PAPER
Solvent-Free Synthesis of Chiral N,N¢-Disubstituted Thioureas
1957
the corresponding thioureas 3a–f. For method (iii), a published pro-
refined, giving R1[I≥2s(I)] = 4.01% and wR2 (all data) = 9.56%.
Flack parameter: 0.00(5).
cedure was used.5b
(R,R)-N,N¢-Bis(1-phenylethyl)thiourea (R,R-3a)
Mp 198–200 °C; [a]D25 –115.7 (c = 1, CHCl3).
(S,S)-N,N¢-Bis[1-(1-naphthyl)ethyl]thiourea (S,S-3c)
Mp 163–165 °C; [a]D25+172.5 (c = 1, CHCl3).
IR (KBr): 3261 (N–H), 1548, 1347 cm–1 (C=S).
1H NMR (CDCl3/TMS): d = 1.45 (d, J = 6.6 Hz, 6 H, 2 CH3), 5.08
(br s, 2 H, 2 CH), 6.3 (br s, 2 H, 2 NH), 7.02–7.22 (m, 10 H, Ar).
13C NMR (CDCl3/TMS): d = 23.00 (CH3), 53.99 (CH), 125.55,
127.46, 128.80, 142.13 (Ar), 179.86 (C=S).
MS-EI: m/z = 284 (M+).
(R,R)-N,N¢-Bis(1-cyclohexylethyl)thiourea (R,R-3d)
Mp 181–183 °C; [a]D25 –31.2 (c = 1, CHCl3).
IR (KBr): 3226 (N–H), 1541, 1447, 1382 cm–1 (C=S).
1H NMR (CDCl3/TMS): d = 0.88–1.73 (m, 22 H, CH2 cyclohexyl),
1.08 (d, J = 6.7 Hz, 6 H, 2 CH3), 3.93 (br s, 2 H, 2 CH), 5.72 (br s,
2 H, 2 NH).
13C NMR (CDCl3/TMS): d = 17.39 (CH3), 26.00, 26.08, 26.22,
28.87, 29.48 (CH2 cyclohexyl), 43.24 (CH cyclohexyl), 54.64
(CHNH), 180.03 (C=S).
Anal. Calcd for C17H20N2S: C, 71.79; H, 7.09; N, 9.85; S, 11.27.
Found: C, 71.83; H, 7.27; N, 9.81; S, 10.93.
(S,S)-N,N¢-Bis(1-phenylethyl)thiourea (S,S-3a)
Mp 198–200 °C; [a]D25 +114.3 (c = 1, CHCl3).
MS-EI: m/z = 296 (M+).
Anal. Calcd for C17H32N2S: C, 68.86; H, 10.88; N, 9.45; S, 10.81.
Found: C, 68.81; H, 11.57; N, 9.52; S, 10.66.
A single crystal gave identical space group and cell parameters than
those previously reported for the same compound.13
(S,S)-N,N¢-Bis(1-cyclohexylethyl)thiourea (S,S-3d)
Mp 181–183 °C; [a]D25+31.3 (c = 1, CHCl3).
(R,R)-N,N¢-Bis[1-(4-methylphenylethyl)]thiourea (R,R-3b)
Mp 140–143 °C; [a]D25 +99.7 (c = 1, CHCl3).
IR (KBr): 3304 (N–H), 1533, 1352 cm–1 (C=S).
N,N¢-Bis[(1R,2R,3R,5S)-isopinocamphyl]thiourea (3e)
Mp 215–218 °C; [a]D25 –48.8 (c = 1, CHCl3).
1H NMR (CDCl3/TMS): d = 1.41 (d, J = 6.6 Hz, 6 H, 2 CH3), 2.29
(s, 6 H, 2 ArCH3), 4.99 (br s, 2 H, 2 CH), 6.06 (br s, 2 H, 2 NH),
6.88–7.01 (m, 8 H, Ar).
13C NMR (CDCl3/TMS): d = 21.12 (CH3), 23.19 (ArCH3), 54.00
(CH), 125.67, 129.58, 137.27, 139.27 (Ar), 180.02 (C=S).
IR (KBr): 3260 (N–H), 1542, 1454, 1383 cm–1 (C=S).
1H NMR (CDCl3/TMS): d = 0.99 (s, 6 H, 2 CCH3), 1.10 (d, J = 6.7
Hz, 6 H, 2 CHCH3), 1.18 (s, 6 H, 2 CCH3), 1.55 [m, 2 H, 2
CHC(CH3)2], 1.78–1.92 (m, 8 H, 4 CH2), 2.33 (m, 2 H, 2 CH), 2.63
(m, 2 H, 2 CHCH3), 4.34 (br s, 2 H, 2 CHNH), 5.85 (br s, 2 H, 2
NH).
13C NMR (CDCl3/TMS): d = 20.98 (CHCH3), 23.53 (CCH3), 27.85
(CCH3), 34.89 (CH2CH), 37.10 (CHCH3), 38.35 (CCH2), 41.45
[C(CH3)2], 46.41 (CHCH2), 47.64 [CHC(CH3)2], 53.12 (CHNH),
180.68 (C=S).
MS-EI: m/z = 312 (M+).
Anal. Calcd for C19H24N2S: C, 73.03; H, 7.74; N, 8.97; S, 10.26.
Found: C, 72.93; H, 7.81; N, 9.02; S, 10.11.
Crystal Structure of 3b
C19H24N2S, orthorhombic, P22121. a = 5.5492(8), b = 9.1610(8),
c = 17.6175(13) Å, V = 895.61(16) Å3, Z = 2, Z¢ = 1/2, Dc = 1.159
g·cm–3. 1533 reflections were collected with Mo-Ks radiation
(l = 0.71073 Å) up to 2Qmax = 52.5° of which 1377 are independent
MS-EI: m/z = 348 (M+).
Anal. Calcd for C21H36N2S: C, 72.36; H, 10.41; N, 8.04; S, 9.20.
Found: C, 72.75; H, 10.56; N, 7.98; S, 9.33.
(Rint = 2.10%). 102 parameters were
refined, giving
R1[I≥2s(I)] = 3.93% and wR2 (all data) = 9.56%. Flack parameter:
0.1(2) (see Figure 1).
Crystal Structure of 3e
C21H36N2S, triclinic, P1. a = 10.3699(15), b = 11.0903(15),
c = 11.1125(16)
Å,
a = 91.047(11),
b = 112.620(12),
(S,S)-N,N¢-Bis[1-(4-methylphenylethyl)]thiourea (S,S-3b)
Mp 140–143 °C; [a]D25 –99.8 (c = 1, CHCl3).
g = 111.838(11)°, V = 1679.3(7) Å3, Z = Z¢ = 2, Dc = 1.076 g·cm–3.
Transmission factors: 0.731–0.891. 5163 reflections were collected
with Mo-Ka radiation (l = 0.71073 Å) up to 2Qmax = 52.6°. 433 pa-
rameters were refined, giving R1[I≥2s(I)] = 4.43% and wR2 (all
data) = 11.97%. Flack parameter: –0.04(7).
(R,R)-N,N¢-Bis[1-(1-naphthyl)ethyl]thiourea (R,R-3c)
Mp 163–165 °C; [a]D25 –171.4 (c = 1, CHCl3).
IR (KBr): 3259 (N–H), 1536, 1325 cm–1 (C=S).
1H NMR (CDCl3/TMS): d = 1.54 (d, J = 6.6 Hz, 6 H, 2 CH3), 5.79
(br s, 2 H, 2 CH), 6.09 (br s, 2 H, 2 NH), 7.03–7.74 (m, 14 H, Ar).
N,N¢-Bis[(–)-cis-myrtanyl)]thiourea (3f)
Mp 102–105 °C; [a]D25 –20.4 (c = 1, CHCl3).
IR (KBr): 3252 (N–H), 1555, 1469, 1382 cm–1 (C=S).
13C NMR (CDCl3/TMS): d = 21.68 (CH3), 50.41 (CH), 122.67,
125.18, 125.77, 126.64, 128.32, 128.95, 130.19, 133.74, 137.04
(Ar), 179.67 (C=S).
1H NMR (CDCl3/TMS): d = 1.00 (s, 6 H, 2 CCH3), 1.16 (s, 6 H, 2
CCH3), 1.45 (m, 2 H, 2 CHCH2), 1.76–1.90 (m 12 H, 6 CH2), 2.24–
2.35 (m, 2 H, CH), 3.36 (br s, 4 H, 2 CH2NH), 5.85 (br s, 2 H, 2 NH).
MS-EI: m/z = 384 (M+).
13C NMR (CDCl3/TMS): d = 19.91 (CCH3), 23.30 (CH2CH), 25.97
(CCH3), 27.94 (CH2CH), 33.27 (CCH2), 38.70 [C(CH3)2], 40.92
(CHCH2), 41.30 [CHC(CH3)2], 43.80 (CHCH), 50.05 (CH2NH),
181.53 (C=S).
Anal. Calcd for C25H24N2S: C, 78.09; H, 6.29; N, 7.28; S, 8.34.
Found: C, 78.15; H, 6.17; N, 7.32; S, 8.26.
Crystal Structure of 3c
MS-EI: m/z = 348 (M+).
C25H24N2S, triclinic, P1. a = 10.0934(11), b = 14.2147(13),
c = 15.9910(16) Å, a = 84.789(5), b = 73.844(8), g = 77.361(7)°,
V = 2149.2(4) Å3, Z = Z¢ = 4, Dc = 1.188 g·cm–3. Transmission fac-
tors: 0.660–0.707. 10291 reflections were collected with Mo-Ka ra-
diation (l = 0.71073 Å) up to 2Qmax = 52.5°. 1010 parameters were
Anal. Calcd for C21H36N2S: C, 72.36; H, 10.41; N, 8.04; S, 9.20.
Found: C, 72.17; H, 10.29; N, 8.11; S, 9.41.
Synthesis 2004, No. 12, 1955–1958 © Thieme Stuttgart · New York