Isocyanates from Primary Amines and Carbon Dioxide
J . Org. Chem., Vol. 64, No. 11, 1999 3945
F or m a tion of Ca r ba m oylh yd r a zin es 6, Tr ia zolin on es
Ar ) 2,4,6-tri-MeC6H2) (0.54 g, 69%): mp 137-138 °C; 1H
NMR (200 MHz, CDCl3) δ 1.25 (d, 6H, J ) 6.2 Hz), 1.35 (d,
6H, J ) 6.2 Hz), 2.22 (s, 6H), 2.26 (s, 3H), 4.99 (b sept, 1H, J
) 6.1 Hz), 5.08 (b sept, 1H, J ) 6.3 Hz), 6.57-6.76 (bm, 1H),
6.89 (s, 2H), 9.63 (bs, 1H); 13C NMR (50.3 MHz, CDCl3) δ 18.2,
20.9, 21.7, 21.8, 70.3, 72.4, 128.8, 130.9, 135.2, 136.8, 151.3,
155.3, 155.5. Anal. Calcd for C18H27N3O5: C, 59.16; H, 7.45;
N, 11.50. Found: C, 59.11; H, 7.56; N, 11.46.
2,6-Diisop r op yla n ilin e. The products from a reaction of
2,6-diisopropylaniline (0.28 g, 1.6 mmol) were shown to be
isocyanate (5; R ) 2,6-di-iPrC6H3) with spectral data identical
to that of an authentic sample as above and N-(2,6-diisopro-
pylphenylcarbamoyl)-N,N′-bis(isopropylcarboxy)hydrazine (6;
Ar ) 2,6-di-iPrC6H3). Flash chromatography (SiO2, 20% ethyl
acetate/petroleum ether) gave a pure sample of (6; Ar ) 2,6-
di-iPrC6H3) as a waxy solid (0.46 g, 71%): mp 101-104 °C; 1H
NMR (200 MHz, CDCl3) δ 1.18-1.37 (m, 24H), 3.12 (bm, 2H),
5.09 (overlapping septs, 2H, J ) 6.3 Hz), 6.85 (bm, 1H), 7.13-
7.31 (m, 3H), 9.68 (s, 1H); 13C NMR (50.3 MHz, CDCl3) δ 21.87,
21.93, 23.7, 28.8, 70.3, 72.5, 123.6, 128.4, 130.8, 146.3, 152.4,
155.5, 155.7; HRMS (EI) m/z calcd for C21H33N3O5 407.2420,
found 407.2426.
7, a n d Dica r ba m oylh yd r a zin es 10. Reactions of unhindered
aromatic amines with CO2 and iPrO2C-N(Ph3P+)-N--CO2 Pr.
i
An ilin e. Reaction of aniline (0.31 g, 3.3 mmol) in CH2Cl2 (20
mL) with CO2 and the zwitterion derived from PPh3 (1.0 g,
3.9 mmol) and DIAD (0.80 g, 3.9 mmol) in CH2Cl2 (20 mL)
under the conditions described previously gave a viscous yellow
oil (2.1 g) which was shown to contain a mixture of the
carbamoylhydrazine (6; Ar ) Ph) and the triazolinone (7; Ar
1
) Ph) in the ratio ca. 2:3 with ca. 2% isocyanate by H NMR
and IR. Flash chromatography (SiO2, 30% ethyl acetate/
petroleum ether) gave samples of N-(phenylcarbamoyl)-N,N′-
bis(isopropylcarboxy)hydrazine (6; Ar ) Ph) as a yellow viscous
oil which solidified on standing (0.22 g, 20%) [mp 89.5-92.5
°C; 1H NMR (300 MHz, CDCl3) δ 1.28 (d, 6H, J ) 5.8 Hz),
1.34 (d, 6H, J ) 6.2 Hz), 5.02 (overlapping septs, 2H, J ) 6.2
Hz), 6.99 (bs, 1H), 7.10 (t, 1H, J ) 7.3 Hz), 7.31 (t, 2H, J ) 7.4
Hz), 7.50 (d, 2H, J ) 7.4 Hz), 10.53 (s, 1H); 13C NMR (50.3
MHz, CDCl3) δ 21.8, 22.0, 70.5, 72.9, 119.0, 124.4, 129.1, 137.5,
155.4, 155.2; HRMS (EI) m/z calcd for C15H21N3O5 323.1481,
found 323.1479] and isopropyl 3-isopropoxy-5-oxophenyl-
∆2,1,2,4-triazoline-1-carboxylate (7; Ar ) Ph) [mp 87.5-90 °C;
1H NMR (200 MHz, CDCl3) δ 1.39 (d, 6H, J ) 6.4 Hz), 1.43 (d,
6H, J ) 6.4 Hz), 5.23 (sept, 1H, J ) 6.3 Hz), 5.28 (sept, 1H, J
) 6.2 Hz), 7.34-7.51 (m, 5H); 13C NMR (50.3 MHz, CDCl3) δ
21.69, 21.71, 72.3, 75.0, 125.8, 128.4, 129.1, 130.8, 148.7, 149.0,
150.4; MS(EI) m/z 305 (M+, 2). Anal. Calcd for C15H19N3O4:
C, 59.01; H,6.27; N, 13.79. Found: C, 59.19; H, 6.18; N, 13.76.]
Authentic samples of this and other triazolinones were
prepared by the literature method16 and were found to have
identical physical and spectroscopic properties to the materials
obtained from the amine-CO2 reactions.
Ben zyla m in e. The products from a reaction of benzylamine
(0.29 g, 2.7 mmol) were benzyl isocyanate (5; R ) C6H5CH2),
carbamoylhydrazine (6; Ar ) C6H5CH2), and triazolinone (7;
Ar ) C6H5CH2). Flash chromatography (SiO2, 60% ethyl
acetate/petroleum ether) gave N-(benzylcarbamoyl)-N,N′-bis-
(isopropylcarboxy)hydrazine (6; Ar ) C6H5CH2) (0.84 g, ca.
1
90%). H NMR (200 MHz, CDCl3) δ 1.25-1.30 (m, 12H), 4.49
(m, 2H), 4.98 (sept, 2H, J ) 6.2 Hz), 7.21 (bm, 1H), 7.29 (m,
5H), 8.70 (bm, 1H); 13C NMR (50.3 MHz, CDCl3) δ 21.7, 22.0,
44.9, 70.1, 72.2, 127.5, 127.6, 128.4, 138.0, 153.4, 155.2, 155.5;
MS (ES) m/z 697 (2M+ + Na). Anal. Calcd for C16H23N3O5: C,
56.96; H, 6.87; N, 12.46. Found: C, 57.05; H, 7.02; N, 12.40.
Benzyl isocyanate was identified by IR with an NdCdO
stretch at 2273 cm-1 and isopropyl 3-isopropoxy-5-oxo-4-
benzyl-∆2,1,2,4-triazoline-1-carboxylate (7; Ar ) C6H5CH2) by
comparison of spectroscopic data with that of an analytically
pure authentic sample16 prepared by reaction of benzyl isocy-
anate with the zwitterion derived from DIAD and PPh3. 1H
NMR (200 MHz, CDCl3) δ 1.36 (d, 6H, J ) 6.2 Hz), 1.40 (d,
6H, J ) 6.3 Hz), 4.68 (s, 2H), 5.17 (overlapping septs, 2H, J )
6.3 Hz), 7.27-7.38 (m, 5H); 13C NMR (50.3 MHz, CDCl3) δ 21.9,
44.0, 72.3, 74.8, 128.4, 128.6, 128.8, 135.2, 148.9, 150.1, 151.5;
MS (EI) m/z 319 (M+, <1). Anal. Calcd for C16H21N3O4: C,
60.20; H, 6.60; N, 13.20. Found: C, 59.97; H, 6.67; N, 12.98.
L-P h en yla la n in e Eth yl Ester . Reaction of L-phenylalanine
ethyl ester (0.39 g, 2.0 mmol) afforded a trace of the isocyanate
(5; R ) EtO2C(PhCH2)CH). Flash chromatography of the
product (SiO2, 20% ethyl acetate/petroleum ether) yielded
N-((1-(ethoxycarbonyl)-2-phenylethyl)carbamoyl)-N,N′-bis(iso-
propylcarboxy)hydrazine (6; R ) EtO2C(PhCH2)CH) as a
colorless oil which slowly solidified on standing (0.55 g, 64%):
1H NMR (400 MHz, CDCl3) δ 1.20 (t, 3H, J ) 7.1 Hz), 1.23-
1.32 (m, 12H), 3.15 (m, 2H), 4.15 (q, 2H, J ) 7.1 Hz), 4.72 (m,
1H), 4.99 (overlapping septs, 2H, J ) 6.2 Hz), 6.75 (bm, 1H),
7.16-7.30 (m, 5H); 8.75 (d, 1H, J ) 6.0 Hz); 13C NMR (50.3
MHz, CDCl3) δ 14.2, 21.8, 22.0, 38.0, 55.4, 61.5, 70.3, 72.4,
127.1, 128.6, 129.5, 135.8, 152.6, 154.7, 155.3, 171.2; MS (EI)
m/z 424 (M+, <1); HRMS (EI) m/z calcd for C20H29N3O7 + Na
446.1904, found 446.1907.
4-Meth oxya n ilin e. Reaction of 4-methoxyaniline (0.31 g,
2.50 mmol) as above gave a product (1.62 g) which on flash
chromatography (SiO2, 30% ethyl acetate/petroleum ether)
gave N-(4-methoxyphenylcarbamoyl)-N,N′-bis(isopropylcarboxy)-
hydrazine (6; Ar ) 4-MeOC6H4) as a colorless oil (0.21 g,
23%): 1H NMR (200 MHz, CDCl3) δ 1.28 (bd, 6H, J ) 6.5 Hz),
1.34 (d, 6H, J ) 6.2 Hz), 3.78 (s, 3H), 5.03 (sept, 2H, J ) 6.2
Hz), 6.82-6.89 (m, 2H), 6.98 (bs, 1H), 7.36-7.44 (m, 2H), 10.35
(bs, 1H); 13C NMR (50.3 MHz, CDCl3) δ 21.7, 21.9, 55.4, 70.3,
72.6, 114.1, 121.9, 130.3, 150.5, 155.3, 155.4, 156.4; HRMS (EI)
m/z calcd for C16H23N3O6 353.1587, found 353.1575. Further
elution gave isopropyl 3-isopropoxy-5-oxo-4-(methoxyphenyl)-
∆2,1,2,4-triazoline-1-carboxylate (7; Ar ) 4-MeOC6H4) as a
white precipitate: mp 88-91 °C; IR (Nujol) 1802, 1626 cm-1
;
1H NMR (200 MHz, CDCl3) δ 1.38 (d, 6H, J ) 6.2 Hz), 1.41 (d,
6H, J ) 6.3 Hz), 3.82 (s, 3H), 5.22 (sept, 1H, J ) 6.2 Hz), 5.27
(sept, 1H, J ) 6.2 Hz), 6.96 (m, 2H), 7.27 (m, 2H); 13C NMR
(50.3 MHz, CDCl3) δ 21.7, 55.5, 72.3, 74.8, 114.4, 123.5, 127.3,
148.8, 149.3, 150.8, 159.5; MS(EI) m/z 335 (M+, 7). Anal. Calcd
for C16H21N3O5: C, 57.30; H, 6.30; N, 12.53. Found: C, 57.17;
H, 6.35; N, 12.45.
3-Nitr oa n ilin e. This reaction gave only the triazolinone (7;
Ar ) 3-O2NC6H4). Spectroscopic data were identical with those
for an analytically pure authentic sample16 prepared by
reaction of 3-nitrophenyl isocyanate with the zwitterion de-
rived from DIAD and PPh3. Isopropyl 3-isopropoxy-5-oxo-4-
(nitrophenyl)-∆2,1,2,4-triazoline-1-carboxylate (7; Ar ) 3-O2-
NC6H4): mp 120-122.5 °C; 1H NMR (200 MHz, CDCl3) δ 1.43
(d, 6H, J ) 6.2 Hz), 1.46 (d, 6H, J ) 6.3 Hz), 5.25 (sept, 1H, J
) 6.3 Hz), 5.33 (sept, 1H, J ) 6.2 Hz), 7.69 (t, 1H, J ) 8.0
Hz), 7.85 (ddd, 1H, J ) 8.1, 2.1 and 1.2 Hz), 8.27 (ddd, 1H, J
) 8.3, 2.2 and 1.2 Hz), 8.37 (t, 1H, J ) 2.0 Hz); 13C NMR (50.3
MHz, CDCl3) δ 21.7, 72.7, 75.9, 120.5, 123.0, 130.1, 131.0,
132.0, 148.36, 148.40, 149.5; MS (EI) m/z 308 (M+ - (CH3)2O,
1). Anal. Calcd for C15H18N4O6: C, 51.43; H, 5.18; N, 15.99.
Found: C, 51.42; H, 5.27; N, 16.02.
2,4,6-Tr im eth yla n ilin e. The product from a reaction of
2,4,6-trimethylaniline (0.29 g, 2.14 mmol) on chromatography
(SiO2, 20% ethyl acetate/petroleum ether) gave 2,4,6-trimeth-
ylphenyl isocyanate (5; R ) 2,4,6-tri-MeC6H2) (0.05 g, 15%),
mp 40-42 °C, with spectral data identical to that of an
authentic sample described previously and N-(2,4,6-trimeth-
ylphenylcarbamoyl)-N,N′-bis(isopropylcarboxy)hydrazine (6;
Rea ction s of Un h in d er ed Ar om a tic Am in es w ith CO2
a n d iP r O2C-N(Bu 3P +)-N--CO2 P r . 2-Isop r op yla n ilin e.
i
Reaction of 2-isopropylaniline (0.29 g, 2.1 mmol) yielded a trace
amount of isocyanate (5; R ) 2-iPrC6H4). Three other products
carbamoylhydrazine (6; Ar ) 2-iPrC6H4), dicarbamoylhydra-
zine (10; Ar ) 2-iPrC6H4), and the corresponding symmetrical
urea were isolated by careful chromatography (SiO2, 20% ethyl
acetate/petroleum ether). N,N′-Bis(2-isopropylphenylcarbam-
oyl)-N,N′-bis(isopropylcarboxy)hydrazine (10; Ar ) 2-iPrC6H4)
was eluted first and obtained as an oil which solidified on
standing (0.12 g, 11%): mp 142-145.5 °C; 1H NMR (200 MHz,
CDCl3) δ 1.27-1.35 (m, 24H), 3.15 (sept, 2H, J ) 6.8 Hz), 5.13
(sept, 2H, J ) 6.2 Hz), 7.12-7.32 (m, 6H), 7.79-7.84 (m, 2H),
10.35 (s, 2H); 13C NMR (50.3 MHz, CDCl3) δ 21.8, 21.9, 22.9,