CA1126759A - Intermediate in the preparation of cyclopropanecarboxylate esters and process for its manufacture - Google Patents
Intermediate in the preparation of cyclopropanecarboxylate esters and process for its manufactureInfo
- Publication number
- CA1126759A CA1126759A CA331,943A CA331943A CA1126759A CA 1126759 A CA1126759 A CA 1126759A CA 331943 A CA331943 A CA 331943A CA 1126759 A CA1126759 A CA 1126759A
- Authority
- CA
- Canada
- Prior art keywords
- carene
- compound
- preparation
- formula
- process according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/04—Saturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/185—Saturated compounds containing keto groups bound to acyclic carbon atoms containing —CHO groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
- C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
- C07C45/60—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in six-membered rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
Abstract
ABSTRACT
Novel intermediate in the manufacture of pyrethroid insecticides has the following formula
Novel intermediate in the manufacture of pyrethroid insecticides has the following formula
Description
h~759 "Novel intermediate in the preparation of cyclopropanecarboxylate esters and process for its manufacture"
The invention relates to a compound which is a useful intermediate in the preparation of cyclopropanecarboxylate esters. The invention also relates to a process for the preparation of this intermediate.
The cyclopropanecarboxylate esters are insecticidally-active com-pounds known as "pyrethroids" and as they combine exceptionally good insec-ticidal properties with a very low mammalian toxicity, they are of consider-able interest to the agrochemical industry and much effort has been expend-ed in finding economic routes to them and to their principal intermediates.
The general formula of one class of these pyrethroid compounds may be represented as follows:-H CH=CX2 / \
CH3 ~ 3 1 \* COOR
where each asterisk denotes an asymmetric carbon atom; each X is a halogen atom; and R is a member of a group of radicals known to impart insecticidal activity to the molecule, e.g. 3-phenoxybenzyl or alpha-cyano-3-phenoxy-benzyl. It is known that the stereoisomeric form of the acid portion of the ester of formula I should be in the (lR,c ) form for maximum insecticidal activity, i.e. the absolute configuration at carbon atom 1 is R and the two hydrogen atoms on carbon atoms 1 and 2 are in a cis relationship. This nom-enclature is known as the Elliott nomenclature and is defined in M. Elliott, A.W. Farnham, N.F. James, P.H. Needham and D.A. Pullman, Nature, 1974, 248, 710.
'~
- .: - .-: .:
i7Si9 It follows, therefore, that if these stereoisomeric esters of formula I are to be prepared, either a stereospecific chemical route is re-quired or the desired stereoisomer must be obtained from a racemic form by physical separation techniques. The latter are expensive and laborious and not readily employed on an industrial scale. The Applicant has found a stereospecific route which uses as starting material the naturally-occurring substance (+)-3-carene whose formula is as follows:-H~ ~ ~h (II) CH3 / ~
CH3 HThis compound is an inexpensive readily-available natural terpene and the present application relates to an intermediate which can be used in a route to the ~lR,c )-acid portion of the pyrethroid ester of formula I starting from ~+)-3-carene.
The present invention provides a cyclopropane compound of the for-mula:-/ \ , (III) 3 / \ Cll2-cH-co-cH3 This compound may be named 1-(2-hydroxy-3-oxobutyl)-3,3-dimethylcycloprop-ane-2-carbaldehyde. Preferably the compound of formula III is in the same stereoisomeric form as that of the cyclopropane ring present in naturally-occurring (+)-3-carene.
The present invention also provides a process for the preparation - . , .- : : . , ~
., : , , , . . ~ :
of 1-(2-hydroxy-3-oxobutyl)-3,3-dimethylcyclopropane-2-carbaldehyde of for-mula III which comprises hydrolysing a 4-acetyl-2-alkoxy-7,7-dimethyl-3-oxabicyclo[4.1.0]heptane of formula IV
R O ~ ~ CO-CH3 (IV) 3 f ~/
wherein Rl is an alkyl group. The alkyl group preferably contains 1 to 6 carbon atoms, for example methyl, ethyl and propyl. The preferred starting material is 4-acetyl-2-methoxy-7,7-dimethyl-3-oxabicyclo[4.1.0]heptane. The hydrolysis is preferably carried out in the presence of an aqueous acidic medium, e.g. an aqueous organic or inorganic acid such as acetic acid or 10 sulphuric acid. Other examples of suitable hydrolysis media are given in "Methoden der organischen Chemie" (Houben-Weyl), Volume VII, Part 1~1954) 423-428.
The starting material, compound IV, is a novel compound and is claimed in our copending application 331,951 filed July 17, 1979 (K 357~. A
method of preparation of compound IV is also disclosed therein involving ozonolysis of 4-hydroxy-2-carene in the presence of an alkanol, preferably methanol, and reduction of the resulting ozonide.
The starting material is preferably derived from naturally-occur-ring (+)-3-carene as this enables the process according to the invention to 20 yield a novel intermediate of formula III in a stereoisomeric form which, after conversion to a pyrethroid insecticide produces the highest level of pyrethroid insecticide-activity.
The compound and process according to the invention are of interest as part of a multi-step process to pyrethroid insecticides, e.g. esters based on (lR,c )-2-(2,2-dichlorovinyl)-3,3-dimethylcyclopropane carboxylic .: .. : , . ~ ,, . -7~
acid.
The following Examples further illustrate the invention.
Example 1 - Preparation of 1-(2-hydroxy-3-oxobutyl)-3,3-dimethyl-cyclopropane-2-carbaldehyde (Compound III) A 50 ml flask was charged with 4-acetyl-2-methoxy-7,7-dimethyl-3-oxabicyclo[4.1.0]heptane (Compound IV) derived from (+)-3-carene ~21.7 mmol, 100% lR,cis) and a 1:1 (v) mixture (10 ml) of acetic acid and water.
After stirring of the contents of the flask for five hours at 20C water (30 ml) was added and the resulting mixture was extracted with two 25 ml portions of dichloromethane. The combined extract phases were washed with two 25 ml portions of a saturated aqueous solution of sodium hydrogen car-bonate and then with a 10% w aqueous solution (25 ml) of sodium chloride.
The washed organic phase was dried over anhydrous magnesium sul-phate and the solvent was evaporated from the dried organic phase at 1.3 kPa to leave a residue (3.5 g) containing compound III ~100% lR,cis, yield 88%). The nuclear magnetic resonance spectrum of compound III showed the following absorptions (using a solution of compound III in deuterochloro-form and relative to a tetramethylsilane standard):
~ = 1.24 ppm singlet H3C-C-CH3 ~ = 1.33 ppm singlet H3C-C-CH3 ~ = 2 22 ppm singlet H3C-C=O ~ = 3.6 ppm (variable) broad-OH
~ = 4.23 ppm doublet of doublets HC-OH ~ = 9.69 ppm doublet H-C=O
multiplets for each of the H atoms bound to the ring.
Example 2 - Preparation of 1-(2-hydroxy-3-oxobutyl)-3,3-dimethyl-cyclopropane-2-carbaldehyde (Compound III) A 50 ml flask was charged with Compound IV (10.1 mmol, 100%
lR,cis), a 1:1 (v) mixture (20 ml) of water and acetone and concentrated sul-phuric acid (1.5 mmol), sp. gr. 1.84. Compound IV had been prepared as a derivative of (+)-3-carene and had the same stereochemical configuration.
. .
~: . . .
.- ' ~
fi~
After stirring of the contents of the flask for one hour at 20C the major-ity of acetone was distilled off at 1.3 kPa. The residue was extracted with two 10 ml portions of dichloromethane. The combined extract phases were washed with two 20 ml portions of a saturated aqueous solution o~ so-dium hydrogen carbonate and then with a 10% w aqueous solution (20 ml) of sodium chloride. The washed organic phase was dried over anhydrous magnes-ium sulphate and the solvent was evaporated from the dried organic phase at 1.3 kPa to leave a residue (1.6 g) containing compound III (100% lR,cis, yield 86%).
~r,, , :: : :: .,~, , :
The invention relates to a compound which is a useful intermediate in the preparation of cyclopropanecarboxylate esters. The invention also relates to a process for the preparation of this intermediate.
The cyclopropanecarboxylate esters are insecticidally-active com-pounds known as "pyrethroids" and as they combine exceptionally good insec-ticidal properties with a very low mammalian toxicity, they are of consider-able interest to the agrochemical industry and much effort has been expend-ed in finding economic routes to them and to their principal intermediates.
The general formula of one class of these pyrethroid compounds may be represented as follows:-H CH=CX2 / \
CH3 ~ 3 1 \* COOR
where each asterisk denotes an asymmetric carbon atom; each X is a halogen atom; and R is a member of a group of radicals known to impart insecticidal activity to the molecule, e.g. 3-phenoxybenzyl or alpha-cyano-3-phenoxy-benzyl. It is known that the stereoisomeric form of the acid portion of the ester of formula I should be in the (lR,c ) form for maximum insecticidal activity, i.e. the absolute configuration at carbon atom 1 is R and the two hydrogen atoms on carbon atoms 1 and 2 are in a cis relationship. This nom-enclature is known as the Elliott nomenclature and is defined in M. Elliott, A.W. Farnham, N.F. James, P.H. Needham and D.A. Pullman, Nature, 1974, 248, 710.
'~
- .: - .-: .:
i7Si9 It follows, therefore, that if these stereoisomeric esters of formula I are to be prepared, either a stereospecific chemical route is re-quired or the desired stereoisomer must be obtained from a racemic form by physical separation techniques. The latter are expensive and laborious and not readily employed on an industrial scale. The Applicant has found a stereospecific route which uses as starting material the naturally-occurring substance (+)-3-carene whose formula is as follows:-H~ ~ ~h (II) CH3 / ~
CH3 HThis compound is an inexpensive readily-available natural terpene and the present application relates to an intermediate which can be used in a route to the ~lR,c )-acid portion of the pyrethroid ester of formula I starting from ~+)-3-carene.
The present invention provides a cyclopropane compound of the for-mula:-/ \ , (III) 3 / \ Cll2-cH-co-cH3 This compound may be named 1-(2-hydroxy-3-oxobutyl)-3,3-dimethylcycloprop-ane-2-carbaldehyde. Preferably the compound of formula III is in the same stereoisomeric form as that of the cyclopropane ring present in naturally-occurring (+)-3-carene.
The present invention also provides a process for the preparation - . , .- : : . , ~
., : , , , . . ~ :
of 1-(2-hydroxy-3-oxobutyl)-3,3-dimethylcyclopropane-2-carbaldehyde of for-mula III which comprises hydrolysing a 4-acetyl-2-alkoxy-7,7-dimethyl-3-oxabicyclo[4.1.0]heptane of formula IV
R O ~ ~ CO-CH3 (IV) 3 f ~/
wherein Rl is an alkyl group. The alkyl group preferably contains 1 to 6 carbon atoms, for example methyl, ethyl and propyl. The preferred starting material is 4-acetyl-2-methoxy-7,7-dimethyl-3-oxabicyclo[4.1.0]heptane. The hydrolysis is preferably carried out in the presence of an aqueous acidic medium, e.g. an aqueous organic or inorganic acid such as acetic acid or 10 sulphuric acid. Other examples of suitable hydrolysis media are given in "Methoden der organischen Chemie" (Houben-Weyl), Volume VII, Part 1~1954) 423-428.
The starting material, compound IV, is a novel compound and is claimed in our copending application 331,951 filed July 17, 1979 (K 357~. A
method of preparation of compound IV is also disclosed therein involving ozonolysis of 4-hydroxy-2-carene in the presence of an alkanol, preferably methanol, and reduction of the resulting ozonide.
The starting material is preferably derived from naturally-occur-ring (+)-3-carene as this enables the process according to the invention to 20 yield a novel intermediate of formula III in a stereoisomeric form which, after conversion to a pyrethroid insecticide produces the highest level of pyrethroid insecticide-activity.
The compound and process according to the invention are of interest as part of a multi-step process to pyrethroid insecticides, e.g. esters based on (lR,c )-2-(2,2-dichlorovinyl)-3,3-dimethylcyclopropane carboxylic .: .. : , . ~ ,, . -7~
acid.
The following Examples further illustrate the invention.
Example 1 - Preparation of 1-(2-hydroxy-3-oxobutyl)-3,3-dimethyl-cyclopropane-2-carbaldehyde (Compound III) A 50 ml flask was charged with 4-acetyl-2-methoxy-7,7-dimethyl-3-oxabicyclo[4.1.0]heptane (Compound IV) derived from (+)-3-carene ~21.7 mmol, 100% lR,cis) and a 1:1 (v) mixture (10 ml) of acetic acid and water.
After stirring of the contents of the flask for five hours at 20C water (30 ml) was added and the resulting mixture was extracted with two 25 ml portions of dichloromethane. The combined extract phases were washed with two 25 ml portions of a saturated aqueous solution of sodium hydrogen car-bonate and then with a 10% w aqueous solution (25 ml) of sodium chloride.
The washed organic phase was dried over anhydrous magnesium sul-phate and the solvent was evaporated from the dried organic phase at 1.3 kPa to leave a residue (3.5 g) containing compound III ~100% lR,cis, yield 88%). The nuclear magnetic resonance spectrum of compound III showed the following absorptions (using a solution of compound III in deuterochloro-form and relative to a tetramethylsilane standard):
~ = 1.24 ppm singlet H3C-C-CH3 ~ = 1.33 ppm singlet H3C-C-CH3 ~ = 2 22 ppm singlet H3C-C=O ~ = 3.6 ppm (variable) broad-OH
~ = 4.23 ppm doublet of doublets HC-OH ~ = 9.69 ppm doublet H-C=O
multiplets for each of the H atoms bound to the ring.
Example 2 - Preparation of 1-(2-hydroxy-3-oxobutyl)-3,3-dimethyl-cyclopropane-2-carbaldehyde (Compound III) A 50 ml flask was charged with Compound IV (10.1 mmol, 100%
lR,cis), a 1:1 (v) mixture (20 ml) of water and acetone and concentrated sul-phuric acid (1.5 mmol), sp. gr. 1.84. Compound IV had been prepared as a derivative of (+)-3-carene and had the same stereochemical configuration.
. .
~: . . .
.- ' ~
fi~
After stirring of the contents of the flask for one hour at 20C the major-ity of acetone was distilled off at 1.3 kPa. The residue was extracted with two 10 ml portions of dichloromethane. The combined extract phases were washed with two 20 ml portions of a saturated aqueous solution o~ so-dium hydrogen carbonate and then with a 10% w aqueous solution (20 ml) of sodium chloride. The washed organic phase was dried over anhydrous magnes-ium sulphate and the solvent was evaporated from the dried organic phase at 1.3 kPa to leave a residue (1.6 g) containing compound III (100% lR,cis, yield 86%).
~r,, , :: : :: .,~, , :
Claims (7)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A cyclopropane compound of the formula III:-,
2. A compound according to claim 1 in the same stereoisomeric form as that of the cyclopropane ring present in naturally-occurring (+)-3-carene.
3. A process for the preparation of 1-(2-hydroxy-3-oxobutyl)-3,3-di-methylcyclopropane-2-carbaldehyde of formula III, as defined in claim 1, which comprises hydrolysing a 4-acetyl-2-alkoxy-7,7-dimethyl-3-oxabicyclo [4.1.0]
heptane of formula IV
(IV) wherein R1 is an alkyl group.
heptane of formula IV
(IV) wherein R1 is an alkyl group.
4. A process according to claim 3 wherein the starting material is 4-acetyl-2-methoxy-7,7-dimethyl-3-oxabicyclo [4.1.0] heptane.
5. A process according to claim 3 wherein the starting material of formula IV as defined in claim 3 is in the same stereoisomeric form as that of the cyclopropane ring present in naturally-occurring (+)-3-carene.
6. A process according to claims 3, 4 or 5, wherein the hydrolysis is carried out in the presence of an aqueous acidic medium.
7. A process according to claims 3, 4 or 5 wherein the hydrolysis is carried out in the presence of acetic acid or sulphuric acid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7830336 | 1978-07-19 | ||
| GB30.336/78 | 1978-07-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1126759A true CA1126759A (en) | 1982-06-29 |
Family
ID=10498513
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA331,943A Expired CA1126759A (en) | 1978-07-19 | 1979-07-17 | Intermediate in the preparation of cyclopropanecarboxylate esters and process for its manufacture |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS5515490A (en) |
| BE (1) | BE877745A (en) |
| CA (1) | CA1126759A (en) |
| CH (1) | CH641139A5 (en) |
| DE (1) | DE2928833A1 (en) |
| DK (1) | DK300379A (en) |
| FR (1) | FR2431476A1 (en) |
| NL (1) | NL7905552A (en) |
-
1979
- 1979-07-17 CA CA331,943A patent/CA1126759A/en not_active Expired
- 1979-07-17 NL NL7905552A patent/NL7905552A/en not_active Application Discontinuation
- 1979-07-17 JP JP8995479A patent/JPS5515490A/en active Pending
- 1979-07-17 BE BE0/196338A patent/BE877745A/en not_active IP Right Cessation
- 1979-07-17 FR FR7918455A patent/FR2431476A1/en active Granted
- 1979-07-17 DK DK300379A patent/DK300379A/en not_active Application Discontinuation
- 1979-07-17 DE DE19792928833 patent/DE2928833A1/en not_active Withdrawn
- 1979-07-17 CH CH664679A patent/CH641139A5/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FR2431476B1 (en) | 1984-04-27 |
| NL7905552A (en) | 1980-01-22 |
| BE877745A (en) | 1980-01-17 |
| FR2431476A1 (en) | 1980-02-15 |
| DE2928833A1 (en) | 1980-01-31 |
| DK300379A (en) | 1980-01-20 |
| JPS5515490A (en) | 1980-02-02 |
| CH641139A5 (en) | 1984-02-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |