2-Chloromethylphenylcarbamic acid fluoride is prepared by reacting 2-chloromethylphenylisocyanate with anhydrous hydrofluoric acid. The product prepared can be reacted further with anhydrous hydrofluoric acid under pressure to prepare 2-aminodiphenylmethane-2'-carboxylic acid lactam.

This invention relates to 2-chloromethylphenylcarbamic acid fluoride, a 
process for its preparation and its use for the preparation of 
2-aminodiphenylmethane-2'-carboxylic acid lactam. 
The preparation of certain arylcarbamic acid fluorides by addition of 
hydrogen fluoride to the corresponding isocyanates is known. Thus, 
Houben-Weyl, 4th Edition, Volume V/3 page 113 et seq., describes the 
preparation of, for example, phenylcarbamic acid fluoride by reaction of 
phenylisocyanate with hydrofluoric acid. 
SUMMARY 
It has now been found that 2-chloromethylphenylcarbamic acid fluoride can 
be obtained by reacting 2-chloromethylphenylisocyanate with anhydrous 
hydrofluoric acid. 
DESCRIPTION 
The fact that the reaction of 2-chloromethylphenylisocyanate with 
hydrofluoric acid leads, in such a simple manner and without 
side-reactions, to the corresponding stable carbamic acid fluoride, was 
surprising since in general it is known that compounds of the character of 
benzyl chloride react very vigorously with Friedel-Crafts catalysts to 
form polybenzyls (see Beilstein, E III 5, page 638). 
In general, the procedure followed in the preparation of 
2-chloromethylphenylcarbamic acid fluoride is that the anhydrous 
hydrofluoric acid is first charged in at temperatures of 0.degree. to 
10.degree. C and then 1 mol of 2-chloromethylphenylisocyanate is added per 
0.5 to 1 mol of hydrofluoric acid. After the material has been added, the 
temperature of the reaction mixture is in general allowed to rise slowly 
to room temperature and left there for a prolonged period of time, in 
general until the reaction mixture has crystallised completely. The 
crystals are covered once with petroleum ether and then sucked dry on a 
suction filter. 
2-Chloromethylphenylisocyanate is known and is, for example, obtainable in 
good yield and high purity by side-chain chlorination of 2-tolylisocyanate 
(see Houben-Weyl, Methods of Organic Chemistry, 4th Edition, Volume V/3, 
page 746 (1968)). 
Commercial grades of anhydrous hydrofluoric acid can be employed. 
The 2-chloromethylphenylcarbamic acid fluoride obtained according to the 
invention has a melting point of 64.degree. C. The IR spectrum shows a C=O 
band at 1,762 cm.sup.-1 and characteristic N-H adsorptions at 3272 and 
1525 cm.sup.-1. The .sup.19 F nuclear resonance spectrum shows a resonance 
at -71.3 ppm (measured against CF.sub.3 COOH as the external standard). In 
the mass spectrum, the molecular peak appears at 187 m/e. 
Further, it has been found that 2-chloromethylphenylcarbamic acid fluoride 
can be used in a technically advantageous manner for the preparation of 
2-aminodiphenylmethane-2'-carboxylic acid lactam. For this, the procedure 
followed is generally that anhydrous hydrofluoric acid and 
2-chloromethylphenylcarbamic acid fluoride, preferably dissolved in 
benzene, are reacted under pressure, for example by introducing the 
reactants into an autoclave at low temperatures and the autoclave is then 
sealed and warmed. In this reaction 2-chlormethyl-phenylcarbamic acid 
fluoride is generally employed in amounts of 0.1 to 0.2 mols, relative to 
hydrofluoric acid. Benzene is present in excess relative to 
2-chlormethylphenylcarbamic acid fluoride employed, and in general molar 
ratios of carbamic acid fluoride to benzene of 1 : 2 - 5 are chosen. In 
general, the carbamic acid fluoride/benzene and the hydrofluoric acid are 
mixed at temperatures of 0.degree. to 5.degree. C, whilst the cyclysation 
reaction takes place at higher temperatures, for example at temperatures 
from room temperature to 180.degree. C, temperatures of 40.degree. to 
120.degree. C being advantageous. The reaction time is in general 1/2 to 
12 hours, reaction times of 1 to 2 hours being preferred. After the 
reaction has taken place, the hydrofluoric acid and benzene are distilled 
off in a manner which is in itself known and the residue which remains is 
washed with alkali metal hydroxide solution, generally potassium 
hydroxide, filtered and dried. 2-Aminodiphenylmethane-2'-carboxylic acid 
lactam, thus obtained, is a valuable starting material for the synthesis 
of a wide range of pharmaceutical compounds. Thus it is known, for 
example, that N-dialkyl-aminoalkyl derivatives of 
2-aminodiphenylmethane-2'-carboxylic acid lactam have a good antispasmodic 
action (Journal of Medical Chemistry, Volume 8, page 76 (1965)). 
In a particularly advantageous embodiment of the preparation of 
2-aminodiphenylmethane-2'-carboxylic acid lactam, the 
2-chloromethylphenylcarbamic acid fluoride is not isolated as such. Here, 
the procedure followed is that hydrofluoric acid, in amounts of 2 to 10 
mols, is initially introduced into an autoclave at temperatures of -10 to 
10.degree. C and 2-chloromethylphenylisocyanate, dissolved in benzene, is 
added dropwise thereto. After completion of the addition, the reaction 
mixture is then warmed to higher temperatures, for example to temperatures 
of 20.degree. to 180.degree. C, preferably to 40.degree. to 120.degree. C. 
Hereupon, a pressure of 2 to 50 atmospheres gauge in general becomes 
established in the autoclave. After cooling, and releasing the pressure, 
hydrofluoric acid and benzene are distilled off under atmospheric pressure 
until the internal temperature reaches 50.degree. C and the residue in the 
autoclave is poured onto ice. The product is washed with dilute alkali 
metal hydroxide solution, in general with aqueous potassium hydroxide 
solution, filtered off, rinsed thoroughly with water and dried. 
2-Aminodiphenylmethane-2'-carboxylic acid lactam can thus be obtained in a 
technically advantageous manner in one step directly by the reaction of 
2-chloromethylphenylisocyanate with hydrofluoric acid.

EXAMPLE 1 
5 g of anhydrous hydrofluoric acid are initially introduced into a stirred 
vessel made of stainless steel and 41.5 g of 
2-chloromethylphenylisocyanate are added dropwise at 0.degree. to 
10.degree. C. The reaction mixture is allowed to warm to room temperature 
and is left to stand at this temperature overnight. The batch which has 
crystallised throughout is covered once with petroleum ether and the 
product is then sucked dry on a suction filter. Yield: 44 g (91% of 
theory), melting point: 64.degree. C. 
EXAMPLE 2 
40 ml of anhydrous hydrofluoric acid are initially introduced into an 
autoclave and 41 g of 2-chlorophenylcarbamic acid fluoride dissolved in 68 
g of benzene are added at 0.degree. to 5.degree. C. The autoclave is 
sealed and warmed to 100.degree. C for 1 hour. Hydrofluoric acid and 
benzene are distilled off and the residue which remains is washed with 
aqueous potassium hydroxide solution, filtered and dried. 44 g (= 96% of 
theory) of 2-aminodiphenylmethane-2'-carboxylic acid lactam of melting 
point 193.degree. - 196.degree. C are thus obtained. 
EXAMPLE 3 
400 ml of anhydrous HF are initially introduced into a stainless steel 
autoclave, fitted with a stirrer, at about 0.degree. C. A solution of 340 
g of 2-chloromethylphenylisocyanate in 800 ml of benzene is added dropwise 
thereto over the course of 45 minutes, during which the temperature is 
allowed to rise to 15.degree. C. After completion of the addition the 
mixture is stirred for a further 15 minutes and the autoclave is then 
sealed and heated to 100.degree. C for 15 minutes. In the course thereof, 
the pressure assumes a value of about 16 atmospheres gauge. After cooling, 
and releasing the pressure, the mixture is distilled under atmospheric 
pressure until the internal temperature is 50.degree. C, and the residue 
in the autoclave, while still liquid, is poured onto ice. The product is 
washed with dilute aqueous KOH, filtered off, rinsed thoroughly with water 
and dried. 
Yield: 408 g (96.2% of theory) of 2-aminodiphenylmethane-2'-carboxylic acid 
lactam of melting point 196.degree. - 199.degree. C.