DE2123417A1 - - Google Patents

Description

PATENT LAWYERS

dr. W. Schalk. · Dipl.-Ing. P.Wirth dipl.-ing. G. Dannenberg DR.V. SCHMIED-KOWARZIK · DR. P. WEINHOLD · DR. D. GUDEL

6 FRANKFURT AM MAIN

CR. ESCHENHEIMER STRASSE 39

SK / SK Z-46

Zoecon Corporation
975 California Avenue Palo Alto, ca.94304 / USA

Stereoselective Processes for the Production of Juvenile Hormones, Analogs, and New Intermediates for These Lives

The present invention relates to new syntheses and intermediates for juvenile hormones and analogs.

Juvenile hormone has been isolated from adult male Hylaphora cecropia, the silkworm penguin. The first juvenile monomer was known as trans, titans, cis-methyl-10, H-oxido-3,11-dimethyl-7-ethyltrideca-2,6-dienoate (cf. Angew. Chem. 79, 190 (1967) and J. Am. Chem. Soc. 69, 5292 (1967)). A second juvenile hormone was identified as trans, trans-cis-methyl-10,11-oxi'da-3,7,11-trimethyldeca-2,6-dienoate (cf. Proc.Nat.Acad.Sci. US 60, 853 -660 (1968)).

Juvenile hormones and analogs are used to control insects by disrupting metamorphosis suitable . Studies have shown the need for the trans configuration on the C-2,3 and C-S, 7 positions for maximum effectiveness.

209848/121 1
BATH ORIGINAL

2123A17

The present invention provides syntheses for stereoselective production of the two juvenile hormones, their analogues and essential intermediates.

According to the invention - in general terms - a halo ketal (i) or a Halogenol ether (il) with a trans-allylic alcohol (ill) for formation of the essential intermediate (IV) implemented with the transjtrans configuration, that is reduced to halohydrin (v). The halohydrin (v) provides after treatment with a base, the epoxy (vi).

R ^J

CH ₃

X-C C-OR

X-

) R OR • ³ CHo

> 0R

(D

(H)

HC = C-CLI (CIL ₂₎ 2-C =

(IT-I)

OH

209848/121 1
BAD ORIGJNAL

f f

(IV)

'C- CIl- (CII ₂ ) ₂ -C-CH-

R ^J

-c- = ai ~ c-oR '

(V)

R ^J

R ° R ^

R ^ -C CH- (CH ₂ ) ₂ -C = CH- (CH ₂ ) ₂ -C = CH-C-OR ^f

(VI).

12 3

In the above formulas, R, R ¹ , R and R each represent lower alkyl, R

4th
and R each represent hydrogen or lower alkyl, and X represents bromine or chlorine.

The main intermediate (IV) with the trans configuration at C-2,3 and C-6.7 is produced in one step by adding the allylic alcohol (ill.) with the halogen ketal (i) or the halogen oil ether (il) or a mixture from (l) and (ll) heated above room temperature. At least 1 molar equivalent, and usually more than 1 molar equivalent, from (i) or (ll), based on the allylic alcohol (ill), used. The reaction takes place above room temperature, e.g. between about 40 ° C. up to about 20D ° C. odor the boiling point of the reaction mixture; usually the temperature is between about 7Ü-1G0 G. Uiu most suitable temperature for the generation of (IV)

209848/1211

BAD ORIQfNAL

2123A17

Aest can easily be determined by routine experiments, taking into account the reactants used, the presence or absence of solvents, catalysts and with regard to the following examples. The reaction forms the alcohol (R-OH), which can be removed to shorten the reaction time, although this is not necessary to complete the reaction. The alcohol (R-DH) can be removed by fractional distillation, passage through molecular sieves or other conventional means in the course of the reaction or, after the reaction has ended, by washing. It is preferred to use a weakly acidic catalyst to carry out the reaction, although this is not critical. The usual weakly acidic catalysts are suitable, a hindered acid being preferred to reduce transesterification. Suitable weakly acidic catalysts include the ΟΒΓ-οοηΞαμΓεη, such as propionic acid, acetic acid, pivalic acid, phenols such as mono- or dinitrophenol, chlorinated phenols, inorganic acids such as phosphoric acid, ammonium nitrate, etc. You can also optionally use a conventional polymerization inhibitor such as hydroquinone, especially when the reaction is carried out in the absence of an organic solvent. The reaction can be carried out in the absence or presence of an organic reaction solvent medium. Any organic solvent which is inert towards the reaction and which has a sufficiently high boiling point for the reaction temperature can be used. Typical solvents include aromatic and aliphatic hydrocarbons, chlorinated hydrocarbons and ethers such as toluene, xylene, monoglyme, diglyme or dioxane. The reaction time varies according to such factors as the reaction temperature. The completion of the reaction can be followed by the formation of the theoretical amount of alcohol (R-OH). A common method of conducting the reaction in the absence of a solvent is to conduct the reaction under a fractionation column "» 209848/1211

And the alcohol (R-OH) / collect as it forms. When the theoretical alcohol equivalents have been collected, the reaction has ended. Depending on the desired purity, the residue is then diluted with dilute base
washed and then distilled or chromatographed.

Then the ii-halo-IO-oxo intermediate (iv) using a

Reducing agent, such as sodium borohydride, is reduced to the halohydrin (v).
The halohydrins can be separated at this point by chromatography on silica gel. Treatment of the halohydrins (v) with a base yields the epoxy (Vl).

In another embodiment of the present invention, a compound of formula (VIl) or (VIII) converted into the haloketone (IV). the The reaction takes place at a temperature above room temperature in the presence or absence of a weakly acidic catalyst and in the presence or the absence of an organic solvent.

209848/1211

H ₂ C =

R ¹ O

Ϊ I

H C-C-CH- (CH) -C = CH-C-OR '

I ^{2 2}

(VII)

(IV)

2.

-CH- (CH,

R ¹ O

H ₂ C = C-CH- (CH ₂ ) ₂ -C = CH-C-OR 'O

(viii) ■

H ₃ CC-OR

(IV)

In the above formulas and in other formulas, R ₁ R ', R, R ₁ R ₁ R and X have the meanings already given.

In the syntheses VII - ^ IV and VIII -> IV, a compound of formula (VII) or (VIII) to above room temperature, for example about 50-200 ⁰ C., generally at about 150 ° C-8Q. _f to form the haloketone [iv). heated. This can be done in the presence or absence of a weakly acidic catalyst; usually a weakly acidic catalyst such as the above-mentioned catalysts is used. The reaction can also be carried out in the presence or absence of an inert organic solvent such as a hydrocarbon, ether or chlorinated hydrocarbon.

209848/121 1

Allyl vinyl ether (VIl) is produced by reacting a halogen oil (il) with an allylic alcohol of the formula (ill) in the presence of a Mercuriscylates, such as Mercuriacetat.Die.Reaktion takes place in ether at a Temperature of about 20-50 C, using equimolar amounts of (il) and (ill) or more than 1 molar equivalent (il), usually about 1-5 moles.

The mixed ketal (VIII) is prepared by reacting des'-allylic Alcohol (ill) with dsm halo ketal (i) or the halo enolather (il) in Absence of an acidic catalyst such as phosphoric acid or p-toluenesulfonic acid, at a relatively low temperature, e.g. below 5D ° C. They became equimolar Amounts of allylic alcohol (III) or compound (I) or (II) or more than 1 molar equivalent (i) or (il), based on (ill), used.

The allylic alcohols (in) are described in ^the Applications P 21 03 074.0 and P 21 03 075.1, which are hereby incorporated into the present application.
The halogen ketals (i) are synthesized according to the synthesis shown below

manufactured:
R ³ CH-

II ³ .

HCC
R ⁴ 0

αχ)

R ³ CH

II ³

X-C C-OR

R ⁴ OR

CD

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-B-

In carrying out the above synthesis, a methyl ketone (iX) is prepared with cupric chloride and lithium chloride or cupribromide and lithium bromide in an organic solvent such as dimethylformamide according to the method in J.Org.Chem. 28 , 630 (1963) implemented. The halo ketone (x) is then treated with trialkyl orthoformate and the corresponding alcohol, such as trimethyl orthoformate and methanol, triethyl orthoformate and ethanol, with an acid catalyst such as p-toluenesulfonic acid to form the halo ketal (i).

The halo oil ether (II) is made from the halo ketal, (i). The reaction can be carried out by boiling the haloketal (i) over a trace of a weakly acidic catalyst to liberate the theoretical amount of alcohol (R-OH.) And then neutralizing the residue with a base such as a weak carbonate and distillation. The reaction is reversible and removal of the alcohol (R-GH) allows the reaction to proceed. The reaction can be carried out in the presence or absence of an inert organic solvent. The preparation of (II) is carried out by distillation of the Halogenketals (i) über.einer track of a weak acid catalyst under vacuum at a temperature of 50-105 C, usually at about 1OÜ ^D C, to form (II) with the corresponding alcohol as a distillate which, after washing with water, yields the halogen oil ether. ,

The methyl ketones of formula (ix) are commercially available or can be prepared by known methods. The methyl ketones (IX) include methyl isobutyl ketone, acetone, methyl ethyl ketone, methyl n-propyl ketone, methyl isopropyl ketone, methyl n-butyl ketone, methyl s-butyl ketone, methyl n-amyl ketone _t ketone, 3-methyl-2-hexanone-, S-ethyl-S-pentanone, 3,4-dimethyl-2-petanone, methyl-n-hexyl ketone, methyl isohexyl ketone, 3-methyl-2-heptanone, 3,4-dimethyl-2-hexanone, 4-ethyl-2- hexanone and 4-methyl-2-octanone. A process for the production of the ketones (ix) can be represented as follows:

209848/1211

\ _η C = O

/ _m < ^ΧΙ > -

(Ph) ₃ P

Cl-

BuLi

(ix)

C /

(XII)

_0R

^ f

In the above scheme, .Ph stands for phenyl. The triphenylphosphonium salt is prepared by reacting triphenylphosphine and the corresponding Chlorathylalkylathsr, such as methyl-ct-chloroethyl ether, in an organic solvent such as benzene. The reaction takes place at room temperature, the salt formation taking about 24-48 hours. The phosphonium salt, with or without purification with n-butyllithium, sodium tert-butoxide, etc., is stirred in an organic solvent such as tetrahydrofuran at a low temperature, e.g. -78 C _1, until a negative Gilmen test is obtained, which is usually about 1 hour requires. Then, the ketone (Xl) diluted in an organic solvent such as tetrahydrofuran is added to the latter in an amount of about 1 mole of ketone (Xl) per 1-3 moles of phosphonium salt while maintaining a low temperature. The formation of Enolätheis (XIl) requires at -78 ° C. about 2-15 hours. The enol ether (XIl) is isolated by adding water and extracting with a solvent such as ether-hexane, and the insoluble triphenylphosphine oxide is filtered off. After hydrolysis, the enol ether (XIl) gives the methyl ketone (ix). The hydrolysis can take place at

209848/121 1

Room temperature in a few minutes using a medium of dilute Perchloric acid in tetrahydrofuran-water ("« 4: 1) can be carried out. The enol ether (XIl) can by treatment with about 1.1 equivalents of N-chlorosuccinimide or N-bromosuccinimide in dry alcohol at low temperature, e.g. 0 ° C. to 5 ° C., can be converted directly into the halo ketal (i). The alcohol used is a lower aliphatic alcohol, such as methanol or ethanol, used, which depends on the desired ketal.

The compounds of the formula (IV) are, in addition to their suitability as intermediates also valuable for combating insects. The compounds of the formula (VI) are suitable as insect control agents. As such means are the compounds of formulas (IV) and (vi) when applied locally, e.g. by spraying in xylene solution or another inert carrier with or without emulsification, extremely effective. The compounds can be applied by dusting using solid carriers such as talc, silica, etc. There can be concentrations of active compound around 0.5-75 ° /> or more, depending on the effectiveness of the device. Typical Insects which are combated by using the compounds of the formulas (IV) and (VI) include Pyrrhocoris paterus, Tenebrio molitor, Galleria mellonella, Tribolium confusum, Aphidiae, Lygus Periplaneta americana, Schistocerca vaga, Aedes aegypti and Dysdercus. The connections are effective Control agents by inhibiting metamorphosis, chemosterilization cause or interrupt the diapause. They are preferably applied to the immature insect, i.e. in the embryonic, larval or pupal stage .

209848/1211

- 1Ί -

As used herein, the term "lower alkyl" refers to a straight line or branched chain alkyl group with a chain length of 1-6 carbon atoms .

The following examples illustrate the present invention without it to restrict.

Example 1

To a solution of 48.5 g of cuprichloride dihydrate, 5.9 g of lithium chloride and 70 ecm of dimethylformamide were at 7G ° C. 11.6 g of 3-methylpentan ~ 2 - one added. The reaction mixture was stirred for 7 hours at about 70 C. and then for 9 hours at I. Stirred at room temperature and poured into water. Ammonium chloride was added and the mixture was extracted with ftentane. The combined pentane extracts were washed neutral with saturated sodium chloride solution, dried over magnesium sulfate and the pentane is distilled off; thus obtained 3-chloro-3-methylpentan-2-one.

To a mixture of 15 g trimethyl orthoformate, 15 g methanol and 150 mg. All of the chloroketone prepared above was added to p ~ toluenesulfonic acid. The mixture was left at 50-60 ° C for 5 hours. and then stirred for 10 hours at room temperature and then poured into dilute sodium bicarbonate overall \ and extracted with ether. The combined ether extract was washed neutral with saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The residue was fractionated under reduced pressure, and the Chlorketal (2 _f 2-dimethoxy-3-chloro-3-methylpentane) distilled at 83-84 C. ^D (18 mm).

209848/1211

Example 2 -

A mixture of 1.06 g of trans-methyl-3-methyl-7-methylene-6-hydroxynone-2-enoate, 3.61 g of the chloro ketal from Example 1, 7.5 ecm of toluene and 92 mg of 2,4-dinitrophenol was stirred for 14 hours at 95 ° C. and then for 6 hours at room temperature. The mixture was evaporated to remove tolupil and excess ketal. The residue was chromatographed on silica gel, eluting with hexane: ether (9: 1); This gave trans, trans-methyl-3,1i-dimethyl-10-αχα-Ιi-chloro - ^ - äthyltrideca - ^, 6-dienaate, which at 125 ° C. (D, 02 mm) distilled.
Example 3

A solution of 100 mg of the chloroketone from Example 2 in 5 ecm of methanol was added at OC. 50 mg sodium borohydride added. The mixture was ^{stirred at 0 °} C. for about 30 minutes, poured into water and extracted with ether. The combined ether extract was washed neutral with water, dried over magnesium sulfate and concentrated under reduced pressure; This gave trans, trans-methyl-11-chloro-10-hydroxy-3,11-dinethyl-7-ethyltrideca-2,6-dienoate, which was purified by chromatography on silica gel.

To a solution of 60 mg of the chlorohydrin prepared above in 1.8 ecm 60 mg of potassium carbonate were added to methanol. The mixture was stirred at room temperature for 45 minutes, poured into water and extracted with ether. The combined ether extract was washed neutral with saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The residue was distilled at 90 ° C. (0.01 mm) and yielded a mixture of the trans, trans, cis and trans, Iran, trans isomers of methyl 10, H-oxido-3,11-dimethyl-7-ethyl trideca-2,6-dienoate.

209848/121 1

Example 4_

Example 2 was repeated, but instead of trans-methyl-S-methyl -? - methylene-6-hydroxynon-2-enoate an equivalent amount of trans-methyl-3-methyl-7-methylene-6-hydroxyoct-2-enoate, trans-methyl ~ 3-methyl-7-methylene-β-hydroxydec-2-enoate and trans-methyl-3-ethyl -? - methylene-6-hydroxynone-2-enoate are used became; so one got,

trans, trans-methyl-1i-chloro-IO-oxo-3,7,11-trimethyltrideca-2,5-dienoate, trans, trans-Methyl-1 i-chlar-IO-oxo-3,1 i-dimethyl ^ -n-propyltrideca ^, 6-dienoate

trans, trans-methyl-ii-chloro-IG ^ oxo-S ^ -diäthy 1-1 i-methyl-trideca ^ ö-dienoate.

Each of the H-chloro-IO-oxo compounds prepared above was used as the starting material used in the procedure of Example 3 and provided the corresponding chlorohydrin and then the corresponding epoxy, i.e. ". Methyl 10.1 i-oxido-3,7,1 i-trimethyltrideca-2,6-dienoate, Methyl 10,1 i-oxido-3,1 i-dimethyl ^ -n-propyltrideca ^, 6-dienoate and Methyl 10,11-oxido-3,7-diethyl-1i-methyltrideca-2,6-dienoate. Each epoxide was made as a mixture of the trans, trans, cis and trans, trans, trans isomers obtain.

Example 5 ^s

Example 1 was repeated, but instead of 3-methylpentan-2-one, an equivalent amount of 3-ethylpentan-2-one, 3-ethylhexan-2-one, 3-methylhexan-2-one, 3,4-dimethylpentan-2- one, pentan-2-one, propan-2-one and 3- (isopropyl) -4-methyl- ■ pentan-2-οπ was used; so one obtained first: 3-chloro-3-ethylpsntan-2-one,
3-chloro-3-ethylhexan-2-one,
3-chloro-3-methylhexan-2-one,
3-chloro-3,4-dimethylpentane-2-an _>

209848/1211

3-chloropentan-2-one,
Ci-chlorpropart-vi-an and

3-chloro-3- (isopropyl) -4-methylpentan-2-one and secondly the corresponding chloro ketal, i.e. 2,2-dimethoxy-S-chloro-S-ethylpentane, 2,2-Dimethoxy-3-chloro-3-ethylhexan-2-one, 2,2-dimethoxy-3-chloro-3-methylh8xane, 2,2-dimethoxy-3-chloro-3,4-dimethylpentane, 2,2-dimethoxy-3-chloropentane, 2,2-dimethoxy-3-chloropropane and, 2,2-dimethoxy-3-chloro-3- (isopropyl) -4-methylpentane.

By repeating Example 1 using an equivalent amount Cupribromide and lithium bromide instead of cupric chloride and lithium chloride 3-bromo-3-methylpentan-2-one and 2,2-dimethoxy-3-bromo-3-methyl - pentane.

By repeating the procedure from Part 2 of Example 1 using other trialkyl orthoformates and the corresponding alcohol, such as triethyl orthoformate and ethanol instead of trimethyl orthoformate and methanol, the corresponding ketal such as 2,2-dimethoxy-3-chloro-3-methylpentane was obtained.

Example 6_

Was used in the procedure of Example 2 instead of 2,2-Dimethaxy-3-chloro-3-mE3thyl ~ pentane used an equivalent amount of the chloro ketal from Example 5, the corresponding 11-chloro-IO-oxo compounds were obtained, i.e.

209848/1211

trans, trans-methyl-S-methyl- ?, 11-diethyl-IO-Dxa-1 i-chlorotrideca ^ G-dienoate, trans, trans-methyl-3-methy1-7,1i-diethyl-10-oxo-ii-chlorotetradeca ^ ö-dienoate, trans, trans-methyl-3, 1 i-dimethyl-7-ethyl-IO-oxo-i i-chlortetradeca ^ jö-dienoate, trans, trans-Methy 1-3,11, 12-trimethyl-7-ethyl-10-oxo ~ 1i-chlorotrideca-

2,6-dienoate,

trans, trans-Methyl-a-methyl-3-ethyl-IO-oxo-H-chlorotrideca-S.ß-dienaat, trans, trans-Methyl-3-methyl-7-ethyl-10-oxo-11-chlorundeca 2 _} 6-dienoate and trans, trans-methyl-3,12-dimethyl-7-ethyl-11- (isopropyl) - 1G "OXü-11-chlorotri-

deca-2,6-dienaat.

According to Example 2, the allylic alcohol, trans-methyl-3-methy1-7-methylene-6-hydroxyoct-2-enoate, reacted with each of the chloro ketals from Example 5 to give the following compounds: trans, trans-methyl-3,7-dimethyl-1i-ethyl-10-oxo-ii-chlorotrideca ^ jG-dienoate,

trans, trans-Methy 1-3,7-dimethy 1-1 i-ethyl-IO-oxo .-— 1 i-chlorotetradeca ^ .edienoat,

trans, trans-T \ / lethyl-3,7, ii-trimethyl-IO-oxo-ii-chlDrtetradeca ^ jG-dienoate, trans, trans-methyl-3,7,11,12-tetramethyl-IO-oxo-i1-chlorotrideca-2, (> - dienaat, trans, trans-4 ^ ethyl-3,7-dimethyl-IO-oxo-i1-chlorotrideca-2,6-dienoate,

trans, trans-methyl 1-3,7-dimethyl 1-10-oxo-11-chlorundeca-2,6-dienoate and ™

trans, trans-methyl-3,7,12-trimethyPl i- (isopropyi) -10-oxo-i1-chlorotrideca-

2,6-dienoate.

The IO-oxo-11-chloro compounds prepared above were used as the starting material used in the procedures of Example 3 to give the corresponding chlorohydrins and then the epoxies with trans, trans configuration at C-2,3 and C-G, 7 positions and a trans configuration or no isomerism at C-10.11, depending on the C-11 substituent. The epoxies obtained were:

2098Λ8 / 1211

Methyl-10, H-oxida-a-methyl- ?, Ii-diethyltrideca ^ je-dienaat, Methyl-10,1i-oxido-S-methyl- ?, 1f-diethyltetradeca ^ jG-dienaat, methyl-10,11- oxirio-3,1i-dimethyl ^ -äthyltetradeca ^ je-dienoate, methyl-10,11-oxido-3,11, ^ -trimethyl ^ -äthyltrideca ^ ö-dienaat, methyl-10,11-oxido-3-methyl- 7 ~ ethyl trideca-2,6-dienoate, methyl-10, H-oxido-3-methyl-7-ethylundeca-2,6-dienoate, .: '■■■ methyl-10,11-oxido-3,12- dimethyl-7-ethyl-11- (isoprapyl) -trideca-2,6-dienoate, methyl-10,11-oxido-3,7-dimethyl-11-ethyltrideca-2,6-dienoate, methyl-10 , 11-oxido-3,7-dimethyl-11-ethyl-tetradeca-2,6-dienoate, methyl-10,11-oxido-3,7,1 i-trimethyltetradeca ^ .G-dienoate, methyl-10,11-axido -3,7,11, ^ -tetramethyltrideca ^ jS-dienoate, methyl 10,11-oxido-3 _f 7-dimethyltrideca-2,6-dienoate, methyl 10,11-oxide D-3,7-dimethylundeca-2 , 6-dienaate and methyl 10,11-oxido-3,7,12-trimethyPl 1- (isopropyl) -trideca-2,6-dienoate.

Example 7

r3 HH ₃ -ROH 'f f ²

r n

R Δ. . R ^ OR

15 g of the chloro ketal of Example 1, viz pehtan were made from a trace of phosphoric acid under reduced pressure at about Distilled 100 ° C. and gave 2-methaxy-3-chloro-3-methylpent-1-ene with methanol as a distillate which was washed with water to remove methanol,

Each of the ketals of Example "5 were converted into the corresponding chloro-enol ether converted, namely:

209848/1211

2-methoxy-S-chloro-ß-ethylpent-i-en,
2-methoxy-3-chloro-3-ethylhexene,
2-methoxy-3-chloro-3-methylhex-1-en,
2-methoxy-3-chlar ~ 3,4-dimethylpent-1-en,
2-methoxy-3-chloropent-1-en,

. 2-MBtHoXy-S-ChIOrPrOp-1-en and., ·

2-M8thoxy-3-chloro-3- (isDpropyl} -4-methylpent-1-ene.

After following Vsrfahren the Chlorenol- and Bromenoläther manufacturer A can be provided.

20 g of 2,2-dimethoxy-3-chloro-3-methylpentane and a trace of phosphoric acid were used heated to boiling until the theoretical amount of methanol is driven off. The residue was neutralized by adding weak potassium carbonate and then distilled to form 2-methaxy-3-chloro ~ 3-methylpent-1-ene.

Example B.

A mixture of 10 g of trans-methyl-3-methyl-7-methylene-ß-hydroxynon-2-enoate, 2 molar equivalents of 2-methoxy-3-chloro-3-methylpent-1-ene and 0.4 g of mercury

acetate was heated .Approximately 10 hours at 50 C., i then off in an ice bath

cools and neutralized by adding sodium carbonate. Then the

Mixture distilled and gave the ether (VIl) (R '= R ¹ = R ⁴ = methyl; R ² = R ³ = ethyl; X = chlorine).

The above ether (VIl) can also be obtained by fractional distillation of a mixture from the allylic alcohol (HI), a molar excess of the vinyl ether (il) and a small amount of mercuric acetate as a catalyst will. The distillation is continued until the theoretical alcohol

2098Λ8 / 1211

- 1B - ·

quantity (R-OH) continued and the crude product purified by chromatography. Example '9

A mixture of 10 g of trans-MBthyl-S-methyl- ^ - methylene-β-hydroxynon ^ -enoate, 0.05 g of phosphoric acid and 2 molar equivalents of S-methoxy-S-chloro-S-methyl-pent-1-ene was heated to 45 ° C. for about 14 hours. Then the reaction mixture was cooled and neutralized with triethylamine. The crude, mixed ketal (VIII) (R '= R = R = R ⁴ = methyl; R ² = R ³ = ethyl; X = chlorine) was purified by distillation and subsequent chromatography.

Example 10_

A mixture of 5 g of trans-methyl-3-methyl-7-methylene-ß-hydroxynon-2-enaate, 2 molar equivalents of 2,2-dirnethaxy-3-chloro-3-methylpentane and 0.1 g of phosphoric acid was about 12 Heated to about 40 C. for hours. The reaction mixture was then cooled and neutralized by adding triethylamine. The crude mixed ketal (VIII) (R = RW ¹ = R ⁴ = methyl; R ² = R ³ = ethyl; X = chlorine) was purified by distillation and subsequent chromatography.

Example 1_1

10 g of the ether (VIl) obtained in Example 8 and 0.2 g of phosphoric acid were treated at about 100 ° C. for 7 hours. After cooling, the crude product was chromatographed on silica gel, eluting with hexane: ether became; This gave trans, trans-methyl-3,11-dimethy1-10-oxox-II-chloro-7-ethyltrideca-2,6-dienoate.

Following the above procedure, the mixed ones obtained in Example 9 or 10 were obtained Ketals in trans, trans-methyl-ii-chloro-IO-oxo-3,11-dimethy1-7-ethyl trideca-2,6-dienoate converted.

209848/121 1

Claims (1)

Claims R * \ 1. ~ Process for the preparation of a compound of the formula: f 1 -CH- (CH ₂ ) ₂ -C> = CH-C-OR ' K « X
characterized in that an allylic alcohol of the formula: R ² R ^{1 n} H ₂ Cs = C-CH- (CH ₂ ) ₂ -C = CH-C-OR ' All with a compound of the formula: R ³ CH ₂ XC C-OR R ⁴ 1 in the presence of mercuric acid, where in the formulas R, R ¹ , R 2 and R each represents lower alkyl, X represents bromine or chlorine and R and R are each hydrogen or lower alkyl. 1 2.- The method according to claim 1, characterized in that R, R ¹ , R and R each stand for low alkyl with 1-3 carbon atoms and R and R ^ each for hydrogen or low alkyl with 1-3 carbon atoms. 3 3.- The method according to claim 2, characterized in that R and R each stand for lower alkyl. 4, - Method according to claim 3, characterized in that said lower alkyl group is methyl or ethyl. 209848/1211 - 2ύ - 5, - method according to claim 2, characterized in that the Mercuri— acylate is mercuric acetate. 6.- The method according to claim 5, characterized in that the reaction in an inert organic solvent takes place. 7.- The method according to claim 4, characterized in that the mercuric acid Is mercuric acetate. · -'- ■ B.- Process for the preparation of a compound of the formula: R ¹ Q -C = CH-C-OR ' R ² H ₂ CC-CH- (CH _{2) 2-0} H ₃ CC-OR pj characterized in that an allylic alcohol of the formula: ■ - ■■ "" - · R ² .R ¹ '- C-CH- (CHo) ₉ -C-CH-C-OR ' H ₂ C = C-CH- (CH ₂ ) 2 - ■ - OH- with a halogen ketal of the formula: R ³ ChL II ^J X_C _ C-OR R ⁴ Or or a halogen oil ether of the formula: R ³ CH ₂ XC - C-OR R ⁴ in the presence of a weakly acidic catalyst, wherein in the form 1 2 my R, R ', R and R each represent lower alkyl, X bromine or chlorine and R and R each represent hydrogen or lower alkyl. 209848/1211 BATH ORIGINAL - Σ1 - 9.- The method according to claim 8, characterized in that R, R ¹ , R and 2 3 R each stand for lower alkyl with 1-3 carbon atoms and R and R each denotes hydrogen or lower alkyl with 1-3 carbon atoms. 10. Method according to claim 9, characterized in that R and R mean lower alkyl. 11.- The method according to claim 10, characterized in that. the low one Alkyl group is methyl or ethyl. 12. - Method according to claim 10, characterized in that the acidic The catalyst is phosphoric acid or p-toluenesulfonic acid. \ 13.- Process for the preparation of a compound of the formula: : f T - "Ti. XC-C- (CH ₂ ) ₂ -C = CH- (CH ₂ ) ₂ -C = CH-C-OR .Ul
R 0 characterized in that there is a compound of the formulas f fs, f ti, 3 - C-CH- (CH ₀ ) ..- C-CH-C-OS. ' H ₀ C = C-CH- (CH ₀ ) ₀ -C = CH-C-OR ' II 2 _J 22 H ₃ CC-OR " ⁵ N. 1 2 heated, where in the formulas R, R ¹ , R and R each for lower alkyl 3 4 stand, X stands for bromine or chlorine and R and R each stand for hydrogen or lower alkyl _s Vi ..-- / srrahren n ^ ch Annpruou '13, characterized in that R ₃ R ¹ , R and r; for r: i3uriof, ^< - ,. 'j -; /. l : ^' ^r 'tJ i'ahlsnstorvatonisn stand and R and R respectively BAD ORIGINAt 3 4 15.- The method according to Amspruch 14, characterized in that R and R each signify lower alkyl. 16 - The method of claim 15 _{5 5} characterized in that the lower alkyl group is methyl or ethyl, 17 "- The method of claim 13, characterized in ¹ that the process in the presence of a weakly acidic catalyst is carried out. 18 _o - Process according to claim 13 _5, characterized in that the process is carried out in an inert organic solvent. 19, - Process for the preparation of a compound of formula ^1? R ² S ¹ Q ) ₂ -C = CH- (CH ₂ ) ₂ -C = CH-C-OR characterized ₅ that an allylic alcohol of the formula: R ² R ¹ 0 ■ I ₀ C = C-CH- (CH ₉ ), - with a halogen ketal of the formula: R ³ CH " ι t ^J X-C —-C-QR R DR or a halogen oil ether of the formula ⁰ . R ³ CH ₉ X_C -— C-DR R ⁴ in the presence of a weakly acidic catalyst, wherein in the form 1 2 my R, R '. _B R and R each denote lower alkyl, X denotes bromine or chlorine 3 4
and R and R each represent hydrogen or lower alkyl. BATH ORIGINAL 20.— The method according to claim 19, characterized in that R, R ', R and 2 3 R each stand for lower alkyl with 1-3 carbon atoms and R and R each denotes hydrogen or lower alkyl with 1-3 carbon atoms. ρ 21, - Method according to claim 20, characterized in that R, R ¹ , R and 4 · ■ 1 3 ·· R each denotes methyl or ethyl, R is methyl and R is ethyl. 22. - The method according to claim 21, characterized in that the reaction in an inert organic solvent takes place. 209848/12 11
BAD ORiGiNAL 2123 A17 - 24 23.- Compounds of the formula: R ³ CH ₃
XC - C-OR II R OR 3 4 in which R stands for lower alkyl, R and R each for hydrogen or are lower alkyl and X is bromine or chlorine. 3 4 24.- Compounds according to claim 23, characterized in that R _1, R and R are each lower alkyl with 1-3 carbon atoms. 25. Compounds according to claim 24, characterized in that the lower Wk alkyl group is methyl or ethyl. 26.- Compounds according to claim 24, characterized in that R is methyl or ethyl, R is ethyl and R is methyl. 27.- Compounds according to claim 24, characterized in that R is methyl or Means ethyl and R and R each stand for ethyl. 3 4 28, - Compounds according to claim 23, characterized in that R and R each represent hydrogen or lower alkyl of 1-3 carbon atoms. 29.- Compounds according to claim 28, characterized in that at least 3 4
one of the substituents R or R is hydrogen and R is a lower alkyl group having 1-3 carbon atoms.
30.- Compounds of the formula: • R ³ CH ι ti ^ - X-C - C-OR '4
R. in which R is lower alkyl, R and R are each hydrogen or lower Are alkyl and X is bromine or chlorine. 2098Λ8 / 1211 BATH ORIGINAL 31.- Compounds according to claim 30, characterized in that R ₁ and R 4th
R each for low. Are alkyl of 1-3 carbon atoms. 32, - connections according to claim 31, characterized in that the low Alkyl group is methyl or ethyl. 33.— Compounds according to claim 31, characterized in that R is methyl or ethyl, R ^{3 is} ethyl and R ^{4 is} methyl. 34.- Compounds according to claim 31, characterized in that R is methyl or ethyl and R and R each represent ethyl. 3 4 35, - Compounds according to claim 30, characterized in that R and R j each denotes hydrogen or lower alkyl with 1-3 carbon atoms. 36.- Compounds according to claim 35, characterized in that at least 3 4
one of the substituents R or R is hydrogen and R is a lower alkyl group having 1-3 carbon atoms. 37, - compounds of the formula: R ² R ¹ 0 · H ₂ CC-CH- (CH ₂ ) ₂ ~ C = CH-C-OR ^! ' R ⁴ in which R ¹ , R and R are each lower alkyl, R and R are each hydrogen or lower alkyl and X is bromine or chlorine. A p 38, - Compounds according to claim 37, characterized in that R ¹ , R _1, R ₁ 3 4
R and R each represent lower alkyl with 1-3 carbon atoms. 209848/1211 BATH ORIGINAL - 2b ~ 39, - compounds according to claim 38, characterized in that the _fl lower alkyl group is methyl or ethyl. 40, - Compounds according to claim 3B _5, characterized in that the configuration in the C-2 _S 3 position is a trans configuration. 41.- Compounds according to claim 39, characterized in that the configuration in the G-2,3 position is a trans configuration. , - 2 42.- Compounds according to claim 41, characterized in that R ¹ and R each- 14th
^ because methyl or ethyl mean, R and R each stand for methyl and R ^{3 is} ethyl. 43.- Compounds according to claim 41, characterized in that R ⁰ and R 1 3 4 each represent methyl or ethyl, R represents methyl and R 'and R each Mean ethyl. 3 4 44.- Compounds according to claim 37, characterized in that R and R are each hydrogen or lower alkyl having 1-3 carbon atoms and the configuration in the C-2,3 position is a trans configuration. " 45.- Compounds according to claim 44, characterized in that R is methyl J ^ , R ¹ and R are each methyl or ethyl, R and R are each hydrogen, methyl or ethyl. 46.— Compounds according to claim 45, characterized in that at least one of the substituents R or R ^ is hydrogen. 209848 / I ₂ η _{ßAD 0R1Q | NAL} 47.- Compounds of the formula: R ² - R ¹ 0 7/2 H ₂ CC-CH- (CII ₀ ). -C = ClJ-OR ¹
0 .1 H C-C-OR 12 3 4 Λ in which R, R ¹ , R and R each represent lower alkyl, R and R each represent hydrogen or lower alkyl and X represents bromine or chlorine. 1 2 48.— Compounds according to claim 47, characterized in that R, R ^f , R ₁ R, 3-4 R and R each represent lower alkyl of 1-3 carbon atoms. 49, - Compounds according to claim 4B, characterized in that the lower alkyl group is methyl or ethyl. 50, - connections according to claim 48, characterized in that the configuration in the C-2,3 position is a trans configuration. 51.— Compounds according to claim 49, characterized in that the confi- J guration in the C-2,3 position is a trans configuration. ρ 52.— Compounds according to claim 51, characterized in that R ¹ , R and R ^{4 are} each methyl or ethyl, R ^{1 is} methyl and R ^{3 is} ethyl. 53.— Compounds according to claim 47, characterized in that R and R each denotes hydrogen or lower alkyl with 1-3 carbon atoms and the configuration in the C-2,3 position is a trans configuration. 209848/1211
BATH ORIGINAL 54.- Compounds according to claim 53, characterized in that R, R ¹ and F each denote methyl or ethyl, R denotes methyl and R and R each denote hydrogen, methyl or ethyl. 55, - Connections according to claim 54, characterized in that at least 3 4
one of the substituents R and R represents hydrogen. 56, - compounds of the formula:
, 3 Ϊ I ly ^^ V * ν Oil ·} J r * Kß ~ 12th A in which R ', R and R are lower alkyl, X is bromine or chlorine 3 4
and R and R are hydrogen or lower alkyl, where at least one 3 4
the substituents R and R represent hydrogen. 5? .- Connections according to claim 56, characterized in that the low Alkyl group contains 1-3 carbon atoms. 1 58, - Compounds according to claim 57, characterized in that R is methyl 2 3 4 R ¹ , R and R each represent methyl or ethyl, and R represents hydrogen. 59.- Compounds according to claim 57, characterized in that the configuration W tion in the C-2.3 and C-6 position ^ a trans-configuration. 60, - connections according to claim 58, characterized in that the configuration in the C-2,3 and C-6,7 positions is a trans configuration. ": The patent attorney; 209848 / 12Π BATH ORIGINAL