Studies of the mechanistic diversity of sodium cyanoborohydride reduction of tosylhydrazones

Journal Article · Fri Aug 18 04:00:00 EDT 1989 · Journal of Organic Chemistry; (USA)

DOI:https://doi.org/10.1021/jo00278a035· OSTI ID:7156234

Miller, V P; Yang, Dingyah; Weigel, T M; Han, O; Liu, Hungwen ^[1]

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1. Univ. of Minnesota, MN (USA)

Reduction of tosylhydrazone derivatives of ketones and aldehydes with sodium cyanoborohydride in acid medium is a mild, albeit versatile, deoxygenation reaction. The reaction mechanism has been proposed to proceed via either a direct hydride attack route or a tautomerization-then-reduction route. By using a mild reduction procedure (NaBH{sub 3}CN, THF-MeOH, 0{degree}C), it has been possible to stop the deoxygenation halfway and isolate the nascent tosylhydrazine product. Characterization of the resulting hydrazine to define the origin of the hydrogen being delivered to the former carbonyl carbon has allowed us to unambiguously distinguish between these two possible mechanisms. Studies of reduction of tosylhydrazones derived from conjugated and saturated ketones confirmed earlier speculation that these reductions occur through a direct hydride attack mechanism. The reduction of para-substituted methyl phenyl ketone tosylhydrazones revealed a competition between these two mechanisms. Substrates bearing electron-donating substituents prefer the direct hydride attack pathway, while those with electron-withdrawing substituents favor an initial tautomerization prior to reduction. Sugar and hydroxyl ketone tosylhydrazones are also reduced by competing mechanisms. The mechanistic diversity in those cases may be attributed to the inductive effects compelled by the {alpha} substituents and the conformational constraints imposed by the ring structure. The mechanistic insights gained from these studied indicate that the direct hydride attack mechanism is the main reaction pathway due to the propensity of NaBH{sub 3}CN to selectively attack the iminium ion. The tautomerization-then-reduction mechanism prevails only when the tautomerization of hydrazone to azohydrazine is facilitated.

• OSTI ID: 7156234
• Journal Information: Journal of Organic Chemistry; (USA), Journal Name: Journal of Organic Chemistry; (USA) Vol. 54:17; ISSN JOCEA; ISSN 0022-3263
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400201* -- Chemical & Physicochemical Properties
ALDEHYDES
BORON COMPOUNDS
CHEMICAL REACTIONS
DATA
DATA ANALYSIS
EXPERIMENTAL DATA
HYDRAZONES
INFORMATION
KETONES
MEASURING INSTRUMENTS
MEASURING METHODS
MECHANICS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
REDUCTION