Weygand/Hilgetag Preparative Organic Chemistry

C-C linkage by replacement of hydroxyl by carbon 953

can be used to introduce a chloromethyl group directly into an aromatic

system. On an industrial scale this reaction is effected without a solvent,

675

but in

preparations on a laboratory scale chloroform, carbon tetrachloride, light
petroleum, or acetic acid saturated with hydrogen chloride is employed as

solvent. Zinc chloride is usually prescribed as condensing agent or catalyst.

Adding phosphoric acid sometimes improves the yield. According to Wey-
gand a mixture of benzyl chloride and co,co-dichloroxylene is obtained as

follows:

Zinc chloride (84 g), trioxymethylene (90 g), chloroform or carbon tetrachloride (200 ml),
and benzene (78 g) are placed in a sulfonation flask (11) fitted with a gas-inlet tube, reflux
condenser, and stirrer and are stirred while a rapid stream of hydrogen chloride is led in.
The mixture becomes warm and is cooled at the beginning of the reaction but is warmed to
50-60° towards the end. After 2h the mixture is washed successively with water (several
times), dilute sodium carbonate solution, and water; it is then dried over calcium chloride,
and most of the chloroform is distilled off. Distillation of the residue in a vacuum affords
benzyl chloride (84 g, 66%) and a),co-dichloroxylene (55 g, 30%), the latter consisting mainly
of the para-compound.
The dichloroxylene can also be obtained analogously from benzyl chloride (127 g) by
means of zinc chloride (42 g), trioxymethylene (45 g), and carbon tetrachloride (100 ml).
After the reaction the product is taken up in ether, washed with water and dilute sodium
carbonate solution, and worked up as above. 83 % (145 g) of the dichloroxylenes-are obtained,
from which the /?ara-compound (100 g) crystallizes.
Naphthalene can be chloromethylated at position 1 in 74-77% yield.^676

Chloromethyl methyl ether may be used in place of the formaldehyde and

hydrogen chloride:

ArH + CH 3 OCH 2 C1 > ArCH 2 Cl + CH 3 OH + H 2 O

for example, 1,3,5-triisopropylbenzene is converted by this chloro ether in

carbon disulfide with tin tetrachloride as catalyst into 2,4,6-triisopropyl-

benzyl chloride in 85% yield.^592 Less reactive aromatic compounds can also

be chloromethylated — by longer heating with the chloro ether in the presence

of aluminum chloride; 2-hydroxy-5-nitrobenzaldehyde, for instance, is chloro-

methylated at position 3 in 90% yield after reaction for 80 hours.^677 Mono-

chloro ethers have been used also for chloromethylation of a considerable range

of styrene-divinylbenzene polymers

678

(for the literature see Gross and

Hoft^679 ); and the preparation of the chloromethyl derivative of polystyrene

for use in peptide synthesis has been described by Merrifield.

680

A review

of halomethylation by mono- and symmetrical di-halo ethers has been given

by Gross and Hoft^679 and others.271b

co-Chloromethylation of styrene has been reported by Wichterle and

Cerny.

681

(^675) Ger. Pat. 508,890; Chem. Abstr., 25, 716 (1931).
(^676) O. Grummitt and A. Buck, Org. Syn., 24, 30 (1944).
(^677) L. D. Taylor and R. B. Davis, /. Org. Chem., 28, 1713 (1963).
(^678) U.S. Pat. 2,694,702; Chem. Abstr., 49, 6551 (1955).
(^679) H. Gross and E. Hoft, Angew. Chem. Int. Ed., Engl, 6, 335 (1967).
(^680) R. B. Merrifield, /. Amer. Chem. Soc, 85, 2149 (1963); Biochemistry, 3, 1385 (1964);
Science, 150, 178 (1965); G. R. Marshall and R. B. Merrifield, Biochemistry, 4, 2394 (1965).
(^681) O. Wichterle and J. Cerny, Collect, Czech. Chem. Commun., 20, 1288 (1955).