CA2063648A1

CA2063648A1 - Process for the preparation of n-alkylsulfonamides

Info

Publication number: CA2063648A1
Application number: CA002063648A
Authority: CA
Inventors: Stephen Lachhein; Klaus Dehmer
Original assignee: Individual
Current assignee: Hoechst AG
Priority date: 1991-03-21
Filing date: 1992-03-20
Publication date: 1992-09-22
Also published as: IL101304A0; EP0504873A1; AU645182B2; JPH0687820A; AU1306992A

Abstract

Abstract:

Process for the preparation of N-alkylsulfonamides Compounds of the formula (I) R1-SO2NH-R2 (I) in which R1 is alkyl, alkenyl or alkynyl, which are optionally substituted by halogen, alkoxy or alkoxycar-bonyl, and R2 is hydrogen or (C1-C4)alkyl, are intermediates in the preparation of sulfonylurea her-bicides. According to the invention, they can be prepared by reacting a compound of the formula R1SO2C1 (II) in the presence of approximately equimolar amounts of an auxiliary base with approximately equimolar amounts of a compound of the formula R2-NH2 (III) in a halogenated aromatic solvent, then reacting the reaction mixture with aqueous alkali metal hydroxide or with alcoholates to neutralize the hydrochloride of the auxiliary base and distilling off the auxiliary base. The otherwise cus-tomary large excess of amine component (II) and disad-vantages which are associated with the use of aqueous or polar solvents are avoided in the process.

Description

2~6~
HOECHST AK'rIENGESELLSC~FT HOE 91/F 088 Dr. WE/pe Description Process for the preparation of N-alkylsulfonamides The invention relates to a process for the preparation of sulfonamides of the formula (I~
Rl--SO2NH-R2 (I) in which Rl is (Cl-C6)alkyl, (C2-C6)alkenyl or (C2-C6)alkynyl, each of which is optionally substituted by halogen, ( Cl C4 )alkoxy or (Cl-C4-alkoxy)carbonyl, and R2 is hydrogen or (C1-C4)alkyl, which comprises reacting a compound of the formula R1SO~Cl (II) in the presence of approximately equimolar amounts of an auxiliary base with approximately equimolar amounts of a compound of the formula R2-NH2 (III) in a halogenated aromatic solvent, then reacting the reaction mixture with aqueous alk:ali metal hydroxide or with alcoholates to neutralize the hydrochloride of the auxiliary base and removing the auxiliary base by distil-lation.
R1 in the abovementioned formulae is preferably ( Cl-C6 ~ alkyl, in particular methyl or ethyl.
R2 is preferably meth~l or ethyl.

The compounds of the formula ~I) are useful intermediates in the preparation of sulfonylureas having herbicidal action (USPatent4,l69,~19;EP-A 071958= US ~ 4,4g2,598).

The preparation of the compounds of the formula (I) by reaction of sulfonyl chlorides of the formula (II~ with ammonia or amines is already known.

These known processes, however, are carried out in ~he presence of aqueous, alcoholic, benzene or ethereal solven~s at low temperatures (s OVC~ and a large excess (~ 3 mol equivalents~ of amine component (see Houben-Weyl, Methoden der organischen Chemie (Methods of Organic 2~3~8 Chemistry), Volume IX, pp. 398-400, 424-425 and 605-622;
Baxter et al., J. Chem. Soc. 1955 pp. 669 and 670, Asinger, Chem. Ber. 75 B, 40 (1942). In these processes, the amine component is alwayq employed in a large excess in order $o suppre~s the ~ormation o~ by-products (form-ation of sulfimides and sulfonic acid am~onium salts).

Only in the caæe of a larg~ excess of amine can satisfac-~ory yields be obtained in these proc~sses.

The use of a large excess of amine, however, is accom-panied by great economical ~nd ecological disadvantages,as excess amine has to be remo~ed after i~s neutraliza-tion or the hydrochloride of the amine has to be isolated by extraction or filtration and disposed of.

Extractions and filtrations axe additionally complicated by the high solubility of the products I in aqueous medium and by the high solubility of the amine hydrochlorides of the auxiliary base in the product I
(100 g of hydrochloride of the auxiliary base dissolve in 1000 g of product I).

This means additional industrial expenditure.

Considerable waste air or waste water problems ha~e to be dealt with. Per mol of excess amine, an additional mol of acid is required which produces a mol of salt in the waste water (Houben-Weyl, Volume IX, p. 606).

Cooling during the reaction is also necessa~y, as other-wise the yields fall markedly, S.Pantlitschko, Monatshefte 89 (1958~ pp. 285-287; FieldJ
Grunwald, J. Am. Chem. Soc. 75 (1953) p. 936.

The reaction of amines with sulfonyl chlorides in ~he presence of nitroalkanes is also known (Genman Published 5pecification 1,929,295). The r~action is carried out using a slight excess of amine component.

~3~

Because of the high toxicity of the nitroalkanes, how-~ ever, carrying out the process on the industrial scale is va~y problematical.

For economical reasons, the ùse of nitroalkane~ in an industrial process would be very unfavorable owing to thehigh production costs of this solvent and the complicated work-ups (German Published Specification 1929295 = US-A

3,574,740)~

Surprisingly, the sulfonamides of the formula ~I) are obtained in quantitative yields and purities of over 99%
in the process according to the invention, although only approximately the equimolar amounts of amine are employed.

The process according to the invention is distinguished by a high s01ectivity and high reaction rate.

The molar ratio II:III is about 1:1 with variations of up to 10~ due to technical reasons.

The reaction temperatures for the reaction of the com-ponents II and III are between 0 and 100C, preferably between 10 and 70C.

The auxiliary bases used in the process according to the invention serve to neutralize the hydrogen chloride forn~ed as a by-product. ~uxiliary bases which can be u~ed are organic bases such as, for example, organic amines, for example triethylamine. The amine component III is preferably used as the auxiliary base.

Halogenated aromatic hydrocarbons which can be employed are, for exampler chlorobenzene or dichlorobenzene.

In the solvents to be employed according to the inven-tion, the products of the formula I have unexpectedlypoor solubilities: they are therefore obtained as oils : : :
.

2 ~ 8 suspended in the reaction mixture. In 1000 ml of chloro~
benzene, only a~out 15-20 g of CH3SO2NHCH3 dissol~e at room temperature.

The hydrochlorides of the auxiliary bases, fonmed during the reaction, are obtained as a dispersion so that a heterogeneous 3-phase mixture is formed. The hydrochlori-des would be isolatable from this mixture only with yreat industrial expenditure.

However, another working up method has been found in which the auxiliary base can be quantitatively recovered.
To do this~ the hydrochloride is neutralized with alkali metal hydroxide or alcoholates, for example alkali met~l alcoholates, optionally in a corresponding alcoholic solution, and the liberated amine is directly distilled off from the reaction mixture.

Working up is carried out by metering in to the heterogeneous 3-phase mixture the approximately equimolar amount of alkali metal hydroxide solution or alcoholates at temperatures between 0 and 100C and, by increasing the temperature to the reflux temp~erature of the solvent, liberating the auxiliary base from the hydrochlorides and distilling it of.

After the complete removal of the auxiliary base by distillation from the reaction mixture J the water is removed from the circulation by distilling off at reflux temperatures or the al~ohol is distilled off.

Surprisingly, the sulfonamides of he formula I, which are sensitive to hydrolysis per se (cf. ~ouben-Weyl, Vol.
I~ p. 398, 3rd paragraph from the bottom) r are not hydrolyzed although high reaction temperatures are used.

As the sulfonamides I are stronger acids than the hydrochlorides of the auxiliaxy base (N-methylmethanesulfonamide: pK~ = 9.3/methylamine 2~3~

hydrochloride: pK~ = 10.6~, it was to be expected that instead of the hydrochlorides the sul~onamides I would preferentially react with the alkali metal hydroxide solution or alkali metal alcoholates with the formation of sulfonamide salts.

In spite of the strong pRn differences, however, only the hydrochloride reacts with the added alkali metal hydroxide or alcoholate, approximately only the equimolar amounts of hydroxide or alcoholate being required. Th~
auxiliary bases and the sulfonamides I are obtained in virtually ~uantitative yields and purities > 99~.

For further industrial reactions, the crude suspensions of the compounds of the formula ~I) in chlorobenzene, which still contain alkali metal chloride, can be used directly without prior purification for further reactions (for example reaction with chlorosulfonyl isocyanate for the preparation of herbicides), or can be filtered off from the alkali metal chloride, preferably hot.

After working up, the auxiliary bases can be employed in the reaction again, i.e. quantital:ively recycled.

~he sol~ents are also virtually quanti~atively recyclable.

The process according to the invention is expediently carried out by metering the amine of the formula (III~
into the solution of the compounds of the formula (II).
Equally, however, the ~mine component can also be initially in~roduced together with the solvent and the sulfonyl chloride metered into this solution. The simul-taneous addition of the components II and III to the solvent is also possible.

It is expedient, even if not absolutely necessary, to carry out the process under an inert gas atmosphere, for example under ni~rogen, in oxder to avoid interfering 6- 20~3~
effects of oxygen on the reaction.

The process according to the invention can be carried out continuously or ba~chwise. It is illustrated by the ~ollowing examples:

Example 1 N Methylmethanesulfonamide In a 10-liter 4-necked flask, a total of 251 g of methyl-amine are added as a gas to a solution of 4000 ml of chlorobenzene and 458 g of methanesulfonyl chloride at 20-25C over a period of 3-4 hours.

After reaction is complete, the mixture is subsequently stirred for 3 hours. 321 g of 50~ strength sodium hydrox-ide solution are added dropwise at 25C and the mixture is heated to 100C for 2 hours.

During this time, a total of 12S g of methylamine are distilled off and collected in a cold trap. The water is then removed from circulation at :reflux temperature in a separator. The solvent is distilled off in vacuo.

After separating from sodium chloride, 438 g of crude product having a purity of 99.0~ are obtained, cor-responding to a yield of 99~ of theory; ~2: 1.4509.

Example 2 N-Methylethanesulfonamide In a 2-liter 4-necked flask, 125 g of methylamine are initially introduced into 2000 ml of chlorobenzene ~nd 257 g of ethanesulfonyl chloride are added dropwise at 20-25C.

After reaction is complete, the mixture is subsequently stirred for 2 hours. 321 g of 25~ strength sodium hydro~-ide solution are added dropwise at 25C and heated at thereflux temperature of the reaction mixture for 2 hours.

2 ~

During this time, a total of 62 g of methylamine are distilled off and collected in a cold trap. ~he water is then ramoved from circulation at reflux temperature in the separator.

The solvent is distilled off in vacuo. After separa~ing from sodium chloride, 247 g of crude product are obtained having a purity of g9.6~. Af~r thin film distillation, 242 g of distilled product of 99.8% purity are obtained, corresponding to a yield of 98.4~; n~S - 1.4530.

Example 3 N-Ethylmethanesulfonamide 458 g of methanesulfonyl chloride and 360 g of ethylamine are sLmultaneously metered into a solution of 400 ml of chlorobenzene under a nitrogen protective gas atmospher2 at 20-30~C over a period of 4 hours. After reaction is complete, the mixture is subsequently stirred for 3 hours and treated with 642 g of 25~ strength sodium hydroxide solution. The ethylamine is liberated in the cour~e of 2 hours at the reflux temperature of the reaction mixture and dis~illed off. After distill.ing off the ethylamine (178 g)/ the water (480 g) is removed ~rom circulation at the reflux temperature of the reaction mixture.

After distilling off, 4493 ml of a chlorobenzene ~olution of N-ethylmethanesulfonamide are obtained, which contains 493 g of the product having a purity of 99.7%.

Example 4 N-Methylmethanesulfonamide In a 10-litre 4-necked flask, ~50 g of methylamine are added as a gas to 200G ml OI chlorobenzene.
458 g of methanesulfonyl ~hloride are metered into this solution at 40C under an inert gas atmosphere in the course of 4 hours. After reaction is complete, the mixture is subsequently stirred for 2 hours and treated with 642 g of 25% strength sodium hydroxide solu~ion and 125 g of methylamine i~ distilled off for 2 hours under ~3~

reflux conditions.

The water i5 then removed from circulation at reflux temperature in the separator. The solvent is distilled off in vacuo.

After separating from sodium chloride, 436 g of crude product having a purity of 99.2~ are obtained; n 1.4510.

Example 5 N-Methylmethane~ulfon~mide In a 10-litxe 4-necked flask, 458 g of m~thanesulfonyl chloride are added dropwise under an inert gas atmosphere to 2000 ml of chlorobenzene. 260 g of methylamine are added as a gas to this solution between 1~ - 40~C in the course of 2 hours. After subsequently stirring for 2 hours, the mixture is treated with 660 g of 25~
~trength sodium hydroxide solution and 135 g of methylamine are distilled off whiLe heating the reaction mixture to reflux. The slight excess of sodium hydroxide solution is recovered with dil. hydrochloric acid.

The water is then remo~ed from circulation in the course of 2 hours at reflux temperature.

After distilling off the chlorobenzene and separating from sodium chloride, 437 g of crude product having a purity of 99.5% are obtained; yield: 99.5~; nD2: 1.4512.

The following compounds of the formula (I), for example, can be prepared analogously to the procedures described in Examples 1 - 5:

Exampls Rl R2 6 C~3 C3H7 7 C2H5 ~2H5 8 C3~7 CX3 , fi ~ ~
_ 9 _ Exam~le R1 - R2 11 Cl-CH2 H
12 Cl-CH2-~H2 ~3H7 14 Cl-CH2 CH3 ~2H~ C3H7 Compari~on exampleq A Preparation of N-methylmethanesulfonamide according to Houben-Weyl, Volume IX p. 606 A cooled solution of 250 g of methylamine in 3000 ml of ether is added ~o 458 g of methanesulfonyl chloride at 0C in the cour~e of 3 hours. Aftex a subsequent stirring time of 10 min at 0C, conc. hydrochloric acid is added in the same volume of water and the ~olvent is then distilled off. The remaining oily residue is taken up in ethyl acetate, the aqueous filtrate is extracted twice by shaking with ethyl acetate and the combined organic phases are distilled.

344 g of distilled product havin~ a purity of 9~.8~ are obtained. Yield: 76.9~.

B Preparation of N-methylmethanesulfonamide according to Baxter et al., J. Chem. Soc. l9S5, p.

A solution of 458 g of methanesulfony~ chloride in 3000 ml of dry ether is slowly added at 0C to a solution of 375 g of methylamine in 2000 ml of ether. The reaction mixture is subseguently stirred at room temperature for one hour and the resulting methylamine hydrochl~ride i~
filter d of.

The filter residue i~ washed with ether and chloroform.
22~.5 g of methylamine hydrochloride (85%) are obtained.
After distillation, 384 g of product having a purity of lo- 2~36~
97.9~ are obtained; yield: 86~.

Comparison Example A shows that on use of equimolar - amounts of amine in the known processes only unsati fac-to~y product yields are obtained. The results do not come up to the industrial standard. Even when larger amounts of amine are used, see Comparison Example B, the known processes yield the desired product in only about 85%
yield.

C Preparation of N-methylmethanesulfonamide in the 10presence o water without distilling of the auxili-ary base In a 10-1 4-necked flask, 251 g of methylamine are passed as a gas into a mixture of 3000 g of chlorobenzene and 1500 g of water. 458 g of methanesulfonyl chloride are 15added dropwise at 20 to 25C in the course of 3 to 4 hours, the pH being kept between 7 and 9 by addition of sodium hydroxide solution. After addition is complete, the mixture is subse~lently stirred for 3 hours and the organic phase is separated off. Aiter distilling off the chlorobenzene, 62 g of crude product having a content of 95.8% of N-methylmethanesulfonamide remain, which cor-responds to a yield of 25.8~ of theory.

Claims

1. A process for the preparation of a compound of the formula (I) R1-SO2NH-R2 (I) in which R1 is (C1-C6)alkyl, (C2-C6)alkenyl or (C2-C6)alkynyl, each of which is optionally substituted by halogen, (C1-C4)alkoxy or (C1-C4-alkoxy)carbonyl and R2 is hydrogen or (C1-C4)alkyl, which comprises reacting a compound of the formula R1SO2C1 (II) in the presence of approximately equimolar amounts of an auxiliary base with approximately equimolar amounts of a compound of the formula R2-NH2 (III) in a halogenated aromatic solvent, then reacting the reaction mixture with aqueous alkali metal hydroxide or with alcoholates to neutralize the hydrochloride of the auxiliary base and removing the auxiliary base by distil-lation.

2. The process as claimed in claim l, wherein the auxili-ary base employed is a compound of the formula (III).

3. The process as claimed in claim 1 or 2, wherein the solvent employed is chlorobenzene or dichlorobenzene or mixtures thereof.

4. The process as claimed in one or more of claims 1 to 3, wherein the reaction temperature for the reaction of the components II and III is between 0° and 100°C.

5. The process as claimed in one or more of claims 1 to 4, wherein the reaction temperature for the reaction of the components II and III is between 10° and 70°C.

6. The process as claimed in one or more of claims 1 to 6, wherein the reaction mixture is heated to the reflux temperature of the solvent to neutralize the hydrochloride of the auxiliary base.