MXPA97002316A

MXPA97002316A - Processes for the preparation of ciclopropancarboxilico acid and its deriva

Info

Publication number: MXPA97002316A
Application number: MXPA/A/1997/002316A
Authority: MX
Inventors: Liang Shaowo; Warren Price Timothy
Original assignee: Eastman Chemical Company
Priority date: 1994-09-30
Filing date: 1997-03-26
Publication date: 1997-06-01

Abstract

A process for the preparation of cyclopropanecarboxylic acid by the non-catalytic oxidation of cyclopropancarboxaldehyde using molecular oxygen as the oxidant is described. The processes for the preparation of amides, ethers and chlorides of acid from the cyclopropanecarboxylic acid are also described

Description

PROCESSES FOR THE PREPARATION OF CICLOPROPANCARBOXILIC ACID AND ITS DERIVATIVES DESCRIPTION OF THE INVENTION This invention pertains to a process for the preparation of cyclopropanecarboxylic acid by noncatalytic oxidation of cyclopropanecarboxaldehyde. This invention also pertains to processes for the preparation of esters and amide and the acid chloride of cyclopropanecarboxylic acid. Cyclopropanecarboxylic acid and its derivatives, especially cyclopropylamine, are useful in the synthesis of pharmaceutical agents and insecticides. See, for example, European Patent Publications EP 237,955 A2, EP 273,862 A2 and EP 430,847 Al. The synthesis of cyclopropanecarboxylic acid by a 3-step process consisting of (1) the reaction of a metal cyanide with 1-bromine -3-chloropropane to obtain 4-chlorobutyronitrile, cyclization of 4-chlorobutyronitrile to obtain cyclopropanonitrile and (3) hydrolysis of cyclopropanonitrile to obtain cyclopropanecarboxylic acid is described in Japanese Patent Kokai 04077453, Org. Synthesis, Coll. Vol. 1, 156 (1941) and Org. Synthesis, Coll. Vol. 3 221 (1955). This process requires the handling of an extremely toxic metal cyanide and extensive extractions in the insulation of the product. Additional processes for the synthesis of cyclopropanecarboxylic acid at a laboratory scale are described by J. Tu et al., Youj i Huaxue 12., pp. 48-50 (1992); J. Yang et al., Huaxue Shijie 31, pp. 356-358 (1990); M. A. Coh n et al. Tetrahedron Letter 31, 7223-7226 (1990); C. W. JefEord et al., J. Chem. Soc. Chem. Co mun., Pp. 634-635 (1988i; SC Bunce et al., Prep., Int.Proc., 6, pp. 193-196 (1974); GM Lampan et al., J. Chem. Eng. Data. 14, pp. 3S »6-397 (1969) Although suitable for use in the laboratory, the procedures in these articles are not suitable for commercial use on a large scale, due to low yields and / or the use of expensive reagents. No. 3,711,549 describes the preparation of methyl cyclopropancarboxylate by the steps of (1) converting / -butyrolactone to 4-chlorobutyric acid by cleavage of / -butyrolactone in the presence of zinc chloride at 120 ° C and 20.7 bars, (2) reacting 4-chlorobutytic acid with methanol and (3) cyclizing methyl 4-chlorobutyrate The cyclization reaction requires pre-esterification of the acid, since the cyclization condition in any other form would result in the conjugate polymerization of the portion of the butyric acid or the ring closure to return af Ormar the gamma-butyrolac one. The process of US Pat. No. 3,711,549 requires the handling of hydrogen chloride which is strongly corrosive and dangerous in the gaseous state at elevated temperatures and pressures. The process also involves the use of the sodium metal in the manufacture of the freshly prepared sodium methoxide necessary for the ring closure of the ester 4-chlorobutyrate to produce the cyclopropane carboxylate ester. The aforementioned requirements of the process described in U.S. Patent 3,711,549 present serious problems with respect to safety in equipment design and material handling. U.S. Patent 4,590,292 discloses a route for cyclopropancarboxamide from / -butyrolactone by means of a four-step process. The / -butyrolactone is split with hydrogen chloride gas in the presence of aqueous sulfuric acid solution to form 4-chlorobutyric acid, which is converted to a chlorobutyrate ester. The chlorobutyrate ester is cyclized by the sodium hydroxide in the presence of a phase transfer catalyst to produce a cyclopropane carboxylate ester. This ester is treated with ammonia in the presence of a sodium alkoxide as a catalyst to form the cyclopropanecarboxamide. Like the process of US Pat. No. 3,711,549, this process requires the handling of hydrogen chloride gas at elevated temperatures and pressures. To facilitate the closure of the 4-chlorobutyrate ester ring to produce the cyclopropane carboxylate ester, the use of a secondary or tertiary alcohol in the esterification of 4-chlorobutyric acid is essential. In any other form the hydrolysis of the ester becomes a major competitive reaction leading to low yields (US Pat. No. 3,711,549). It is known that esterification using hindered alcohols presents difficulties in carrying the reaction to term. Prolonged reaction times and continuous water removal (azeotroped with an organic solvent) are required, which leads to higher manufacturing costs. The cyclization step of this process requires the handling of a chlorinated solvent such as dichloromethane, to effect the cyclization catalyzed by phase transfer. In the amidation step of the process of U.S. Patent 4,590,292, typically more than 20 mole percent of the sodium alkoxide is needed for the effective reaction rates. As a result, the isolation of a product from the reaction mixture is difficult and based on the examples given, the product is usually obtained as a methanol solution. In the case of the isolation of a pure product, less than a yield of 46% is reported. The recycling and repetition of the amidation of the mother liquor is required to obtain higher yields. Since large amounts of the catalyst (sodium ethylene glyoxide) are necessary, the preparation of the catalyst constitutes an additional stage of the process. It is apparent that the process described in U.S. Patent 4,590,292 has problems with respect to safety and economy. U.S. Patent 5,068,428 (equivalent to European Patent Specification EP 365,970) describes a process for the production of cyclopropanecarboxamide by amidation of cyclopropanecarboxylate, or of isobutyl in the presence of sodium isobutoxide / isooutanol. The isolation of the product from the reaction mixture is not trivial with a salt-containing, moist product that is usually obtained. The process has limitations similar to those described in U.S. Patent 4,590,292. The present invention pertains to the preparation of cyclopropanecarboxylic acid by the non-catalytic oxidation of cyclopropanecarboxaldehyde, which can be obtained by thermal isomerization or rearrangement of 2,3-dihydrofuran. For example, US Pat. No. 4,275,238 discloses passing 2,3-dihydrofuran through a column at 480 ° C to obtain cyclopropanecarboxaldehyde having a purity of 90% and containing 6.2-6.7% croton-aldehyde . A similar procedure is described by Wilson, J. Amer. Chem. Soc. 69, 3002 (1947). 2,3-Dihydrofuran can be obtained according to the process described in US Pat. No. 5,254,701 by the isomerization of 2,5-dihydrofuran, which in turn can be produced by the isomerization of 3,4-epoxy. -1-butene as described in U.S. Patents 3,932,468, 3,996,248 and 5,082,956. U.S. Patents 4,397,498 and 4,950,773 describe the preparation of 3,4-epoxy-1-butene by selective mono-epoxidation of butadiene. The process of the present invention comprises the preparation of the cyclopropanecarboxylic acid by contacting the cyclopropanecarboxaldehyde with molecular oxygen at an elevated temperature. It has been discovered that the new oxidation process proceeds at an acceptable rate in the absence of a catalyst and a solvent which reduces operating costs and greatly simplifies both the isolation of the carboxylic acid product and the equipment required for the operation of the process. The oxidation rate of cyclopropanecarboxaldehyde to cyclopropanecarboxylic acid has been found to be dependent primarily on oxygen mass transfer in place of any catalyst action. Since the oxidation of an aldehyde to a caroxylic acid is a free radical process [see, for example, Riley et al., J. Org. Chem. 52., 287 (1987)], partial or complete decomposition of the cyclopropane ring was a potential problem of the oxidation process. Another advantage provided by the oxidation process is that it causes the decomposition of crotonaldehyde, an inevitable impurity of the cyclopropancarboxaldehyde obtained from 2,3-dihydrofuran. Since the boiling points of cyclopropanecarboxylic acid and crotonic acid are 182-184 ° C and 180 -: - 81 ° C respectively, the conversion of the impurity crotonaldehyde to crotonic acid during the oxidation of cyclopropencarboxaldehyde to cyclopropanecarboxylic acid would present a purification problem very difficult. The elevated temperatures which can be used in the operation of the present oxidation process are in the range of 10 to 200 ° C although the temperatures in the range of E > 0 to 100 ° C are preferred. The process pressures of 0.5 to 50 absolute bars can be used with pressures of 1 to 10 absolute bars being preferred. The molecular oxygen used in the process of the invention can be provided as pure substance oxygen, air, air enriched with oxygen or oxygen diluted with one or more inert gases. Normally, the source of molecular oxygen is air. In the process air operation or other gas containing oxygen is fed with sufficient agitation to the liquid cyclopropancarboxaldehyde at a rate which results in complete conversionor substantially complete of the cyclopropanecarboxaldehyde from 2 to 12 hours. Agitation can be provided by mechanical agitators and by bubbling air into a column oxidation vessel. The second stage of the process of this invention can be carried out in a discontinuous, semi-continuous or continuous mode of operation. The oxidation process of the present invention is non-catalytic and proceeds at good speeds and selectivities in the absence of a catalyst and is therefore preferably carried out in the absence of an added oxidation catalyst. However, it is possible to employ a catalyst in the process. Examples of such catalysts include transition metals and their compounds, such as cobalt acetate, chromium acetate, platinum acetate hydroxide and chromium, and alkali metal carboxylate salts such as sodium acetate and sodium cyclopropane carboxylate. Although it is not essential for the successful operation of the process, an inert organic solvent can also be used. Examples of such solvents include aliphatic and aromatic hydrocarbons such as cyclohexane, heptane, toluene, xylene and the mixed xylene isomers; ethers such as tetrahydrofuran; alcohols such as methanol and ethanol; or the oxidation product. A preferred embodiment of the invention comprises a process for the preparation of cyclopropanecarboxylic acid, which comprises the steps of (1) contacting a mixture of 99.5 to 70 percent by weight of cyclopropanecarboxaldehyde and 0.5 to 30 percent by weight of crotonaldehyde with molecular oxygen at a temperature of 50 to 100 ° C and a pressure of 1 to 10 absolute bar; s; and (2) recover free cyclopropane carboxylic acid from crotonic acid. As mentioned in the above, crotonaldehyde is an inevitable impurity of cyclopropancarboxaldehyde obtained from 2,3-dihydrofuran. The oxidation process of this invention causes the decomposition of crotonaldehyde and / or crotonic acid and in this way the purification of cyclopropanecarboxylic acid is greatly simplified. In this embodiment of the invention the mixture of cyclopropanecarboxaldehyde / crotonaldehyde more typically comprises from 99 to 85 percent by weight of cyclopropanecarboxaldehyde and from 1 to 15 percent by weight of crotonaldehyde. The cyclopropancarboxylic acid obtained from the oxidation process can be converted to various derivatives: such as esters, acid chlorides and amides. The esters of cyclopropanecarboxylate, for example the compounds that have the structure 9 \ / \? R in which R is as defined in the following, are prepared by reacting the cyclopropanecarboxylic acid with various hydroxy compounds at a temperature of 20 to 200 ° C, preferably 60 to 150 ° C in the presence of an acid esterification catalyst. Examples of typical hydroxy compounds include aliphatic, cycloaliphatic and non-aromatic heterocyclic alcohols containing up to 30, preferably up to 12, carbon atoms; aromatic, carbocyclic and hetericyclic hydroxy compounds containing from 4 to 14 carbon atoms in the ring such as phenols, naphthols and the like. Examples of the reagents: of the hydroxy compound include compounds having the structural formula R-OH in which R is (i) a linear or branched alkyl, alkenyl or alkynyl radical containing up to 30 carbon atoms (ii) a cycloalkyl radical or cycloalkenyl containing from 3 to 7 carbon atoms, (iii) a carbocyclic or aromatic heterocyclic aromatic radical which may carry one or more substituents, or (iv) a non-aromatic 5- or 6-membered heterocyclic radical, comprising one or more heteroatoms. Exemplary compounds contemplated for use in the practice of the present invention include methanol, ethanol, propanol, isopropanol, butanol, 2-butanol, isobutanol, t-butanol, phenol and benzyl alcohol. The primary and secondary alkanols containing up to 8 carbon atoms constitute the preferred hydroxy compound reagents. The alcohol is generally used in an amount of 1 to 200 equivalents per equivalent of cyclopropanecarboxylic acid to be converted, preferably from 5 to 20 equivalents. The acids that can be used as a catalyst for this transformation are: (1) inorganic acids such as sulfuric acid, hydrochloric acid and phosphoric acid; (2) organic acids such as trifluoroacetic acid, p-toluenesulfonic acid, methylsulfonic acid and the same cyclopropanecarboxylic acid. Particularly useful for this reaction is the use of insoluble, acidic ion exchange resins such as sulfonated polystyrene resins, for example resin beads Amberlyst XN-1010 and Amberlyst-15, and sulfonated polyfluorocarbon resins, for example Naphionium resin. H. These solid acid resins are easily separated from the product mixture by filtration and the recovered resins are reusable. The process can be operated discontinuously, semi-continuously or continuously. For example, in the semi-continuous or continuous operation, the cyclopropanecarboxylic acid and an alcohol can be fed to a packed column of the solid acid resin. The recovery and isolation of the excess alcohol and the ester product can be carried out by distillation.

The esterification reaction, optionally, can be carried out in the presence of an organic solvent, which forms an azeotrope (constant boiling mixture) with water and in this form facilitates the removal of the water by-product by azeotropic distillation during the esterification process. Examples of such solvents include aromatic hydrocarbons such as benzene, toluene, xylene and mixed xylene isomers. The cyclopropanecarbonyl chloride can be prepared by contacting the cyclopropanecarboxylic acid with a chlorinating agent at a temperature of 10 to 120 ° C. Examples of the chlorinating agents include thionyl chloride (see the procedure described in J. Chem Soc. Perkin I, pp. 146-147 1976), tetrachloroethylene carbonate (European Patent Specification EP 215,517), phosphorus pentachloride, trichloride of phosphorus, oxalyl chloride or phosgene. The molar ratio of the chlorinating agent to cyclopropanecarboxylic acid is usually at least 1: 1 and is preferably 1.1: 1 to 1.2: 1. The reaction of the cyclopropanecarboxylic acid and the chlorinating agent is usually carried out in the absence of either a solvent or a catalyst. The chlorination preferably uses thionyl chloride at a temperature of 50 to 100 ° C. At the end of the reaction (when the release of the gas has stopped), the cyclopropanecarbonyl chloride having a purity of at least 98% can be recovered by distillation in yields in the range of 90 to 96%. The cyclopropanecarboxamide can be obtained by contacting the cyclopropanecarboxylic acid with ammonia at a temperature of 20 to 400 ° C, preferably 180 to 2 (0 ° C and a pressure in the range of 1 to 345 absolute bars:. used usually depends on the size of the reactor used and preferably is in the range of 10 to 100 absolute bars.The satisfactory yields are usually achieved using the reaction times of 1 to 10 hours.The amount of ammonia employed in the reaction is in the range from 1 to 50 moles, preferably from 3 to 6 moles per mole of cyclopropanecarboxylic acid.The discontinuous reaction is made by venting the reactor with nitrogen at 100 to 150 ° C to remove the water together with the excess ammonia. cooling to room temperature, the product is obtained as a solid which is washed with heptane and collected by filtration to give 99% pure cyclopropanecarboxamide. Typically, an isolated yield of cyclopropanecarboxamide of about 90% to more than 96% conversion of cyclopropanecarboxylic acid. The reaction of cyclopropanecarboxylic acid with ammonia is preferably carried out in the absence of solvent and catalyst. The exclusion of the catalyst and the solvents not only provides cost advantages, but also simplifies the isolation of the product to give pure cyclopropanecarboxamide, suitable for pharmaceutical and agrochemical uses. However, the amidation reaction can optionally be carried out in the presence of an inert organic solvent. Examples of such solvents include aliphatic and aromatic hydrocarbons such as cyclohexane, heptane, toluene, xylene and mixed xylene isomers, ethers such as tetrahydrofuran, alcohols such as methanol and ethanol. A particularly useful process for the preparation of the cyclopropanecarboxamide comprises the steps of: (1) contacting the cyclopropanecarboxylic acid with ammonia in a reactor at a temperature of 200 to 260 ° C, preferably 230 to 240 ° C and a pressure of 10 to 100 absolute bars in the absence of both of a catalyst and a solvent to form a melt of the cyclopropanecarboxamide; (2) Ventilate the reactor at a temperature above the melting point (120-122 ° C) of the cyclopropanecarboxamide, preferably 130 to 150 ° C, to reduce atmospheric pressure and remove excess ammonia and water of reaction of the cyclopropanecarboxamide; and (3) obtaining from the reactor essentially free cyclopropanecarboxamide, for example containing less than 0.5 percent by weight of each of water and ammonia. This procedure simplifies the purification of the cyclopropanecarboxamide and avoids a potential loss in yield, due to the presence of water in which the cyclopropanecarboxamide is soluble. The processes provided by the present invention are further illustrated by the following examples. Gas chromatographic (GC) analyzes are performed on a Hewlett-Packard 15890 series II gas chromatography with 30-meter DB-Wax capillary columns and 30-meter DB-17. The quantities of the products obtained were confirmed by nuclear magnetic spectrometry and gas chromatography mass spectroscopy as compared to authentic samples purchased from Aldrich Chemical Company. EXAMPLE 1 Cyclopropancarboxaldehyde (105 g, 95% pure, containing 4-4.5% crotonaldehyde) is placed in a vessel with a steam jacket equipped with a mechanical stirrer and a gas inlet at the base of the vessel, which then it is heated with steam (95-100 ° C). The air is introduced at a rate of 400 ml / minute with stirring during a period of about 8 hours, after which the consumption of the cyclopropancarboxaldehyde is completed as shown by chromatography Of gas. Distillation of the crude product under reduced pressure gives the cyclopropencarboxylic acid (113 g, 98% purity) in a 90% yield. EXAMPLE 2-7 The procedure described in Example 1 is repeated using 45 g of cyclopropancarboxaldehyde (except in Example 4 in which 56 g of cyclopropancarboxaldehyde was used) and varying the air flow rates and the reaction temperature. The materials listed in the following are used in Examples 4,6 and 7: Example 4 - 2.16 g of sodium cyclopropanecarboxylate Example 6 - 0.5 g of platinum in carbon Ejenplo 7 - 22.5 mg of cobaltose acetate and 22.5 mg of acetate hydroxide of chromium (III). The results obtained are shown in Table I, in which: the Flow Rate is the speed in me per minute at which the air is fed to the gas saturator; the Reaction Temperature is the temperature in ° C at which the slightly exothermic oxidation takes place; and the Term Time is the period of time in hours required to consume all the cyclopropanecarboxaldehyde. The purity of the cyclopropanecarboxaldehyde obtained was 98% or higher.

TABLE ode Temperature Time of Performance Example Flow Rate d? Reaction Term Isolated 2 400 25 8 85 3 400 95-100 5 88 4 200 95-100 8 85 5 200 25 12 75 6 200 25 12 68 7 200 25 10 92 EXAMPLE 8 To a 10-ml three-necked flask equipped with a condenser, a magnetic stir bar and a thermometer is charged the cyclopropanecarboxylic acid (1 g), methanol [5 ml] and 1 drop of concentrated sulfuric acid. The mixture is brought to reflux (about 70 ° C) for 3 hours. The GC analysis shows the complete consumption of cyclopropanecarboxylic acid and that a quantitative yield of methyl cyclopropancarboxylate is obtained. EXAMPLE 9 Cyclopropanecarboxylic acid (8.6 g), ethanol is charged to a 10 ml three-necked flask equipped with a condenser, a magnetic stir bar and a thermometer. (23 ml) and 2 drops of concentrated sulfuric acid. The mixture is brought to reflux (about 85 ° C) for 16 hours.

GC analysis showed that 98% of the cyclopropanecarboxylic acid had been consumed and 98% yield of the ethyl cyclopropane carboxylate was obtained. EXAMPLE 10-13 In those examples the acidic ion exchange resin Amberlyst-15 and Nafion-H were evaluated as catalysts for the esterification of cyclopropanecarboxylic acid with methanol and ethanol to produce ethyl and methyl cyclopropane carboxylate. In each example, 2 g of the ion exchange resin, 20 g of the cyclopropane carboxylic acid and 100 ml of either methanol or ethanol are heated to reflux for a reaction time of up to 20 hours. The consumption of cyclopropanecarboxylic acid is monitored every 2 hours by GC analysis. In addition to the cyclopropanecarboxylic acid, the materials used in each of Examples 10-13 are: Example 10 - Amberlyst-15 resin and methanol Example 11 - Naphion-H resin and methanol Example 12 - Amberlyst-15 resin and ethanol Example 13 - Resin Nafion-H and ethanol. The results obtained are shown in the Table II, in which the Total Reaction Time is the hours of the reaction time in which the reaction mixture is sampled for GC analysis and the Term Percentage is the mole percent of the cyclopropanecarboxylic acid consumed in the time of each analysis.

TABLE Percent Term Example Time Example Example Example Reaction Total 11 12 _13 ... 2 50.85 76.70 28.57 39.09 4 68.66 83.38 42.48 58.30 6 71.21 88.27 51.95 67.70 8 85.09 93.18 67.18 75.73 10 87.54 96.07 66.78 80.07 12 90.30 96.21 71.46 83.84 14 92.78 96.78 76.11 86.02 16 94.00 96.94 79.10 89.12 18 94.28 - 81.33 - 20 95.61 97.88 81.80 _ EXAMPLE 14 To a 50 ml flask equipped with a condenser and addition funnel, cyclopropanecarboxylic acid (8.6 g, 95% test) is placed. Thionyl chloride is added to this (13.1 g) in droplets through the addition funnel while stirring. After the completion of the addition, the reaction mixture is heated at 80 ° C for 30 minutes period of time after which the gas release is stopped. The mixture is fractionated under reduced pressure to give the cyclopropanecarbonyl chloride as a colorless oil (9.4 g, 90% yield, 98% purity by GC).

EXAMPLE 15 To a 500 ml flask equipped with a condenser and an addition funnel is placed the cyclopropanecarboxylic acid (131.6 g, 95% test). To this is added thionyl chloride (218.9 g) in droplets through the addition funnel while stirring. After the end of the addition, during a period of 1.5 hours, the reaction mixture is heated at 80 ° C for 30 minutes (release of stopped gas). The mixture is fractionated under reduced pressure to give the cyclopropanecarbonyl chloride as a colorless oil (164.2 g, 96% yield, 98% purity by GC).

EXAMPLE 16 A 300 ml autoclave is charged with cyclopropanecarboxylic acid (86 g, 95% test) and ammonia (100 ml), sealed and heated to 240 ° C. The contents of the autoclave are maintained at 240 ° C and from 42 to 45 absolute bars for 2 hours. The reaction mixture is cooled to 150 ° C, the autoclave is vented and the nitrogen is circulated through the autoclave at atmospheric pressure. The reaction mixture is allowed to cool to room temperature and the cyclopropanecarboxamide product is collected as solids. CG analysis indicated 96% consumption of cyclopropanecarboxylic acid. The product is washed with heptane and filtered by suction to give 73 g of the cyclopropanecarboxamide having a purity of 99% (mp 120-122 ° C) in an isolated yield of 90%. EXAMPLE 11 A 300 ml autoclave is charged with cycloprops.ncarboxylic acid (129 g, 98% test) and ammonia (100 ml), sealed and heated to 240 ° C. The contents of the autoclave are heated with agitation at 240 ° C and 41-44 absolute bars for 2 hours. The reaction mixture is cooled to 150 ° C, le. The autoclave is vented and the nitrogen is circulated through the autoclave at atmospheric pressure. The reaction mixture is allowed to cool to room temperature and the cyclopropanecarboxamide product (119 g, 95% yield, 93% purity by GC) is collected as a solid. GC analysis indicated 94% consumption of cyclopropanecarboxylic acid. The product is washed with heptane and filtered by suction to give the cyclopropanecarboxamide having a purity of 99%. The invention has been described in detail with particular reference to its preferred embodiments, but it will be understood that variations and modifications may be made within the spirit and scope of the invention.

Claims

CLAIMS 1. A process for the preparation of cyclopropanecarboxylic acid, characterized in that it comprises contacting the cyclopropanecarboxaldehyde with molecular oxygen at a temperature of 10 to 200 ° C.
2. The process according to claim 1, characterized in that the process is carried out at a temperature of 50 to 100 ° C and the molecular oxygen is provided as substantially pure oxygen, air, or air enriched with oxygen.
3. The process according to claim 1, characterized in that the molecular oxygen is provided as substantially pure oxygen, air, or air enriched with oxygen and the process is carried out at a temperature of 50 to 100 ° C and a pressure of 1 to 10 absolute bars in the absence of an oxidation catalyst.
4. A process for the preparation of cyclopropanecarboxylic acid, characterized in that it comprises the steps of: (i) contacting a mixture of 99.5 to 70 percent by weight of cyclopropanecarboxaldehyde and 0.5 to 30 percent by weight of crotonaldehyde with oxygen molecule]: at a temperature of 50 to 100 ° C and a pressure of 1 to 10 absolute bars; and (ii) recovering the cyclopropanecarboxylic acid without crctonic acid.
5. The process according to claim 4 for the preparation of cyclopropanecarboxylic acid, characterized in that it comprises the steps of: (i) contacting a mixture of 99 to 85 percent by weight of cyclopropanecarboxaldehyde and from 1 to 15 percent by weight weight of crotonaldehyde with molecular oxygen supplied as substantially pure oxygen, air, or air enriched with oxygen at a temperature of 50 to 100 ° C and a pressure of 1 to 10 absolute bars; and (ii) recovering the cyclopropanecarboxylic acid without the crotonic acid.
The process according to claim 1, characterized in that in a second step the cyclopropanecarboxylic acid is reacted with a hydroxy compound having the structure R-OH in the presence of an acid catalyst to produce a cyclopropane carboxylate ether having the structure: Wherein R is (i) a linear or branched alkyl, alkenyl or alkynyl radical containing up to 30 carbon atoms, (ii) a cycloalkyl or cycloalkenyl radical containing from 3 to 7 carbon atoms, (iii) a radical carbocyclic aromatic or heterocyclic aromatic which can carry one or more substituents or (iv) a non-aromatic 5- or 6-membered heterocyclic radical comprising one or more heteroatoms.
The process according to claim 3, characterized in that in a second step, the cyclopropenecarboxylic acid is reacted with a primary or secondary alcohol containing up to 8 carbon atoms at a temperature of 60 to 150 ° C in the presence of an acid catalyst to produce an alkyl cyclopropane carboxylate.
The process according to claim 1, characterized in that in a second step the cyclopropanecarboxylic acid is reacted with a chlorinating agent selected from thionyl chloride, tetrachloroethylene carbonate, phosphorus pentachloride, phosphorus trichloride and phosgene at a temperature from 10 to 120 ° C to produce the cyclopropanecarbonyl chloride.
9. The process according to claim 3, characterized in that in a second step, the cyclopropanecarboxylic acid is reacted with thionyl chloride at a temperature of 50 to 100 ° C to produce the cyclopropanecarbonyl chloride.
10. The process according to claim 1, characterized in that in a second step the cyclopropanecarboxylic acid is reacted with ammonia at a temperature of 20 to 400 ° C and a pressure of 1 to 345 bar absolute to produce the cyclopropanecarboxamide.
11. The process according to claim 3, characterized in that in a second step, the cyclopropencarboxylic acid is reacted with ammonia at a temperature of 180 to 260 ° C and a pressure of 10 to 100 absolute bars to produce the cyclopropanecarboxamide.
12. A process for the preparation of the cicloprope.ncarboxamida, characterized in that it comprises the steps of: (i) contacting the cyclopropane carboxylic acid with ammonia in a reactor at a temperature of 200 to 26C ° C and a pressure of 10 at 100 absolute bars in the absence of both of a catalyst and a solvent to form a melt of the cyclopropanecarboxamide; (ii) venting the reactor at a temperature above the melting point of the cyclopropanecarboxamide to reduce the pressure at atmospheric pressure and remove excess ammonia and water from the reaction of the cyclopropanecarboxamide; and (iii) obtaining the cyclopropanecarboxamide essential from the reactor without water and ammonia.
13. The process according to claim 12, characterized in that step (i) is carried out from 230 to 240 ° C and step (ii) is carried out from 130 to 150 ° C.