. the compound of a following formula:
Figure FSA00000039172800011
Wherein:
A) R 3And R 4Be H, R 1And R 2Be independently selected from the group of H and following formula:
-(CH 2)n-Z
Wherein:
I) n is 0 to 8 integer;
Ii) Z is selected from independently of one another:
A) H, carboxyl, 2-phenyl-third-2-base, chlorine, bromine, butyl dimetylsilyl, ethyl dimetylsilyl, trimethyl silyl, 3,5-dimethylphenyl silyl, t-butyldimethylsilyl oxygen base, diphenyl amino, mesyloxy, diethoxy sulfenyl phosphoryl sulfenyl methyl, carbonyl (acetoxy-methyl), carbonyl oxyethyl group, boric acid, 2-(2-boron-1,3-dioxy butane) and boric acid isopropyl ester; Or
B) group G, wherein G is selected from cyclohexyl, suberyl, phenyl, 4-chloro-phenyl-, 4-chloro-phenyl-sulfenyl, the 4-fluorophenyl, 4-bromophenyl, 2-p-methoxy-phenyl, the 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, the 4-methyl-benzyl, 2-methoxy-benzyl, 3-phenyl propyl, the 4-ethylphenyl, styroyl, 4-phenyl butyl, the 4-chlorobenzene ethyl, 4-chloro-phenyl-sulfenyl, 2,4,6 ,-trimethyl benzyl, cyclopentyl-methyl, 3-trifluoromethyl, 4-aminomethyl phenyl carbonyl oxygen base, 2-(2-pyridyl sulfenyl), 2-methyl-3-p-methoxy-phenyl, 2-hydroxy 3-methoxybenzene base, 2,4-dibromo phenyl, 3, the 5-difluorophenyl, 3, the 5-3,5-dimethylphenyl, 2,4, the 6-trichlorophenyl, the 4-p-methoxy-phenyl, 2, the 4-Dimethoxyphenyl, 4-(trifluoromethyl) phenyl, benzenesulfonyl, 1-imidazolyl, pyridine-2-base, pyridin-3-yl, pyridin-4-yl, pyrazinyl, 4,6-dimethyl pyrimidine-2-base, pyrimidine-4-base, pyrimidine-5-base, pyridazinyl, triazol-1-yl, imidazoles-1-base, sulfenyl benzene-2-base, 2-furans-2-base furans-2-base carbonyl oxygen base, 3-furyl carbonyl oxygen base, furans-3-base, 2-(1-(4-bromine pyrazolyl)), 2-carboxy-N-morpholinyl, pyrryl, pyrazolyl, 4-pyridyl sulfenyl, cumarone-2-base furans-2-base carbonyl oxygen base, 5,6-dichloropyridine-3-base carbonyl oxygen base, 2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base carbonyl oxygen base) ， oxazolyl isoxazolyl, 1,2, the 4-triazole, 2-(N-t-BOC-isothiazolidine-4-base carbonyl oxygen base, (4-methylsulfonyl oxygen base phenyl)-carbonyl oxygen base, 2-tetrahydrofuran base carbonyl oxygen base, 2-pyridyl sulfenyl propyl group, benzenesulfonyl oxygen base, 4-aminomethyl phenyl sulfenyl, 1H-1,2,4-triazole-2-base sulfenyl, 1-methyl-2-pyrroles's carbonyl oxygen base, 3-(4-chloro-phenyl-)-rattle away-6-ketone-1-base, 3-(pyrazine-2-base carbonyl oxygen base), 4-(1H-pyrroles-1-base phenyl) carbonyl oxygen base, thiazolyl, isothiazolyl ， oxadiazole base, thiadiazolyl group, tetrahydrofuran base, pyrrolidyl, piperidyl, THP trtrahydropyranyl, morpholinyl, piperazinyl, 1,3-dioxolane base ， alkyl dioxin and thienyl;
B) non-hydrogen atom in each compound adds up to 50 or still less; And
C) at-(CH 2) heteroatomic among the n-Z add up to 0 to 4; And
D) one of following any condition:
I) R 1Comprise at least one group G; Or
Ii) at least one R 1And R 2Comprise one to four non-hydrogen atom and at least one R 1And R 2Comprise and surpass four non-hydrogen atoms;
And enantiomorph, steric isomer, salt and its mixture;
Condition is:
R 1Not the amino cyclonene of 3-, the dialkoxy benzylamino carbonyl of benzenesulfonyl, phenyl sulphur ethyl, phenylbenzene hydroxymethyl, benzo (g) quinoline-4-alcohol-1-methyl, malonic ester derivative, replacement.
2. compound as claimed in claim 1 is characterized in that R 1Be selected from: benzyl; 4-benzyl chloride base; the 4-methoxy-benzyl; 2-(4-chloro-phenyl-sulfenyl)-ethyl; 2-(thienyl) methyl; 7-(1-imidazoles)-heptyl; 1-(4-bromine pyrazoles); 7-(diphenyl amino)-heptyl; 2-(2-carboxy-N-morpholinyl)-ethyl; 2-propyl group-[1; 3] dioxs; 6-(phenyl dimetylsilyl)-hexyl; cyclohexyl methyl; 2-cyclohexyl ethyl; the suberyl methyl; 7-(1-pyrazoles)-heptyl; (2-(1 for 3-; the 3-dioxolane)-propyl group; (1-(1 for 7-; 2; the 4-triazole))-heptyl; 2-(2-pyridyl sulfenyl)-ethyl; 1-(7-(N-piperidyl imino-)) heptyl; 3-trifluoromethoxy phenoxy ylmethyl; 2-hydroxyl-3-methoxy-benzyl; 2-(4; 6-dimethyl pyrimidine-2-yl) ethyl; 2-(4-pyridyl sulfenyl) ethyl; 1-(4-aminomethyl phenyl ketonic oxygen Ji Dingji)-; 1-(2-furans-2-base ketonic oxygen base ethyl)-; 2-(3-furyl carbonyl oxygen base)-ethyl; 2-(cumarone-2-base ketonic oxygen base)-ethyl, 2-(5,6-dichloropyridine-3-base ketonic oxygen base)-ethyl; 2-(4-methyl isophthalic acid; 2,3-thiadiazoles-5-base ketonic oxygen base)-ethyl, 2-(N-t-BOC-isothiazolidine-4-base ketonic oxygen base)-ethyl; 7-(4-methylsulfonyl oxygen base phenyl)-ketonic oxygen base)-heptyl; 7-(2-tetrahydrofuran base ketonic oxygen base)-heptyl, 2-pyridyl sulfenyl propyl group, 8-(benzenesulfonyl oxygen base)-octyl group; 8-(4-aminomethyl phenyl sulfenyl)-octyl group; 8-(1H-1,2,4-triazole-2-base sulfenyl)-octyl group; 3-(1-methyl-2-pyrrolylcarbonyl oxygen base)-propyl group; 3-(4-chloro-phenyl-)-rattle away-6-ketone-1-base, 3-(pyrazine-2-base ketonic oxygen base)-propyl group, 2-(4-(1H-pyrroles-1-base phenyl) ketonic oxygen base)-ethyl; 2-(carbonyl (acetoxy-methyl)) ethyl; 2-(carbonyl oxyethyl group)-ethyl, 2-carboxy ethyl, 7-t-butyldimethylsilyl oxygen base heptyl; diethoxy-sulfenyl phosphoryl sulfenyl methyl and 4-methylsulfonyl oxygen Ji Dingji.
3. compound as claimed in claim 1 is characterized in that R 2Be selected from methyl, ethyl, heptyl, octyl group, bromine and chlorine.
4. method that suppresses the ethene effect in the plant comprises with the cyclopropene derivatives of the following formula of ethene suppressing effect significant quantity or the step of its composition and plant contact:
Figure FSA00000039172800031
Wherein:
A) R 3And R 4Be H, R 1And R 2Be independently selected from the group of H and following formula:
-(CH 2)n-Z
Wherein:
I) n is 0 to 8 integer;
Ii) Z is selected from independently of one another:
A) H, carboxyl, 2-phenyl-third-2-base, chlorine, bromine, butyl dimetylsilyl, ethyl dimetylsilyl, trimethyl silyl, 3,5-dimethylphenyl silyl, t-butyldimethylsilyl oxygen base, diphenyl amino, mesyloxy, diethoxy sulfenyl phosphoryl sulfenyl methyl, carbonyl (acetoxy-methyl), carbonyl oxyethyl group, boric acid, 2-(2-boron-1,3-dioxy butane) and boric acid isopropyl ester; Or
B) group G, wherein G is selected from cyclohexyl, suberyl, phenyl, 4-chloro-phenyl-, 4-chloro-phenyl-sulfenyl, the 4-fluorophenyl, 4-bromophenyl, 2-p-methoxy-phenyl, the 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, the 4-methyl-benzyl, 2-methoxy-benzyl, 3-phenyl propyl, the 4-ethylphenyl, styroyl, 4-phenyl butyl, the 4-chlorobenzene ethyl, 4-chloro-phenyl-sulfenyl, 2,4,6 ,-trimethyl benzyl, cyclopentyl-methyl, 3-trifluoromethyl, 4-aminomethyl phenyl carbonyl oxygen base, 2-(2-pyridyl sulfenyl), 2-methyl-3-p-methoxy-phenyl, 2-hydroxy 3-methoxybenzene base, 2,4-dibromo phenyl, 3, the 5-difluorophenyl, 3, the 5-3,5-dimethylphenyl, 2,4, the 6-trichlorophenyl, the 4-p-methoxy-phenyl, 2, the 4-Dimethoxyphenyl, 4-(trifluoromethyl) phenyl, benzenesulfonyl, 1-imidazolyl, pyridine-2-base, pyridin-3-yl, pyridin-4-yl, pyrazinyl, 4,6-dimethyl pyrimidine-2-base, pyrimidine-4-base, pyrimidine-5-base, pyridazinyl, triazol-1-yl, imidazoles-1-base, sulfenyl benzene-2-base, 2-furans-2-base furans-2-base carbonyl oxygen base, 3-furyl carbonyl oxygen base, furans-3-base, 2-(1-(4-bromine pyrazolyl)), 2-carboxy-N-morpholinyl, pyrryl, pyrazolyl, 4-pyridyl sulfenyl, cumarone-2-base furans-2-base carbonyl oxygen base, 5,6-dichloropyridine-3-base carbonyl oxygen base, 2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base carbonyl oxygen base) ， oxazolyl isoxazolyl, 1,2, the 4-triazole, 2-(N-t-BOC-isothiazolidine-4-base carbonyl oxygen base, (4-methylsulfonyl oxygen base phenyl)-carbonyl oxygen base, 2-tetrahydrofuran base carbonyl oxygen base, 2-pyridyl sulfenyl propyl group, benzenesulfonyl oxygen base, 4-aminomethyl phenyl sulfenyl, 1H-1,2,4-triazole-2-base sulfenyl, 1-methyl-2-pyrroles's carbonyl oxygen base, 3-(4-chloro-phenyl-)-rattle away-6-ketone-1-base, 3-(pyrazine-2-base carbonyl oxygen base), 4-(1H-pyrroles-1-base phenyl) carbonyl oxygen base, thiazolyl, isothiazolyl ， oxadiazole base, thiadiazolyl group, tetrahydrofuran base, pyrrolidyl, piperidyl, THP trtrahydropyranyl, morpholinyl, piperazinyl, 1,3-dioxolane base ， alkyl dioxin and thienyl;
B) non-hydrogen atom in each compound adds up to 50 or still less; And
C) at-(CH 2) heteroatomic among the n-Z add up to 0 to 4; And
D) one of following any condition:
I) R 1Comprise at least one group G; Or
Ii) at least one R 1And R 2Comprise one to four non-hydrogen atom and at least one R 1And R 2Comprise and surpass four non-hydrogen atoms;
And enantiomorph, steric isomer, salt and its mixture;
Or its composition.
5. method as claimed in claim 4 is characterized in that R 1Be selected from: benzyl; 4-benzyl chloride base; the 4-methoxy-benzyl; 2-(4-chloro-phenyl-sulfenyl)-ethyl; 2-(thienyl) methyl; 7-(1-imidazoles)-heptyl; 1-(4-bromine pyrazoles); 7-(diphenyl amino)-heptyl; 2-(2-carboxy-N-morpholinyl)-ethyl; 2-propyl group-[1; 3] dioxs; 6-(phenyl dimetylsilyl)-hexyl; cyclohexyl methyl; 2-cyclohexyl ethyl; the suberyl methyl; 7-(1-pyrazoles)-heptyl; (2-(1 for 3-; the 3-dioxolane)-propyl group; (1-(1 for 7-; 2; the 4-triazole))-heptyl; 2-(2-pyridyl sulfenyl)-ethyl; 1-(7-(N-piperidyl imino-)) heptyl; 3-trifluoromethoxy phenoxy ylmethyl; 2-hydroxyl-3-methoxy-benzyl; 2-(4; 6-dimethyl pyrimidine-2-yl) ethyl; 2-(4-pyridyl sulfenyl) ethyl; 1-(4-aminomethyl phenyl ketonic oxygen Ji Dingji)-; 1-(2-furans-2-base ketonic oxygen base ethyl)-; 2-(3-furyl carbonyl oxygen base)-ethyl; 2-(cumarone-2-base ketonic oxygen base)-ethyl, 2-(5,6-dichloropyridine-3-base ketonic oxygen base)-ethyl; 2-(4-methyl isophthalic acid; 2,3-thiadiazoles-5-base ketonic oxygen base)-ethyl, 2-(N-t-BOC-isothiazolidine-4-base ketonic oxygen base)-ethyl; 7-(4-methylsulfonyl oxygen base phenyl)-ketonic oxygen base)-heptyl; 7-(2-tetrahydrofuran base ketonic oxygen base)-heptyl, 2-pyridyl sulfenyl propyl group, 8-(benzenesulfonyl oxygen base)-octyl group; 8-(4-aminomethyl phenyl sulfenyl)-octyl group; 8-(1H-1,2,4-triazole-2-base sulfenyl)-octyl group; 3-(1-methyl-2-pyrrolylcarbonyl oxygen base)-propyl group; 3-(4-chloro-phenyl-)-rattle away-6-ketone-1-base, 3-(pyrazine-2-base ketonic oxygen base)-propyl group, 2-(4-(1H-pyrroles-1-base phenyl) ketonic oxygen base)-ethyl; 2-(carbonyl (acetoxy-methyl)) ethyl; 2-(carbonyl oxyethyl group)-ethyl, 2-carboxy ethyl, 7-t-butyldimethylsilyl oxygen base heptyl; diethoxy-sulfenyl phosphoryl sulfenyl methyl and 4-methylsulfonyl oxygen Ji Dingji.
CN2010101281818A 2001-02-26 2002-02-25 A method to inhibit ethylene responses in plants Expired - Fee Related CN101979394B (en)

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