HUP0300215A2 - Method for producing chlorocarboxylic acid chlorides - Google Patents

Abstract

The subject of the invention is the process of chlorocarboxylic acid chlorides of the general formula - where R1 - R2 are independently a hydrogen atom, a carbon-containing organic group, a halogen atom or a nitro- or cyano group; Y is an alkylene chain with 1-10 carbon atoms, which is unsubstituted or substituted with carbon-containing organic groups, a halogen atom, a nitro and/or cyano group, and the alkylene chain can be interrupted by an ether, thioether, tertiary amino or keto group; and the carbon-containing organic groups Y and/or R1 and/or R2 can be connected to each other to form a non-aromatic system - to produce lactones of general formula - where R1 and R2 and Y are given above - by reacting with a chlorinating agent in the presence of a chlorinating catalyst, during which the reaction is carried out in the presence of a boron compound. HE

Description

S. B. G. & K.

: ’·?:&:ίί2ΰ/ΒΕ

H-1062 Budapest, Andrássy út 113. / - PUBLICATION PAGE

Phone: 461-1000, Fax: 461-1099

Process for the preparation of chlorocarboxylic acid chlorides

The invention relates to a method for the ^R1 NP

CCI-YC. (Í) r2 ^{z X} CI chlorocarboxylic acid chlorides— in which formula

R ¹

R ² is independently hydrogen, carbon-containing organic group, halogen, nitro or cyano;

means an alkylene chain of 1-10 carbon atoms, which is unsubstituted or substituted with carbon-containing organic groups, halogen atom, nitro and/or cyano group, and the alkylene chain may be interrupted by an ether, thioether, tertiary amino or keto group;

and the Y and/or taste/ 9

The carbon-containing organic groups of R and/or R can be linked together to form a non-aromatic system — for the preparation of

R1

--HE

Lactones of general formula R2 (II) — in which formula

R ¹ and R ² and Y are as defined above — by reacting with a chlorinating agent in the presence of a chlorinating catalyst.

Chlorocarboxylic acid chlorides are important reactive intermediates in the production of pharmaceutical and agrochemical active ingredients.

Chlorocarboxylic acid chlorides can be prepared, for example, by reacting the corresponding lactones with a chlorinating agent in the presence of a catalyst. The chlorinating agents used are typically phosgene or sulfinyl chloride, as these yield exclusively gaseous coupling products (carbon dioxide or sulfur dioxide and hydrogen chloride).

When sulfinyl chloride is used as the chlorinating agent, zinc (II) chloride is usually used as the catalyst. Suitable procedures are described by I.I. Grandberg et al. [Izv. Timiryazevsk. S.kh. Akad, 6, 198-204 (1974)] and O.P. Goel et al. [Synthesis, 538-539 (1973)]. The conversion of γ-butyrolactone to 4-chlorobutyryl chloride was carried out in 65-80% yield.

If phosgene is used as the chlorinating agent, various catalyst systems are generally used. US Patent No. 2,778,853 mentions the following as suitable catalysts: pyridines, tertiary amines, heavy metals and acids, such as sulfuric acid, phosphoric acid, phosphorus (III) chloride, phosphorus oxychloride, aluminum (III) chloride, sulfuryl chloride and chlorosulfuric acid. Suitable catalysts are urea compounds according to DE-A 19,753,773, phosphine oxides according to EP-A 0,413,264 and EP-A 0,435,714, and nitrogen-containing organic compounds, such as quaternary ammonium salts, heterocyclic nitrogen compounds, amines and formamides according to EP-A 0,253,214 and EP-A 0,583,589.

US Patent No. 2,778,852 describes the preparation of 4-chlorobutyryl chloride by reacting γ-butyrolactone with phosgene in the presence of pyridine.

To increase the yield, additional hydrogen is usually added.

75.220/BE

-chloride is introduced. However, the use of hydrogen chloride is disadvantageous, especially for ecological and economic reasons, since it is used in quantities significantly higher than the stoichiometric one and the excess has to be purified and neutralized, which leads to significant sophistic accumulation. Furthermore, the use of large quantities of hydrogen chloride gas imposes additional technological and logistical requirements.

Therefore, the object of the invention is to provide a process for the preparation of high purity chlorocarboxylic acid chlorides in high yield by reacting the corresponding lactone with a chlorinating agent, which process is free from the disadvantages of the additional feed of hydrogen chloride gas.

Accordingly, we found a method for ^R1 \

^R2z

Chlorine carboxylic acid chlorides of the general formula CCI—y—cC Cl (I) — in which formula

R R independently represents a hydrogen atom, a carbon-containing organic group, a halogen atom, or a nitro or cyano group;

Y represents an alkylene chain of 1-10 carbon atoms, which is unsubstituted or substituted with carbon-containing organic groups, halogen atom, nitro and/or cyano group, and the alkylene chain may be interrupted by an ether, thioether, tertiary amino or keto group;

and the carbon-containing organic groups of Y and/or R ¹ and/or R ² may be linked together to form a non-aromatic system to produce the

75.220/BE

by reacting lactones of the general formula — in which R ¹ and R ² and Y have the meanings given above — with a chlorinating agent in the presence of a chlorinating catalyst, characterized in that the conversion is carried out in the presence of a boron compound.

An essential feature of the process according to the invention is the presence of a boron compound. Examples of suitable boron compounds include the compounds and groups of substances listed below, and mixtures of different boron compounds may be used similarly:

• boron oxide, for example boron(III) oxide (B ₂ 0 ₃ );

• boron oxyacids, such as boric acid (H3BO3, more precisely “orthoboric acid”), metaboric acids (of the HBO ₂ type, such as α-ΗΒΟ ₂ , β-ΗΒΟ ₂ or γ-ΗΒΟ ₂ ), oligoboric acids or polyboric acids;

• salts of boronic acids, such as borates ([B0 ₃ ] ³ , more precisely: “orthoborates) , oligoborates (such as [B3O3 (OH) 5] ² ~, [B4O ₅ (OH) ₄ ] ² ' r [B5O5 (OH) 6] ³ or [BgOv (OH) 6] ² ~) or polyborates (such as [B02] ^- ) with inorganic or organic cations, such as alkali metal ions (such as Li ⁺ , Na ⁺ or K ⁺ ), alkaline earth metal ions (such as Mg ²⁺ , Ca or Sr ), ammonium ion (NH ₄ ⁺ ) or primary, secondary, tertiary or quaternary amines (such as tetramethylammonium, tetraethylammonium, tetrapropylammonium, tetraisopropylammonium, salts of phenyltrimethylammonium, phenyltriethylammonium, trimethylammonium, triethylammonium, tripropylammonium, triisopropylammonium, phenyldimethylammonium, phenyldiethylammonium, or phenylammonium ion ("anilinium ion");

75.220/BE • boric acids [RB(OH) ₂ ] and their inorganic or organic salts, such as benzoboric acid (dihydroxyphenylborane) or disodium phenylboronate;

• boronic acid esters, for example mono-, di- or tri-(C1-6 alkyl) esters, the alkyl groups of which are identical or different, straight-chain or branched (for example methyl, ethyl, propyl, isopropyl, butyl, 1-methylpropyl, 2-methylpropyl, tert-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or 1-ethyl-2-methylpropyl group), for example trimethylborate, triethylborate or tripropylborate;

• boron halides containing fluorine, chlorine, bromine and/or iodine, such as BF ₃ (boron trifluoride), BC1 ₃ (boron trichloride), BBr ₃ (boron tribromide), BI ₃ (boron triiodide), BF ₂ C1, BFC1 ₂ , BF ₂ Br, BFBr ₂ , BF ₂ I, BFI ₂ , BFCIBr, BFC1I, BFBrI, BCl ₂ Br, BClBr ₂ , BC1 ₂ I, BC1I ₂ , BClBrl, BBr ₂ I, BBrI ₂ , B ₂ F4, B ₂ C14, B ₂ Br4, B ₂ l4 and their complexes, such as complexes with oxygen, sulfur or nitrogen compounds, such as hydrates, alkoxides, etherates, sulfides, ammonia, amines and pyridines, such as [water-BF ₃ ], [methanol-BF ₃ ], [ethanol-BF ₃ ], [dimethyl ether-BF ₃ ], [diethyl ether-BF ₃ ], [n-

-propyl ether-BF ₃ ] , [diisopropyl ether-BF ₃ ] , [tetrahydrofuran-BF ₃ ] ,

[dimethyl sulfide-BF ₃ ] , [ammonia-BF ₃ ] , [methylamine-BF ₃ ] , [dimethyl

75.220/BE

-amine-BF ₃ ] , [trimethylamine-BF ₃ ] , [ethylamine-BF ₃ ] , [diethylamine-BF ₃ ] , [triethylamine-BF 3 ] , [urea--BF ₃ ] , [pyridine-BF _{3 ]} , [2-methylpyridine-BF ₃ ] or [3-methylpyridine-BF ₃ ] .

The compounds preferably used according to the invention are: • boron oxide (B ₂ 0 ₃ );

• boric acid (H ₃ BO ₃ );

• tri(C3-C4 alkyl)borates, such as trimethylborate, triethylborate, tripropylborate, triisopropylborate or tributylborate;

• boron trifluoride, boron trichloride or complexes thereof, for example with water, alcohols (especially methanol), ethers (especially diethyl ether), sulfides (especially dimethyl sulfide) or amines (especially ethylamine), for example boron trifluoride dihydrate or boron trifluoride etherates (especially diethyl ether);

or mixtures thereof.

Very preferably used compounds are halogen-free boron compounds, boron oxide (B ₂ 0 ₃ ), boric acid (H ₃ BO ₃ ) and tri (C 3-4 alkyl) borates. Boric acid (H ₃ BO ₃ ) and trimethyl borate are particularly preferred. The advantage of using such boron compounds is that the reaction mixture is free of fluoride ions. This simplifies the entire apparatus technology compared to reactions requiring boron halides.

In the process according to the invention, the boron compound or a mixture thereof is used in a concentration of 0.1-20 mol%, preferably 0.1-10 mol% and most preferably 0.5-5 mol%, based on the amount of the lactone of general formula (II).

75.220/BE

With the method according to the invention,

R1

R2

O CCI-Y-cf (l) C/l chlorocarboxylic acid chlorides are prepared, — in which R ¹ - R ² independently represent a hydrogen atom, a carbon-containing organic group, a halogen atom or a nitro or cyano group.

The carbon-containing organic group means an unsubstituted or substituted aliphatic, aromatic or aralkyl group having 1 to 20 carbon atoms. This group may contain 1 or more heteroatoms, for example oxygen, nitrogen and sulfur, for example -O-, -S-, -NR-, -C0 and/or -N= in aliphatic or aromatic systems, and/or may be substituted by one or more functional groups, for example oxygen, nitrogen, sulfur and/or halogen, for example fluorine, chlorine, bromine, iodine and/or cyano. If the carbon-containing organic group contains one or more heteroatoms, it may also be linked via the heteroatom. This includes, for example, ether, thioether and tertiary amino groups. Preferred examples of the carbon-containing organic group include alkyl groups having 1-20 carbon atoms, especially alkyl groups having 1-6 carbon atoms, aryl groups having 6-10 carbon atoms, aralkyl groups having 7-20 carbon atoms, especially aralkyl groups having 7-10 carbon atoms, and alkylaryl groups having 7-20 carbon atoms, especially alkylaryl groups having 7-10 carbon atoms.

Examples of halogen atoms include fluorine, chlorine, bromine, and iodine.

According to the invention, those of general formula (I) are preferred.

75.220/BE chlorocarboxylic acid chlorides, in which R ¹ and R ² independently represent a hydrogen atom, a C 1-6 alkyl, a C 6-10 aryl, a C 7-10 aralkyl, a C 7-10 alkaryl group, for example methyl, ethyl, propyl, isopropyl, butyl, 1-methylpropyl, 2-methylpropyl, tert-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, phenyl, 2-methylphenyl (o-toluoyl), 3-methylphenyl (m-toluoyl), 4-methylphenyl (p-toluoyl), naphthyl or benzyl. Hydrogen and C1-4 alkyl, especially hydrogen, are particularly preferred.

Y is an alkylene chain of 1-10 carbon atoms, which may be unsubstituted or substituted by carbon-containing organic groups, halogen, nitro or cyano groups, and the alkylene chain may be interrupted by ether (-O-), thioether (-S-), tertiary amino (-NR-) or keto (=C=O) groups. The carbon-containing organic group and halogen are as defined above.

Examples of the Y group include alkenyl groups of the general formula -(CH ₂ ) _n -, where n is 1-10 and one or more or even all of the hydrogen atoms may be replaced by C 1-6 alkyl, C 6-10 aryl, C 7-10 aralkyl, C 7-10

75.220/BE with a carbon alkylaryl group, for example methyl, ethyl, propyl, isopropyl, butyl, 1-methylpropyl, 2-methylpropyl, tert-butyl, pentyl, Ι-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, phenyl, 2-methylphenyl (o-toluoyl), 3-methylphenyl (m-toluoyl), 4-methylphenyl (p-toluoyl), naphthyl or benzyl group.

According to the invention, preferred chlorocarboxylic acid chlorides of the general formula (I) are those in which Y represents an unsubstituted alkenyl group of the general formula -(CH ₂ ) _n -, where n is 2-8, preferably 2-4, for example ethylene, trimethylene and tetramethylene groups.

It is possible that the organic groups of R ¹ and/or R ² and/or Y are linked to each other to form a non-aromatic system. An example of this is hexahydrophthalide.

The highly preferred chlorocarboxylic acid chloride product of the general formula (I) of the process according to the invention is 4-chlorobutyryl chloride (4-chlorobutanoyl chloride), 5-chlorovaleryl chloride (5-chloropentanoyl chloride) or 6-chlorocaproyl chloride (6-chlorohexanoyl chloride).

The lactones used are

75.220/BE

Lactones of the general formula R2 — in which R ¹ and R ² and Y are as defined above. Of course, mixtures of different lactones can also be used if desired. We prefer to use γ-butyrolactone, δ-valerolactone or ε-caprolactone.

The chlorinating agent used is preferably phosgene, diphosgene [trichloromethyl-(chloroformate)], triphosgene [bis(trichloromethyl)carbonate] and/or sulfinyl chloride. The use of phosgene or sulfinyl chloride is particularly preferred, especially phosgene in gaseous and/or liquid form.

Suitable chlorination catalysts are all theoretically known chlorination catalysts, in particular nitrogen and phosphorus compounds, such as open-chain or cyclic, unsubstituted or substituted ureas, di-N,N-substituted formamides (for example Ν,ΔΤ-dimethylformamide), trialkylphosphine oxides or unsubstituted or substituted triarylphosphine oxides, substituted or unsubstituted pyridines, quaternary ammonium salts [for example benzyl-(trimethylammonium chloride)] amidines or salts thereof, including hydrogen chlorides, unsubstituted mono- or poly-substituted guanidines or hexaalkylguanidinium salts.

A chlorination catalyst preferably used is a urea compound, phosphine oxide, pyridine compound or a mixture thereof.

The urea compounds preferably used are disclosed, for example, in the published specification DE-A 19,753,773. We are particularly

75.220/BE is preferred

X

who _is

The use of open-chain, substituted urea compounds of the general formula R4 R5 —wherein X represents an oxygen or sulfur atom;

R -R independently represent preferably an alkyl group having 1-10 carbon atoms; or

One of the R or R groups together with one of the R -R groups forms an alkylene chain of 2-4 carbon atoms.

Urea compounds which are liquid under the reaction conditions are particularly preferred, such as N,N'-dimethylethyleneurea (1,3-dimethyl-2-imidazolidinone), N,ΔΓ-dimethylpropyleneurea (1,3-dimethyltetrahydro-2(1H)-pyrimidinone), N,N,N',N'-tetrabutylurea or N,N,N',7V'-tetramethylthiourea. The urea compounds mentioned can be used in this state or in the form of their salts with hydrogen chloride, for example as hydrogen chlorides or in the form of their Vilsmeier-type salts which can be obtained by reaction with phosgene, but hydrogen chlorides are preferred.

The phosphine oxides preferably used are described, for example, in EP-A 0,413,264. We particularly prefer the trialkylphosphine oxides or the

HE

II n R?—P—R9 (arc)

R8 is an unsubstituted or substituted triaryl

75.220/BE

-phosphine oxides, in which R ⁷ -R ⁹ independently represent preferably an alkyl group having 1-10 carbon atoms, or an unsubstituted or (1-4 carbon alkyl)-substituted phenyl group. Phosphine oxides which are liquid under the reaction conditions, such as straight-chain or branched trioctyl, trihexyl or tributyl phosphine oxides, and also triphenyl phosphine oxide and mixtures of various trialkyl phosphine oxides (e.g. Cyanex® sold by Cytec Industries) are particularly preferred.

Preferably used are r12

unsubstituted or substituted pyridines of the general formula, wherein R ¹⁰ -R ¹⁴ independently represent preferably hydrogen or a C 1-4 alkyl group. Another possibility is to link two adjacent groups to form an aromatic or non-aromatic system. Mono(C 1-4 alkyl)pyridines are particularly preferred, and monomethylpyridines, especially 3-methylpyridine (β-picoline), are most preferred.

In the process according to the invention, 3-methylpyridine, triphenylphosphine oxide and/or trialkylphosphine oxide are mainly used.

The use of a liquid chlorination catalyst has primarily technical advantages. For example, the process is free from the complicated handling, dosing and transport of solids. Furthermore, it is

75.220/BE, significantly less viscous bottom product is produced in the subsequent distillation processing step and clogging is avoided.

In the process according to the invention, the chlorination catalyst is used in a concentration of 0.1-20 mol%, preferably 0.1-10 mol% and most preferably 0.5-5 mol%, based on the amount of lactone of general formula (II).

In another preferred embodiment of the invention, the catalyst used is a complex of a boron compound and a chlorination catalyst. This can be prepared, for example, by mixing the two components before or in the reactor. An example of a suitable complex is the 3-methylpyridine-BF ₃ complex.

The reactor used for chlorination can theoretically be any apparatus for vapor-liquid or liquid-liquid reactions described in the relevant technological literature. In order to achieve high space-time yields, it is important to achieve intensive mixing between the solution containing the lactone, the chlorination catalyst and the bromine compound and the added chlorinating agent. Non-limiting examples include shaken tanks, stirred tank reactor cascades, counter-flow reaction columns, flow tubes (preferably equipped with baffles), bubble columns and loop reactors.

The process is preferably carried out without the use of a solvent. However, it is possible to add a solvent that is inert to the chlorinating agent used. Examples of inert solvents include aromatic hydrocarbons, such as toluene, chlorobenzene, o-, m- or p-dichlorobenzene, o-, m- or p-xylene, cyclic carbonates, such as ethylene carbonate or propylene carbonate, the

75.220/BE chlorocarboxylic acid chloride or a mixture thereof. If a solvent is used, it is preferable to use the chlorocarboxylic acid chloride to be prepared. Adding a solvent may be advantageous, for example, if the lactone of general formula (II) used has a large molecular weight, is highly viscous, or is solid under the reaction conditions.

The process according to the invention can be carried out at 50-80°C, preferably 80-200°C, more preferably 110-160°C. The process is generally carried out at a pressure ^{of 1x103-5x105} Pa, preferably ^5x104-2x105 Pa, particularly preferably ^atmospheric .

In the process according to the invention, the amount of phosgene introduced per 1 mol of lactone of general formula (II) is generally 0.1 - 1.5 mol and preferably 0.9 - 1.2 mol.

The addition of the starting materials [lactone of formula (II) and chlorinating agent] and catalysts (chlorinating catalyst and boron compound) can generally be carried out in any order. In one embodiment, it is preferred to use the lactone of formula (II), the chlorinating catalyst, the boron compound and optionally the solvent as the starting mixture and add the chlorinating agent later, or in another embodiment, all components are introduced at the same time. Embodiments between these two embodiments are of course possible and may be advantageous.

The various components can be brought into contact with each other before the addition of the starting materials and catalysts, or in the reactor, as desired. It is therefore possible, for example, to carry out the preliminary formation of a complex of the boron compound and the chlorination catalyst (for example, the 3-methylpyridine-BF ₃ complex).

75.220/BE tani. It is also possible to bring about a reaction beforehand between the chlorination catalyst and the chlorinating agent (for example the Vilsmeier salt of N,N-dialkylformamide and phosgene or sulfinyl chloride).

The process according to the invention can be carried out in batch or continuous operation.

a) Intermittent operation mode

In batch production, the reaction mixture containing the lactone of the general formula (II), the chlorination catalyst, the boron compound and optionally a solvent is generally metered into a reactor, for example a stirred tank, as a starting mixture, and stirred intensively. The desired amount of liquid or gaseous chlorinating agent is then added at the desired temperature and pressure. After the chlorinating agent has been added, the reaction mixture is allowed to react further for a period of a few minutes to a few hours. This further reaction can take place in the reactor or in a vessel below it.

In a special variant of the batch operation, the liquid chlorinating agent (e.g. sulfinyl chloride) is used as the starting mixture, optionally together with the chlorinating catalyst and/or the boron compound and/or the solvent. The lactone of the general formula (II), optionally together with the chlorinating catalyst and/or the boron compound and/or the solvent, is then added at the desired temperature and pressure over a given period of time.

b) Continuous operation mode

Reactors suitable for continuous operation are, for example, stirred tanks, stirred tank reactor cascades or counter-flow reactors.

75.220/BE flow reaction towers. At the start of the continuous process, a solvent (for example, the chlorocarboxylic acid chloride to be produced), the chlorination catalyst and the boron compound are usually metered into the reactor, the system is heated to the desired temperature, and then the liquid or gaseous chlorination agent is added. In parallel with the continuous feed of the chlorination agent, the continuous introduction of the lactone of the general formula (II) is started, which usually contains additional chlorination catalyst and additional boron compound and is optionally dissolved in a solvent. After the reactor contents have been converted into chlorocarboxylic acid chloride, the feeding rate of the lactone of the general formula (II) and the chlorination agent is adjusted so that both compounds are introduced in essentially equimolar amounts. The reaction mixture is fed to the feed! is removed from the reactor at a rate corresponding to the reaction rate, for example through a riser or overflow. Preferably, the reaction solution is passed into another vessel for further reaction.

It is generally advantageous to then drive off the unreacted chlorinating agent from the reaction solution, for example by passing through the reaction solution a gas inert to the reaction solution, such as nitrogen.

Unconverted chlorinating agent, which for example escapes from the reactor during synthesis or is subsequently blown out, can advantageously be collected and reused. Suitable collection containers are, for example, cold traps in which the chlorinating agent is condensed.

The reaction solution leaving the reaction of the lactone of general formula (II) and the chlorinating agent can be processed by conventional methods. Purification by distillation is preferred, and if necessary, the extraction is carried out by

75.220/BE is carried out in or before the distillation column.

It is possible and advantageous to recycle the bottom product remaining after distillation purification, including the chlorination catalyst and the boron compound, in part or in full. Of course, before the aforementioned recycling, it is possible to carry out another processing of the bottom product, for example distillation, in order to separate the chlorination catalyst and/or the boron compound. In the case of a process implemented by recycling the chlorination catalyst and/or the boron compound, it is advantageous to recycle only a part of these in order to remove the by-products and to replace the other part with fresh catalysts.

In a general embodiment of the invention, in the batchwise synthesis of the chlorocarboxylic acid chlorides of the general formula (I), the desired lactone of the general formula (II), the chlorinating agent (preferably liquid), the boron compound and optionally a solvent (for example the chlorocarboxylic acid chloride to be produced) are all metered into a stirred tank. The reaction system is then heated to the desired temperature and liquid and/or gaseous phosgene or liquid sulfinyl chloride is introduced continuously at ambient pressure with continuous vigorous stirring. The gaseous coupling product formed, carbon dioxide or sulfur dioxide and hydrogen chloride, are also removed. After the desired amount of chlorinating agent has been fed, the reaction solution is left alone for a period of time at a controlled temperature and with continuous stirring to react further. During the further reaction, the chlorinating agent still present in the reaction solution reacts with the remaining lactone of the general formula (II). In order to drive off some or all of the excess chlorinating agent and its reaction products, carbon dioxide or sulfur dioxide, and hydrogen chloride from the reaction solution, it is possible to pass an inert gas through it with vigorous stirring. The resulting reaction solution is then fed to the work-up step. The work-up is generally carried out by distillation, optionally under vacuum. In the case of high-molecular-weight chlorocarboxylic acid chlorides, other purification processes are possible, such as crystallization.

In a general embodiment of the invention, in the continuous production of chlorocarboxylic acid chlorides of the general formula (I), the solvent (for example, the chlorocarboxylic acid chloride to be produced), the chlorination catalyst and the boron compound are metered into the reactor, for example, a stirred tank, and the system is heated to the desired temperature and a liquid or gaseous chlorinating agent is added thereto. Subsequently, in parallel with the continuous feeding of the chlorinating agent, the continuous introduction of the lactone of the general formula (II), which generally contains additional chlorinating catalyst and additional boron compound and is optionally dissolved in a solvent, is started. After the reactor contents have been converted to chlorocarboxylic acid chloride, the feeding rate of the lactone of the general formula (II) and the chlorinating agent is adjusted so that both compounds are introduced in essentially equimolar amounts. The reaction mixture is fed to the feed! The removed reaction solution is collected in a tank downstream of the reactor, such as a stirred tank, for further reaction.

75.220/BE ion. When the above-mentioned container is filled with the above-mentioned effluent, the overflow is optionally freed from the carbon dioxide and hydrogen chloride produced in the coupling reaction, as described above, and forwarded for processing. The processing is carried out, for example, by distillation.

The process according to the invention allows the preparation of high purity chlorocarboxylic acid chlorides in high yield by reacting the corresponding lactone with a chlorinating agent, and the process is free from the disadvantages of the additional feed of hydrogen chloride gas. During the work-up, the chlorocarboxylic acid chloride can be easily separated from the boron compound added according to the invention.

Experimental equipment:

The experimental apparatus consists of a 1 L glass vessel with a double-walled jacket and stirrer, a thermostatic controller, a pipe for introducing a gaseous or liquid chlorinating agent, and a two-stage condenser cascade. The two-stage condenser cascade consists of a jacketed coil condenser maintained at -10 °C and a carbon dioxide condenser maintained at -78 °C. The experiments are carried out at ambient temperature.

Example 1: (according to the invention)

200 g (2 mol) of δ-valerolactone, 9.3 g (0.1 mol) of β-picoline (3-methylpyridine) and 3.1 g (0.05 mol) of boric acid are used as the starting mixture in the double-walled jacketed glass vessel. A total of 229 g (2.32 mol) of gaseous phosgene are introduced at 144-148 °C over 5 hours with vigorous stirring. The system is then allowed to react for another hour without

75.220/BE phosgene would be fed. After stripping the remaining, unconverted phosgene with nitrogen, 310 g of crude effluent were obtained. The crude effluent was subjected to fractional distillation at 70-75 °C and 0.7x10 ³ Pa absolute pressure (7 mbar absolute). 255 g of 5-chlorovaleryl chloride with a purity of >98 GC area% were isolated.

Yield: 82%.

Example 2: (according to the invention)

172 g (2 mol) of γ-butyrolactone, 9.3 g (0.1 mol) of β-picoline (3-methylpyridine) and 3.1 g (0.05 mol) of boric acid are used as the starting mixture in the double-walled jacketed glass vessel and heated to 140 °C. A total of 242 g (2.45 mol) of gaseous phosgene are introduced at 140-147 °C over 4 hours and 15 minutes with vigorous stirring. The system is then allowed to react for a further hour without feeding phosgene. After stripping the remaining, unconverted phosgene with nitrogen, 289 g of crude effluent are obtained at 100 °C. The crude effluent contains 93.6 GC area% 4-chlorobutyryl chloride.

Example 3: (according to the invention)

172 g (2 mol) of γ-butyrolactone, 34.8 g (0.1 mol) of Cyanex® 923 (a commercial product from Cytec Industries, with an average molecular weight of 348 g/mol and containing a mixture of various trialkylphosphine oxides) and 3.1 g (0.05 mol) of boric acid are used as the starting mixture in the double-walled jacketed glass vessel. A total of 251 g (2.54 mol) of gaseous phosgene is introduced at 144-148 °C over 4 hours and 20 minutes.

75.220/BE with vigorous stirring. The system is then allowed to react for a further hour without feeding phosgene. After the remaining, unconverted phosgene is driven off with nitrogen at 100 °C for 7 hours, 314 g of crude effluent are obtained. The crude effluent is subjected to fractional distillation at 87 °C and 5.1 x 10 ³ Pa absolute pressure (51 mbar absolute). 242 g of 4-chlorobutyryl chloride with a purity of >99 GC area % are isolated.

Yield: 86%.

Example 4: (according to the invention)

200 g (2 mol) of δ-valerolactone, 9.3 g (0.1 mol) of β-picoline (3-methylpyridine) and 5.2 g (0.05 mol) of trimethyl borate are used as the starting mixture in the double-walled jacketed glass vessel and heated to 140 °C. A total of 242 g (2.45 mol) of gaseous phosgene are introduced at 140-146 °C with vigorous stirring. The system is then allowed to react for another hour without feeding phosgene. After the remaining unconverted phosgene is driven off with nitrogen at 100 °C, 318 g of crude effluent are obtained. The crude effluent is subjected to fractional distillation at 75-77 °C and an absolute pressure of 0.9x10 ³ Pa (9 mbar absolute). After the 10 g predistillate, which already contains 96.6 GC area% 5-chlorovaleryl chloride, 256 g of a pure fraction are isolated. This is 98.2 GC area% pure 5-chlorovaleryl chloride.

Yield: 85%.

75.220/BE

Example 5: (According to the invention) g (0.1 mol) δ-valerolactone, 1.14 g (0.006 mol) (benzyltrimethylammonium) chloride and 0.31 g (0.005 mol) boric acid are used as the starting mixture in the double-walled jacketed glass vessel. A total of 15.5 g (0.13 mol) of liquid sulfinyl chloride is introduced at 120-125 °C over 7 hours with vigorous stirring. The system is then allowed to react for a further hour without feeding sulfinyl chloride. The effluent contains 70 GC area% 5-chlorovaleryl chloride and 7 GC area% unconverted δ-valerolactone.

Example 6: (comparative example)

192 g (2.23 mol) of γ-butyrolactone and 2 g (0.025 mol) of pyridine are used as the starting mixture in the double-walled jacketed glass vessel and heated to 120 °C. A total of 60 g (0.61 mol) of gaseous phosgene are introduced at 120-124 °C over 8 hours with vigorous stirring. After driving out the remaining, unconverted phosgene with nitrogen, the crude effluent is subjected to fractional distillation. The first fraction weighing 76 g contains 21.6 GC area%, the second fraction weighing 110 g contains 2.6 GC area% of 4-chlorobutyryl chloride.

Yield: 6%.

Comparative Example 6 shows that only inadequate yields can be achieved without the presence of boron compounds and the introduction of hydrogen chloride.

75.220/BE

Claims (10)

·»·· ’· Patent claims 1. Procedure for ^R k /2 CGI—Y—0. (I) Chlorocarboxylic acid chlorides of the general formula R2 ^z Cl — in which formula R - R independently represent a hydrogen atom, a carbon-containing organic group, a halogen atom, or a nitro or cyano group; Y represents an alkylene chain of 1-10 carbon atoms, which is unsubstituted or substituted with carbon-containing organic groups, halogen atom, nitro and/or cyano group, and the alkylene chain may be interrupted by an ether, thioether, tertiary amino or keto group; and the carbon-containing organic groups of Y and/or R ¹ and/or R ² may be linked to each other to form a non-aromatic system — for the preparation of By reacting lactones of the general formula R2 — in which ^R1 and ^R2 and Y are as defined above — with a chlorinating agent in the presence of a chlorinating catalyst, characterized in that the reaction is carried out in the presence of boron oxide, oxoboric acids, oxoboric acid salts or mixtures thereof. 2. The process according to claim 1, characterized in that boric acid is used. 75.220/BE 3. The process according to claim 1 or 2, characterized in that the boron compound is used in a concentration of 0.1-20 mol%, based on the amount of the lactone of general formula (II). 4. The process according to any one of claims 1-3, characterized in that phosgene, diphosgene, triphosgene or sulfinyl chloride is used as the chlorinating agent. 5. The process according to any one of claims 1-4, characterized in that a urea compound, a phosphine oxide, a pyridinium compound or a mixture thereof is used as the chlorination catalyst. 6. The process according to claim 5, characterized in that 3-methylpyridine, triphenylphosphine oxide and/or trialkylphosphine oxide are used as chlorination catalysts. 7. The process according to any one of claims 1-6, characterized in that the chlorination catalyst is used in a concentration of 0.1-20 mol%, based on the amount of lactone of general formula (II). 8. The process according to any one of claims 1-7, characterized in that the chlorination catalyst and the boron compound are used in the form of a complex of the two components. 9. The process according to any one of claims 1-8, characterized in that the reaction is carried out at 50-200 °C and a pressure of 0.01x10 ⁶ -5x10 ⁶ Pa. 10. The process according to any one of claims 1-9, characterized in that the lactone of general formula (II) used is γ-butyrolactone, δ-valerolactone or ε-caprolactone. ^The authorized person: 75.220/BE