IE42287B1 - Process for the preparation of aminophenyl chloroformate hydrochlorides - Google Patents

Abstract

1475259 Aminophenyl chloroformate hydrochlorides SOC NATIONALE DES POUDRES ET EXPLOSIFS 2 Dec 1975 [17 Dec 1974] 49459/75 Heading C2C The invention relates to (a) the preparation of N,N-dialkylaminophenyl chloroformate hydrochlorides by reacting an N,N-dialkylaminophenol with COCl 2 , the reaction being carried out in solution in a chlorinated aliphatic hydrocarbon below 0‹ C.; and (b) 3- or 4-(N,N-di- (C 1 -C 5 alkyl)amino)phenyl chloroformate hydrochlorides per se which may be obtained by the method (a). A specified solvent is dichloromethane. N1N1 - Dialkylaminophenyl N - alkylcarbamates are obtained by reacting the N,N-dialkylaminophenyl chloroformate hydrochlorides obtained as above with primary alkylamines.

Description

The present invention is concerned with a process for the preparation of aminophenyl chloroformate hydrochlorides, with, certain novel aminophenyl chloroformate hydrochlorides, and with the use of such chloroformate hydrochlorides in the preparation of aminophenyl carbamates.

The known processes for the preparation of aromatic chloroformates require the use of hydrochloric acid acceptors. The latter may be aliphatic or aromatic tertiary amines; the use of such amines is described particularly in German Patent 118,536 and by Oesper, Broker and Cook, J. Amer.' Chem. Soc., 47, 2609 (1925) . The use of inorganic bases, such as sodium hydroxide, as acid acceptors has also been suggested; their use is described particularly by Wittbecker and Katz, J. Polymer. Sci., 40, 289 (1959).These known processes axe unsuitable when one of the substituents of the aromatic nucleus is or contains an amine group. Thus, it is known that chloroformates are decomposed in the presence of tertiary amines and react rapidly with primary or secondary amines. The use of a hydrochloric acid acceptor prohibits, in practice, the blocking of the amine in the form of the hydrochloride.

Thus, the reaction of Ν,Ν-dialkyl—aminophenols with phosgene in the presence of a tertiary amine or in the presence of an inorganic base, does not lead to welldefined compounds'. - 2 4228 7 An analogous problem arises in the reaction of phosgene with nitrogen-containing diols of the formula: X—-N and we found that, for this type of compound, the corresponding bis-chloroformate hydrochlorides can be obtained in a pure state and in a form which can be isolated, by treating the diol hydrochloride with phosgene without an acid acceptor, that is to say, by saturating a solution of the nitrogen-containing diol with hydrogen chloride, prior to the treatment with phosgene, so as to block the catalytic action of the nitrogen atom. This process is described in French Patent 2,230,605.

We have now found that N,N-dialkylamino-phenyl chloroformate hydrochlorides can be efficiently prepared, in the pure state and in a form which can be isolated, by reacting the aminophenol with phosgene directly, in the absence of an acid acceptor, the hydrochloric acid which is liberated as the chloroformate is formed serving to block the tertiary nitrogen atom of the aminophenol in the form of the hydrochloride.

According to the present invention, therefore, there is provided a process for the preparation of N,N-dialkylaminophenyl chloroformate hydrochlorides, which comprises reacting an Ν,Ν-dialkylaminophenol with phosgene, the reaction being carried out in solution in a chlorinated aliphatic hydrocarbon at a temperature below 0°C.

In a preferred manner of carrying out this process, the aminophenol, dissolved in the Organic solvent, is run into a bottom layer of liquid phosgene at a temperature below 0°C. and preferably at from -15° to -10°C. During the formation of the chloroformate, hydrochloric acid is liberated and is bound by the nitrogen atom of the amino group in the form of a hydrochloride in order to prevent the amino group from playing its role of a catalyst for the decomposition of the chloroformates formed. It is thus necessary that the chloroformate formed should be soluble in the solvent used for the aminophenol. Furthermore, the solvent must be compatible with the aminophenol hydrochloride and with the corresponding chloroformate hydrochloride; chlorinated aliphatic hydrocarbons meet these requirements, dichloromethane being the preferred solvent. Once all the aminophenol solution has been added, the excess phosgene is removed by passing in an anhydrous inert gas, such as nitrogen.

One of the advantages of the process according to the invention resides in the fact that there is no excess hydrochloric acid, since the hydrochloric acid originates from the reaction of the aminophenol with phosgene and serves to block the nitrogen atom of the aminophenol in accordance with the following equation: OCOC1 42387 OH + COCI '2 A XX V OCOC1 HC1 '2 in which R'^ and R'j, which may be the same or different, are alkyl groups.‘ The amount of hydrochloric acid liberated by the reaction of the aminophenol with phosgene is the same as that necessary for the formation of the hydrochloride of the aminophenol; at the end of the reaction, there is thus no excess hydrochloric acid.

After removal of the excess phosgene, the reaction mixture is preferably worked up as follows. The solution is concentrated by evaporation in vacuo so as to cause the chloroformate hydrochloride formed to precipitate. The precipitate obtained is washed with anhydrous ether and dried in vacuo, in the presence of a drying agent such as phosphorus pentoxide, at approximately 0°C.

Certain of the aminophenyl chloroformate hydrochlorides obtainable by the process according to the invention are novel and, according to a further aspect of the invention, there are provided, as new compounds, N,N-dialkylaminophenyl chloroformate hydrochlorides of the formula: 2 2 8 7 Ο II o-c—ci . HCl and / \ R, R.

(I) (II) in which R^ and Rg, which may be the same or different, are linear or branched alkyl groups having up to 5 carbon atoms.

A preferred compound according to the invention is 3-(Ν,Ν-dimethylamino)-phenyl chloroformate hydrochloride, i.e. the compound of formula 1 above in which both R^ and Rg are methyl.

The Ν,Ν-dialkylaminophenyl chloroformate hydrochlorides obtained by the process according to the invention are advantageously used in the production of the corresponding Ν,Ν-dialkylaminophenyl carbamates which are valuable phytosanltary pesticidal agents. Such carbamates are described, for example, in French Patent 1,432,508. By reacting the chloroformates prepared according to the invention with a primary alkylamine, such carbamates are obtained more advantageously than by the conventional process for their preparation. The two reaction schemes are as follows: - 6 4 2 2 8 7 (a) Conventional process RNH2 + COC12 ->RCNO + 2HC1 RCNO + OH -> / Q \—OCONHR rxr2n R-^N (b) Process using chloroformate hydrochloride (the formation of the hydrochloride salt has been omitted to facilitate comparison).

In theory, the two synthesis routes are equivalent from the point of view of the starting materials used, but it is found in practice that the isocyanate, RCNO, is difficult to prepare and the reaction requires excess phosgene, a catalyst (such as, a tin salt) and the product has to be purified by distillation. Additionally, the isocyanate intermediate is toxic.

The synthesis route via the chloroformate hydrochloride is simpler and less expensive (because there is no loss of phosgene). - 7 4 2 2 8 7 According to a further aspect of the present invention, therefore, there is provided a process for the preparation of Ν',Ν'-dialkylaminophenyl N-alkylcarbamates , which comprises reacting an Ν,Ν-dialkylaminophenyl chloro5 formate hydrochloride prepared according to the invention with a primary alkylamine.

In order that the invention may be more fully understood, the following Examples are given by way of illustration only: Example 1. ml. of phosgene were condensed in a 250 ml reactor provided with a phosgene condenser, a device for cooling to -40°C., a magnetic stirrer, a dropping funnel and a thermometer. A solution of 34.25 g (0.25 mol) of 3-(N,N15 dimethylamina)-phenol (freshly distilled) in 150 ml of dry dichloromethane was then introduced slowly, over the course of approximately 2 hours.

The temperature of the reaction mixture was kept at -10°C. The mixture was stirred for a further two hours at this temperature and was then allowed to return to ambient temperature.

The solution obtained was freed from excess phosgene by bubbling nitrogen through it, whilst stirring. Any insoluble material present was filtered off and the filtrate was concentrated in vacuo at 20°C.

A white precipitate was obtained and was collected by filtration out of contact with the moisture in the air. The product was then washed with anhydrous ether and dried over phosphorus pentoxide in vacuo at 0°C. - 8 4 2 2 8 7 The infra-red spectrum confirmed the structure of the product by: presence of the absorption band at 1,780 cm 1 corresponding to the C = 0 frequency of — O-C-Cl ; li o no band at about 1,750 cm (absence of carbonate); and presence of a very broad band at about 2,300 cm·1· corresponding to the hydrochloride.

Analysis: CgH^ClNOj-HCl. Molecular weight: 236.

C% H% N% Cl% Calculated 45.76 4.66 5.93 30.08 Found 45.44 5.06 5.64 27.6 Example 2. 3-(Ν',Ν'-Dimethylamino)-phenyl N-methylcarbamate was synthesised, in part (a) below, in accordance with the conventional method using an isocyanate and, in part (b) below, using the corresponding chloroformate hydrochloride prepared according to the invention. a) Conventional method 11.4 g (0.2 mol) of methyl isocyanate, 100 ml of dichloromethane and a few drops of dibutyl tin dilaurate were introduced into a 500 ml reactor provided with a stirrer, a thermometer and a dropping funnel. 27.4 g (0.2 mol) of dlmethylaminophenol dissolved in 200 ml of 2 2 8 7 dichloromethane were run in at ambient temperature. The temperature rose to 33°C. The mixture was left to stand overnight and the solvent was removed by evaporation under reduced pressure. 28 g (72% yield) of a highly coloured and impure product were collected.

Recrystallisation from 70% aqueous ethanol gave 8 g of crystals (m.p. 88°C.), corresponding to a 35% yield.

The IR and NMR spectra were identical to those obtained with an authentic sample of the product, b) Process according to the invention A suspension of 55 g (0.233 mol) of 3-(N,N-dimethylamino)-phenyl chloroformate hydrochloride and 30 g of methylamine hydrochloride in 500 ml of anhydrous dichloromethane was introduced into a 2 litre reactor provided with a stirrer, a thermometer, a dropping funnel and a reflux condenser.

The mixture was cooled to 0°C. and 30% aqueous solution of sodium hydroxide was run in dropwise until alkalinity persisted.

When the introduction of the sodium hydroxide solution was complete, the temperature was maintained at 0°C. and stirring was continued for one hour. 400 ml of distilled water were then added and the mixture was stirred for % hour at ambient temperature.

The organic phase was separated, washed twice with 150 ml of water, dried over anhydrous sodium sulphate and evaporated to dryness under reduced pressure.

The residue was recrystallised from 70% aqueous ethanol; m.p. 88°C. 36.2 g of purified product were obtained, corresponding 2 3 8 7 to an 80% yield. The IR and NMR spectra were in agreement with those of an authentic sample.

Analysis; cioH14N2°2· Molecular weight; 194.

C% H% N% Calculated 61.8 7.22 14.4 Found 61.9 7.3 14.3 The difference between the yield (80% instead of 35%) 5 and the high cost of methyl isocyanate used as a starting material in the conventional process, show the value of synthesising the carbamate by the process according to the invention. '

Claims (11)

1. CLAIMS : 1. A process for the preparation of N,N-dialkylaminophenyl chloroformate hydrochloride, which comprises reacting an N,N-dialkylaminophenol with phosgene, the reaction being carried out in solution in a chlorinated alipahtic hydrocarbon at a temperature below 0°C.

2. A process according to claim 1, in which the * o o temperature is from -15 to -10 C.

3. A process according to claim 1 or 2, in which the solvent is dichloromethane.

4. A process according to any of claims 1 to 3, in which the N,N-dialkylaminophenol is a 3- or 4-(N,N-di(C^-Cg alkyl)amino)-phenol.

5. A process for the preparation of an N,N-dialkylaminophenyl chloroformate hydrochloride, substantially as herein described in Example 1.

6. Ν,Ν-Dialkylaminophenyl chloroformate hydrochlorides when prepared by the process claimed in any of claims 1 to 5.

7. Ν,Ν-Dialkylaminophenyl chloroformate hydrochlorides of the formula / \ R, R. in which R^ and R 2 , which may be the same or different, are linear or branched alkyl groups having up to 5 carbon atoms. 4 2 2 8 7

8. 3-(Ν,Ν-Dimethylamino)-phenyl chloroformate hydrochloride.

9. A process for the preparation of an Ν',Ν'-dialkylaminophenyl N-alkylcarbamate, which comprises reacting an 5 N,N-dialkylaminophenyl chloroformate hydrochloride prepared by the process according to any of claims 1 to 4, with a primary alkylamine.

10. , A process for the preparation of an Ν',Ν'-dialkylaminophenyl N-alkylcarbamate according to claim 9, Substan10 tially as described in Example 2(b).

11. Ν',Ν'-Dialkylaminophenyl N-alkylcarbamates when prepared by the process claimed in claim 9 or 10.