A Route to Carbasugar Analogues - Jonathan Clayden - The ...

Experimental for chapter 3.1
128.9, 128.3, 127.9 (para-Ph), 127.7, 127.6, 127.5, 127.0 (para-Ph), 126.8, 126.7,
126.6 (para-Ph), 126.3, 74.5 (CHO), 58.9 (CHN).
Synthesis of 4-cyano-N-((1R*,2S*)-2-hydroxy-1,2-diphenylethyl)benzamide (165g)
Ph
O OH
Ph
i) DMF, (COCl) 2 HO
ii)
O NH
Ph
1
Ph
NH 2
2
CN
OH
3
(±)
4
CN (±)
One drop of DMF was added to a stirred solution of para-cyanobenzoic acid (500 mg,
3.4 mmol) and oxalyl chloride (0.33 cm 3 , 3.74 mmol) in CH 2 Cl 2 (5 cm 3 ). Once
effervescence had stopped the solution was allowed to stir for 1 hr and the solvent was
removed under reduced pressure. The crude acyl chloride in CH 2 Cl 2 (5 cm 3 ) was
added drop wise over a period of 1 hr to a stirred solution of amine 174 (586 mg, 2.75
mmol) in CH 2 Cl 2 (20 cm 3 ) and Et 3 N (0.69 cm 3 , 5 mmol) at 0 °C. After warming to
room temperature, the solution was diluted in CH 2 Cl 2 (10 cm 3 ) and washed with
saturated aqueous sodium bicarbonate (20 cm 3 ), the aqueous extract washed with
further CH 2 Cl 2 (2 x 20 cm 3 ) and the combined organic extracts dried over sodium
sulphate and concentrated under vacuum. The resulting orange oil was purified by
flash chromatography (4:1 to 2:1 petrol:EtOAc) to yield amide 165g (480 mg, 41%) as
colourless cubes.
R f : 0.39 (1:1 petrol:EtOAc); Mpt: 199-200 °C (EtOAc); MS m/z (CI+): 343 (90%,
MH + ), 344 (26%, (M+1)H + ), 325 (100%, [M - H 2 O]H + ); HRMS (ESI+) m/z found
343.1434 (MH calcd. 343.1441); IR ν max (film)/cm -1 : 3324 (br, OH), 2232 (m, CH),
1638 (C=O), 1539, 699; 1 H-NMR (CDCl 3 , 500 MHz) δ 7.85 (d, 2H, J 8.0, H2), 7.73
(d, 2H, J 8.0, H3), 7.30-7.22 (m, 6H, Ph), 7.13-7.03 (m, 5H, Ph, NH), 5.45 (dd, 1H, J
8.0, 4.0, CHNH), 5.23 (d, 1H, J 4.0, CHOH); 13 C-NMR (CDCl 3 , 125 MHz) δ 165.2
(C=O), 139.5 (ipso-Ph), 138.2 (ipso-Ph), 136.5 (C1), 132.5 (C2), 128.3, 128.2 (Ph),
128.2 (para-Ph), 128.0 (para-Ph), 127.9, 127.7 (Ph), 126.3 (C3), 117.9 (C4), 115.2
(CN), 76.7 (COH), 59.6 (CNH).
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