CN107325100A - The preparation method of piperidines with insecticidal activity and pyridinone derivatives - Google Patents
The preparation method of piperidines with insecticidal activity and pyridinone derivatives Download PDFInfo
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- 0 *N(CC1)CCC1=O Chemical compound *N(CC1)CCC1=O 0.000 description 10
- LZPDPOXQKWLKDH-UHFFFAOYSA-N CC(C(CCNCC1)=C1N1)=CC11OC1 Chemical compound CC(C(CCNCC1)=C1N1)=CC11OC1 LZPDPOXQKWLKDH-UHFFFAOYSA-N 0.000 description 1
- SRKVYDDGZZYYKR-UHFFFAOYSA-N CC(C)(C)N(C(CCN(C1)C(OC(C)(C)C)=O)=C1C(Cl)=C1)C1=O Chemical compound CC(C)(C)N(C(CCN(C1)C(OC(C)(C)C)=O)=C1C(Cl)=C1)C1=O SRKVYDDGZZYYKR-UHFFFAOYSA-N 0.000 description 1
- RDMLKVWMUSZEGD-UHFFFAOYSA-N CC(CCNC(OC(C)(C)C)=O)NC Chemical compound CC(CCNC(OC(C)(C)C)=O)NC RDMLKVWMUSZEGD-UHFFFAOYSA-N 0.000 description 1
- DKZBLXUAJDHZQQ-UHFFFAOYSA-N CC(CCNC)NC Chemical compound CC(CCNC)NC DKZBLXUAJDHZQQ-UHFFFAOYSA-N 0.000 description 1
- TXWQWZUOYAQDRV-UHFFFAOYSA-N CCOC(c(c(O)nc(CC1)c2CN1C(OC(C)(C)C)=O)c2O)=O Chemical compound CCOC(c(c(O)nc(CC1)c2CN1C(OC(C)(C)C)=O)c2O)=O TXWQWZUOYAQDRV-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
Abstract
The invention discloses the preparation method of a kind of piperidines for having an insecticidal activity and pyridinone derivatives, belong to pharmaceutical chemistry synthesis technical field.Technical scheme main points are：
Description
Technical field
The invention belongs to pharmaceutical chemical synthesis technical field, and in particular to a kind of new piperidines with insecticidal activity is simultaneously
The preparation method of pyridinone derivatives.
Background technology
In recent years, heterocyclic compound is because structure is changeable, active high, toxicity is low and turns into the master of medicine and agricultural chemicals innovation
Stream, plurality of new varieties just continuously put goods on the market, and study on the synthesis is more towards baroque condensed hetero ring, double miscellaneous
Ring and poly-heterocyclic compounds.Piperidines and azole compounds are all the nitrogen-containing heterocycle compounds with good biological activity, extensively should
For medicine and the study on the synthesis of agricultural chemicals.Piperidines is mainly used in synthesis medicine, agricultural chemicals and rubber chemicals, is mainly used in pesticide industry
It is a kind of selective non-hormone-type thiocarbamic acid class herbicide, very with hair in synthesis herbicides for use in paddy dimepiperate
Exhibition prospect.It is used to synthesize medicine for digestive system hydrochloric acid acetyl Roxatidine, cardiovascular disease medicine Dipyridmole in pharmaceuticals industry
Deng.It is used to synthesize the super vulcanization accelerator bis-pentamethylenethiuram tetrasulfide of thiurams in Rubber Chemicals Industries, two is thio
Super accelerator pentamethylene aminodithioformic acid piperidinium salt of Carbamates etc..Other piperidines can also synthesize a variety of new
Type fine-chemical intermediate, many products belong to the centre of small tonnage newly developed, the medicine of high added value, agricultural chemicals and auxiliary agent
Body, such as pipecoline, 3- aminomethylpiperidines, 4- hydroxy piperidines.Pyridine is also a kind of important nitrogen heterocyclic ring, because it has
Good bioactivity is widely used in medical research.For example, its derivative can be used as 5HT2A receptor antagonists, cell
External signal regulatory protein kinase inhibitor, mammal P2X7 conditioning agents, and increase with anti-breast cancer cell MDA-MB-231
Grow activity and suppress the propagation of hepatocellular carcinoma H22.
We have synthesized a series of piperidines with insecticidal activity and pyridinone derivatives in laboratory by new method,
And carried out corresponding bioactivity detection.
The content of the invention
Present invention solves the technical problem that there is provided, a kind of synthetic method is simple, the novel piperidines of molecular structure and pyridine
The preparation method of ketones derivant.
The present invention adopts the following technical scheme that simultaneously pyridinone derives a kind of new piperidines to solve above-mentioned technical problem
The molecular structure of thing is：Wherein R is benzene, adjacent fluorobenzene and to trifluoromethylbenzene
The present invention adopts the following technical scheme that simultaneously pyridinone derives a kind of new piperidines to solve above-mentioned technical problem
The preparation method of thing, it is characterised in that concretely comprise the following steps：
A, N-Boc-4- piperidones and dimethyl carbonate react in the presence of potassium tert-butoxide obtains N-Boc-3- formic acid first
Ester -4- piperidones
B, N-Boc-3- methyl formate -4- piperidones are under ammonium acetate effect, and ketone carbonyl redox is changed into amino
Compound N-Boc-3- methyl formate -4- amino -3- alkene-piperidines
C, N-Boc-3- methyl formate -4- amino -3- alkene-piperidines and chloroformyl ethyl acetate take under TEA effects
Generation reaction obtains compound N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines
D, N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines occur in the presence of potassium tert-butoxide
Intramolecular cyclization obtains compoundThen the compound carries out intramolecular in acid condition
Hydrogen migration and carbonyl reduction obtain compound
E、Under strongly acidic conditions, ester group and Boc groups are sloughed in heating, obtain compound
F、Under POCl3 effect, hydroxyl is replaced by chlorine obtains compound
G、Chloro carbon-to-nitrogen double bon is changed into amido link under concentrated hydrochloric acid effect and obtain compound
H、In the basic conditions, Boc amido protectings are carried out, are obtained while carrying out intramolecular hydrogen migration
Compound
I、Under cesium carbonate effect compound is obtained with iodo-tert-butane reaction
J、Chloro carbon-carbon double bond is changed into amido link under organic acid effect and obtain compound
K、Compound is obtained with azido compound reaction
L、Slough Boc groups and the tert-butyl group obtains compound
M、Obtained with sulfoacid compound reaction
Further limit, step A detailed process is：In reaction bulb, 1eq N-Boc-4- piperidones is added to
In the toluene of 10V volumes, 2eq dimethyl carbonate and 2eq potassium tert-butoxide are added, 70 DEG C of reaction 1h is heated to, is cooled to
Room temperature, adds water and is quenched, and it is 7 to adjust reaction solution pH with 1mol/L HCl, ethyl acetate extraction, after anhydrous sodium sulfate drying, is spin-dried for
Obtain yellow oil N-Boc-3- methyl formate -4- piperidones
Further limit, step B detailed process is：1eq N-Boc-3- methyl formate -4- piperidones is added to 10
In the methanol of times volume, 3eq ammonium acetate is added, reaction is stayed overnight, be spin-dried for methanol, add the water of 3 times of volumes, dichloromethane extraction
Anhydrous sodium sulfate drying is used after extracting reaction solution, red oily liquids N-Boc-3- methyl formate -4- amino -3- is obtained after being spin-dried for
Alkene-piperidines
Further limit, step C detailed process is：By 1eq N-Boc-3- methyl formate -4- amino -3- alkene-piperidines
In the DCM for being added to 8 times of volumes, 1.05eq TEA is added, 10 DEG C are cooled to, 1.05eq 4- chloromethane ethyl acetoacetic acid second is added dropwise
Ester, room temperature reaction is stayed overnight, and adds the DCM dilute reaction solutions of 8 times of volumes, twice, anhydrous sodium sulfate drying is spin-dried for both obtaining for washing
Red oil product N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines
Further limit, step D detailed process is：1eq N-Boc-3- methyl formate -4- carbamyl acetic acid second
Ester -3- alkene-piperidines is added in the THF of 10 times of volumes, then is added portionwise 2.0eq t-BuOK, reaction temperature control less than
25 DEG C, frozen water is added after reaction 1h and is quenched, it is 3 to adjust reaction solution pH with 2mol/L HCl, filtering, and it is white that vacuum drying obtains class
Color solid product
Further limit, step E detailed process is：In 10eq 6mol/L HCl solution, it is added portionwise 1.0eq's100 DEG C are heated to, reaction is stayed overnight, are spin-dried for reaction dissolvent, then washed with ether, is dried in vacuo
Obtain off-white powder
Further limit, step F detailed process is：To 5eq POCl3In be added portionwise 1.0eq's100 DEG C are heated to, reaction is stayed overnight, are spin-dried for POCl3Obtain Red oil product
Further limit, step G detailed process is：It is added to the 1,4- dioxies six of 4 times of volumes
In ring, the concentrated hydrochloric acid of 4 times of volumes is added, 100 DEG C are heated to, back flow reaction 2 days is spin-dried for adding the second of 10 times of volumes after solvent
Acetoacetic ester, is washed three times, is dried and is obtained brown solid after being spin-dried for
Further limit, step H detailed process is：1eq'sIt is added to the 1,4- of 10 times of volumes
In dioxane and the water of 10 times of volumes, then 3.0eq sodium carbonate and 1.5eq (Boc) is added portionwise2O, reacts at room temperature 10h
Afterwards, filter, then wash with ethyl acetate reaction solution is extracted with ethyl acetate after filter cake, then washed with sodium chloride solution, dried, revolved
Reaction solution is obtained
Further limit, step I detailed process is：1.0eq'sIt is added to 10 times of volumes
DMF in, add 1.5eq Cs2CO3, 1.3eq iodine is with tertiary butane, and room temperature reaction is stayed overnight, and adds frozen water and reaction solution is quenched,
Ethyl acetate extractive reaction liquid, sodium chloride solution washing, dries, is spin-dried for, then is beaten with ether, filters, and vacuum drying obtains white
Color solid
Further limit, step J detailed process is：By 1.0eq'sIt is added to 4 times of volumes
In Isosorbide-5-Nitrae-dioxane, a certain amount of organic acid is added, 100 DEG C are heated to, back flow reaction 2 days is spin-dried for adding after solvent
The ethyl acetate of 10 times of volumes, is washed three times, is dried and is obtained brown solid after being spin-dried for
Further limit, step K detailed process is：In reaction bulb, 1.0eq'sIt is added to
In the tert-butyl alcohol of 20 times of volumes, 3.0eq potassium carbonate and 1.2eq TMSN are added3, react at room temperature after a period of time,
TLC monitoring raw material reactions are complete, obtain compound
Further limit, step L detailed process is：In reaction bulb, by 1.0eq'sPlus
Enter in the HCl/1 to the methanol of 10 times of volumes and the 12mol/L of 10 volumes, 4- dioxane, room temperature reaction is stayed overnight, and is spin-dried for, second
Ether is washed, and is obtained
Further limit, step M detailed process is：In reaction bulb,It is added in DMF,
Triethylamine and sulfoacid compound are added, 70 DEG C are heated to, reaction a period of time obtains compound
Synthetic route of the present invention with insecticidal activity new piperidine and pyridinone derivatives is：
The present invention has synthesized a kind of new piperidine and pyridinone derivatives and has carried out insecticidal activity test, it is found that this spreads out
Biology has good insecticidal activity.
Embodiment
The above to the present invention is described in further details by the following examples, but this should not be interpreted as to this
The scope for inventing above-mentioned theme is only limitted to following embodiment, and all technologies realized based on the above of the present invention belong to this hair
Bright scope.
Embodiment 1
In reaction bulb, N-Boc-4- piperidones 20g (0.1mol) is added in toluene 200mL, carbonic acid two is added
Methyl esters 18g (0.2mol) and potassium tert-butoxide 22g (0.2mol), is heated to 70 DEG C of reaction 1h, is cooled to room temperature, the 100mL that adds water quenches
Go out, it is 7 to adjust reaction solution pH with 1mol/L HCl, ethyl acetate extraction, after anhydrous sodium sulfate drying, be spin-dried for obtaining yellow oil
Shape thing N-Boc-3- methyl formate -4- piperidones 25g；1HNMR(400MHz,CD3Cl)δ:3.81 (s, 1H), 3.71 (d, J=
8.4Hz, 1H), 3.68 (d, J=8.4Hz, 1H), 3.45 (s, 3H), 3.07-3.05 (m, 2H), 2.76-2.73 (m, 2H), 1.37
(s,9H).MS-ESI(m/z):258.3[M+H+]。
Embodiment 2
In reaction bulb, N-Boc-3- methyl formate -4- piperidones 25g (0.1mol) are added in methanol 300mL, then
Ammonium acetate 22g (0.3mol) is added, reaction is stayed overnight, TLC monitoring raw material reactions are complete, are spin-dried for methanol, water 900mL added, with two
Chloromethanes 300mL extractive reactions liquid three times, merges and anhydrous sodium sulfate drying is used after organic phase, red oily liquids is obtained after being spin-dried for
N-Boc-3- methyl formate -4- amino -3- alkene-piperidines 25g；1HNMR(400MHz,CD3Cl)δ:8.56(s,2H),3.93(s,
2H),3.77(s,3H),3.57-3.55(m,2H),2.16-2.13(m,2H),1.37(s,9H).MS-ESI(m/z):257.3[M
+H+]。
Embodiment 3
In reaction bulb, N-Boc-3- methyl formate -4- amino -3- alkene-piperidines 26g (0.1mol) is added to dichloromethane
In alkane 200mL, TEA11g (0.11mol) is added, 10 DEG C are cooled to, 4- chloroformyl ethyl acetate 16g is slowly added dropwise
(0.105mol), room temperature reaction is stayed overnight, and TLC monitoring raw material reactions are complete, add dichloromethane 200mL dilute reaction solutions, water
Wash twice, anhydrous sodium sulfate drying, be spin-dried for both obtaining Red oil product N-Boc-3- methyl formate -4- carbamyl acetic acid second
Ester -3- alkene-piperidines 25g；1HNMR(400MHz,CD3Cl)δ:4.71(s,2H),3.93(s,2H),3.79(s,3H),3.57-
3.55(m,2H),3.53(s,2H),2.16-2.13(m,2H),1.37(s,9H),1.29(s,3H).MS-ESI(m/z):371.4
[M+H+]。
Embodiment 4
In reaction bulb, N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines 37g (0.1mol)
It is added in THF400mL, then t-BuOK 23g (0.2mol) is added portionwise, reaction temperature control is reacted after 1h less than 25 DEG C
Add frozen water 300mL to be quenched, it is 3 to adjust reaction solution pH with 2mol/L HCl, and filtering, vacuum drying obtains off-white powder production
Product32g；1H NMR(400MHz,DMSO-d6)δ:11.51(s,1H),5.35(s,1H),
4.71 (s, 2H), 4.33 (d, J=4.0Hz, 2H), 3.66-3.62 (m, 2H), 3.25 (d, J=12.0Hz, 2H), 1.41-1.39
(m,9H),1.33-1.32(m,3H)。
Embodiment 5
In reaction bulb, the HCl solution 200mL in 6mol/L is added, then be added portionwise
34g (0.1mol), is heated to 100 DEG C, reaction is stayed overnight, and is spin-dried for reaction dissolvent, then is washed with ether, and vacuum drying obtains off-white color
Solid15g；1H NMR(400MHz,DMSO-d6)δ:11.47(s,1H),5.95(s,1H),5.41(s,
1H), 3.86-3.85 (m, 2H), 3.71 (d, J=12.0Hz, 2H), 3.11-3.09 (m, 2H), 1.90 (s, 1H).
Embodiment 6
In closed reaction bulb, it is added portionwise into POCl3 50g (0.5mol)16g
(0.1mol), is slowly heated to 100 DEG C, reaction is stayed overnight, and after TLC monitoring raw material reactions completely, vacuum is spin-dried for POCl3 and obtained
Red oil product16g；1H NMR(400MHz,DMSO-d6)δ:7.61(s,1H),3.81(s,2H),
3.37 (d, J=12.0Hz, 2H), 3.13-3.12 (m, 2H), 1.87 (s, 1H).
Embodiment 7
In the reaction bulb with thermometer and stirring,20g is added to 1,4- dioxane
In 100mL, concentrated hydrochloric acid 100mL is slow added into, 100 DEG C are heated to, back flow reaction 2 days, TLC is monitored after raw material reaction completely,
It is spin-dried for solvent and concentrate is added the ethyl acetate of 10 times of volumes, washes three times, separate organic phase, dry and obtain palm fibre after being spin-dried for
Color solid
Embodiment 8
In reaction bulb,18g (0.1mol) is added to 1,4- dioxane 200mL and water 200mL
In, then sodium carbonate 30g (0.3mol) and (Boc) is added portionwise2After O 33g (0.15mol), room temperature reaction 10h, TLC monitoring is former
Material reaction is complete, filtering reacting liquid, then is washed with ethyl acetate 100mL after filter cake with ethyl acetate 200mL extractive reactions liquid three
It is secondary, then washed with sodium chloride solution, dry, rotation reaction solution is obtained20g；1H NMR(400MHz,DMSO-
d6)δ:6.61 (s, 1H), 3.93 (s, 2H), 3.54 (s, 3H), 3.57 (d, J=12.0Hz, 2H), 2.07-2.05 (m, 2H),
1.39(s,9H).
Embodiment 9
In reaction solution,28g (0.1mol) is added in DMF 300mL, adds carbonic acid
Caesium 50g (0.15mol), iodo-tert-butane 24g (0.13mol), room temperature reaction is stayed overnight, and TLC monitoring raw material reactions are complete, add ice
Water 100mL is quenched reaction solution, ethyl acetate 200mL extractive reactions liquid three times, saturated nacl aqueous solution 200mL washing reaction liquids,
Dry, be spin-dried for, then be beaten with ether, filtered, vacuum drying obtains white solid26g
Embodiment 10
, will in reaction solution34g (0.1mol) is added in Isosorbide-5-Nitrae-dioxane 200mL, then
Trifluoromethanesulfonic acid 20mL is slowly added to, under nitrogen protection, 100 DEG C are heated to, back flow reaction 3h, TLC monitoring raw material has reacted
Entirely, reaction solution is poured into frozen water 1000mL, then the pH for adjusting reaction solution with saturated solution of sodium carbonate is neutral, then use acetic acid second
Ester 300mL extractive reactions liquid three times, merge organic phase, be washed with water three times, separate organic phase dry be spin-dried for after obtain brown consolidate
Body26g；1H NMR(400MHz,DMSO-d6)δ:4.17(s,2H),3.83(s,2H),3.54(s,
2H),2.07-2.05(m,2H),1.45(s,9H),1.37(s,9H)；MS-ESI(m/z):323.4[M+H+]。
Embodiment 11
In reaction bulb,32g (0.1mol) is added in tert-butyl alcohol 400mL, adds carbon
Sour K42 g (0.3mol) and TMSN314g (0.12mol), reacts after a period of time at room temperature, and TLC monitoring raw materials have reacted
Entirely, reaction solution is poured into water 500mL, with ethyl acetate 200mL extractive reactions liquid three times, merges organic phase, solvent is evaporated off and obtains
To compound29g；1H NMR(400MHz,DMSO-d6)δ:12.3(s,1H),3.96(s,2H),
3.54-3.53(s,2H),2.07-2.06(m,2H),1.39(s,9H),1.26(s,9H)；MS-ESI(m/z):348.4[M+H+]。
Embodiment 12
, will in reaction bulb35g (0.1mol) is added to methanol 300mL's and 12mol/L
In HCl/1,4- dioxane 200mL, room temperature reaction is stayed overnight, and TLC monitoring raw material reactions are complete, are spin-dried for, ether washing concentrate,
Obtain17g；1H NMR(400MHz,DMSO-d6)δ:12.3(s,1H),3.95-3.94(m,1H),
3.33-3.32(m,2H),2.95(s,2H),2.07-2.06(m,2H)；MS-ESI(m/z):192.2[M+H]+
Embodiment 13
In reaction bulb,19g (0.1mol) is added in DMF 200mL, adds triethylamine
30mL and benzene sulfonic acid 31g (0.2mol), is heated to 70 DEG C, reaction a period of time obtains compound
31g；1H NMR(400MHz,DMSO-d6)δ:12.3(s,1H),7.86-7.84(m,2H),7.62-7.61(m,2H),7.41(s,
1H),3.95-3.94(m,1H),3.33-3.32(m,2H),2.95(s,2H),2.07-2.06(m,2H)；MS-ESI(m/z):
332.3[M+H]+
Embodiment 14
In reaction bulb,19g (0.1mol) is added in DMF 200mL, adds triethylamine 30mL
With adjacent fluorobenzene sulfonic acid 35g (0.2mol), 70 DEG C are heated to, reaction a period of time obtains compound
29g
Embodiment 15
Insecticidal activity is tested
It is 1 to take 2.5mL volume ratios:The mixed solvent of 1 acetone-methanol is added separately to fill the piperidines obtained by 4mg
And in the measuring cup of pyridinone derivatives, stirring makes it fully dissolve, add 2.5mL and contain mass fraction and told for 0.2%
The standing running water of temperature 80, obtains 800mg/L piperidines and pyridinone derivatives solution 5mL after stirring, further dilute
Release the solution for obtaining various concentrations.Sprayed using Airbrush spray-on processes.Peach aphid larva processing after day by day observation take food and
Death condition, if test worm eats the feed of chemicals treatment to the greatest extent, supplements investigation survival borer population after untreated fresh feed, 120h
Amount, calculates the death rate.
As seen from the above table, the piperidines and pyridinone derivatives that we invent have preferable killing to peach aphid larva
Effect.
Embodiment above describes general principle, principal character and the advantage of the present invention, the technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, the original for simply illustrating the present invention described in above-described embodiment and specification
Reason, under the scope for not departing from the principle of the invention, various changes and modifications of the present invention are possible, and these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (6)
1. the preparation method of piperidines and pyridinone derivatives with insecticidal activity, it is characterised in that concretely comprise the following steps：
A, N-Boc-4- piperidones and dimethyl carbonate react in the presence of potassium tert-butoxide obtains N-Boc-3- methyl formates -4-
Piperidones；
B, N-Boc-3- methyl formate -4- piperidones are under ammonium acetate effect, and ketone carbonyl redox obtains compound into amino
N-Boc-3- methyl formate -4- amino -3- alkene-piperidines；
It is anti-that under TEA effects substitution occurs for C, N-Boc-3- methyl formate -4- amino -3- alkene-piperidines and chloroformyl ethyl acetate
Compound N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines should be obtained；
Molecule occurs in the presence of potassium tert-butoxide for D, N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines
Interior cyclization obtains compoundThen the compound carries out intramolecular hydrogen turn in acid condition
Move and carbonyl reduction obtains compound
E、Under strongly acidic conditions, ester group and Boc groups are sloughed in heating, obtain compound
F、Under POCl3 effect, hydroxyl is replaced by chlorine obtains compound
G、Chloro carbon-to-nitrogen double bon is changed into amido link under concentrated hydrochloric acid effect and obtain compound
H、In the basic conditions, Boc amido protectings are carried out and obtains compoundI、Under cesium carbonate effect compound is obtained with iodo-tert-butane reaction
J、Chloro carbon-carbon double bond is changed into amido link under organic acid effect and obtain compound
K、Compound is obtained with azido compound reaction
L、Slough Boc groups and the tert-butyl group obtains compound
M、Obtained with sulfoacid compound reactionR is benzene, adjacent fluorobenzene and to three
Methyl fluoride benzene.
2. the preparation method of the piperidines according to claim 1 with insecticidal activity and pyridinone derivatives, its feature
The detailed process for being step A is：In reaction bulb, 1eq N-Boc-4- piperidones is added in the toluene of 10V volumes,
2eq dimethyl carbonate and 2eq potassium tert-butoxide are added, 70 DEG C of reaction 1h is heated to, is cooled to room temperature, adds water and be quenched, use
1mol/L HCl regulation reaction solutions pH is 7, ethyl acetate extraction, after anhydrous sodium sulfate drying, is spin-dried for obtaining yellow oil N-
Boc-3- methyl formate -4- piperidones；Described step B detailed process is：By 1eq N-Boc-3- methyl formate -4- piperazines
Pyridine ketone is added in the methanol of 10 times of volumes, adds 3eq ammonium acetate, and reaction is stayed overnight, and is spin-dried for methanol, 3 times of volumes of addition
Anhydrous sodium sulfate drying is used after water, dichloromethane extractive reaction liquid, red oily liquids N-Boc-3- formic acid first is obtained after being spin-dried for
Ester -4- amino -3- alkene-piperidines；Described step C detailed process is：By 1eq N-Boc-3- methyl formate -4- amino -3-
Alkene-piperidines is added in the DCM of 8 times of volumes, adds 1.05eq TEA, is cooled to 10 DEG C, and 1.05eq 4- chloroformyls are added dropwise
Ethyl acetate, room temperature reaction is stayed overnight, and adds the DCM dilute reaction solutions of 8 times of volumes, twice, anhydrous sodium sulfate drying is revolved for washing
It is dry both to obtain Red oil product N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines.
3. the preparation method of the piperidines according to claim 1 with insecticidal activity and pyridinone derivatives, its feature
The detailed process for being step D is：1eq N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines is added
Enter into the THF of 10 times of volumes, then 2.0eq t-BuOK is added portionwise, reaction temperature control adds less than 25 DEG C after reaction 1h
Enter frozen water to be quenched, it is 3 to adjust reaction solution pH with 2mol/L HCl, and filtering, vacuum drying obtains off-white powder productDescribed step E detailed process is：In 10eq 6mol/L HCl solution, add in batches
Enter 1.0eq's100 DEG C are heated to, reaction is stayed overnight, are spin-dried for reaction dissolvent, then washed with ether
Wash, vacuum drying obtains off-white powderDescribed step F detailed process is：To 5eq POCl3In
It is added portionwise 1.0eq's100 DEG C are heated to, reaction is stayed overnight, are spin-dried for POCl3Obtain Red oil productDescribed step G detailed process is：It is added to the 1,4- dioxies of 4 times of volumes
In six rings, the concentrated hydrochloric acid of 4 times of volumes is added, 100 DEG C are heated to, back flow reaction 2 days is spin-dried for 10 times of volumes of addition after solvent
Ethyl acetate, is washed three times, is dried and is obtained brown solid after being spin-dried for
4. the preparation method of the piperidines according to claim 1 with insecticidal activity and pyridinone derivatives, its feature
The detailed process for being step H is：1eq'sBe added to 10 times of volumes 1,4- dioxane and 10 times
In the water of volume, then 3.0eq sodium carbonate and 1.5eq (Boc) is added portionwise2After O, room temperature reaction 10h, filtering, then use second
Reaction solution is extracted with ethyl acetate after acetoacetic ester washing filter cake, then is washed with sodium chloride solution, dries, rotation reaction solution is obtainedDescribed step I detailed process is：1.0eq'sIt is added to 10 times of bodies
In long-pending DMF, 1.5eq Cs is added2CO3, 1.3eq iodine is with tertiary butane, and room temperature reaction is stayed overnight, and adds frozen water and reaction is quenched
Liquid, ethyl acetate extractive reaction liquid, sodium chloride solution washing is dried, is spin-dried for, then is beaten with ether, is filtered, vacuum drying is obtained
White solid
5. the preparation method of the piperidines according to claim 1 with insecticidal activity and pyridinone derivatives, its feature
The detailed process for being step J is：By 1.0eq'sIn the Isosorbide-5-Nitrae-dioxane for being added to 4 times of volumes,
A certain amount of organic acid is added, 100 DEG C are heated to, back flow reaction 2 days is spin-dried for adding the acetic acid second of 10 times of volumes after solvent
Ester, is washed three times, is dried and is obtained brown solid after being spin-dried forDescribed step K detailed process is：
In reaction bulb, 1.0eq'sIn the tert-butyl alcohol for being added to 20 times of volumes, 3.0eq potassium carbonate is added
With 1.2eq TMSN3, react at room temperature after a period of time, TLC monitoring raw material reactions are complete, obtain compoundDescribed step L detailed process is：In reaction bulb, by 1.0eq'sIt is added in the methanol of 10 times of volumes and the 12mol/L of 10 volumes HCl/1,4- dioxane, room
Temperature reaction is stayed overnight, and is spin-dried for, ether washing, is obtainedDescribed step M detailed process is：In reaction bulb
In,It is added in DMF, adds triethylamine and sulfoacid compound, be heated to 70 DEG C, reacts one section
Time obtains compound
6. the preparation method of the piperidines according to claim 1 with insecticidal activity and pyridinone derivatives, its feature
It is that the specific synthetic route in preparation process is：
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09291034A (en) * | 1996-02-27 | 1997-11-11 | Yoshitomi Pharmaceut Ind Ltd | Condensed pyridine compound and its use as medicine |
| WO2007090788A2 (en) * | 2006-02-03 | 2007-08-16 | Basf Se | Use of fungicides for increasing the quality and optionally the quantity of oil-plant products |
| WO2009003953A2 (en) * | 2007-06-29 | 2009-01-08 | Basf Se | Strobilurins for increasing the resistance of plants to abiotic stress |
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2017
- 2017-06-05 CN CN201710414579.XA patent/CN107325100A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09291034A (en) * | 1996-02-27 | 1997-11-11 | Yoshitomi Pharmaceut Ind Ltd | Condensed pyridine compound and its use as medicine |
| WO2007090788A2 (en) * | 2006-02-03 | 2007-08-16 | Basf Se | Use of fungicides for increasing the quality and optionally the quantity of oil-plant products |
| WO2009003953A2 (en) * | 2007-06-29 | 2009-01-08 | Basf Se | Strobilurins for increasing the resistance of plants to abiotic stress |
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