GB2038317A - Cyclic diacids & diesters their preparation and use as chromatographic standards - Google Patents
Cyclic diacids & diesters their preparation and use as chromatographic standards Download PDFInfo
- Publication number
- GB2038317A GB2038317A GB7936780A GB7936780A GB2038317A GB 2038317 A GB2038317 A GB 2038317A GB 7936780 A GB7936780 A GB 7936780A GB 7936780 A GB7936780 A GB 7936780A GB 2038317 A GB2038317 A GB 2038317A
- Authority
- GB
- United Kingdom
- Prior art keywords
- chloro
- bromo
- compound
- dichlorovinyl
- formula
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/16—Unsaturated compounds
- C07C61/40—Unsaturated compounds containing halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Novel diacids and diesters of Formula I wherein X is chloro, bromo, fluoro or trifluoromethyl, Y is chloro, bromo or fluoro, and R is hydrogen or C1 to 4 alkyl. The compounds may be prepared by a sequence of reactions from alkyl tiglate, and are useful as chromatographic reference standards for use in evaluation of the metabolic breakdown of pyrethroid insecticides. <IMAGE>
Description
SPECIFICATION
Cyclic diacids and diesters, their preparation and use as chromatographic standards
This invention relates to novel cyclopropane derivatives and their preparation.
The invention provides new compounds of formula:
wherein X is chloro, bromo, fluoro or trifluoromethyl, and Y is chloro, bromo or fluoro, and R is hydrogen, or alkyl of one to four carbon atoms.
Specific examples of compounds according to the invention include the following: 3-(2-2-dichlorovinyl)-1-methylcyclopropane 1,2-dicarboxylic acid 3-(2-2-dibromovinyl)-1 -methylcyclopropane 1 ,2-dicarboxylic acid 3-(2-chloro-3,3,3-trifluoromethyl)-1-methylcyclopropane 1,2-dicarboxylic acid and the corresponding methyl and ethyl monoesters and diesters of these acids.
It will be appreciated that the compounds of formula I are capable of existence in several isomeric forms, and the scope of the invention embraces each of these isomeric forms in isolation from other isomeric forms as well as mixtures thereof.
The compounds wherein R is alkyl may be prepared by treating a compound of formula:
wherein X, Y AND Rare as defined above and Z and Q are each chloro, bromo orfluoro, provided that 0 is not chloro if any one of X, Y and Z is bromo and Q is not fluoro if any one of X, Y and Z is chloro or bromo with at least two molar equivalents of a base This process involves two separate stages, cyclisation and ss-elimination of hydrogen halide, and there are three possible intermediate species through which the process may proceed (IIIA, IIIB, and IIIC), but it is not clear which of these is actually involved. It is quite possible that more than one intermediate is formed, and that different bases will produce I from II by different mechanisms.
x Y-c-cIf -Cl Z n base base/ (IAI CII I-lIz / I~llQfi Z) X IT X Q Clf3 \9 -I---, c-cs--css--c-co, (-((1 / I (-llO) y C(l2-CO2R (ITIB base base (-nO X Cl l-llt) 1-C-C(lC((-C-CO S I 1 Z CS2 -CO2 I (IIIC) Suitable bases for carrying out the process include tertiary amines, for example pyridine, triethylamine, diethylaniline, N-methyl piperidine, and also alkali metal alkoxides, for examples sodium methoxide, sodium ethoxide, and potassium t-butoxide.The step is conveniently carried out in a diluent or solvent for the reactant and the base. A particularly convenient manner of conducting this step is to heat a solution of the reactant in an alcohol corresponding to the alkali metal alkoxide being used for a period of from 0.5 to 20 hours.
The compounds of formula I wherein R is hydrogen may be prepared by hydrolysis of the compounds wherein R is alkyl. Alkaline hydrolysis is preferred.
The compounds of formula II may be prepared from the compound of formula:
wherein R is alkyl, by reacting the compound offormula IV with a compound offormula:
wherein X, Y, Z and Q are as defined above, in the presence of a free radical initiator. Examples of compounds of formula IV include carbon tetrachloride, bromotrichloromethane, and 1,1,1 trichlorotrifluoroethane.
This reaction is free radical in nature and is carried out in the presence of a free radical initiator which may be a physical initiator such as irradiation with a suitable, e.g. Ultra violet, light source, or a conventional chemical free radical catalyst such as for example benzoyl peroxide or azobisisobutyronitrile.
The reaction may conveniently be carried out using an excess of the compound of formula Vas a diluent, at temperatures in the range 50" to 100"C, preferably 80-90"C, at periods from 1 to 20 hours.
The compound of formula IV may be prepared by reacting alkyl tiglate with alkyl haloacetate, using a base such as lithium diisopropylamide in the presence of hexamethylphosphorictriamide to preclude Michael addition. The reaction may be summarised thus:
The compounds of formula I are useful as reference standards for the chromatographic evaluation of the metabolic breakdown products of the insecticidal esters of acids of formula:
including for example the 3-phenoxybenzyl or a-cyano-3-phenoxybenzyl esters of 3-(2,2-dichlorovinyl)-2,2dimethylcyclopropane carboxylic acid, 3,-(2,2-dibromovinyl)-2, 2-dimethylcyclopropane carboxylic acid, and 3-(2-chloro-3,3,3-trifl uoroprop-l-en-l-yl)-2, 2-dimethylcyclopropane ca rboxylic acid.
The following Examples illustrate the invention.
Example I
This Example illustrates the preparation of diethyl 2-methyl-2-vinylsuccinate.
n-Butyl lithium (0.05 mole; 15% solution in hexane) was added under argon to a solution of diisopropylamine (5.1 g, 0.05 mole) in dry tetrahydrofuran (50 ml) at 4"C. After 15 minutes at this temperature, the solution was cooled to -75 C and hexamethylphosphorictriamide (10g, 0.055 mole) followed by ethyl tiglate (6.6g, 0.05 mole) were added. The mixture was left at -75 C for 30 minutes and then ethyl bromoacetate (10g, 0.065 mole) was added. After 10 minutes the mixture was allowed to warm to room temperature, water was added and the solution extracted with hexane.After washing the hexane phase with water (4 times), drying with magnesium sulphate and evaporating, the residue was distilled in a bulb tube (oven temperature 900C/0.lmm) to give diethyl 2-methyl-2-vinylsuccinate, (9.29, 87%).
N.m.r. 6 ppm : 6.l0(dd, 1 H); 5.16(dd, 2H); 4.16(dg, 4H); 2.72(dd, 2H); 1.40(5, 3H); 1.24(dt, 6H);
IR cm~1 (liq film).
Example 2
This Example illustrates the preparation of diethyl 2-methyl-2-(1 -brnmo-3,3,3-trichlornprnpyl)succinate of formula:
Diethyl 2-methyl-2-vinylsuccinate (9.29) was refluxed with an excess of bromotrichloromethane (30 ml) under argon for 9 hours in the presence of benzoyl peroxide (300 mgs). A further addition of peroxide (200 mgs) was made after the initial 4 hours. The excess of bromotrichloromethane was removed under reduced pressure and the residue distilled in a bulb tu be (oven temperature 1500.001 mm) to give the adduct (15.8g; 90%).
N.m.r. b ppm : 4.24(m, lah); 4.14(m, 4H); 3.34(m, 2H); 2.72(m, 2H); 1.29(m, 9H).
IR cm-1 (liq. film) :1730 (C=O).
Example 3
This Example illustrates the preparation of diethyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1 ,2- dicarboxylate of formula:
^o:-':Llm hydride (2.29) was added to a solution of dry t-butanol (60 ml) in dry tetrahydrofuran (120 ml) under argon, and stirred until evolution of hydrogen had ceased. The suspension was cooled to 10"C and the bromotrichloromethane adduct (1 5.7g) in dry tetrahydrofuran (50 ml) was added dropwise, with stirring.
After 1 hour at 0 C followed by 2 hours at ambient temperature, the mixture was neutralised with concentrated hydrochloric acid, filtered and concentrated under reduced pressure. The residue was taken up in hexane, washed with saturated sodium bicarbonate solution, then water, and finally dried with magnesium sulphate. Removal of the solvent and distillation of the residue in a bulb tube (oven temperature 120"10.05 mm) gave diethyl-3-(2,2-dichlorovinyl)-2-methylcyclopropane-1 ,2-dicarboxylate.
N.in.r 6 ppm : 6.26,5.86,5.60 (3ds, 1H); 4.6 (m,4H); 2.50(m, 2H): 1.44(2ss, 3H); 1.30(m, 6H).
IR cm-1 (liq. film) 1720 (C=O),
1620 (C=C).
Example 4
This Example illustrates the preparation of 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane 1,2 dicarboxylicacid of formula:
The product of Example 3 was refluxed with a 1:1 mixture of methanol and N-sodium hydroxide solution for 2 hours. Acidification of the mixture and extraction with hexane yielded the required diacid.
This diacid is capable of existing in four possible isomeric forms, and the n.m.r. spectrum of the product indicated the presence of three of these in the reaction product. The methyl esters (obtained by reacting the incid with an ethereal solution of diazomethane for 1 hour, after which the excess diazomethane and the ether was removed by evaporation under a gentle air flow) were subjected to high pressure liquid chromatography on a reversed phase column. The conditions were as follows:
Pump : Waters Associates M-6000Awith model U6Kvalve injector
Column : Waters C18 ffi bondapack reversed phase, 30 cm x 4.6 mm
Mobile phase : methanol/water (55:45)
Flow rate 2ml/min.
The eluates were monitored at a wavelength of 220mm using a CE 212 variable wavelength UV monitor (Cecil Instruments Ltd). Following spearation the three components were examined by n.m.r. spectroscopy and assigned configurations as set out in the following table.
Chemlcal Shifts (ppm) Relative to T.HS and Coupling Constants (Hz) (hole Rt-6 4 In topic Rt-13.4 'sin) (hplc RtslS 'sin) ~ ~ ~.~~~ , . ~.~ ~~~ ~ ~ ~~~~~~ ~, ~~~~~~~~~ 1.-S 5.62,d, J-8.5 Hz S.80.d, J;8.5 Hz 6.20 is I -S 1.87.d. J < 6 Hz 2.83,d, J=6.5 Hz 1-ll 2.96.dd. J-8 5z6 Hz 2.45,dud, J'6't & 5.Hz 2.5 w 2 CS3 1.42,s , 1.43,s 1.37, I-cd2-Ct9JCIS3 3.69.s; 3.71,s 3.67,: 3.68.s 3.66.s; 3.68.s Conf Iguratton )4 H H H Asslrtnl:d- n w Cl' H %QoocH3 ,1 '98C83 3 CH3 , i" C113 Cil3 COOCH3 COaCH3 ~ ~ ~ ~ ' conftqurtion displayed Is for one enantiomer of each colsponent Only - to the mixture each component is present in two enantirmrrle florins, but these are not e,rately tdentiflable by the n.m.r. technique used.
Claims (11)
1. Acompound offormula:
wherein Xis chloro, bromo, fluoro or trifluoromethyl, Y is chloro, bromo orfluoro, and R is hydrogen or alkyl of one to four carbon atoms.
2. A compound as claimed in Claim 1 wherein X and Y are both chloro.
3. 3-(2,2-Dichlorovinyl)-1 -methylcyclopropane 1 ,2-dicarboxylic acid.
4. Diethyl 3-(2,2-dichlorovinyl)-1 -methylcyclopropane 1 ,2-dicarboxylate.
5. Dimethyl 3-(2,2-dichlorovinyl)-1 -methylcyclopropane 1 ,2-dicarboxylate.
6. A process for preparing a compound according to Claim 1 which comprises the step of treating a compound of formula:
wherein X, Y, Z and Q are chloro, bromo orfluoro, and X may additionally be trifluoromethyl, and R is alkyl of one to four carbon atoms (provided that Q is not fluoro or chloro if any one of X, Y and Z is bromo, and 0 is not fluoro if any one of X, Y and Z is chloro or bromo), with at least two molar equivalents of a base.
7. A process as claimed in Claim 6 wherein the base is an alkali metal alkoxide.
8. A process as claimed in Claim 6 comprising the additional step of hydrolysing the diester product under alkaline conditions to produce the diacid.
9. A process in which the compound of Claim 5 is prepared by treating the compound of Claim 3 with diazomethane.
10. A method of chromatographically evaluating the metabolic breakdown products of insecticidal esters of acids of formula:
wherein X and Y are as defined in Claim 1 in which a compound according to Claim 1 is used as a reference standard.
11. A method according to Claim 11 in which the insecticidal ester is the 3-phenoxybenzyl or a-cyano-3-phenoxybenzyl ester of 3-(2,2-dichlorovinyl)-2, 2-dimethylcycloprnpane carboxylic acid.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB7936780A GB2038317A (en) | 1978-11-10 | 1979-10-23 | Cyclic diacids & diesters their preparation and use as chromatographic standards |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB7843953 | 1978-11-10 | ||
GB7936780A GB2038317A (en) | 1978-11-10 | 1979-10-23 | Cyclic diacids & diesters their preparation and use as chromatographic standards |
Publications (1)
Publication Number | Publication Date |
---|---|
GB2038317A true GB2038317A (en) | 1980-07-23 |
Family
ID=26269529
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB7936780A Withdrawn GB2038317A (en) | 1978-11-10 | 1979-10-23 | Cyclic diacids & diesters their preparation and use as chromatographic standards |
Country Status (1)
Country | Link |
---|---|
GB (1) | GB2038317A (en) |
-
1979
- 1979-10-23 GB GB7936780A patent/GB2038317A/en not_active Withdrawn
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4999451A (en) | Process for preparing dihalovinylcyclopropanecarboxylates | |
US3123629A (en) | Ch-chj-c-c-chs | |
GB2038317A (en) | Cyclic diacids & diesters their preparation and use as chromatographic standards | |
Jewett et al. | Preparation and use of sex attractants for four species of pine sawflies | |
US3652652A (en) | 3-methallyllevulinates and preparation thereof | |
JP4044923B2 (en) | Halogenated esters useful as pesticide intermediates | |
NO153098B (en) | 3-SUBSTITUTED 2,2-DIMETHYL-CYCLOPROPANCARBOXYL ACIDES AND LOWER ALKYLESTERS THEREOF USE AS OUTSIDE MATERIALS IN THE PREPARATION OF PYRETHROIDS WITH INSECTICID EFFECT | |
Miyano et al. | Carbon-carbon bond formation by the use of chloroiodomethane as a C1 unit. II. The preparation and synthetic application of 1-chloro-3-iodoheptane. | |
KR100239232B1 (en) | Preparation of halogenated alcohols | |
US4442301A (en) | Process for stereoselectively synthesizing cyclopropane carboxylates | |
CA1219002A (en) | Process for the production of dimedone | |
Fliche et al. | An Enzymatic Enantioselective Route to Methyl Carboxylate 2, 3-Methanohomoserine γ-Lactone; A Precursor of Chiral 2, 3-Methanohomoserine | |
RU2144528C1 (en) | Halogenated ester, method of preparing thereof, and method of preparing 3-(2-chloro-3,3,3-trifluoroprop-1- ene-1-yl)-2,2-dimethyl cyclopropanecarboxylic acid alkyl ester | |
MXPA97003663A (en) | Halogenated eteres useful as intermediaries for insecticide | |
US5670697A (en) | Preparation of cyclopropane esters | |
DE2439059C2 (en) | Process for the preparation of mixtures of decadienoic acid esters | |
GB2110686A (en) | Preparation of 2,2-dimethyl-cyclopropanecarboxylate having in the 3-position a halosubstituted dienic substituent | |
Petrilka | A convenient high yield version of the ester Claisen rearrangement. Preliminary communication | |
JPS5559129A (en) | Preparation of cis-7-alken-11-one compound | |
GB590951A (en) | An improved process for converting lower into higher molecular weight glycerides | |
PL112075B2 (en) | Process for preparing novel derivative of trimethylcyclopentene | |
GB2295389A (en) | Halogenated acyclic carboxylic acid intermediates | |
JPS5828263B2 (en) | 3 3-dimethyl-2-(2 2-dihalovinyl) cyclopropane carbonate ester | |
JPS6029375B2 (en) | Method for producing 2,2-dimethyl-3-(2',2',2'-trihalogenoethyl)cyclopropanecarboxylic acid halide | |
PL135154B2 (en) | Method of obtaining novel alpha,beta- unsaturated alkyl esters of javenile activity |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |