Synlett 2007(7): 1026-1030  
DOI: 10.1055/s-2007-973890
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Efficient Synthesis of Amides and Esters via Triacyloxyboranes

Zhongping Huang*, John E. Reilly, Ronald N. Buckle
Department of Medicinal Chemistry, Albany Molecular Research Inc., Albany, NY 12212, USA
Fax: +1(518)4640289; e-Mail: zhongping.huang@albmolecular.com ;
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Publikationsverlauf

Received 6 November 2006
Publikationsdatum:
13. April 2007 (online)

Abstract

Borane-tetrahydrofuran complex or borane-methyl ­sulfide complex is used to activate carboxylic acids to generate triacyloxyboranes. The triacyloxyboranes can be effectively reacted with various nucleophiles including alkylamines, arylamines, hydrazides, alcohols and phenols at reflux in toluene to provide the corresponding amides and esters in excellent yield. Aliphatic carboxylic acids are selectively esterified in the presence of aromatic carboxylic acids under the borane conditions.

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General Procedure for Formation of Amides and Esters: To a carboxylic acid (1-2 mmol) in toluene (10 mL) was added a solution of borane-THF (1 M) in THF in an ice bath. The mixture was warmed to r.t. for 1 h. An amine or an alcohol was added and the mixture was heated at reflux for 12 h or 24 h. The resulting mixture was cooled to r.t. and treated with HCl (1 M), and then diluted with EtOAc (20 mL). The organic phase was washed with H2O and concentrated under reduced pressure and purified by flash chromatography. The physical data of compounds are provided below.
N -Butylhexanamide (Table 3, Entry 1): 1H NMR (500 MHz, CDCl3): δ = 5.37 (br s, 1 H), 3.25 (t, J = 7.0 Hz, 2 H), 2.14 (t, J = 8.0 Hz, 2 H), 1.64-1.60 (m, 2 H), 1.47-1.46 (m, 2 H), 1.36-1.30 (m, 6 H), 0.94-0.88 (m, 6 H). 13C NMR (125 MHz, CDCl3): δ = 170.6, 36.8, 34.5, 29.4, 29.1, 23.1, 20.0, 17.7, 11.5, 11.4. APCI-MS: m/z = 172 [M+].
1-Morpholinononan-1-one (Table 3, Entry 2): 1H NMR (500 MHz, CDCl3): δ = 3.68-3.61 (m, 6 H), 3.48-3.44 (m, 2 H), 2.33-2.28 (m, 2 H), 1.62-1.55 (m, 2 H), 1.30-1.27 (m, 10 H), 0.90-0.85 (m, 3 H). 13C NMR (125 MHz, CDCl3): δ = 171.9, 66.9, 66.7, 46.0, 41.8, 33.1, 31.8, 29.4, 29.3, 29.1, 25.2, 22.6, 14.0. APCI-MS: m/z 228 [M+].
N -Benzylcyclohexanecarboxamide (Table 3, Entry 3): 1H NMR (500 MHz, CDCl3): δ = 7.34-7.26 (m, 5 H), 5.70 (br s, 1 H), 4.44 (d, J = 5.6 Hz, 2 H), 2.16-2.05 (m, 1 H), 1.90-1.87 (m, 2 H), 1.80-1.78 (m, 2 H), 1.60-1.59 (m, 1 H), 1.47-1.45 (m, 2 H), 1.28-1.22 (m, 3 H). 13C NMR (75 MHz, CDCl3): δ = 175.8, 138.5, 128.7, 127.7, 127.4, 45.6, 43.4, 29.7, 25.7. APCI-MS: m/z 218 [M+].
N -Benzyl-4-methylbenzamide (Table 3, Entry 4):2 1H NMR (500 MHz, CDCl3): δ = 7.69 (d, J = 8.1 Hz, 2 H), 7.36 (d, J = 4.3 Hz, 4 H), 7.31-7.33 (m, 1 H), 7.23-7.22 (m, 2 H), 6.32 (br s, 1 H), 4.65 (d, J = 5.6 Hz, 2 H), 2.39 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 167.2, 141.9, 138.3, 131.5, 129.2, 128.7, 127.9, 127.6, 126.9, 44.1, 21.4. APCI-MS: m/z = 226 [M+].
N -Benzyl-2-methylbenzamide (Table 3, Entry 5): 1H NMR (500 MHz, CDCl3) δ = 7.38-7.35 (m, 5 H), 7.32-7.28 (m, 2 H), 7.22-7.18 (m, 2 H), 6.10 (br s, 1 H), 4.64 (d, J = 5.7 Hz, 2 H), 2.47 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 169.8, 138.1, 136.2, 136.2, 131.0, 129.9, 128.8, 127.8, 127.6, 126.6, 125.7, 43.9, 19.8. APCI-MS: m/z = 226 [M+].
N -Benzyl-3-cyanobenzamide (Table 3, Entry 6): 1H NMR (300 MHz, CDCl3): δ = 8.08 (s, 1 H), 8.07 (d, J = 8.1 Hz, 2 H), 8.03 (d, J = 7.9 Hz, 1 H), 7.79 (t, J = 7.5 Hz, 1 H), 7.37-7.33 (m, 5 H), 6.47 (br s, 1 H), 4.65 (d, J = 5.6 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 165.1, 137.5, 135.6, 134.7, 131.2, 130.7, 129.6, 128.9, 128.0, 127.9, 117.9, 113.0, 44.4. APCI-MS: m/z = 237 [M+].
N , N -Diphenylacetamide (Table 3, Entry 7): 1H NMR (300 MHz, CDCl3): δ = 7.36-7.28 (m, 10 H), 2.05 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 170.4, 129.6, 128.9, 126.4, 23.8. APCI-MS: m/z = 212 [M+].
N ′-(Cyclohexanecarbonyl)-4-methylbenzenesulfono-hydrazide (Table 3, Entry 8): 1H NMR (500 MHz, CDCl3): δ = 7.78 (d, J = 8.2 Hz, 2 H), 7.52 (d, J = 6.0 Hz, 1 H), 7.30 (d, J = 8.0 Hz, 2 H), 7.23 (d, J = 6.2 Hz, 1 H), 2.42 (s, 3 H), 1.99-1.97 (m, 1 H), 1.70-1.68 (m, 2 H), 1.63-1.60 (m, 3 H), 1.21-1.13 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 174.0, 144.8, 133.0, 129.4, 128.7, 43.0, 28.9, 25.3, 25.2, 21.7. APCI-MS: m/z = 297 [M+].

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Methyl 2-Hydroxy-2-phenylacetate (Table 4, Entry 1): 1H NMR (300 MHz, CDCl3): δ = 7.41-7.34 (m, 5 H), 5.19 (d, J = 5.6 Hz, 1 H), 3.76 (s, 3 H), 3.44 (d, J = 5.6 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 174.1, 138.2, 128.6, 126.6, 120.0, 72.9, 53.0.
Butyl Hexanoate (Table 4, Entry 2): 1H NMR (300 MHz, CDCl3): δ = 4.09 (t, J = 6.6 Hz, 2 H), 2.31 (t, J = 7.4 Hz, 2 H), 1.63-1.60 (m, 4 H), 1.36-1.30 (m, 6 H), 0.95-0.87 (m, 6 H). 13C NMR (125 MHz, CDCl3): δ = 174.0, 64.1, 34.3, 31.3, 30.7, 24.7, 22.3, 19.1, 13.9, 13.7.
4-Bromophenyl Acetate (Table 4, Entry 3): 1H NMR (500 MHz, CDCl3): δ = 7.50 (d, J = 6.7 Hz, 2 H), 7.00 (d, J = 6.7 Hz, 2 H), 2.29 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 169.1, 149.6, 132.4, 123.3, 118.9, 21.0.
4-Methoxyphenyl Acetate (Table 4, Entry 4): 1H NMR (300 MHz, CDCl3): δ = 7.01 (d, J = 6.7 Hz, 2 H), 6.90 (d, J = 6.7 Hz, 2 H), 3.79 (s, 3 H), 2.28 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 169.1, 157.2, 144.2, 122.3, 114.4, 55.5, 21.0.
4-Cyanophenyl Acetate (Table 4, Entry 5): 1H NMR (300 MHz, CDCl3): δ = 7.71 (d, J = 8.8 Hz, 2 H), 7.26 (d, J = 8.8 Hz, 2 H), 2.33 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 168.4, 153.9, 133.6, 122.7, 118.2, 109.7, 21.1.
4-Bromophenyl Cyclohexanecarboxylate (Table 4, Entry 6): 1H NMR (300 MHz, CDCl3): δ = 7.48 (d, J = 6.7 Hz, 2 H), 6.96 (d, J = 6.7 Hz, 2 H), 2.58-2.51 (m, 1 H), 2.08-2.00 (m, 2 H), 1.88-1.80 (m, 2 H), 1.74-1.50 (m, 3 H), 1.47-1.37 (m, 3 H). 13C NMR (125 MHz, CDCl3): δ = 174.2, 149.9, 132.3, 123.3, 118.6, 43.1, 28.9, 25.6, 25.3.
2-{[(Benzyloxy)carbonyl]methyl}benzoic Acid (Table 4, Entry 7): 1H NMR (300 MHz, CDCl3): δ = 8.15 (d, J = 7.7 Hz, 1 H), 7.55 (t, J = 6.1 Hz, 1 H), 7.44 (t, J = 8.5 Hz, 1 H), 7.34-7.28 (m, 6 H), 5.15 (s, 2 H), 4.11 (s, 2 H). 13C NMR (125 MHz, CDCl3): δ = 171.3, 136.7, 135.9, 133.3, 132.4, 131.9, 128.5, 128.2, 128.1, 127.6, 66.6, 40.7. APCI-MS: m/z = 269 [M-].