Reductive alkylation of secondary amines with hydrosilane

DETAILED DESCRIPTION OF THE INVENTION In its broadest aspect, the present invention provides a more efficient process for the preparation of tertiary amines (IV) from secondary amines (I) and carbonyl compounds (II).
The process involves reaction of a secondary amine (I) with a carbonyl compound (II) using a hydrosilane (III) in the presence of a Lewis acid (Scheme 1).
##STR1## In a more narrow aspect, the invention deals with the preparation of 1-alkyl-2,3,4,5-tetrahydro-1,4-benzodiazepines (VII) from 4-substituted-2,3,4,5-tetrahydro-1,4-benzodiazepines (V) with an aldehyde (VI) using hydrosilane (III) in the presence of Lewis acid (Scheme 2).
##STR2## In compounds I, II, III, IV, V, VI and VII, the functional groups R, R.
sup.
1, R.
sup.
2, R.
sup.
3, R.
sup.
4, R.
sup.
5, R.
sup.
6, R.
sup.
7 and R.
sup.
8 can be C.
sub.
1 -C.
sub.
12 alkyl or C.
sub.
1 -C.
sub.
30 aryl groups.
X can be one or a combination of hydrogen, halogen, R, RO--, RCOO--, ROCOO--, R.
sup.
1 R.
sup.
2 NCOO--, R.
sup.
1 R.
sup.
2 N--, RS--, RS(O).
sub.
2 --, ROS(O).
sub.
2 --, R.
sup.
1,R.
sup.
2 NS(O).
sub.
2 --, CN, NO.
sub.
2.
Y can be RC(O)--, ROC(O)--, R.
sub.
1 R.
sub.
2 NC(O)--, RS(O).
sub.
2 --, ROS(O).
sub.
2 --, R.
sub.
1 R.
sub.
2 NS(O).
sub.
2 --.
Unless otherwise indicated, as used herein the term "alkyl" or derivative forms thereof, refers to straight chain or branched alkyl groups of 1 to 12 carbon atoms, the term "aryl" or derivative forms thereof refers to aryl groups of 1-30 carbon atoms.
Examples of alkyl groups include methyl, ethyl, propyl, butyl, isobutyl, pentyl, hexyl and the like.
Examples of aryl groups include phenyl, naphthyl, anthryl, biphenyl and the like.
The term "halo" refers to Cl, Br, and l.
Lewis acid includes protonic acids and non-protonic acids.
Examples of protonic acids include trifluoroacetic acid, trifluoromethanesulfonic acid and the like.
Examples of non-protonic acids include boron trifluoride.
As set forth in Scheme 2, the process for the preparation of 1-alkyl-2,3,4,5-tetrahydro-1,4-benzodiazepines involves reaction of a 4-substituted-2,3,4,5-tetrahyrdro-1,4-benzodiazepine with an aldehyde in the presence of a hydrosilane and Lewis acid in a suitable solvent or solvent mixtures