IE42100B1 - Process for the preparation of 2,2,2-trichloroethyl chloroformate - Google Patents

Abstract

1474867 2,2,2 - Trichloroethyl chloroformate SOC NATIONALE DES POUDRES ET EXPLOSIFS 2 Dec 1975 [31 Dec 1974] 49460/75 Heading C2C 2,2,2-Trichloroethyl chloroformate is prepared by reacting 2,2,2-trichloroethanol with COCl 2 at an elevated temperature, in the absence of a solvent and in the presence of an organic compound containing a tert-N atom and having a boiling point of at least 120‹ C., as catalyst. The catalyst is preferably N,N-dimethylformamide or dimethylaniline and is usually present in an amount of 0À5-7 molar per cent. A reaction temperature of 100- 105‹ C. is advantageously employed.

Description

The present invention is concerned with a process for the preparation of 2,2,2 —trichloroethyl chloroformate. 2,2,2-Trichloroethyl chloroformate, which has the formula CCl^-CH^-OCOCl, is a widely used synthesis intermediate, being used in the pharmaceutical industry for the synthesis of certain antibiotics, particularly cephalosporins, and in the chemical industry for the synthesis of various carbamates and carbonates.

Xt is thus important to have available a convenient Ιθ method for the preparation of trichloroethyl chloroformate on an industrial scale. The best process for malting this compound is to react trichloroethyl alcohol with phosgene. However, because of the very great inductive effect of the three chlorine atoms situated in the g-positioa relative to the alcohol group, trichloroethyl alcohol is a compound which reacts very unsatisfactorily with phosgene. Thus the conventional technique for reacting with phosgene in the presence of active charcoal, such as described in German Patent 283,896, does not enable this alcohol to be reacted; likewise, the well-known technique for reacting with phosgene in the cold and in the presence of an acid acceptor, such as sodium hydroxide or a tertiary amine, only gives relatively low yields of trichloroethyl chloroformate.

French Patent 1,338,931 describes the reaction of phenols and naphthols with phosgene at elevated temperatures in the presence of a solvent, such as xylene, and in the presence of a catalyst consisting of a tertiary amine with an ionisation constant at 25°C of less than 5 X 10~4» such as Ν,Ν-dimethylaniline. The process described in this French Patent enables trichldroethanol to be reacted with phosgene, but possesses the following two disadvantages: the process makes use of large amounts of solvent which have to be recovered if the process is to be economically competitive and this makes it complicated to carry out and, in practice, the yield of trichloroethyl chloroformate, with respect to trxchloroethanol, does not exceed 60 to 70% by weight.

French Patent 2,143,363 describes the reaction of phenols and naphthols with phosgene at elevated temperatures and in the absence of a solvent, in the presence of catalytic amounts of an Ν,Ν-dialkyl-carboxamide or Ν,Ν,NJjN*-tetraalkyl-urea, such as Ν,Ν-dimethylformamide, Ν,Ν-diethylformamide, Ν,Ν-dimethylacetamide, N,N,N*,N’tetramethyl-urea, N-methylpyrrolidone and N-acetylpiperidine.

The process described in French Patent 2,143»363 enables aryl chloroformates to be obtained quantitatively, but the description of the process is strictly limited to phenols and naphthols.

We have now found that 2,2,2 «-trichloroethyl chloroformate can be efficiently prepared by reacting trichloroethanol with phosgene at an elevated temperature, in the absence of a solvent and in the presence of a catalyst having a tertiary nitrogen atom and a boiling point of at least 120°C.

According to the present invention, therefore, there is provided a process for the preparation of 2,2,2trichloroethyl chloroformate, which comprises reacting 2,2,2-trichloroethanol with phosgene at an elevated temperature, in the absence of a solvent - 3 42100 and. in the presence of an organic compound, containing a tertiary nitrogen atom and having a boiling point of at least 120°C, as catalyst.

Suitable catalysts for use in the process according 5 to the invention include amides, such as Ν,Ν-dimethylformamide, N,N-diethylformamide, Ν,Ν-dimethylacetamide, Ν,Ν,Ν’,Ν’tetramethyl-urea, N-methylpyrrolidone and N-acetylpiperidine^ and tertiary amines which have an ionisation constant at 25°C of less than 5 X 10 more particularly dimethyl-aniline, ^-picoline, 2-methyl-5-ethylpipcridine, N,N-di-methyl-ptoluidine,£Upicoli.ne, 2,4,6-eollidine, 2-ethyl-pyridine hydrochloride, 2,4-butidine, 2-isopropyl-pyridine, a-picoline hydrochloride, p-chloro-N,N-dimethyl-aniline hydrochloride and triethylamine hydrochloride. The preferred catalysts are dimethylaniline and Ν,Ν-dimethylformamide.

The reaction is carried out with liquid trichloroethanol (m.p. ahout 18° C) in a reactor suitable for carrying out reactions with phosgene. The catalyst is preferably added in a molar amount of from 0.5 bo 7%, more preferably approximately 5ft, and the reaction mixture is : preferably heated to 80°C. Phosgene is then introduced and, since the reaction is very exothermic, heating is no longer necessary and the flow rate of phosgene is regulated so as to maintain the temperature of the reaction mixture substantially constant, preferably at not more than 105°C and, more preferably, at from 100°C to 105°C.

It is very important in this process to monitor the temperature efficiently. We have found, in fact, that the reaction is a zero order reaction with respect to the reactants; the rate of reaction is thus solely a function of the temperature. - 4 _ Xn any preparation of a ohloroformate by reacting an alcohol with phosgene, there is a side reaction, namely the formation of the corresponding carbonate; in the present case, what is involved is the formation of trichloroethyl carbonate by the reaction of trichloroethyl chloroformate with trichloroethanol. The faster the reaction is carried out, the lower the final proportion of carbonate. It is thus valuable to have the fastest possible reaction rate, that is to say to operate at the highest possible temperature. However, we have found that above 105°C, the formation of trichloroethyl carbonate becomes significant and it is for this reason that the most preferred temperature range is from 100° to 1O5°C.

In a preferred embodiment of the invention, an effective system for cooling the reactor and a series of condensers to enable the vapours evolved from the reaction mixture to be condensed and recycled are provided. In general, two consecutive condensers are used, the first being cooled to approximately 0°C and the second to “20°C so as to ensure complete recycling of the alcohol and the phosgene.

Under these conditions, the reaction with phosgene generally takes from 4 to 10 hours; the end of the reaction is manifested by the sudden occurrence of vigorous refluxing of phosgene. The introduction of phosgene is then immediately stopped and the temperature is maintained at about 100°C for a further 2 hours by recommencing heating and providing good stirring. - 5 42100 , The trichloroethyl chloroformate obtained, may then be recovered by distillation under reduced pressure.

In order that the invention may be more fully understood, the following examples are given by way of illustration only. Examples 1 to 5 are examples of the process according to the invention; Example 6 is given for the purpose of comparison.

Example 1 The reaction was carried out in a 800 litre reactor which was connected to two condensers arranged in series which were respectively operated at 10% and - 20°C. 593 kg of liquid triehloroethanol and 14-9 kg of dimethylformamide were introduced into the reactor and the mixture was heated. When the temperature reached 8o°C, phosgene was introduced and the temperature rose to 100°C. The flow rate of phosgene was then regulated in order to maintain a temperature of between 100 and 105°C. After heating had been stopped, equilibrium was achieved at a phosgene flow rate of 70 kg/hour. Under these conditions^ refluxing in the second condenser was Very slight. The end of the reaction was noted by the sudden occurrence of vigorous refluxing in the second condenser. The introduction of phosgene was stopped and the mixture was maintained for two hours at 100°C by recommencing heating.

Analysis of the crude product, the proportions of phosgene and hydrochloric acid (approx.5% ) being deduced, gave the following results : impurities 7.0% alcohol 0.8% chloroformate 88.2% carbonate 4.0% ΊΊιο reactor was then connected to a vaccum pump and the pressure was reduced. The first fraction was distilled under a pressure of 65 to 70 nun Hg; the fraction which passed over up to 70°C was collected. This fraction contained the catalyst, most of the impurities present in the alcohol starting material and, when present, the residual alcohol. The middle fraction was then distilled (boiling point under 22 mm Hg = 84°C). The final distillation fraction was run out and allowed to set solid. This last fraction consisted of trichloroethyl carbonate and tars formed during the reaction and the distillation.

The results were as follows: amount of trichloroethanol amount of phosgene dimethylfo rmarnide flow rate of phosgene duration of reaction stirring at 100°C first distillation fraction 593 kg 620 kg 14-9 kg 70 kg/hour 9 hours 2 hours (weight 40.5 kg ( distillation 7&C/ ( conditions 65 cm Hg ί proportion of w ' chloroformate ( middle distillation fraction ( ( weight 683.kg distillation 84DC/ conditions 22 min Hg proportion of chloroformate final distillation fraction 130 kg overall yield/alcohol - 7 42100 Examples 2 to 5 A series of runs were carried out involving, in each case, the reaction of 6 kg of trichloroethyl alcohol with phosgene in a 10 litre reactor provided with a stirrer, a condenser, a temperature probe, and a device for introducing phosgene. The amount of catalyst (dimethylaniline in each case) and/or the reaction temperature were varied from one run to the next.

The molar percentages of trichloroethyl chloroformate and trichloroethyl carbonate obtained were measured after a reaction time of 4 hours. The results obtained are given in the table below: Example No. Working conditions % chlorpformate $ carbonate 2 catalyst = 2$ temperature = 100°C 40.3 1.3 3 catalyst .= 5$ temperature •rlOCTC 48.2 2.6 4 catalyst = 5$ tempegature 61.2 4-6 5 catalyst = 5$ temperature = 120°C 66.2 7-5 ................... - 8 42100 It will be seen that at a temperature above 110°C, the amount of trichloroethyl carbonate formed increased substantially and it is for this reason that it is preferred to use a reaction temperature below 1O5°C.

Example 6 5 Trichloroethyl chloroformate was synthesised in accordance with the process described in French Patent 1,338,931. A solution of trichloroethanol in xylene was reacted with phosgene at a temperature of 12O°-125°C in the presence of dimethylaniline, which is present in a proportion of 0.05 mol per mol of trichloroethanol.

Trichloroethyl chloroformate was obtained in 65% yield.

The invention thus provides an industrial process for the preparation of pure trichloroethyl chloroformate in good yields, without using a solvent, and this makes .. the process simpler and less expensive to carry out.

Claims (8)

1. CLAIMS:1. A process for the preparation of 2,2,2 —trichloroethyl chloroformate, which comprises reacting 2,2.,2-trichloroethanol with phosgene at an elevated temperature, 5 in the absence of a solvent and in the presence of an organic compound containing a tertiary nitrogen atom and having a boiling point of at least 120°C, as catalyst.

2. A process according to claim 1, in which the catalyst is Ν,Ν-dimethylformamide or dimethylaniline. 10

3. A process according to claim 1 or 2 in which the temperature of the reaction mixture is not more than 105°C.

4. · A process according to any of claims 1 to 3, in which the temperature of the reaction mixture is from 100°C to 105°C. 15

5. · A process according to any of claims 1 to 4, in which the molar amount of catalyst used is from 0.5% to 7%·

6. A process according to any of claims 1 to 5, in which the molar amount of catalyst used is approximately 5%. 20

7. · A process for the preparation of 2,2,2—trichloroethyl chloroformate substantially as herein described in any of Examples 1 to 5·

8. 2,2,2-Trichloroethyl chloroformate when prepared by the process claimed in any of the preceding claims.