956 Formation of new carbon-carbon bonds
For the preparation of primary amines by Mannich reaction it is useful
to start from dibenzylamine as the two benzyl groups can be removed later
by catalytic hydrogenation.
A further side reaction is occasionally the introduction of a second amino-
methyl group, e.g.:
C 6 H 5 COCH 3 C 6 H 5 COCH 2 CH 2 NR 2 C 6 H 5 COCH(CH 2 NR 2 ) 2The annexed Table gives a few examples of the application of Mannich
reactions to compounds of the types mentioned above.
RHAcetylene
(Ethylthio)acetylene
Phenylacetonitrile
m-Nitroacetophenone
Tetralone
Isobutyraldehyde
Phenol
iVjiV-Diethylaniline
2,4,6-Trinitrotoluene
2-Nitropropane
Azulene
2-Methylfuran
Indole
Indole
Naphthol
cpdCH 2 O
CH 2 O
CH 2 O
CH 2 O
CH 2 O
CH 20
CH 2 O
CH 2 O
CH 2 O
CH 2 O
CH 2 O
CH 2 O
CH 2 O
CH3CHO
CHOCOOHAmineDiethylamine
Diethylamine
Morpholine
Diethylamine
Tetrahydroisoquinoline
Methylamine
Ammonia
Piperidine
Diethanolamine
Diallylamine
[(CH 3 ) 2 N] 2 CH 2
Morpholine
Dimethylamine
Isopropylamine
MorpholineYield
(%)76
100
51
80-90
66
70
92
74
95
89
66
78
80
39-60
85-90Ref.700
701
702
703
704
705
706
707
708
709
710
711
712
713
714In structurally suitable cases the Mannich condensation may be intra-
molecular, leading to heterocycles, notably when the CH-acidic component
group is suitably placed in the same molecule:
CH 2 O
NH 2(^700) J. C. Sauer, B. W. Howk, and R. T. Stiehl, /. Amer. Chem. Soc, 81, 693 (1959).
(^701) H. J. Boonstra and J. F. Arens, Rec. Trav. Chim., 79, 866 (1960).
(^702) H. E. Zaugg, B. W. Horrom, and M. R. Vernsten, /. Amer. Chem. Soc, 75, 288
(1953).
(^703) C. Mannich and M. Dannehl, Arch. Pharm., 276, 206 (1938).
(^704) E. Mosettig and E. L. May, /. Org. Chem., 5, 528 (1940).
(^705) C. Mannich and H. Wieder, Ber. Deut. Chem. Ges., 65, 385 (1932).
(^706) G. K. Abdullaev and A. S. Arabova, Uch. Zap., Azerb. Gos. Univ., Ser. Fiz.-Mat.
i Khim. 707 Nauk, 1962, 43; Chem. Abstr., 60, 1627 (1964).
H. Bohme, E. Mundlos, W. Lehners, and O. E. Herboth, Chem. Ber., 90, 2008 (1957).
(^708) H. A. Bruson and G. B. Butler, /. Amer. Chem. Soc, 68, 2348 (1946).
(^709) G. B. Butler, /. Amer. Chem. Soc, 78, 482 (1956).
(^710) K. Hafner, Angew. Chem., 70, 419 (1958).
(^711) R. F. Holdren and R. M. Hixon, /. Amer. Chem. Soc, 68, 1198 (1946).
(^712) H. R. Snyder, C. W. Smith, and J. M. Stewart, /. Amer. Chem. Soc, 66, 200 (1944).
(^713) H. R. Snyder and D. S. Matteson, /. Amer. Chem. Soc
714 9 79, 2217 (1957).
E. Biekert and T. Funck, Chem. Ber., 97, 363 (1964).