HU176610B - Process for producing cyclobutanones - Google Patents

Abstract

Cyclobutanones of the formula I or cyclobutenones of the formula II are prepared by reacting haloacyl halides of the formula III with an alkene or alkyne in an inert aprotic polar solvent above 5 DEG C in the presence of zinc or tin. Cyclopropanoic acids of the formula V can be prepared from the compounds of the formula I by heating them in water with a base. If the starting material used is a cyclobutenone of the formula II, the double bond is first hydrogenated. <IMAGE>

Description

The present invention relates to a process for the preparation of cyclobutanones of the formula I and cyclobutenones of the formula II wherein A is a halogen atom, a hydrogen atom or a substituted or unsubstituted hydrocarbon group.

No. 1,194,604. The alpha-halo-cyclobutanones listed in British Patent No. 4,600,198 are prepared by the (2 + 2) -cycloaddition reaction of halogens and olefins. This cycloaddition reaction is carried out as described in J. Am. Chem. Soc. 87, 5257 (1965) and Tetrahedron Letters No. 1,135 (1966) by dehydrochlorination of dichloroacetyl chloride with triethylamine to form dichloroethene in the reaction mixture itself. which reacts with the olefin present to form α-chlorocyclobutanone. However, in this process, α-chlorocyclobutanone can be produced in low yields, which is due to the fact that α-chlorocyclobutanone reacts with the triethylamine present to form a quaternary ammonium chloride compound.

J. Org. Chem., 31, 626 (1966), in the first step of the cycloaddition reaction, α-haloacetyl bromide is dehalogenated in an inert solvent with r ™ powder. However, this article describes only the trio of trichloroacetyl bromide and zinc leading to dichloro ketene. The dichloroethene is isolated in the form of a solution of a hydrocarbon type solvent, such as hexane or octane, and this solution is used in the next cycloaddition step. According to the previously cited British Patent, interfering by-products are separated from a solution of halogen ketene before carrying out the cycloaddition reaction. J. Org. Chem. 31, G26 (1966) does not disclose any information on the separation of dihaloacetyl halides and monohalo ketones formed by the reaction of zinc, suggesting that these compounds, due to their lability and their ability to polymerize at very low temperatures, do not can be separated. This assumption is largely supported by Synthesis 415-422. (August 1971). According to the latest publication, when monochloroacetyl chloride is dehydrohalogenated with triethylamine in the presence of clathlate to produce monochloro ketene, the product is cis and tert-4-trichloromethyl-2-oxetanone, and when monochloro ketene is dichloroacetyl chloride in the presence of dichloroacetic acid a, p-dichloro vinyl ester. The data in this article thus prove that the dehydrohalogenation method is not equivalent to the dehalogenation method.

In our studies, in full agreement with the foregoing, it was found that monochloro ketene is not truly isolable, i.e., the reaction mixture formed between dichloroacetyl chloride and zinc in an ethereal medium does not contain any monochloro ketene, and Treatment with 3-dimethyl-2-butene affords no cyclobutanone. Surprisingly, however, it has been found that, when tnonochlorochlorene is formed in the reaction mixture itself, the monochlorochlorene reacts with the olefin present in the (2 + 2) -cycloaddition.

The present invention therefore relates to a process for the preparation of cyclobutanones of formula I and cyclobutenones of formula II. In the formulas, Hal represents no more than 35 halogen atoms, R ¹ , R ² , R ³ and R ⁴ may be the same or different and represents hydrogen, (C 1 -C 3) alkyl optionally substituted by alkoxy, benzyloxy or alkoxycarbonyl; C2-C6 alkenyl group, or alkoxy (Cj-Cg) carbonyl group, or R ¹ and R ^3, respectively. R ² and R ⁴ together form a C ₂ -C ₆ alkylidene group, or R ¹ and R ² , respectively. R ³ and R ^{4 taken} together with the carbon atoms to which they are attached form a carbocyclic ring.

According to the invention there is provided a 2,2-dihaloacetylhalide of formula III wherein Hal is as defined above, with 0.5 to 10 mol of an unsaturated compound of formula IV or V per mole thereof, wherein R ¹ , R ² , R ³ and R ⁴ are as defined above, are reacted in an inert aprotic polar solvent at a temperature between 25 ° C and 60 ° C in the presence of zinc and / or tin and optionally an inorganic halide.

The ethylenically unsaturated compounds (IV) and (V) or alkynes (hereinafter referred to as "unsaturated compounds") are hereinafter referred to as "unsaturated compounds".

The reaction according to the invention is preferably carried out in the presence of zinc, in which case the desired end product is generally obtained in a higher yield than when tin metal is used.

In the compounds of formula III, Hal may be a fluorine atom, a chlorine atom or a bromine atom. In these compounds, the two Hal substituents may be the same or different.

Depending on the regiospecificity of the cycloaddition reaction, two different cyclobutanone derivatives can be formed from ethylenically unsaturated compounds having a double bond asymmetric position and two different cyclobutanone derivatives from alkynes having a triple bond asymmetric position. The term "regiospecificity" is described in Houben-Weyl, "Methoden dér Organischen Chemie". Technical Book (4th Edition 1971) IV / 4. 143 of this volume.

The unsaturated compounds of formulas IV and V used in the reaction of the present invention may be hydrocarbons which may be optionally substituted with one or more non-hydrocarbon substituents such as alkoxy, benzyloxy or ethoxycarbonyl. Examples of these substituted compounds are isopropyl (3-methyl-2-butenyl) ether, benzyl (3-methyl-2-butenyl) ether, 2,3,5-trimethyl-2,4-hexadieno-carboxylic acid. ethyl ester and 6-methyl-5-hepten-2-one. Typically, substituted unsaturated compounds can be obtained in relatively low yields (up to 20% relative to acyl halide). When unsubstituted unsaturated compounds are used as reagents, the ring compounds are generally obtained in higher yields. Particularly preferred reagents are alkenes; these compounds generally give the corresponding cyclobutanone derivatives in a yield of 50-75%. Alkene reagents can be straight or branched chain, cis or trans configuration. Examples of these compounds include: food, propene, 1-butene, cis-2-butene, trans-2-bulene, isobutene, 2-pentene, 2-hexene,

3-hexene, 2-heptene, 3 '-sthenium, 2-methyl-2-butene, 3-methyl-2-pentene, 3-methyl-3-hexene, 2,4-dimethyl-3-hexene, 2,3 4-tri-methyl-2-pentene, 1-octene, 2-octene, 3-octene, 1-nonene, 1-decene, 1-dodecene, 1-tetradecene, 1-pcntadecene, 1-hexadecene, 1-eicosene, 1-docosene, methylene cyclobutane, methylene cyclopentane, methylene cyclohexane, the corresponding isopropylidene cycloalkanes and 3-phenyl-1-propene. Particularly good results are obtained when the unsaturated compound is 2,3-dimethyl-2-butene or 2-methyl-2-pentene.

We have found that 2,5-dimethyl-2,4-hexadiene reacts stereospecifically with monochloro ketene and trans-2-chloro-4,4-dimethyl-3- (2-methyl-1-propenyl) cyclobutanone. and forms trans-2-chloro-3,3-dimethyl-4- (2-methyl-1-propenyl) cyclobutanone. These compounds are formed with very good selectivity. The term "stereospecificity" is described in Houben-Weyl, "Methoden dér Organischen Chemie". Technical Book (4th Edition 1971) IV / 4. 143 of this volume. The importance of this stereospecific reaction will be discussed below.

Allenically unsaturated compounds lead to the formation of alkylidene cyclobutanones. Exemplary unsaturated compounds with an allene structure include allene, 1,2-butadiene, 2,3-pentadiene, 2,4-dimethyl-2,3-pentadiene, 3,5-diethyl-3,4-heptadiene, methyl-1,2-hexadiene, 2,8-dimethyl-4,5-nonadiene, 3-nonyl-1,2-dodecadiene, 1,2-pentadecadiene, allenylbenzene and tetraphenylallene.

Starting from ethylenically unsaturated nonocyclic compounds, the product yields bicyclic compounds containing a cyclobutanone ring. For example, the compounds used as starting materials may have a 5-, 6-, 7-, or 8-membered ring and may be optionally substituted with one or more substituents. The ring may also contain a carbon-carbon double bond. Exemplary ring-linked substituents include halogen and alkyl; when the ring contains a single carbon-carbon double bond, the halogen substituent cannot be attached to the carbon atoms bonded to each other by the double bond. Examples of unsaturated ring compounds are cyclohexene, cycloheptene, cyclooctene, 1,2-dimethylcyclopentene, 2-methyl-cyclohexene, 3-methylcyclohexene, 2,5-dimethylfuran, indene, 3-dimethylindene and 2H-3,4-dihydropyran.

Examples of alkyne-type reagents include propine, 1-butine, 2-butine, 1-pentine, 2-pentine, 1-hexin, 1-heptin, 1-dodecin, 2-methyl-1-pentine, phenylethine and 3-phenyl-1 -Propin can be used.

Ethylene-unsaturated compounds or alkynes containing only one double or triple bond may not have unsaturated substituents (e.g., halogens, carboxylic or esterified carboxyl groups), as the unsaturated compounds containing the deactivating substituent can be obtained only in very small amounts. , or these compounds do not form ring compounds at all.

The reaction of the invention is carried out in an inert, polar, aprotic solvent to minimize the side reactions. Especially preferred solvents have been ethers (especially dialkyl ethers) and alkanones (primarily ketones having up to one quaternary carbon atom attached to the carbonyl group).

The reaction may also be carried out in the presence of inert aprotic polar solvents such as diethyl ether and methyl tert-butyl ketone. Small amounts of other inert solvents such as toluene or xylene may also be added to the solvent.

Examples of suitable dialkyl ethers include diethyl ether, di-n-propyl ether, n-propyl isopropyl ether, diisopropyl ether and di-n-butyl ether. Particularly preferred solvents have been diethyl ether; the cyclic compounds are generally formed in diethyl ether in the best yield.

The concentration of the acid halide may be arbitrary, but preferably no more than 1 mol of acid halide per liter of dialkyl ether is used, since the yield of the cyclic compound decreases as the concentration of the acid halide increases. The acid halide is preferably used in a concentration of about 0.1-0.6 mol / liter.

The molar ratio of unsaturated compound to acid halide can vary within wide limits. Increasing the molar ratio of unsaturated compound to acid halide increases the yield of the cyclic compound, for example when the molar ratio of unsaturated compound to acid halide is 4: 1, the yield of the cyclic compound is greater than 90%. In view of the above, the molar ratio of unsaturated compound to acid halide is preferably adjusted to 2-20: 1, preferably 2-10: 1.

In addition, ketones (especially alkanones) have been found to be extremely advantageous solvents, since they can also produce ring compounds at high acid halide concentrations well above 1 mol / liter. Particularly preferred in this respect are ketones having at least two branches in the carbon chain in which up to one quaternary carbon atom is attached to the carbonyl group. The most preferred ketone type solvent is diisobutyl ketone and methyl tert-butyl ketone. When ketone-type solvents are used, some of the acid halide is involved in the formation of the ring compounds, the other part of the acid halide forms polymers, and the acid halide residue remains unchanged. When dialkyl ethers are used as solvents, part of the acid halide is involved in the formation of the ring compounds and the remainder forms high molecular weight materials, i.e., unlike in ketone-type solvents, no unreacted acid halide remains. Some ketone-type solvents produce relatively large amounts of polymeric material; these polymers may be formed from the acid halide and / or the unsaturated compound. If diisobutyl ketone or methyl tert-butyl ketone is used as a solvent, polymer formation can be greatly reduced.

In the case of ketone-type solvents, the effect of increasing the concentration of the acid halide is to reduce the yield of the cyclic compound, but the yield of the cyclic compound is still very good up to the acid halide concentration limit of 15 mol / l (preferably 10 mol / l). In view of the above, when using ketone-type solvents, the concentration of the acid halide is generally adjusted to between 1 and 15 mol / l, preferably between 3 and 10 mol / l.

When using ketone-type solvents, the yield of the cyclic compound, irrespective of the acid halide concentration, drastically decreases when the concentration of the unsaturated compound is greater than 15 mol / liter, in which case the zinc and tin halides formed become increasingly insoluble. in the surrounding liquid phase. At concentrations of more than 40 mol / l unsaturated compounds, the zinc and tin halides are practically completely insoluble, and consequently the ring compounds can be formed at all or at very great difficulty.

When ketones are used as the solvent, the selectivity for the formation of the cyclic compound is practically unchanged at a molar ratio of unsaturated compound: acid halide to greater than 0.5. Accordingly, the molar ratio of unsaturated compound to acid halide is suitably adjusted to 0.5 to 10, preferably 1 to 2.

Increasing the molar ratio of zinc (or tin): acid halide increases the selectivity of the formation of the cyclic compound; therefore, this molar ratio is preferably set to between 1 and 10, preferably between 1 and 5. Maintaining a molar ratio of zinc (or tin): acid halide to 3.5 to 4.5 can provide very good selectivity. The selectivity of the formation of the ring compounds is also favorably influenced by the homogeneous distribution of the zinc or tin in the liquid phase. When zinc powders with a relatively large specific surface area are used, the selectivity of the reaction is relatively low, but the selectivity is significantly increased when zinc particles with a diameter (or largest edge length) greater than about 0.1 mm are used. The reaction is extremely selective when using zinc particles (0.5 to 5 mm in diameter (or longest edge)).

If the reaction according to the invention is carried out at a temperature lower than 5 ° C, no appreciable cycloaddition occurs. Raising the temperature above 5 ° C increases the yield of the cyclic compound as the temperature increases, generally reaching a maximum in the temperature range of 25 ° C to 60 ° C, then decreasing with further temperature increase. In view of the above, the process according to the invention is preferably carried out at 15-100 ° C, preferably 25-60 ° C. The best results are generally obtained when the reaction is carried out at 35-50 ° C.

The reagents may be contacted as desired. For example, the solution of the unsaturated compound may be suspended in zinc or tin, and the acid halide added in one portion or, preferably, in smaller portions while stirring into the suspension. For example, the addition of the acid halide can take up to 5 hours, but preferably the acid halide is added in a much shorter time (e.g. 0.25-0.75 hours). The addition! excessively prolonged time generally results in a reduction in the yield of the cyclic compound. The stepwise addition method has proved to be particularly advantageous when 2,2-dihaloacyl halides or 2,2,2-trihaloacyl halides are used as acid halides, since these compounds form readily polymerizable mono- or dihalo ketenes in the reaction mixture, such as by stepwise addition. the cycloaddition reaction can be used to suppress polymer formation. In some cases, the cycloaddition starts after the bulk or total amount of the acid halide has been added; this sudden onset reaction is usually accompanied by heat generation and significant polymerization. The cycloaddition reaction generally starts immediately and is complete without undue accumulation of the acid halide by first adding up to 25% (usually 2 to 10%) of the total acid halide to be used in the suspension of zinc or tin in a suitable solvent, the unsaturated compound is added to the suspension while stirring, and the acid halide residue is added to the system. The selectivity of the reaction can also be enhanced by first preparing a solution of the unsaturated compound and the acid halide and adding to this solution portions of the zinc or tin to be used, or simultaneously adding the acid halide and the unsaturated solution to a suspension of zinc or tin in a suitable solvent. compound. This latter method is particularly advantageous.

Generally, the selectivity of the cyclization reaction can be enhanced by carrying out the reaction in the presence of inorganic halides. The inorganic halides are generally added in catalytic amounts (preferably 0.1 to 10 mol% per mole of 2-haloacyl halide). As inorganic halides, mercury (II) iodide, sodium chloride or, preferably, potassium iodide or ammonium chloride are particularly preferred.

The ring compounds of the present invention may be isolated by distillation in pure form. Before isolation of the final products, the solid (zinc or tin) is filtered off from the reaction mixture and the filtrate is washed with water to remove the zinc or tin halides. When the process of the present invention is used to prepare 2-halocyclobutanones, it is also possible to heat the system obtained after the removal of the zinc or tin and the zinc or tin halides in the presence of water and a base. In this case, the 2-halocyclobutanones formed during the reaction form cyclopropanecarboxylic acids (V) which form a salt with the base present. The ring narrowing reaction often occurs in 90-100% yield. The cyclopropanecarboxylic acid salts thus obtained are valuable starting materials for the preparation of known cyclopropanecarboxylic acid esters with potent insecticidal activity and low toxicity.

The invention thus also relates to a process for the preparation of cyclopropanecarboxylic acids of formula (V). These compounds are prepared according to the invention by reacting a 2-haloacid halide of formula (III) in an inert polar aprotic solvent in the presence of zinc and / or tin at a temperature above 5 ° C with an ethylenically unsaturated compound or an alkyne. , the compounds of formula (I) or (II) thus obtained are heated in the presence of water and a base, and the resulting cyclopropanecarboxylic acid salt is liberated.

For example, by cyclizing 2,5-dimethyl-2,4-hexadiene and the monochloro-ketene formed in the reaction according to the invention, 2-chloro-4,4-dimethyl-3- (2'-methyl-1'-propenyl) - cyclobutanone and 2-chloro-3,3-dimethyl-4- (2'-methyl-1'-propenyl) cyclobutanone can be prepared. When these two compounds are subjected to the ring reduction reaction described above, the cis and trans-chrysanthemum monocarboxylic acid salts (2,2-dimethyl-3-isobutenylcyclopropanecarboxylic acid salts) are obtained from which the acid can be readily liberated. The resulting mixture of isomers consists mainly (96%) of the trans isomer, which is highly advantageous in practice since it is known that trans-chrysanthemum monocarboxylic acid has a much stronger insecticidal activity than its cis compound.

When 2,4-dimethyl-2,3-pentadiene is reacted directly with the monochloro ketene formed in the reaction mixture, the product is 2-chloro-3,3-dimethyl-4-isopropylidene-cyclobutanone and 2-chloro-4,4-dimethyl-3- isopropylidene cyclobutanone is obtained. From these two compounds, 2,2-dimethyl-3-isopropylidene cyclopropanecarboxylic acid salts can be formed by the ring reduction procedure described above.

The aqueous solution of the cyclopropanecarboxylic acid salts can be precipitated by treatment with an aqueous solution of a strong mineral acid. If a relatively small amount of polymer is formed in the process leading to the formation of cyclobutanones according to the invention, the resulting reaction mixture can be isolated in the form of light-colored products with good purity by the cyclization process described above and subsequent acidification. If it is desired to prepare cyclopropanecarboxylic acids from the cyclobutanones in the next step, the 2-halocyclobutanones are preferably formed in the form of methyl tert-butyl ketone or diisobutyl ketone.

The cyclobutenone compounds of the present invention can be converted to the corresponding cyclobutanones by hydrogenation. The cyclobutasnones thus obtained can be used as described above.

The following examples illustrate the invention without limiting it. The experiments described in the Examples are performed in a three-necked round-bottomed flask equipped with a paddle stirrer, a metering funnel, a thermometer, a nitrogen inlet tube and a calcium chloride tube with a water-cooled reflux condenser. The reactions are carried out under a nitrogen atmosphere.

Unless otherwise stated, see sections 1-5. The experiments described in Example 1A are performed as follows:

The flask was charged with 2,3-dimethyl-2-butene, granulated zinc (maximum edge length: 1 mm) and 1 liter of dried diethyl ether. The suspension is refluxed, dichloroacetyl chloride is added dropwise to the suspension via a funnel over 4 hours, and the resulting reaction mixture is refluxed for a further 8 hours. The mixing serves to ensure a homogeneous distribution of zinc. During the reaction, the total amount of dichloroacetyl chloride added is converted; part of this compound forms 2-chloro-3,3,4,4-tetramethylcyclobutanone (hereinafter "Compound A") and the remainder forms a high molecular weight polymeric material. The total amount of reacted 2,3-dimethyl-2-butene is converted to Compound A. The yield of Compound A is given relative to dichloroacetyl chloride. 2,3-Dimethyl-2-butene is referred to as DMB in the examples, and dichloroacetyl chloride is referred to as DCAC in the examples. The concentrations of these two compounds are expressed in mol / liter of solvent.

Some of the compounds of formula (I), (II) and (V) produced by the process of the present invention are novel.

Example 1

Example 4

Five experiments were performed at the concentrations and molar ratios listed in Table 1. The results of the experiments are also presented in Table 1.

Table 1

Experiment number Concentration, mol / l molar ratio Yield of compound A % DMB DCAC DMB: DCAC Zn DCAC First 0.24 0.77 0.31 9.2 22 Second 0.24 0.32 0.75 7.4 57 Third 0.24 0.18 1.33 10.0 52 4th 0.49 0.10 5.00 2.0 > 90 5th 1.96 0.10 20.00 2.0 > 90

Example 2

Under the conditions described above, five experiments were performed. In each experiment, the DMB and DCAC concentrations were adjusted to 0.24 mol / L and the 25 Zn: DCAC molar ratio was changed as shown in Table 2. The results are reported in Table 2.

Table 2 Experiment number Zn: DCAC molar ratio Yield of Compound A,% First 1.0 17 35 Second 1.1 27 Third 1.5 58 4th 2.0 62 5th 4.0 64 40

Example 3

Under five conditions, five experiments were performed. In each experiment, equimolar amounts of DMB and DCAC were used and the Zn: DCAC molar ratio was set to 2. The concentration of DCAC is reported in Table 3. In Experiments 4 and 5, DCAC was added at 50 and 16 hours, respectively. The results are shown in Table 3.

Table 3 Experiment number The concentration of DCAC is morbid Yield of Compound A,% 1. * 0.24 62 Second 0.42 41 Third 0.84 38 4th 0.42 38 5 ... 0.84 37

* Azoose in Example 2 4. s. experiment. 65

Three experiments were performed under the conditions described above, but DMB was added to the ether suspension of the zinc granulate in admixture with DCAC. The experiments set the Zn: DCAC molar ratio to 2. The concentration of DCAC, the molar ratio DMB: DCAC and the results obtained are reported in Table 4.

Table 4

Experiment number DCAC concentration, Moray DMB: DCAC molar ratio Yield of Compound A,% First 0.42 1.0 53 Second 0.42 1.1 52 Third 0.84 1.0 42

Example 4, Nos. 1 and 3. 2 and 3 of Example 3. The same DCAC concentration as used in the experiment was used. In the same manner as in Example 4, compound A was obtained in higher yield.

Example 5

The experiment

In this experiment, the DMB: DCAC molar ratio was set to 0.75 and the Zn: DCAC molar ratio was set to 7.4. The flask was charged with 400 mL of diethyl ether; the concentration of DCAC is adjusted to 0.16 M / 100 mL of solvent. After addition of DCAC, the reaction mixture was stirred for an additional 2 hours; otherwise, the procedure described above is followed. Compound A was obtained in 57% yield.

Experiment B (comparative experiment):

A suspension of 100 ml of diethyl ether, 0.012 mol of DCAC and 0.036 mol of granulated zinc (maximum edge length: 1 mm) was heated to reflux with vigorous stirring. After stirring for 16 hours, DCAC was fully reactive. The zinc is removed by decantation and 0.012 mole of DMB is added to the resulting liquid phase. The mixture was stirred vigorously for 3 hours at 34 ° C. After this time, no cyclobutanone is detected in the reaction mixture.

6-10. The experiments described in Example 1 are performed as follows:

In a three-necked round bottom flask, 10 mmol DCAC, 0.6 mmol potassium iodide, 96 mmol zinc shavings (maximum edge length 0.841 mm) and 20 mL solvent were weighed. The resulting reaction mixture had an initial temperature of 38 ° C. The mixture was heated to 43 ° C, stirred for 1 hour and then treated with DMB (48 mmol, 5.7 mL) in one portion. Then, 52 mmol of DCAC was added over 35 minutes and the resulting mixture was stirred for an additional 1.25 hours (agitator speed: 2000 rpm).

Example 6

Six experiments were performed using the solvents listed in Table 5. Table 5 also shows the yield of Compound A with respect to DCAC.

Table 7

The polymer formed in Experiments 1 and 2 is formed from DCAC and DMB. In Experiments 3, 4 and 5, the amount of DMB converted is entirely compound A, i.e., DMB is not involved in polymer formation. In Experiment 6, Gink chloride formed on the surface of the zinc particles does not dissolve. The greater the amount of polymer formed, the deeper the color of the reaction mixture.

Table 5

Accompany? let number Solvent Yield % Quantity of polymer Color of reaction mixture First acetone 21 many dark brown Second butanone 30 medium light brown Third methyl isobutyl ketone 38 medium light brown 4th 5th diizpbutil ketone methyl tert-butyl 54 yes keyés yellow ketone 53 few yellow 6th di-tert-butyl ketone <0.8 many dark brown

Example 7

Four experiments were performed under the conditions described above. Diisobutyl ketone is used as the solvent. The DMB and DCAC concentrations, the DMB: DCAC molar ratio, and the yield of Compound A are reported in Table 6.

Table 6

Experiment «zpná Concentration, mol / l DMB: DCAC molar ratio Chemical product A % DMB DCAC 1. * 2.4 0.78 54 Second .4,8 3.1 1.55 58 Third 12.0 3.1 3.87 56 4th 46.5 3.1 3W SHE

* Same as Example 1 in Example 9. experiment.

Very small amounts of polymer are formed during the reactions, and the total amount of DMB that is converted can be "A". The zinc chloride formed in Experiment 3 is only partially soluble, while the zinc chloride formed in Experiment 4 is completely insoluble.

Example 8

Three experiments were performed as previously described. Disobutyl ketone was used as solvent and starting from 62 mM DCAC. The molar ratio of DCAC: Zn is reported in Table 7, where results are reported. The total amount of converted DMB forms compound A '.

Experiment number Zn: DCAC molar gold Month number of compound A,% * First 1.10 51 Second 1.55 70 Third 3.90 75

Example 9

Three experiments were performed as previously described. Diisobutyl ketone was used as solvent and the DMB: DCAC molar ratio was adjusted to 0.78. The DMB and DCAC concentrations and the yield of Compound A are shown in Table 8.

Table 8

Experiment number Concentration, mol / l Yield of Compound A,% ΡΜΒ TCAC 1. * 2.4 3.1 54 Second 4.8 6.2 & Third 9.6 12.3 37

* Same as Example 1 in Example 7. experiment.

Example 10

Three experiments were performed on diisobutyl ketone medium. The reaction temperature and yield of Compound A are shown in Table 9.

Table 9

Experiment number Temperature, ° C Yield of Compound A,% Quantity of polymer Color of reaction mixture First 24 36 few yellow Second 43 54 few yellow

Example 11

140 mmol of zinc shavings (in Example 6 the same manner as in material size), 6 mM ammonium chloride and 0.6 mmol of diisobutyl ketone káüumjodid 20 mL, 38 ^C? to the suspension was added 10.3 mmol DCAC with stirring. After 3 minutes, the solution turns yellow and the temperature of the reaction mixture rises. After 10 minutes at 40-45 ° C, 2-methyl-2-pentene (96 mmol) was added in one portion. Then, DCAC (51.7 mmol) was added over 30 minutes. The reaction mixture was stirred at 40-45 ° C for 1.25 hours.

The resulting orange liquid phase was separated in a separatory funnel. the excess zinc is washed three times with acetone and the washings are combined with the separated liquid phase. The resulting tip was washed with 200 mL of water and a few drops of concentrated aqueous hydrochloric acid was added to dissolve the precipitate which formed.

To the acidic solution containing 2-chloro-3-ethyl-4,4-dimethylcyclobutanone and 2-chloro-4-ethyl-3,3-dimethylcyclobutanone (both new products) was added 110 ml of a 1M aqueous sodium hydroxide solution. and the mixture was stirred for 0.75 hours at 22 ° C. The aqueous phase is then separated and acidified with 7.5 ml of concentrated aqueous hydrochloric acid. The oily precipitate was extracted with diethyl ether. The extract was dried over anhydrous magnesium sulfate and the ether evaporated. The residue obtained was 3.8 g of a viscous oil containing 84% by weight of 2,2-dimethyl-3-ethylcyclopropanecarboxylic acid (new compound). Yield: 42% DCAC. The new compound is formed with greater than 50% selectivity and contains more than 60% trans isomer.

Example 12

To a suspension of 240 mmol of zinc shavings (material of the same size as in Example 6), 6 mmol of ammonium chloride and 0.6 mmol of potassium iodide in 40 ml of diisobutyl ketone was added 10.3 mmol of DCAC. it turns yellow and the temperature of the reaction mixture rises. After 8 minutes at 40-45 ° C, 96 mmol of 2.5 * dimethyl-2,4-hexadiene was added in one portion. DCAC (51.7 mmol) was then added over 30 minutes. After the addition, the mixture was stirred at 40-45 ° C for 1 hour.

The resulting orange liquid phase was separated in a separatory funnel, the excess zinc washed three times with acetone, and the washings were combined with the liquid phase. The mixture was washed with water (175 mL) and then to the organic phase containing 2-chloro-4,4-dimethyl-3- (2-methyl-1-propenyl) cyclobutanone and 2-chloro-3,3-dimethyl-4- ( Contains 2-methyl-1-propenyl) -cyclobutanone (new compounds), 110 ml of 1 M aqueous sodium hydroxide solution are added. After stirring for 0.75 hours at 22 ° C, the aqueous layer was separated and acidified with 7.5 ml of concentrated aqueous hydrochloric acid. The oily precipitate was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate and the chloroform was evaporated. The residue obtained was 3.5 g of a viscous oil containing 70% by weight (37% by weight of DCAC) of chrysanthemum monocarboxylic acid. The product obtained contains about 96% of the trans isomer.

Example 13

To a suspension of 240 mmol of zinc shavings (material of the same size as in Example 6), 6 mmol of ammonium chloride and 0.6 mmol of potassium iodide in 20 ml of diisobutyl ketone at 40 ° C was added 10.3 mmol of DCAC. After 3 minutes at 40-45 ° C, isopropyl (3-methyl-2-butenyl) ether (48 mmol) was added in one portion. Then, DCAC (51.7 mmol) was added over 20 minutes and the resulting mixture was stirred at 40-45 ° C for 0.25 hours.

The resulting yellow liquid phase was separated in a separatory funnel, the excess zinc was washed with acetone and the washings were combined with the slurry.

The mixture was washed with water (175 mL) and then to the organic phase containing 2-chloro-4-isopropoxymethyl-3,3-dimethylcyclobutanone and 2-chloro-3-isopropoxymethyl-4,4-dimethylcyclobutanone (new compounds), 110 ml of 1 M aqueous sodium hydroxide solution are added. After stirring for 0.75 hours at 22 ° C, the aqueous layer was separated and acidified with 7.5 ml of concentrated aqueous hydrochloric acid. The oily precipitate was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate and the chloroform was evaporated. The residue was 2.65 g of a viscous oil containing 64% by weight of 2,2-dimethyl-3-isopropoxymethylcyclopropanecarboxylic acid. This new compound is obtained in a yield of 15% relative to DCAC. The product is about _^2/3 of traíjsz configuration.

Example 14

To a suspension of 1200 mmol of zinc shavings (the same size as in Example 6), 29.9 mmol of ammonium chloride and 3.0 mmol of potassium iodide in 100 ml of diisobutyl ketone at 35 ° C was added 51.7 mmol of DCAC. The solution turns yellow in 5 minutes and the reaction temperature rises. After 5 minutes, 240 mmol of benzyl (3-methyl-2-butenyl) ether was added to the reaction mixture (maintained at 40-45 ° C); the reaction mixture was then heated to 50 ° C. After 10 minutes, 310 mM DCAC was added over 35 minutes and the mixture was stirred at 40-45 ° C for 0.75 hours.

The liquid phase is separated in a separatory funnel, the excess zinc is washed three times with acetone and the washings are combined with the liquid phase. The organic phase was washed with water (500 mL) and added to a solution of 2-benzyloxymethyl-4-chloro-3,3-dimethyl-cyclobutanone and 3-benzyloxymethyl-2-chloro-4,4-dimethyl-cyclobutanone (new compounds). 500 ml of 1M aqueous sodium hydroxide solution are added. After stirring for 0.75 hours at 22 ° C, the aqueous phase was separated and acidified with concentrated aqueous hydrochloric acid (40 mL). The oily precipitate was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate and the chloroform was evaporated. 14.0 g of a viscous oil containing 53% by weight of 2-benzyloxymethyl-3,3-dimethylcyclopropanecarboxylic acid are obtained. This novel compound was fed at 8% Hg / rtOtl PCAG. The product contains about 57% of the isoform of Wflase.

Example 15

1-0 ml of diethyl ether, 3 mmol of unsaturated compound and 6 matt of granulated zinc are added to the flask and the mixture is heated to 35 ° C with stirring. DCAC (6 mmol) was then added in one portion. Seven experiments are performed with this method. The saturated compounds used, the resulting cyclic compound, and the yield of the cyclic compound to DCAC are shown in Table 10. The cyclic compounds listed in Table 10, with the exception of N-dor-S, N, N-dinethyl-ethylfoisutanone, are new substances.

Table 10

Unsaturated compound Ring compound Yield of cyclic compound,% 15 30 60 120 180 minutes propene 2-chloro-4-methylcyclobutanone and 2-chloro-3-methyl- cyclobutanone 28 34 35 cis-2-butene 2-chloro-3,4-dimethyl-cyclobutanone 12 39 43 43 trans-2-butene 2-chloro-3,4-dimethyl-cyclobutanone 45 53 54 isobutene 2-chloro-4,4-dimethylcyclobutanone and 2-chloro-3,3- dimethyl-cyclobutanone 10 21 49 51 2-methyl-2-butene 2-chloro-3,4,4-trimethylcyclobutanone and 2-chloro-3,3,4- trimethylsilane cyclobutanone 50 55 55 67 2,3-dimethyl-2-butene 2-chloro-3,3,4,4-tetramethyl-cyclobutanone 43 59 67 36 2-butyne 4-chloro-2,3-dimethyl-cyclobutene-2-one 29 35

Example 16

Into a three-necked round bottom flask was added 1 liter of anhydrous diethyl ether, 0.54 mmol of granulated zinc (maximum edge length: 1 mm) and 0.24 mol of 2,3-dimethyl-2-butene. The suspension is refluxed and a solution of DCAC (0.24 mol) in 50 ml of anhydrous diethyl ether is added dropwise over 4 hours from the addition funnel to the boiling suspension. The reaction mixture was refluxed for a further 8 hours, then cooled to 20 ° C and washed with an equal volume of water. To the organic phase, containing Compound A, 0.5 molar sodium hydroxide solution in 500 ml of water was added and diethyl ether was distilled off with stirring. The resulting residue is then acidified to pH 2.5 with 20% aqueous hydrochloric acid and the solution is subjected to steam distillation. The solid was isolated from the distillate by filtration. 2,2,3,3-tetramethylcyclopropanecarboxylic acid was obtained in a yield of 57% relative to DCAC.

Example 17

The procedure described in Example 16 was repeated except that other ethylenically unsaturated compounds were used. The starting materials, the resulting cyclobutanone and cyclopropane compounds, their yield and some physical constants are shown in Table 11. Compounds marked with an asterisk in Table 11 are new substances.

Table 11

unsaturated Cyclobutanone szátmazék Month- Cüklopropánkarbousav Month- Physical constant compound Name zam, % Name zam, % 2,4-dimethyl-2,3- 2-chloro-4,4-dimethyl-3-isopropylidene 30 2,2-dimethyl-3-isopropylidene 23 b.p. 70 C710 pentanedione -cyclobutanone * and 4-chloro-3,3-di- methyl-2-isopropylidene-cyclobutanone -cyclopropanecarboxyl Hg 2,5-dimethyl-2,4- 2-chloro-4,4-dimethyl-3- (2-methyl-l- 42 2,2-dimethyl-3- (2-methyl- 25 mp: 53 ° C -hexadién -propenyl) -cyclobutanone * and 2- propenylX cyclopropane chloro-3,3-dimethyl-4- (2-methyl-l- carboxylic acid (chrysanthemum propenyl) cyclobutanone * -monokarbonsav) 2,3,5-trimethyl-2,4- 2-chloro-3,3-dimethyl-4- (l-methyl-2- 38 2- (l-methyl-2-carboxy-l- 14 -hexadiénkarbon- ethoxycarbonyl-l-propenyl) -cyclopropane propenyl) -3,3-dimethyl- acid ethyl ester butanone *, 2-chloro-4,4-dimethyl-3- -cyclopropanecarboxyl * - (1-Methyl-2-ethoxycarbonyl-1-propenyl) -cyclobutanone *, 2-chloro-3,4-dimethyl-3-ethoxycarbonyl-4- (2-methylpropenyl) cyclobutanone * and 2-chloro-3 4-dipjetil-4-ethoxycarbonyl-3 <2-methyl-propenyl) cyclobutanone * and isomers thereof 1,2-dimethylcyclo-, 6-chloro-l, 4-dimethyl-bicyclo [3,2, C8r 20 1,5-dimethyl-bieiklo [3,1,0] - 12 op.:62C° pentene heptanone-5 (exo-endo-isomer) * hexane-6-carboxylic acid *

Example 18

The procedure of Example 16 is repeated, except that 0.5 moles of tin powder are used instead of 0.5 moles of granulated zinc. Compound A was obtained in 25% yield.

Claims (12)

A process for the preparation of cyclobutanones of formula I or cyclobutenones of formula II wherein Hal is a halogen of up to 35, R ¹ , R ² , R ³ , R ^{4 are the} same or different substituents and are hydrogen, optionally alkoxy. C 1 -C 5 alkyl or C 2 -C 6 alkenyl or (C 1 -C 6 alkoxy) carbonyl substituted with benzyloxy or alkoxycarbonyl, or R ¹ and R ³ and R ² and R ^{4 taken} together are C 2 -C Forms ₆ alkylidene groups, or R ¹ and R ² , or R ³ and R ^{4 taken} together with the carbon atoms to which they are attached form a carbocyclic ring characterized in that it is a 2,2-dihaloacetyl halide of formula III wherein Hal is as defined above with 0.5 to 10 moles of unsaturated compound of formula IV or V per mole thereof, wherein R ¹ , R ² , R ³ and R ⁴ are as defined above, in an inert aprotic polar solvent, At a temperature of from 25 ° C to 60 ° C in the presence of zinc and / or tin and optionally an inorganic halide. (Priority: September 4, 1974) 2. A process according to claim 1 wherein the compound of formula III is dichloroacetyl chloride. (Priority: September 4, 1974) 3. A process according to claim 1 or 2 wherein the general compound IV is 2,3-dimethyl-2-butene, 2-methyl-2-pentene or 2,5-dimethyl-2,4-hexadiene. used. (Priority: May 21, 1975) 4. A process according to any one of claims 1 to 3, wherein the solvent is a dialkyl ether or a ketone. (Priority: September 4, 1974) 5. A process according to claim 4, wherein the 2,2-dihaloacetyl halide of formula III is used in a concentration of 0.1 to 1 mol / liter. (Priority: May 21, 1975) 6. A process according to claim 4, wherein the solvent is an alkanone having at least two branches per molecule in its carbon skeleton and wherein at most one of the two carbon atoms attached to the carbonyl group is at least one quaternary carbon. (Priority: May 21, 1975) 7. A process according to any one of claims 1 to 3, wherein 1 mol of 2,2-dihaloacetylhalide of formula III is reacted in the presence of 1 to 10 atomic weight of zinc or tin. (Priority: May 21, 1975) 8. Figures 1-7. A method according to any one of claims 1 to 3, characterized in that the zinc is used in pieces having a maximum dimension of at least 0.1 mm. (Priority: September 4, 1974) 9. Figures 1-8. A process according to any one of claims 1 to 3, wherein the zinc or tin suspension is gradually added with stirring to a suspension of zinc or tin with a solution of an unsaturated compound of formula IV or V 2.2-dihaloacetylhalide. (Priority: 1974. September 4) 10. A process according to any one of claims 1 to 3, characterized in that the zinc or tin is Suspended in a solvent containing up to 25% of 2,2-dihaloacetyl halide, the unsaturated compound of formula IV or V is added to the suspension with stirring, followed by The remaining 2,2-dihaloacetyl halide. (Priority: May 21, 1975) 11. Process according to any one of claims 1 to 3, characterized in that the reaction is carried out in the presence of 0.1 to 10 mol% of inorganic halide based on the dihaloacetyl halide of formula III. (Priority: May 21, 1975) 12. A process according to claim 11 wherein the inorganic halide is potassium iodide and / or ammonium chloride. (Priority: May 21, 1975) 1 drawing For this publication, he is Director of the Economic and Legal Publishing Company 81.1239 * 60 * 42 Alföldi Nyomda, Debrecen - Chief Executive Officer: István Benkő Director (I) (II) Η I Fish — C - Fish Hal I c = o (IV) 176610 International Classification C 07 C 49/26 C 07 C 49/44