Weygand/Hilgetag Preparative Organic Chemistry

954 Formation of new carbon-carbon bonds

A 1-chloroethyl group can be introduced into aromatic compounds by

the reaction:

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ArH + CH3CHO + HCl • ArCHClCH 3 + H 2 O

Thus salicylic acid, chloral, and hydrogen chloride in concentrated sulfuric

acid afford 2-hydroxy-5-(l,2,2,2-tetrachloroethyl)benzoic acid in very good
yield.^683

Bromomethylation is also possible, e.g., the preparation of benzyl bromide

in 86.5% yield from benzene, formaldehyde, and hydrogen bromide in acetic
plus sulfuric acid.^684 '^685 So is iodomethylation of aromatic compounds,

by reaction of bis(chloromethyl) ether and hydrogen iodide in glacial acetic

acid.

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4. Hydroxymethylation

In an alkaline medium formaldehyde reacts with reactive hydrogen atoms,
providing a hydroxymethylation:

RH + CH 2 O • RCH 2 OH

Thus an almost quantitative yield of ethyl l-(hydroxymethyl)-2-oxocyclo-

hexanecarboxylate is obtained from ethyl 2-oxocyclohexanecarboxylate and

aqueous formaldehyde in the presence of calcium oxide;

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and 2-butanone
and formaldehyde in sodium hydroxide solution give a 70% yield of 4-hydroxy-

3-methyl-2-butanone, whence 3-methyl-3-buten-2-one is formed in 74%

yield by removal of water.

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Hydroxymethylation of acetone

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and of
co-nitrotoluene (phenylnitromethane)^690 have also been reported.

A weakly alkaline medium suffices for satisfactory introduction of a hydroxy-
methyl group into phenols; e.g., 2,6-bis(hydroxymethyl)phenols have been

prepared in 50-96% yield.^691 This reaction is of fundamental importance in

condensation of phenols with formaldehyde.

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The Prins reaction has been described elsewhere in this book (page 864).

Acetoxymethylation is observed when a hydrocarbon is treated with meth-

oxymethyl acetate: 2,4,6-trimethylbenzyl acetate is produced in 53% from

mesitylene:

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CH 3 CH 3

CH 3 OCH 2 OOCCH 3 —•

(^682) R. L. Frank, C. E. Adams, R. E. Allen, R. Gander, and P. V. Smith, /. Amer. Chem.
Soc, 68, 1365 (1946); R. Quelet and J. Ducasse, C. R. Hebd. Seances Acad. ScL, 208, 1317
(1939); Bull. Soc. Chim. France, [v], 7, 196, 205 (1940).
(^683) R. Chalaust and G. Quesnel, C. R. Hebd. Seances Acad. ScL, 256, 5154 (1963).
(^684) G. Kubiczek and L. Neugebauer, Monatsh. Chem., 81, 917 (1950).
(^685) G. Darzens, C. R. Hebd. Seances Acad. ScL, 208, 818 (1939).
(^686) E. Matarasso-Tchiroukhine, Bull. Soc. Chim. France, 1962, 851.
(^687) Ki-Wei Hiong, Ann. Chim. (Paris), [xi], 17, 269 (1942).
(^688) J. Colonge and L. Cumet, Bull. Soc. Chim. France, [v], 14, 838 (1947).
689
690 S. Olsen, Chem. Ber., 88,^205 (1955).
L. F. Fieser and co-workers, /. Amer. Chem. Soc, 68, 2248, 2249 (1946).
(^691) J. Strating and H. J. Backer, Rec. Trav. Chim., 62, 57 (1943).
(^692) L. Summers, /. Amer. Chem. Soc, 76, 3481 (1954).