CS216676B2 - Method of making the 3,3-dimethyl-4-subst.-gamabutyrolaktons - Google Patents

Description

The invention describes a process for the production of new

3,3-dimethyl-4-subst.-y-butyrolactones used as starting materials for the preparation of intermediates for the preparation of insecticidally active compounds.

In our related Czechoslovak patent! No. 216,675 describes a novel process for the preparation of 3- (arylvinyl) -2,2-dimethylbicyclopropane-1-carboxylic acid esters by forming a cyclopropane ring by cleavage of hydrogen chloride from the corresponding chloro derivatives while cyclizing. These intermediate chloro derivatives are novel and can be prepared by a variety of processes from different starting materials.

One group of such novel starting materials is the 3,3-dimethyl-4-subst-7-butyrolactones of formula VI

in which

Ar represents a phenyl radical, optionally substituted by one or two of the same or different substituents X, selected from the group consisting of hydrogen, fluorine, chlorine or bromine, cyano, nitro, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy , methylmercapto, trifluoromethyl, methylsulfonyl, trifluoromethylsulfonyl, dimethylamino, diethylamino and optionally halogenated methylenedioxyethylenedioxy.

The present invention provides a process for the preparation of compounds of the above-mentioned general formula VI, characterized in that the compounds of the general formula VII are used

H30 CHs \ /

CH 2 = CH-C-CH 2 CO 2 R (VII) in which

R is C 1 -C 4 alkyl, reacted with compounds of formula VIII

Ar - CO - Hal (VIII),

216876 in which

Air has the meaning given above and

Hal represents a halogen atom, preferably chlorine, in the presence of a Friedel-Crafts catalyst.

If 3,3-dimethylpent-4-enoic acid methyl ester and benzoyl chloride are used as starting materials in the process according to the invention, the reaction may be described as follows:

G ^ ^co ~ ^Ci

-------->

The starting materials used in the process of the invention are defined by formulas VII and VIII.

The compounds of the general formula VII (see DOS No. 2,539,895) and VIII are known.

Examples of compounds of formula VIII include:

benzoyl chloride,

4-chlorobenzoyl chloride,

3-chlorobenzoyl chloride,

2- iChlórbeinzoylohlorid,

4-fluorobenzoyl chloride, d-bromobenzoyl chloride,

3.4- dichlorobeaizoyl chloride,

4-Methylbenzoyl chloride

4-Trifluoromethylbenzoyl chloride

3-Trifluoromethylbenzoyl chloride

3-Trifluoromethyl-4-chlorobenzoyl chloride

4-nitrobenzoyl chloride,

4-methylsulfonylbenzoyl chloride,

4-Methoxybenzoyl chloride

3.4- Dimeith oxybenzoyl chloride id.

As catalysts come essentially in the del-Crafts reaction. Particular preference is given to stannous chloride or, optionally, mixtures thereof with aluminum chloride, titanium tetrachloride, zinc chloride or ferric chloride. The use of aluminum chloride alone produces compounds of formula VI but compounds of formula V '

L.L · .:

o, H 3 C CH 3

II / IAlr — C — CHa — CiHCl — C — CHa — CO2 — R (v), in which

Ar and R are as defined above.

The Friedel-Crafts catalyst is used in an equimolar amount, less than the equimolar amount or in excess. The reaction may be carried out in a diluent or in the absence of a diluent. Suitable diluents are, for example, methylene chloride, chloroform, dichloroethane, tetrachloroethane, nitromethain or nitrobenz.

According to the invention, the above process is carried out by introducing a Friedel-Crafts catalyst, optionally in a diluent, and dropping the acid halide of the formula (VIII) dropwise with cooling. The ester of formula (VII) is then added dropwise to the mixture at a temperature of from -25 to - (-50 ° C, preferably from 0 to 25 ° C).

However, it is also possible to introduce the acid halide (VIII) together with the ester (VII), optionally in a diluent, and to add the Friedel-Crafts catalyst.

In order to accelerate the reaction, it is possible to work at an elevated temperature, for example at 25 to 150 ° C, preferably 30 to 100 ° C, after mixing the reactants. The completion of the reaction signals the disappearance of gas evolution. After acidification, the reaction mixture is worked up by conventional extraction. The crude product of formula VI can be purified by recrystallization.

The course of this reaction can be described as extremely surprising since the formation of lactone under such mild conditions is not known.

It has also been found that compounds corresponding to Formula VI, which can be described by Formula IX

in which

X ‘denotes (hydrogen, methyl, ethyl, isopropyl or tert-butyl, fluorine, chlorine or bromine atom, methoxy, ethoxy or methylmercapto group; and

Y ‘represents a hydrogen atom or has the same meaning as X‘, or

218676

X * and Y * taken together are methylenedioxy or ethylenedioxy, obtained by the formation of compounds of formula X

Y '

in which

X ‘and Y mají are as defined above, reacted with an acid chloride of formula XI

in the presence of a Priedel-Crafts catalyst and optionally in the presence of a diluent.

Furthermore, a process for the preparation of a compound of formula XI has been found, characterized in that the compound of formula XII is used

is reacted with a chlorinating agent. When toluene and 3,3-dimethyl-6-chlorocarbonylmethyl-γ-butyrolactone are used as starting materials for the preparation of the compounds of formula XI, the reaction scheme may be described as follows:

Compounds of formula (X) are known and exemplified by benzene, fluorobenzene, bromobenzene, bromobenzene, toluene, ethylbenzene, diphenyl ether, xylene, o-dichlorobenzene. Suitable catalysts are, in principle, all customary Fridel-Crafts catalysts, such as aluminum chloride, tin tetrachloride, titanium tetrachloride, hydrogen fluoride, boron trifluoride, iron (III) chloride, polyphosphoric acid, perfluoroalkanoic acids (optionally in polymeric form), and optionally mixtures thereof .

The above process is preferably carried out in the presence of a diluent. Suitable diluents are methylene chloride, chloroform, dichloroethane, carbon tetrachloride, nitrobenzene and nitromethane. The preferred diluent is methylene chloride.

This reaction according to the invention can be described as extremely surprising since it was to be expected that the lactone ring would react as follows:

Furthermore, cyclization to tetralone was to be expected. The ring opening of the five-membered lactones by aromatics in the sense of the Frledel-Crafts reaction as described above is known and is carried out under very mild conditions (see Houben-Weyl, Volume VI, 2, page 812 'et seq.).

The fact that such a reaction with aromatic lactone of general formula X ^ does not occur, it is especially surprising ^one also because CraftIsův Friedel-catalyst is also necessary to use at least an equimolar amount, and more preferably in the (excess.

The reaction is preferably carried out as follows:

The Frietel-Crafts catalyst is added to the acid chloride of formula XI in the diluent at a temperature between -10 and -5 ° C, followed by dropwise addition of the flavor, optionally dissolved in the diluent. In the case of the use of highly efficient Friodeil-Crafts catalysts, this dropwise addition is carried out at this temperature of from -10 ° C to -5 ° C (for example in the case of aluminum chloride or tin tetrachloride using less efficient Friedel-Crafts catalysts) for example, zinc chloride, iron (III) chloride, titanium tetrachloride or perfluoroalkanesulfotaic acid], the aroma is added dropwise at room temperature, and the reaction mixture is then stirred at room temperature, optionally using a dense catalyst.

In the case of using less reactive aromatics, such as chlorobenzene, it is not recommended to accelerate the reaction by increasing the temperature, but rather to prolong the reaction time to avoid opening the lactone ring in the above sense.

The reaction mixture is worked up in the usual manner. The resulting lactones can be purified by recrystallization.

The preparation of a compound of formula XI is possible ^. described by the following reaction scheme:

ho ₃ c ~ ch, -2 10 I O.

CH,

Chk

CH,

CKO-CH-f-CH v

O

The acid of the formula XII used as starting material is known (see J. Org. Chem., 38, p. 4148 and J. Chem. Soc. 79, 763), but is not a known acid chloride of the formula XI. The smooth conversion of the acid to the acid chloride is surprising, since under these conditions the lactone ring is usually opened.

The reaction is carried out under conditions generally used to prepare acid chlorides from the corresponding acids. Preferred chlorinating agents are thionyl chloride and phosgene. Care should also be taken to use the shortest reaction time in order to avoid the above-mentioned side reactions. The reaction mixture is worked up in the usual manner. The acid chloride may be purified by distillation or may be used in the crude state for the reaction described above.

The invention is illustrated by the following non-limiting examples.

Example 1

To a mixture of 87.5 g (0.5 moles of p-chlorobenzoyl chloride and 1) 30.3 g (0.5 moles) of tin (II) chloride is added dropwise at 20 ° C with 71 g (0.5 moles of methyl ester 3). The mixture was taken up in methylene chloride, filtered, and the filtrate was shaken with dilute hydrochloric acid, after drying and evaporation of the solvent in vacuo, 111.1 g (ca. 83% of the crude product is recrystallized from 120 ml of ethanol to give 3,3-dimethyl-4- (4'-chlorophenacyl) -y-butyrolactone, m.p. 76-80 ° C.

1 H NMR spectrum (CDCl 3, SS values):

1.15 (sihglet, 3 Hj,

1.25 (singlet, 3H);

2.45 (multiplet, 2HJ,

2.8 to 3.65 (8 1 2 Hj,

4.9 (double doublet, 1 H),

7.3 to 8.05 '(multiplet, 4H).

Example 2

To a solution of 17.5 g (0.1 mol) of p-chlorobenzoyl chloride and 14.2 g (0.1 mol) of 3,3'-dimethyl-4-pentemic acid methyl ester in 100 ml of dichloromethane is added dropwise at 0 ° C. g (0.1 mol) of tin (II) chloride and the resulting mixture was heated to reflux for 8 hours until the gas evolution had subsided. After treatment with dilute hydrochloric acid, 20.9 g of the corresponding lactone are obtained. of the product prepared in Example 1.

Example 1 a d 3i

To a solution of benzoyl chloride (14.1 g, 0.1 mol) and 3,3-dimethyl-4-pentenoic acid methyl ester (14.2 g, 0.1 mol) in methylene chloride (100 ml) was added dropwise 26 g (0.1 ml) at room temperature. mol) of tin (II) chloride and the resulting mixture was heated to reflux for 8 hours until gas evolution ceased. Acidification with dilute hydrochloric acid gave 21.6 g of 3,3-dimime76

216 thyl-4-phenacyl-1-butyrolactone, m.p. 86-88 ° C.

Example 4

In analogy to Example 3, starting from 4-nitrobenzoyl chloride and methyl ester

3,3-dimethyl-4-peintenoic acid gives 3,3-dimethyl-4- (4‘-nitrophenyl) -y-butyrolactone, m.p. 107-110 ° C.

Example 5

Analogously to Example 3, 3,3H-dimethyl-4- (4‘-chloro-3‘-nitrophenyl) -β-butyrolactoin is obtained, m.p. 134-136 ° C.

Example 6

17.2 g of 3,3-dimethyl-4-carboxymethyl-t-butyrolactone are mixed with 60 ml of thionyl chloride, the mixture is heated at 80 ° C for 1 hour, after which excess thionyl chloride is distilled off under atmospheric pressure and vacuum pumps. The residue consists of 3,3-dimethyl-4-chlorocarbonylmethyl-γ-butyrolactone and can be used directly for the next reaction. However, the product can also be further purified by distillation. Boiling point 130-140 ° C / 30 Pa.

Example 7

A solution of 59 g of 3,3-dimethyl-4-chlorocarbonylmethyl-t-butyrolactone in 150 methylene chloride is added dropwise at 0-5 ° C to 80 g of aluminum chloride in 300 ml of methyl chloride, and then dropwise added thereto, also at 0-5 ° C, 39.2 g of chlorobenzene in 50 ml of methylene chloride. The reaction mixture was allowed to warm to room temperature, stirred at room temperature for 7 hours, then poured into ice water. The organic phase was separated, washed until neutral, dried and the solvent was distilled off. 76 g of crude 3,3-dimethyl-444 (4-chlorophenacyl) -y-butyrolactone are obtained, which, after recrystallization from ethanol, melts at 78 to 8.0 ° C.

Examples 8 and 9

In an analogous manner to Example 7:

3.3-dimethyl-4- (4‘-methylphenacyl) -y-butyrolactone, m.p. 96 ° C;

3.3-Dimethyl-4-phenacyl-1-butyrolactone, m.p. 86-88 ° C.

Claims (1)

A process for the preparation of 3,3-dimethyl-4-substituted-γ-butyirolactones of the general formula (VI) in which: Ar represents a phenyl radical optionally substituted by one or two of the same or different substituents X, selected from the group consisting of hydrogen, fluorine, chlorine or bromine, cyano, nitro, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy , methylmercapto, trifluoromethyl, methylsulfonyl, trifluoromethylsulfonyl, dimethylamino, diethylamino, and optionally halogenated methylenedioxy or ethylenedioxy, characterized in that the compounds of formula VII HsC CH3 \ / CH 2 = CH - C - CH 2 CO 2 R (VII 1 in which R is C 1 -C 4 alkyl, reacted with compounds of formula VIII Ar — CO — Hal, (VIII) wherein Ar is as defined above and Hal represents a halogen atom, preferably chlorine, in the presence of a Friedel-Crafts catalyst.