K. Harikrishna, A. Rakshit, I. S. Aidhen
FULL PAPER
4-Oxo-4-(4-tolyl)butanenitrile (3a): Yield 65%; brown oil. Rf = 0.37
3.2 Hz, 2 H, NCH2), 5.60 (br. s, 1 H, NH), 7.13–7.23 (m, 4 H,
(hexane/EtOAc, 7:3). IR (CHCl ): ν
= 1216, 1686, 2926, ArH), 7.63–7.73 (m, 4 H, ArH) ppm. 13C NMR (100 MHz,
˜
3
max
3025 cm–1. H NMR (400 MHz, CDCl3): δ = 2.35 (s, 3 H, CH3), CDCl3): δ = 21.6, 21.9 (2 CH3), 48.6 (NCH2), 127.3 (CH), 128.0
1
2.69 (t, J = 7.6 Hz, 2 H, CH2CN), 3.28 (t, J = 7.2 Hz, 2 H,
CH2CO), 7.21 (d, J = 7.6 Hz, 2 H, ArH), 7.78 (d, J = 8.4 Hz, 2 H,
(CH), 129.7 (CH), 129.9 (CH), 131.4 (C), 136.2 (C), 143.8 (C),
1 4 5 . 6 ( C) , 1 9 2 . 1 ( CO ) p p m . H R M S ( E S I ) : c a l c d . fo r
ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 11.9 (CH2), 21.8 C16H17NO3SNa [M + Na]+ 326.0827; found 326.0827.
(CH3), 34.2 (CH2), 119.4 (CN), 128.2 (CH), 129.6 (CH), 133.2 (C),
4-Methyl-N-[2-oxo-2-(thiophen-2-yl)ethyl]benzenesulfonamide (6b):
Yield 89 %; brown solid, m.p. 114–116 °C. Rf = 0.67 (hexane/
145.0 (C), 195.0 (CO) ppm. HRMS (ESI): calcd. for C11H11NONa
[M + Na]+ 196.0738; found 196.0739.
EtOAc, 6:4). IR (CHCl ): ν
= 1046, 1374, 1739, 2985,
˜
3
max
3465 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.32 (s, 3 H, ArCH3),
4.31 (d, J = 2.8 Hz, 2 H, NCH2), 5.22 (br. s, 1 H, NH), 7.06 (t, J
= 2.5 Hz, 1 H, ArH), 7.19–7.25 (m, 2 H), 7.61–7.65 (m, 2 H, ArH),
7.69 (d, J = 8.0 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3):
δ = 21.6 (CH3), 48.8 (NCH2), 127.3 (CH), 128.5 (CH), 129.8 (CH),
129.9 (CH), 132.6 (CH), 135.1 (C), 136.2 (C), 140.2 (C), 143.9 (C),
185.7 (CO) ppm. HRMS (ESI): calcd. for C13H13NO3S2Na [M +
Na]+ 318.0235; found 318.0246.
(3R,4R)-3,4-Bis(benzyloxy)-5-(4-fluorophenyl)-5-oxopentanenitrile
(4a): Yield 77%; colourless liquid. Rf = 0.6 (hexanes/EtOAc, 7:3).
[α]2D2 = +24.5 (c = 1, CHCl ). IR (CHCl ): νmax = 1446, 1690, 2230,
˜
3
3
2968 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.60–2.68 (dd, J =
3.6, J = 16.4 Hz, 1 H, CHaHbCN), 2.70–2.77 (dd, J = 6.4, J =
17.2 Hz, 1 H, CHaHbCN), 3.94–4.00 (m, 1 H, CH), 4.28 (d, J =
11.6 Hz, 1 H, CHaHbPh), 4.39 (d, J = 11.2 Hz, 1 H, CHaHbPh),
4.48 (d, J = 11.6 Hz, 1 H, CHaHbPh), 4.55 (d, J = 11.6 Hz, 1 H,
CHaHbPh), 4.75 (d, J = 9.0 Hz, 1 H, CHCO), 6.94–7.03 (m, 4 H,
ArH), 7.12–7.20 (m, 5 H, ArH), 7.21–7.28 (m, 3 H, ArH), 7.82–
7.88 (m, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.5
(CH2CN), 72.8, 73.1 (2 CH2Ph), 75.5 (CH), 79.6 (CH), 115.8 (CH),
116.0 (CH), 117.3 (CN), 128.2 (CH), 128.3 (CH), 128.5 (CH), 128.6
(CH), 128.7 (CH), 131.6 (CH), 131.7 (C), 132.7 (C), 136.3 (C),
136.4 (C), 166.2 (d, JC-F = 255.0 Hz, C), 197.3 (CO) ppm. HRMS
(ESI): calcd. for C25H22NO3FNa [M + Na]+ 426.1481; found
426.1468.
N-(Cyanomethyl)-N-[2-oxo-2-(thiophen-2-yl)ethyl]benzenesulfon-
amide (9a): Yield 89%; gummy liquid. Rf = 0.43 (hexanes/EtOAc,
3:2). IR (CHCl ): νmax = 1096, 1168, 1356, 1424, 1471, 1586, 1679,
˜
3
2251, 2926 cm–1. 1H NMR (400 MHz, CDCl3): δ = 4.48 (s, 2 H,
CH2CN), 4.73 (s, 2 H, CH2CO), 7.87 (d, J = 8.0 Hz, 2 H, ArH),
7.81 (br. s, 1 H, thiophene-H), 7.75 (d, J = 4.8 Hz, 1 H, thiophene-
H), 7.66 (t, J = 7.2 Hz, 1 H, ArH), 7.58 (t, J = 8.0 Hz, 2 H, ArH),
7.19 (s, 1 H, thiophene-H), ppm. 13C NMR (CDCl3, 100 MHz): δ
= 36.4 (CH2), 52.1 (CH2), 113.9 (CN), 127.6 (CH), 128.7 (CH),
129.7 (CH), 133.0 (CH), 134.0 (CH), 135.5 (CH), 138.0 (C), 140.5
(C), 185.4 (CO) ppm. HRMS (ESI): calcd. for C14H13N2O3S2 [M
+ H]+ 321.0368 found 321.0374.
(3R,4R)-3,4-Bis(benzyloxy)-5-oxononanenitrile (4b): Yield 67 %;
colourless liquid. Rf = 0.70 (hexanes/EtOAc, 7:3). [α]2D2 = +22.4 (c
= 1, CHCl ). IR (CHCl ): ν = 1422, 1601, 1723, 2930,
˜
max
3
3
3021 cm–1. 1H NMR (400 MHz, CDCl3): δ = 0.75–0.88 (m, 3 H,
CH3), 1.12–1.20 (m, 4 H, 2 CH2), 1.33–1.45 (quint., 2 H, CH2),
2.27–2.52 (m, 2 H, CH2), 3.86–4.03 (m, 2 H), 4.46–4.63 (m, 4 H),
7.20–7.38 (m, 10 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ =
13.9 (CH3), 20.0 (CH2), 22.3 (CH2), 25.0 (CH2), 40.6 (CH2), 73.0
(OCH2), 73.5 (OCH2), 75.7 (CH), 83.3 (CH), 117.4 (CN), 127.6
(CH), 128.2 (CH), 128.4 (CH), 128.5 (CH), 128.7 (CH), 128.8
(CH), 136.7 (C), 148.4 (C), 210.6 (CO) ppm. HRMS (ESI): calcd.
for C23H28NO3 [M + H]+ 366.2069; found 366.2058.
2-[4-(4-Methylbenzoyl)phenyl]acetonitrile (10a): Yield 66%; yellow
solid, m.p. 55–57 °C. Rf = 0.24 (hexane/EtOAc, 1:1.5). IR (CHCl3):
ν
˜
= 1419, 1610, 1658, 1306, 1926, 3055 cm–1 1H NMR
.
max
(400 MHz, CDCl3): δ = 2.44 (s, 3 H, CH3), 3.85 (s, 2 H, CH2CN),
7.29 (d, J = 8.0 Hz, 2 H, ArH), 7.45 (d, J = 8.0 Hz, 2 H, ArH),
7.70 (d, J = 8.0 Hz, 2 H, ArH), 7.80 (d, J = 8.4 Hz, 2 H, ArH) ppm.
13C NMR (100 MHz, CDCl3): δ = 21.8 (CH2CN), 23.7 (CH3),
117.3 (CN), 127.9 (CH), 129.2 (CH), 130.3 (C), 130.8 (CH), 134.0
(C), 134.5 (C), 137.8 (C), 143.7 (C), 195.8 (CO) ppm. HRMS (ESI):
calcd. for C16H14NO [M + H]+ 236.1075; found 236.1082.
(2R,3S,4R,5S,6S)-3,4,5-Tris(benzyloxy)-6-(4-methylbenzoyl)tetra-
hydro-2H-pyran-2-carbonitrile (5a): Yield 74%; colourless liquid.
[α]2D2 = –18.6 (c = 1, CHCl3). Rf = 0.70 (hexanes/EtOAc, 7:3). IR
3-[4-(4-Methoxybenzoyl)phenyl]propanenitrile (11a): Reaction car-
ried out at –65 °C, yield 65%; colourless gummy liquid. Rf = 0.34
(CHCl ): νmax = 1455, 1606, 1688, 2254, 2985, 3054 cm–1. 1H NMR
(hexane/EtOAc, 3:2). IR (CHCl ): ν
= 1644, 2241, 3019 cm–1.
˜
˜
3
3
max
1H NMR (500 MHz, CDCl3): δ = 2.68 (t, J = 7.5 Hz, 2 H,
CH2CN), 3.04 (t, J = 7.5 Hz, 2 H, ArCH2), 3.89 (s, 3 H, OMe),
6.96 (d, J = 8.0 Hz, 2 H, ArH), 7.34 (d, J = 8.0 Hz, 2 H, ArH),
7.74 (d, J = 8.0 Hz, 2 H, ArH), 7.81 (d, J = 9.0 Hz, 2 H, ArH) ppm.
13C NMR (125 MHz, CDCl3): δ = 19.1 (CH2CN), 31.5 (ArCH2),
55.6 (OCH3), 113.7 (CH), 118.9 (CN), 128.3 (CH), 130.5 (CH),
132.6 (CH), 137.4 (C), 142.1 (C), 163.4 (C), 195.1 (CO) ppm.
HRMS (ESI): calcd. for C17H16NO2 [M + H]+ 266.1181; found
266.1192.
(CDCl3/TMS, 400 MHz): δ = 2.33 (s, 3 H, CH3), 3.65 (dd, J = 6.4,
9.2 Hz, 1 H, 3-H), 3.83 (t, J = 9.6 Hz, 1 H, 5-H), 3.97 (t, J =
9.2 Hz, 1 H, 4-H), 4.44 (d, J = 10.4 Hz, 1 H, CHaHb), 4.52–4.58
(m, 2 H, 2-H, ArCH2), 4.64 (d, J = 10.4 Hz, 1 H, CHaHb), 4.76
(d, J = 12.0 Hz, 1 H, ArCH2), 4.81 (d, J = 11.2 Hz, 1 H, ArCH2),
4.90 (d, J = 10.8 Hz, 1 H, ArCH2), 5.04 (d, J = 9.6 Hz, 1 H, 6-H),
6.86 (d, J = 7.2 Hz, 2 H, ArH), 7.06–7.15 (m, 3 H, ArH), 7.15–
7.20 (m, 2 H, ArH), 7.20–7.30 (m, 10 H, ArH), 7.83 (d, J = 8.0 Hz,
2 H, ArH) ppm. 13C NMR (CDCl3/TMS, 100 MHz): δ = 21.9
(CH3), 67.3 (CH), 74.3 (CH), 74.4 (CH2), 75.5 (CH2), 76.2 (CH2),
76.8 (CH), 78.1 (CH), 82.9 (CH), 115.2 (CN), 127.9 (CH), 128.0
(CH), 128.05 (CH), 128.1 (CH), 128.6 (CH), 128.7 (CH), 128.6
(CH), 128.9 (CH), 129.0 (CH), 129.5 (CH), 129.47 (CH), 129.6
(CH), 133.1 (C), 137.1 (C), 137.5 (C), 138.2 (C), 145.4 (C), 193.2
(CO) ppm. HRMS (ESI): calcd. for C35H34NO5 [M + H]+
548.2431; found 548.2437.
N-(3-Cyanopropyl)-4-methyl-N-[3-(4-methylbenzoyl)phenyl]benz-
enesulfonamide (12a): Reaction carried out at –65 °C, yield 79%;
white solid, m.p. 102–104 °C. Rf = 0.15 (hexane/EtOAc, 3:2). IR
(CHCl ): ν
= 1424, 1525, 1652, 2364, 3021 cm–1 1H NMR
.
˜
3
max
(400 MHz, CDCl3): δ = 1.76 (quint., J = 6.8 Hz, 2 H, CH2), 2.36
(s, 6 H, ArCH3), 2.36–2.50 (m, 2 H, CH2CN), 3.59 (t, J = 6.4 Hz,
2 H, NCH2), 7.18–7.23 (m, 4 H, ArH), 7.25 (dd, J = 8.0, J =
8.8 Hz, 1 H, ArH), 7.33–7.37 (m, 1 H, ArH), 7.37–7.47 (m, 3 H,
ArH), 7.59 (d, J = 8.0 Hz, 2 H, ArH),7.69 (d, J = 8.0 Hz, 1 H,
ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.5 (CH2), 21.7
(CH3), 21.8 (CH3), 24.7 (CH2CN), 49.2 (NCH2), 118.9 (CN), 127.7
4-Methyl-N-[2-oxo-2-(4-tolyl)ethyl]benzenesulfonamide (6a): Yield
91%; colourless solid, m.p. 56 °C. Rf = 0.33 (hexanes/EtOAc, 7:3).
IR (CHCl ): ν
= 1160, 1337, 1689, 2924 cm–1 1H NMR
.
˜
3
max
(400 MHz, CDCl3): δ = 2.31, 2.32 (2 s, 6 H, ArCH3), 4.34 (d, J =
4928
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Eur. J. Org. Chem. 2013, 4918–4932