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T. Mizuno et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 1.60–1.63 (m, 6 H, 3 × CH2), 3.44
(s, 4 H, 2 × CH2), 6.58 (br s, 1 H, NH), 7.01(tt, J = 7.7, 1.6 Hz, 1 H,
CH), 7.27 (tt, J = 7.7, 1.6 Hz, 2 H, 2 × CH), 7.33–7.37 (m, 2 H, 2 ×
CH).
13C NMR (75 MHz, CDCl3): d = 13.8, 20.0, 30.1, 34.6, 48.9, 119.0,
121.4, 125.8, 130.1, 132.4, 138.9, 154.8.
MS (EI, 70 eV): m/z (%) = 276 (42) [M+ + 2], 274 (65) [M+], 187
(10), 161 (11), 114 (100), 58 (16), 57 (88).
13C NMR (75 MHz, CDCl3): d = 24.3, 25.6, 45.4, 119.8, 122.9,
128.8, 139.2, 154.9.
HRMS (EI, 70 eV): m/z calcd for C12H16ON2Cl2: 274.0640; found:
274.0635.
MS (EI, 70 eV): m/z (%) = 204 (12) [M+], 112 (54), 92 (64), 77 (70),
69 (100), 65 (69), 56 (63).
Bis(N,N-dipropylcarbamoyl)disulfide (4a)
Pr2NH (2a; 2.73 mL, 20 mmol), powdered sulfur (321 mg, 10
mmol), and DMF (20 mL) were placed in a 100 mL flask under an
argon atmosphere. The flask was charged with CO (0.1 MPa), and
the mixture was vigorously stirred under a balloon of CO (0.1 MPa)
at 20 °C for 16 h. The flask was purged of CO, and charged with O2
(0.1 MPa) at 20 °C, then the solution was stirred under a balloon of
O2 (0.1 MPa) for an additional 6 h at 20 °C. The resulting orange so-
lution was poured into 1 M HCl (100 mL), and extracted with t-
BuOMe (2 × 50 mL). Bis(N,N-dipropylcarbamoyl)disulfide (4a)
was purified as an oil, by short-column chromatography (silica gel;
EtOAc).
HRMS (EI, 70 eV): m/z calcd for C12H16ON2: 204.1263; found:
204.1265.
N-4-Tolyl-1-piperidinecarboxamide (1k)
Compound 1k was purified by washing with hexane.
Yield: 1.79 g (82%); mp 146.9 °C (Lit.17 146–148 °C).
IR (KBr): 3286, 2928, 2847, 1631, 1598, 1531, 1427, 1245, 811,
508 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.63 (s, 6 H, 3 × CH2), 2.29 (s,
3 H, CH3), 3.42 (s, 4 H, 2 × CH2), 6.68 (br s, 1 H, NH), 7.07(d,
J = 8.2 Hz, 2 H, 2 × CH), 7.24 (dt, J = 8.2, 2.0 Hz, 2 H, 2 × CH).
Yield: 374 mg (23%); oil.13
IR (NaCl): 2964, 2933, 2874, 1681, 1404, 1218, 1119, 708 cm–1.
13C NMR (75 MHz, CDCl3): d = 20.7, 24.2, 25.4, 45.6, 120.1, 129.3,
132.6, 136.4, 154.9.
1H NMR (300 MHz, CDCl3): d = 0.90–0.92 (m, 12 H, 4 × CH3),
1.58–1.72 (m, 8 H, 4 × CH2), 3.36 (br s, 8 H, 4 × CH2).
MS (EI, 70 eV): m/z (%) = 218 (100) [M+], 174 (14), 112 (97), 84
(13), 69 (40).
13C NMR (75 MHz, CDCl3): d = 11.2, 20.9, 22.1, 50.5, 163.4.
MS (EI, 70 eV): m/z (%) = 320 (29) [M+], 129 (27), 128 (100), 86
(77).
HRMS (EI, 70 eV): m/z calcd for C13H18ON2: 218.1419; found:
218.1404.
HRMS (EI, 70 eV): m/z calcd for C14H28O2N2S2: 320.1592; found:
320.1576.
N-Phenyl-1-morpholinecarboxamide (1l)
Compound 1l was purified by washing with toluene.
Yield: 1.33 g (65%); mp 160.4 °C (Lit.18 161.5–162 °C).
References
IR (KBr): 3269, 2953, 2858, 1634, 1541, 1444, 1251, 1115, 746
cm–1.
(1) Bioorganic Chemistry of Pesticides; Eto, M., Ed.; Soft
Science Publications: Tokyo, 1985, 73.
(2) Pesticide Data Book, 3rd ed.; Uesugi, Y.; Ueji, M.;
Koshioka, M., Eds.; Soft Science Publications: Tokyo, 1997,
288.
(3) Merck Index, 14th ed.; O’Neil, M. J.; Heckelman, P. E.;
Koch, C. B.; Roman, K. J., Eds.; Merck & Co., Inc.:
Whitehouse Station NJ, 2006, 6435.
(4) Franz, R. A.; Applegath, F. J. Org. Chem. 1961, 26, 3304.
(5) Franz, R. A.; Applegath, F.; Morriss, F. V.; Baiocchi, F.
J. Org. Chem. 1961, 26, 3306.
1H NMR (300 MHz, CDCl3): d = 3.44 (t, J = 4.8 Hz, 4 H, 2 × CH2),
3.68 (t, J = 4.8 Hz, 4 H, 2 × CH2), 6.60 (br s, 1 H, NH), 7.04 (t,
J = 7.0 Hz, 1 H, CH), 7.24–7.35 (m, 4 H, 4 × CH).
13C NMR (75 MHz, CDCl3): d = 44.2, 66.4, 120.2, 123.3, 128.8,
138.8, 155.2.
MS (EI, 70 eV): m/z (%) = 206 (100) [M+], 114 (81), 77 (16), 70
(55), 57 (25).
HRMS (EI, 70 eV): m/z calcd for C11H14O2N2: 206.1055; found:
206.1069.
(6) Franz, R. A.; Applegath, F.; Morriss, F. V.; Baiocchi, F.;
Bolze, C. J. Org. Chem. 1961, 26, 3309.
Large-Scale Preparation of N-Butyl-N-methyl-N¢-(3,4-dichlo-
rophenyl)urea (1m)
(7) Franz, R. A.; Applegath, F.; Morriss, F. V.; Baiocchi, F.;
Breed, L. W. J. Org. Chem. 1962, 27, 4341.
(8) Macho, V.; Kralik, M.; Ligac, G.; Bojsova, E.; Vojcek, L.
Collect. Czech. Chem. Commun. 1996, 61, 381.
(9) Wang, X.; Lu, S. J. Mol. Catal. 2006, 255, 25.
(10) Yang, Y.; Lu, S. Tetrahedron Lett. 1999, 40, 4845.
(11) Mizuno, T.; Iwai, T.; Ishino, Y. Tetrahedron 2005, 61, 9157.
(12) Mizuno, T.; Mihara, M.; Iwai, T.; Ito, T.; Ishino, Y.
Synthesis 2006, 2825.
A dark-red solution containing N-butylmethylamine (2h; 23.6 mL,
200 mmol), 3,4-dichloroaniline (3f; 16.2 g, 100 mmol), and pow-
dered sulfur (3.21g, 100 mmol) in DMF (100 mL), was vigorously
stirred under CO (0.1 MPa) at 20 °C for 24 h. Into the resulting red
solution, molecular O2 (0.1 MPa) was charged at 20 °C (exothermic
reaction). The reaction mixture was stirred for an additional 6 h at
20 °C. The resulting red solution was then poured into 1 M HCl
(200 mL) and the deposited white solid was washed with hexane
(200 mL). N-Butyl-N-methyl-N¢-(3,4-dichlorophenyl)urea (1m)
was purified by recrystallization (hexane–toluene).
(13) Mizuno, T.; Nakai, T.; Mihara, M. Heteroat. Chem. 2009,
20, 64.
(14) Mizuno, T.; Daigaku, T.; Nishiguchi, I. Tetrahedron Lett.
1995, 36, 1533.
(15) Ozaki, S.; Nagoya, T. Bull. Chem. Soc. Jpn. 1957, 30, 444.
(16) Lee, S.-H.; Matsushita, H.; Clapham, B.; Janda, K. D.
Tetrahedron 2004, 60, 3439.
(17) Hoffmann, R. W.; Hagenbruch, B.; Smith, D. M. Chem. Ber.
1977, 110, 23.
(18) Henry, R. A.; Dehn, W. M. J. Am. Chem. Soc. 1949, 71,
2297.
Yield: 21.8 g (79%); mp 100.9 °C (Lit.3 101.5–103 °C).
IR (KBr): 3300, 2959, 2930, 1642, 1581, 1475, 1297, 875 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.95 (t, J = 7.4 Hz, 3 H, CH3), 1.34
(sext, J = 7.4 Hz, 2 H, CH2), 1.56 (quin, J = 7.4 Hz, 2 H, CH2), 2.99
(s, 3 H, CH3), 3.33 (t, J = 7.4 Hz, 2 H, CH2), 6.48 (br s, 1 H, NH),
7.20 (dd, J = 8.8, 2.3 Hz, 1 H, CH), 7.29 (d, J = 8.8 Hz, 1 H, CH),
7.61 (d, J = 2.3 Hz, 1 H, CH).
Synthesis 2009, No. 15, 2492–2496 © Thieme Stuttgart · New York