Weygand/Hilgetag Preparative Organic Chemistry

Replacement of halogen by another halogen or by thiocyanate 213
Iodobenzene from chloro- or bromobenzene: 436 Diiodoacetylene (0.1 mole) in ether (50 ml)
is dropped into an ethereal Grignard solution from chloro- or bromo-benzene (0.2 moles) with
ice-cooling (clouding). The mixture is set aside for 15 min at room temperature and the top
layer is decanted from the bottom syrupy layer deposited from the cloud, or the whole is
decomposed directly by dilute H2SO4. The dried ethereal solution affords a 95% or 97%,
respectively, yield of iodobenzene, b.p. 188°/760mm.
The ethereal Grignard solution obtained from indole and C2H5MgBr similarly affords an
83 % yield of 3-iodoindole.
3. Replacement of halogen by thiocyanate
The classical, generally applicable method of preparing aliphatic thiocyanates
(a) is to treat a halide with an alkali thiocyanate or ammonium
thiocyanate:
RNCS < RX • RSCN
(b) (a)
General procedure: An alkyl bromide (1 mole) is dropped into a stirred, boiling mixture
of finely powdered KSCN (1.5 moles) and ethanol (340 ml; about one-third of the KSCN
dissolves), and the mixture is kept at the b.p. for 2 h. Then part of the solvent is distilled
off, the remaining mixture is diluted with water, the thiocyanate is extracted in ether, and
the ethereal solution is dried over CaCl2 or Na2SO4 and worked up by vacuum-distillation.
Yields for pentyl to tridecyl thiocyanate are about 80-90%. 850
Alternatively ethanolic halide solutions, e.g., Cl(CH2)nOH, 851 and concentrated aqueous
KSCN are mixed, boiled for some hours, diluted with water, and extracted with CHC13.
Dioxan may also be used as solvent. Thiocyanatohydrin derivatives RO(CH2)«SCN are
of value as insecticides. 852
NaSCN in acetone can also be used, as in other halogen exchange reactions. For the
preparation of cw-9-octadecenyl thiocyanate 853 the bromide (54 g) and NaSCN • 2H2O
(75 g) in acetone (500 ml) are allowed to react in an autoclave at 80° for 20 hours.
Lower alkyl thiocyanates are very simply obtained by gradually adding the dialkyl sulfate
(1 mole) to KSCN (1 mole) in water (50 ml) with shaking and, if necessary, cooling. 854
The more mobile the halogen to be replaced from RX, the more easily are
isothiocyanates (mustard oils) (b) formed. Isothiocyanates have lower boiling
points than thiocyanates, are more stable, and can be obtained by heating
thiocyanates; addition of ZnCl2 accelerates the rearrangement. 855 Mixtures
of thiocyanates and isothiocyanates are often obtained in the main reaction.
Halides with readily removable halogen give isothiocyanates directly if higher
temperatures (120-130°) are involved in working up or in the reaction.
Chloromethyl methyl or ethyl ether, for instance, and KSCN in light petroleum form
methoxymethyl or ethoxymethyl isothiocyanate, respectively, 856 and 2,3,4,6-tetra-O-acetyla-D-glucopyranosyl
isothiocyanate is obtained from a-acetobromoglucose and AgSCN in
toluene. 857
850 P. Allen Jr., /. Amer. Chem. Soc, 57, 198 (1935).
851 H.D.Vogelsang, T. Wagner-Jauregg, and R. Rebling, Ann. Chem., 569, 190(1950).
852 T. Wagner-Jauregg, Ann. Chem., 561, 94 (1949).
853 T. Wagner-Jauregg and co-workers, /. Prakt. Chem., 155, 216 (1940).
854 P. Walden, Ber. Deut. Chem. Ges., 40, 3215 (1907).
855 E. Schmidt and co-workers, Ann. Chem., 568, 193 (1950).
856 E. Schmidt and W. Striewsky, Ber. Deut. Chem. Ges., 73, 286 (1940).
857 F. P. van de Kamp and F. Micheel, Chem. Ber., 89, 133 (1956).