JPS5833868B2 - Beta - Halogen alkylaminosulfonyl halogenide - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for the preparation of β-halogen alkylaminosulfonyl halogenides by reaction of aziridine with sufuryl halides.

It is known that N-alkylamidosulfonyl chloride can be produced by the reaction of monoalkylammonium chloride with sulfuryl chloride (Acta chem, 5
17, 1963, p. 2141).

If this reaction is carried out in the presence of strongly polar organic solvents and with the addition of metal halides as catalysts, the yield can be improved as described in German Patent No. 1,242,627.

Although this method gives good yields for lower unbranched alkylamide sulfonyl chlorides, the yield decreases significantly when the alkyl group is branched and the chain length is long.

Furthermore, it is not possible to produce halogen alkylaminosulfonyl chloride using this method.

Another disadvantage of this method is that it requires long reaction times to obtain satisfactory yields.

This method also poses operational difficulties in industrial operations;
Due to the high chlorine content of the by-products, environmental protection issues are also associated.

DE 194 3 233 A1 describes a process for preparing β-chloroethylaminosulfonyl fluoride by halogen exchange of the corresponding aminosulfonyl chloride with hydrogen fluoride under pressure.

This process is unsatisfactory in terms of simple and economical operation, especially on an industrial scale, in view of the reaction conditions and the fact that the reaction is carried out in two stages via the sulfonyl chloride that is first prepared.

It is also known that it can be produced by the reaction of N-N-dimethylaminosulfonyl chloride with dimethylamine (Hemische Perichf, Vol. 14, 1881, pp. 1810-1812).

However, on an industrial scale, this process is complicated, uneconomical and gives unsatisfactory yields.

Moreover, N-halogenalkyl compounds cannot be produced by this method.

The present inventor first reacted an aziridine compound of the following formula with a sulfuryl halide of the following formula to obtain a β-halogenalkylaminosulfonyl halogen represented by the following formula (symbols in these formulas have the meanings given below). Although we succeeded in manufacturing Nido advantageously (Special Publication No. 57-1)
No. 9100), and then further research was conducted to respond to
It has been found that β-halogen alkylaminosulfonyl halogenide can be similarly advantageously obtained when substituted acylidine compound (IV) is used.

The present invention provides an aziridine represented by the general formula (in which residues R1, R2, R3, R4, and R5 have the meanings given below), as well as aziridine represented by the general formula (in the formula, Y and X have the meanings given below). reacted with sulfuryl halide, in which the residues R1, R2, R3 and R4 on the sides may be the same or different, each being a hydrogen atom or an aliphatic, araliphatic or aromatic furthermore, R1 and R
3, R2 and R4 together with two adjacent carbon atoms may mean members of an alicyclic ring, and X and Y may be the same or different, and each represents a chlorine atom or a fluorine atom. and R5 means an aliphatic residue).

picture※
The reaction is N-methylethyleneimine and sulfurylchloride IJ
The following equation shows the case where the code is used.

Compared to the state of the art, the present process can provide β-...rogenalkylaminosulfonyl halogenites disubstituted at the nitrogen atom in good yield and high purity with a simple and economical means.

The reaction time is short, and the finishing treatment of the reaction mixture is simpler from the point of view of environmental protection, and operational safety can be expected.

Starting materials (1) having halogen-containing alkyl groups as substituents and a large number of carbon atoms can also be used in the process of the invention.

These excellent results are unexpected considering the level of technology.

The preferred starting materials 1 and 2 and the corresponding preferred target materials Ia have the following formulas:
4 may be the same or different, each a hydrogen atom, a linear or branched alkyl group having 1 to 20 carbon atoms, preferably 1 to 8 carbon atoms, especially 1 to 3 carbon atoms, 7 to 12 carbon atoms In addition, R1 and R3 and R2 and R4 together with two adjacent carbon atoms represent members of a 5- to 8-membered alicyclic ring, especially a cyclohexyl ring or a cyclopentyl ring. X and Y may be the same or different, each means a chlorine atom or a fluorine atom, and R5 is 1 to 2
an alkyl group having 0, preferably 1 to 10, especially 1 to 4 carbon atoms, or an alkoxyalkyl group having 2 to 20, preferably 2 to 8, especially 2 to 4 carbon atoms (
Any group may be further preferably substituted with 1 to 3 chlorine atoms, fluorine atoms and/or a carbalkoxy group having 2 to 5 carbon atoms.

These groups may further include groups and/or atoms which are inert under the reaction conditions, such as chlorine, fluorine, bromine, nitro, cyanide, alkyl groups having 1 to 4 carbon atoms,
It may also be substituted by carbalkoxy groups having 2 to 4 carbon atoms.

When the starting material (1) is a sulfuryl halide containing at the same time chlorine and fluorine atoms as rogene atoms, the corresponding β-chloro-alkylamino-sulfonyl fluoride is usually obtained.

In the case of an asymmetrically substituted starting material (■) in which R1 is different from R3 and R2 is different from R4, the following two isomeric target substances (■)
A mixture of is obtained.

The starting material (■) is reacted with sulfurylnologenide (■) in stoichiometric amounts or with an excess of the latter, preferably in a ratio of 1 to 4 mol, especially 1 to 2 mol, of starting material (2) for every 1 mole of starting material (1). can be done.

The starting material (2) can be produced by a conventional method, for example, by reacting β-alkylamino-alcohol with sulfuric acid while eliminating water.
prepared by alkylaminosulfate ester and subsequent cyclization to aziridine in alkaline medium (J, Amer.

Chem, Soc, Vol. 87, 1965, p. 755).

Examples of synthesized aziridines are as follows.

For example, the following aziridine is used.

N-methyl-aziridine, N-ethyl-aziridine, N-propyl-aziridine, N-isopropyl-aziridine, N
-butyl-aziridine, N-secondary butyl-aziridine,
N-tertiary butyl-aziridine, N-pentyl-aziridine, N-(2-pentyl)-aziridine, N-(3-pentyl)-aziridine, N-(2-methyl-n-butyl)-aziridine, N- Hexyl-aziridine, N-hebutyl-aziridine, N-octyl-aziridine, N-nonyl-aziridine, N-decyl-aziridine, N-undecyl-aziridine, N-dodecyl-aziridine, N-
) Lysosyl-aziridine, N-tetradecyl-aziridine, 1,2-dimethylaziridine 1,2,3-trimethyl-aziridine, 1,2-dimethyl-3-ethyl-aziridine, 2,3-dimethyl-1-ethyl-aziridine , 2-methyl-1-isopropyl-aziridine, 1.2
-dimethyl-3-inpropyl-aziridine, 2-methyl-1-n-propyl-aziridine 2-methyl-1-
n-butyl-aziridine, 1,2,2-totimethyl-aziridine, 2,2-dimethyl-1-n-propyl-aziridine, ■-chloropropyl-2,3-dimethyl-aziridine, N-(β-carbomethoxy -ethyl)-aziridine, N-(β-carbobutoxypropyl)-aziridine, N-(γ-carbomethoxypropyl)-aziridine, N-fluoropropyl-aziridine, N-methoxymethyl-aziridine, N-chloroethyl -aziridine, N-(2-methoxy-ethyl)-aziridine, N-
(3-methoxy-propyl)-aziridine, N-(4-
methoxy-butyl)-aziridine, N-(5-methoxy-pentyl)-aziridine, N-(2-ethoxy-ethyl)aziridine, N-(3-ethoxyfurovir)-aziridine, N-(6-medoxy- hexyl)aziridine, N-(7-medoxyheptyl)aziridine, N-(
3-n-ptoxyflovir)-aziridine, N-(6
-n-butoxy-hexyl)-aziridine, N-(3-
n-hexyloxy-propyl)-aziridine, 7-methyltoaza-bicyclo(4.1.0)-hebutane, 6
-Methyl-6-aza-bicyclo(3.1.0)-hexane, 2-cyano-1-methyl-aziridine, 2-(3'
-chloropropyl)-1-methylaziridine, ■-methyl-2-butylaziridine, 1-methyl-2-pentyl-aziridine, ■methyl-2,3-diethyl-aziridine, ■-methyl-2,3-dipropyl-aziridine,
■=Methyl-2-benzyruaziridine, 1-methyl-
2-phenyl-aziridine, 1,2-dimethyl-3-phenyl-aziridine, ■-methyl-2-propyl-3-
p-Chlorphenyl-aziridine, ■・2-dimethyl-
3-o-cyanophenyl-aziridine, 2.2-dimethyl-3-p-nitrophenyl-aziridine.

Sulfuryl chloride, sulfuryl chlorofluoride and sulfuryl chloride are suitable as starting materials (1).

The reaction is usually carried out continuously or discontinuously at a temperature of -65 DEG to +110 DEG C. under normal or increased pressure.

-40 to +100 when using sulfuryl chloride
℃, especially -io to +50℃, when using sulfuryl chlorofluoride, -30 to +35℃, especially -20 to +10℃
°C, and -6 when using sulfuryl fluoride.
Temperatures of 0 to +30°C, particularly 60 to -40°C are preferred.

In the latter two cases temperatures of 0 DEG to 30 DEG C. are also advantageously used in the pressurizing device.

The reaction is preferably carried out in a predetermined amount of the starting material (1) and an organic solvent that is inert under the reaction conditions.

The following solvents are particularly suitable.

Chlorinated aliphatic hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,1- and 1,2-dichloroethane, 1,1,1- and 1,1,2-trichloroethane,
■・1,2,2- and 1,1,1,2-tetrachloroethane, n-propyl chloride, n-butyl chloride, secondary butyl chloride, isobutyl chloride, halogenated aromatic hydrocarbons and evachlorbenzole, flom Penzol Op-1m-
dichlorpenzole, 0-lm-dibrompenzole,
o-1m-1 p-chlordolol, ■・2,4-trichlorobenzole, nitrated hydrocarbons such as nitropenzole, nitromethane, nitroethane, o-1m-1
p-chlornitropenzole, aliphatic and cycloaliphatic hydrocarbons such as hexane, petroleum ether, cyclohexane,
Pentane, heptane, especially nitriles such as acetonitrile, propionitrile, butyronitrile, imbutyronitrile, benzonitrile, 0-1m, p-chlorobenzonitrile or ethers such as diethyl ether, dipropyl ether or liquid sulfur dioxide, or mixtures thereof. .

Usually, the solvent or pre-prepared starting material (1) is used in an amount of 200 to 1200% by weight, based on the starting material (2).

The reaction can be carried out as follows.

The mixture of starting material (1) and sulfuryl halide, optionally together with a solvent, is maintained at the reaction temperature for 0.5 to 8 hours.

In a particularly preferred embodiment, the mixture of starting material (1) and solvent is added to the mixture of starting material (1) and solvent at -10 DEG to +10 DEG C. via an inlet device.

When using sulfuryl fluoride as the starting material (1), the addition is preferably carried out at -60 to -48°C.

The starting material ■ as a mixture with the solvent, and the starting material ■
can also be combined by uniformly feeding them as a mixture with a solvent into a brine-cooled reflux condenser, and the reaction mixture is collected in a solvent receiver.

After combining the portions, the mixture is preferably further stirred at the addition temperature for 10-30 minutes, warmed to room temperature during 10-30 minutes, and then stirred at 30-40° C. for 20-30 minutes.

When sulfuryl fluoride is used as the starting material (1), it is preferably stirred at -55 to -45°C for 2 to 8 hours.

The target substance Ia is separated from the reaction mixture in a conventional manner, for example by fractional distillation.

When using sulfuryl fluoride, it is preferable to add a Lewis acid as a catalyst to increase the reaction rate.
The amount thereof is preferably 0.01 to 0.04 mol based on the starting material (1).

A Lewis acid refers to an electrophilic substance that has an imperfect electron configuration that can accept a pair of electrons from a base.

Regarding the definition of Lewis acid, please refer to Haupen-Weyl's ``
Metoden der Organizien Hemi-J 4/
Reference is made to Vol. 2, page 6, and Rondo, Chemistry on Carbon Compounds, JIA, Vol. 103 (Elsvier Publishing, New York 1951).

Preferred Lewis acids are halides of metals from groups I to II of the periodic table, such as chlorides of zinc, boron, aluminum, tin, titanium, antimony, bismuth, molybdenum or tungsten, aluminum bromide and boron trifluoride. is used.

Similarly Lewis acids in the form of complex compounds, such as boron trifluoride etherate, -dihydrate, -ethyl alcoholade and other alcoholades, boric fluoride, boron fluoride -→non-acid, -
Also used are diacetic acid, -phosphoric acid, complex compounds of boron trifluoride and phosphorus trichloride or phosphorus oxychloride.

As a catalyst, especially arsenic fluoride (III), arsenic fluoride (V)
, antimony(III) fluoride and antimony(V) fluoride
is excellent.

The novel compounds produced by the process of the invention are valuable intermediates for the production of plant protection agents, dyes or medicines.

For example, 0-sulfamidobenzoic acid can be produced by reacting it with anthranilic acid.

When this substance is cyclized by the method described in German Patent Application No. 2105687, 3-(β-haloken)-alkyl-2.1.3 substituted at the nitrogen atom
-pentthiadiazin-4-one-2,2-dioxide, which can be made into derivatives in which the halogen is replaced by hydrogen, for example by lithium aluminum hydride, and these are useful as plant protection agents or medicines.

Other uses include Belgian patent no. 757886 and 70
2877 and DE 1120456.

Further, a herbicide can be produced from the target substance (1a) of the present invention by reaction with glycolic acid anilide.

The target substance Ia can also be produced by hydrolysis to the corresponding rogenamine, which is used as a chemotherapeutic agent in the field of cancer and tumor treatment (Ullmans enticlopetei te/l/techniciens).
(See Hemy Vol. 2, pp. 773 et seq.).

In addition, from the target substance Ia, N-N-bis-(β-halogenalkyl)
- Sulfamide hydrazone can be produced, which is effective against cancer and malignant tumors.

Furthermore, the target substance Ia was obtained from German patent application publication No. 232459.
2.3-dihydro-3.3 by the method of specification No. 3
When reacted with -dimethyl-5-hydroxy-benzofuran derivatives, sulfamine esters with herbicidal activity can be produced.

Based on this relationship, among the novel β-halogenalkylaminosulfonyl halogenides, in the following formula, individual residues R1, R2, R3 and R4 may be the same or different, each having 1 to 20 hydrogen atoms. means an alkyl group having 7 to 12 carbon atoms, an aralkyl group having 7 to 12 carbon atoms, or a phenyl group, in which R1 and R3 or R2 and R4 together with two adjacent carbon atoms represent 5
~ may constitute a member of an 8-membered alicyclic ring, Y and X may be the same or different, each represents a chlorine atom or a fluorine atom, and R5 has 1 to 20 carbon atoms means an alkyl group having V or an alkoxyalkyl group having 2 to 20 carbon atoms, in which both groups are further substituted by a chlorine atom, a fluorine atom and/or a carbalkoxy group having 2 to 5 carbon atoms. What could have been better is better.

Specific examples of particularly preferred target substances are those listed below.

N-methyl-N-β-chloroethyl-aminosulfonyl chloride, N-ethyl-N-β-chloroethyl-aminosulfonyl chloride, Nn-propyl-N-β-chloroethyl-aminosulfonyl chloride, N-butyl-
N-β-chloroethyl-aminosulfonyl chlorine 9M, N
-n-butyl-N-2-chloropropyl-3-aminosulfonylchlor! J Do, N-n-hexyl-N-β-chloroethyl-aminosulfonyl chloride, N-n-octyl-N-β-chloroethyl-aminosulfonyl chloride, N-2-chloroethyl-N2'-methoxyethyl-
Aminosulfonyl chloride, N-2-chloroethyl-N
-3'-Methoxypropyl-aminosulfonyl chloride, N-2-chloroethyl-N-3'-ethoxypropyl-aminosulfonyl chloride, N-2-chloroethyl-
N3'-n-butoxypropyl-aminosulfonyl chloride, N-2-chloroethyl-N-3'-nhexyloxypropyl-aminosulfonyl chloride, N-2-chloroethyl-N-2'-butoxyethyl-aminosulfonyl Chloride, Nyl-t#-N-β-chloroethylaminosulfonyl fluoride, N-n-decyl-
N-β-chloroethyl-aminosulfonyl chloride and N-nbutyl-N-3-chloropropyl-2-aminosulfonyl chloride.

Parts in the following examples mean parts by weight.

Example 1 7 N-methylethyleneimine in 85 parts acetonitrile
0 parts (stabilized with 2 parts of sodium hydroxide) are added to a mixture of 288 parts of sulfuryl chloride and 470 parts of acetonitrile at 10-16 DEG C. over 35 minutes with stirring.

After stirring the reaction mixture for 0.5 h at 25-30°C, excess sulfuryl chloride and solvent are removed in vacuo.

When the remaining oil is distilled, the boiling point is 78-82 VO, 2 m
rttHg and nD=1.4820ON-methyl-N-
206 parts (87% of theory) of β-chloroethyl-aminosulfonyl chloride are obtained.

Example 2 N-methylethyleneimine 7 in 80 parts acetonitrile
After adding 0 parts of sulfuryl chloride to 288 parts of sulfuryl chloride in 500 parts of liquid sulfur dioxide, the mixture is reacted with stirring at -10° C. for 1 hour in the same manner as in Example 1.

Boiling point 76°C 10.1 Hg and Np-1,4828 N
174 parts (74% of theory) of -methyl-N-β-chloroethylaminosulfonyl chloride are obtained.

Example 3 When the reaction was carried out in the same manner as in Example 1 using diethyl ether instead of acetonitrile, N-mef-N
-β-chloroethyl-aminosulfonyl chloride is obtained in the same yield and purity.

Examples 4 to 16 Reactions were carried out in the same manner as in Example 1 to obtain the compounds shown in the following table.

Example 17 N-methylethyleneimine 6 in 80 parts acetonitrile
4 parts (stabilized with 1 part of sodium hydroxide), 520 parts of acetonitrile and 291 parts of sulfuryl chlorfur
225 parts of the mixture at 0-o'c in 30 minutes, stirred for 1 hour at 0°C and then 2 hours at room temperature.

When the evaporated concentrate is distilled in vacuum, the boiling point is 60-65
N- at °C10, O5mmHg and nD=1.4369
142 parts of methi/1z-Nβ-chloroethylaminosulfonyl fluoride as a colorless oil (72% of theory)
)can get.

Additional related nuclear power plant patent No. 1128362 (Special Publication No. 57-0
No. 19100) The invention is the method described above, but the present invention further extends this and is a method for similarly producing β-halogenalkylaminosulfonyl halogenide using an N-substituted acylidine of the general formula (2). .

Claims (1)

[Scope of Claims] Aziridine represented by the general formula (wherein the residues R1, R2, R3, R4 and R5 have the meanings given below), represented by the general formula (wherein Y and X have the meanings given below) is reacted with a sulfuryl halide of the general formula (in which the side residues R1, R2, R3 and R4 may be the same or different, each containing a hydrogen atom or an aliphatic, araliphatic or aromatic R1 and R
3 and R2 and R4 together with two adjacent carbon atoms may mean members of an alicyclic ring, and X and Y
may be the same or different, each means a chlorine atom or a fluorine atom, and R3 means an aliphatic residue) A method for producing β-...rogen alkylaminosulfonyl halide.