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Synlett 2002(4): 0646-0648
DOI: 10.1055/s-2002-22704
LETTER
© Georg Thieme Verlag Stuttgart · New York

The Trifluoromethylacetophenone-N,N-dimethyltrimethylsilylamine Adduct - A New Shelf Stable Reagent for Nucleophilic Trifluoromethylation.

William B. Motherwell*, Lynda J. Storey
Department of Chemistry, Christopher Ingold Laboratories, University College London, 20 Gordon Street, London, WC1H 0AJ, U.K.
Fax: +44(207)6797524; e-Mail: w.b.motherwell@ucl.ac.uk;
Further Information

Publication History

Received 5 February 2002
Publication Date:
05 February 2007 (online)

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Abstract

The simple thermal addition product of N,N-dimethyltrimethylsilylamine with trifluoromethylacetophenone provides a shelf-stable reagent for nucleophilic trifluoromethylation of the carbonyl group.

Key words

nucleophilic trifluoromethylation - trifluoromethyl carbinols - aldehydes - ketones

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11

Synthesis of 2: N,N-Dimethylaminotrimethylsilane (5 mL, 0.031 mol) and trifluoroacetophenone (4.34 mL, 0.031 mol) were added to a round bottom flask equipped with a reflux condenser. The neat mixture was heated in an oil bath at
110 °C for 16 h under a nitrogen atmosphere. The product was distilled between 117-118 °C/18 mmHg to give a clear oil (7.93 g, 87% yield). Calculated for C13H20F3NOSi:
C, 53.59; H, 6.92; N, 4.81. Found: C, 53.45; H, 7.07; N, 4.80; IR(neat)/cm-1: 2958, 2846, 2799, 1255, 1163, 1050. δH (300 MHz) 0.20 [9 H, s, Si-(CH3)3], 2.29 [6 H, d, J = 1, N-(CH3)2], 7.35 (3 H, m), 7.58 (2 H, m). δF (282 MHz) -71.3. δC (75 MHz) 1.7 [Si-(CH3)3], 39.9 [N-(CH3)2], 93.1 (q, J = 28.5,
C-CF3), 124.2 (q, J = 292, CF3), 127.5, 127.8, 128.5, 139.2.

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Representative procedure: Dry, distilled THF (5 mL) was added to a round bottom flask equipped with a reflux condenser, containing pre-dried caesium fluoride (15 mg, 0.098 mmol). Benzaldehyde (100 mL, 0.98 mmol)was then added, followed by 2 (466 mL, 1.97 mmol), and the mixture was heated to reflux for 20 h. Hydrochloric acid (2 M, 1 mL) was then added and stirring was continued for 3 h. The mixture was diluted with diethyl ether, washed with water (3 × 5 mL), sat. brine (5 mL), dried with MgSO4, and the solvent removed in vacuo. The crude product was purified by flash chromatography on silica gel using diethyl ether-hexane (1:9) to give the product as a yellow oil (139 mg, 89%) whose properties were identical with those reported in the literature.