Preparation of Isoselenocyanate and Synthesis of Carbodiimide by Oxidation of Selenourea

Full text of DOI:10.1021/jo990096j

J . Org. Chem. 1999, 64, 6473-6475
6473
Ta ble 1. Selen ou r ea 3 Syn th esis of Am in es w ith
Isoselen ocya n a tes Gen er a ted in Situ fr om Nitr ile Oxid e
a n d RC(dSe)NH2
P r ep a r a tion of Isoselen ocya n a te a n d
Syn th esis of Ca r bod iim id e by Oxid a tion of
Selen ou r ea
1
selenoamide
RC(dSe)NH2 (1)
amine R1NH2 (2)
yield (%) of 3
Mamoru Koketsu,* Norihito Suzuki, and
Hideharu Ishihara*
4-CH3C6H4 (1a )
1a
1a
1a
1a
1a
1a
4-CH3OC6H4 (1b)
2-ClC6H4 (1c)
C5H11 (1d )
CH3(CH2)2
CH3(CH2)3
(CH3)2CHCH2
(CH3)3C
C6H5CH2
2-CH3C6H4
C6H5
CH3(CH2)3
CH3(CH2)3
CH3(CH2)3
(2a )
60
74
68
64
53
46
48
51
46
78
(3a )
(3b)
(3c)
(3d )
(3e)
(3f)
(3g)
(3b)
(3b)
(3b)
(2b)
(2c)
(2d )
(2e)
(2f)
(2g)
(2b)
(2b)
(2b)
Department of Chemistry, Faculty of Engineering,
Gifu University, Gifu 501-1193, J apan
Received J anuary 20, 1999
Isoselenocyanates have been shown to be susceptible
to attack by nucleophilic reagents. And although many
studies have reported the synthesis of isothiocyanates,1,2
only limited numbers of studies on isoselenocyanates
have been reported.3,4 The few reported syntheses of iso-
selenocyanates5-7 have included, for example, the reac-
tion of isocyanides with selenium,8 that of phenylimid-
olyl chloride with sodium selenide,9 or that of isocyanates
with phosphorus pentaselenide.10 In the present study,
we confirmed an interesting pathway to isoselenocyanate
via cycloaddition by the reaction of nitrile oxides with
primary selenoamide; in addition, we synthesized sele-
noureas from the isoselenocyanates with amines.
Carbodiimides are also very important for the con-
struction of a wide variety of chemical structures. How-
ever, there currently exist only three practical syntheses
of unsymmetric carbodiimides.11-15 We describe here a
synthesis of carbodiimides via oxidation of the corre-
sponding selenoureas using NaIO4.
Sch em e 1
was added 4-tolylselenoamide 1a (2 equiv), and the
solution was stirred at 0 °C for 1 min. Then, n-propyl-
amine 2a (1.0 equiv) was added to the mixture, which
was stirred at 0 °C for 1.5 h. N-n-Propyl-N′-4-tolylsele-
nourea 3a was obtained in a 60% yield as a yellow oil.
In a similar manner, selenoureas 3 were obtained from
a variety of amines 2. The results of these syntheses are
summarized in Table 1. When CH2Cl2 or Et2O was used
as a solvent instead of THF, the yield of 3a was 55% or
50%, respectively. When 1 equiv of 4-tolylselenoamide 1a
was used in the reaction, the yield of 3a was low, and
urea was obtained as a byproduct. Even when the
primary selenoamides bearing electron-withdrawing
groups, such as 4-CH3OC6H5 1b or 2-ClC6H5 1c, were
used instead of 4-tolylselenoamide 1a , the yields of the
corresponding selenoureas were slightly lower than the
yield when 1a was used. The aliphatic selenoamide 1d
also gave the selenourea in high yield (78%). The yields
of selenourea using arylamines 2f and 2g tended to
decrease slightly compared with other amines because
of the weak nucleophilicity of the aryl group.
Resu lts a n d Discu ssion
The efficient synthesis of selenoureas 3 using iso-
selenocyanates was achieved by the following one-pot
procedure (eq 1). To a THF solution of 4-tolylnitrile oxide
* Corresponding author. Tel: +81-58-293-2619. Fax: +81-58-230-
1893. E-mail: koketsu@cc.gifu-u.ac.jp.
(1) Ramadas, K.; J anarthanan, N. J . Chem. Res., Synop. 1998, 5,
1101.
(2) Ramadas, K.; Srinivasan, N. Synth. Commun. 1995, 25, 3381.
(3) Gilmore, J .; Gallagher, P. T. In Comprehensive Organic Func-
tional Group Transformations; Katritzky, A. R., Meth-Cohn, O., Rees,
C. W., Eds.; Pergamon: Oxford, U.K., 1995; Vol. 5, pp 1021-1059.
(4) Hollingsworth, M. D.; Harris, K. D. M. In Comprehensive
Supramolecular Chemistry; MacNicol, D. D., Toda, F., Bishop, R, Eds.;
Elsevier: Oxford, UK., 1996; Vol. 6, pp 177-237.
(5) Bakhsh, M. T.; Behshtiha, Y. S.; Heravi, M. M. J . Chem. Soc.
Pak. 1996, 18, 159.
Although the detailed mechanism of the above reaction
has not yet been clarified, the formation of isoselenocy-
anate might be explained by the possible mechanism
presented in Scheme 1. The thiocarbonyl group behaves
as a dienophile toward dienes to afford a Diels-Alder
adduct.16,17 Similarly, the selenocarbonyl group of seleno-
amide would react with nitrile oxide (formed from hy-
(6) Ibata, T.; Himori, M.; Fukushima, K.; Suga, H.; Nakano, H.
Heterocycl. Commun. 1998, 2, 87.
(7) Boccanfuso, A. M.; Griffin, D. W.; Dunlap, R. B.; Odom, J . D.
Bioorg. Chem. 1989, 17, 231.
(8) Sonoda, N.; Yamamoto, G.; Tsutsumi, S. Bull. Chem. Soc. J pn.
1972, 45, 2937.
(11) Sheehan, J . C.; Hlavka, J . J . J . Org. Chem. 1956, 21, 439.
(12) Ulrich, H.; Sayigh, A. A. R. Angew. Chem., Int. Ed. Engl. 1966,
5, 704.
(9) Stolte, H. Ber. Dtsch. Chem. Ges. 1886, 19, 2350.
(10) Collard-Charon, C.; Renson, M. Bull. Soc. Chim. Belg. 1962,
71, 531.
(13) Fujinami, T.; Otani, N.; Sakai, S. Synthesis, 1977, 889.
(14) Fell, J . B.; Coppola, G. M. Synthesis, 1995, 25, 43.
(15) Babcock, J . R.; Sita, L. R. J . Am. Chem. Soc. 1998, 120, 5585.
10.1021/jo990096j CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/23/1999

6474 J . Org. Chem., Vol. 64, No. 17, 1999
Notes
Ta ble 2. Oxid a tion of Selen ou r ea 3a w ith Va r iou s
Oxid a n ts
Ta ble 3. Yield s of Ca r bod iim id es (4-CH3C6H4NdCdNR1)
4 Obta in ed by th e Oxid a tion of Selen ou r ea s
yield (%)
R1
yield (%) of 4
run
temp (°C)
time (min)
oxidant
4a
urea
CH3(CH2)2
CH3(CH2)3
CH3CH2(CH3)CH
(CH3)3C
2-CH3C6H4
C6H5
93 (4a )
90 (4b)
95 (4c)
39 (4d )
50 (4e)
50 (4f)
a
1
2
3
4
5
6
7
8
9
25
25
25
reflux
reflux
reflux
reflux
reflux
reflux
reflux
45
45
90
1
10
60
60
1
NaIO4
38
37
46
93
56
>1
0
0
0
0
18
14
5.0
>1
7.1
33
33
48
42
36
NaIO4
NaIO4
NaIO4
NaIO4
NaIO4
of carbodiimides by the oxidation of selenoureas. The
oxidation of selenourea by NaIO4 is a facile method for
preparing the carbodiimides.
without
NaClO4
KMnO4
Na2CrO4
1
1
10
a
Two milliliters of H2O was added.
Exp er im en ta l Section
droximoyl chloride with amine) to afford an initial
formation of intermediate 1,4,2-oxaselenazoline,18 which
could decompose into isoselenocyanate after rearrange-
ment. Next, the amine attacks the carbon of the isosele-
nocyanate to give the corresponding selenourea (Scheme
1). Preisler and Scortia reported that the treatment of
selenourea with oxidants, such as HCl and ferricyanide,
produced the dimer of selenourea.19 Further, Trep-
pendahl20 reported that the oxidation of N,N′-diphenylse-
lenourea with H2O2 produced the benzoselenazolylguani-
dine, cyclic dimers, and trimers of the corresponding
carbodiimides. The products would be distinguished from
each other according to the oxidant used. We found that
a brief oxidation of selenourea with NaIO4 afforded the
carbodiimide (eq 2). For example, to a refluxing DMF
Gen er a l. Tetrahydrofuran was distilled from sodium-ben-
zophenone immediately prior to use. Primary selenocarboxam-
ides were synthesized in accordance with the previously de-
scribed procedure.22 We also prepared 4-tolylnitrile oxide. The
77Se chemical shifts were expressed in ppm deshielded with
respect to neat Me2Se in CDCl3.
Syn th esis of N-n -P r op yl-N′-4-tolylselen ou r ea 3a . To a
THF solution of 4-tolylhydroximoyl chloride was added 1.1 equiv
of Et3N and the mixture stirred at 25 °C for 5 min. After cooling
to 0 °C, 2 equiv of 4-tolylselenoamide 1a was added to the
reaction mixture and it was stirred at the same temperature
for 1 min. Then, 1.0 equiv of n-propylamine 2a was added to
this, with stirring at 0 °C for 1.5 h. The mixture was concen-
trated in vacuo, and the residue was purified by column
chromatography on silica gel using n-hexane: Et2O (3:2) as
eluent to give 3a (60%). Mp: 97.3-98.8 °C. IR (KBr): 3336, 3182,
1541, 1521 cm-1. 1H NMR (400 MHz, CDCl3): δ 0.90 (3H, t, J )
7.2 Hz), 1.60 (2H, dt, J ) 7.2 Hz), 2.36 (3H, s), 3.61-3.71 (2H,
m), 6.24 (1H, br s), 7.11(2H, d, J ) 8.0 Hz), 7.23 (2H, d, J ) 8.0
Hz), 8.61 (1H, br s). 13C NMR (100 MHz, CDCl3): δ 11.1, 20.9,
22.1, 49.5, 125.3, 130.7, 132.9, 137.7, 178.2 (CdSe). 77Se NMR
(76 MHz, CDCl3): δ 198.0. MS (EI): m/z ) 256. Anal. Calcd for
C
11H16N2Se: C, 51.77; H, 6.32; N, 10.98. Found: C, 51.52; H,
6.26; N, 10.85.
solution of NaIO4 (1.1 equiv) was added 3a (1.0 equiv)
under an argon atmosphere. The reaction mixture was
refluxed for 1 min and immediately poured into ice water.
After the usual operations, N-n-propyl-N′-4-tolylcarbo-
diimide 4a was afforded in 93% yield as a yellow oil. In
these preparations of carbodiimides, at 25 °C the yields
were low, and the corresponding urea was generated
(runs 1-3). The longer the reflux time, the lower the yield
of 4a became. The corresponding urea, rather than 3a
or 4a , was obtained (runs 5 and 6). Other oxidants, such
as NaClO4, KMnO4, and Na2CrO4, could not yield the
corresponding carbodiimide from selenourea (runs 8-10)
(Table 2).
Some carbodiimides 4 were obtained in moderate to
high yields by the oxidation of a variety of selenoureas
with NaIO4 (Table 3). The yields of carbodiimide using
selenourea bearing R1 ) tertiary alkyl tended to decrease
compared with those of R1 ) primary and secondary alkyl
because of steric hindrance. Neither the dimer of sele-
nourea nor the trimer of the carbodiimide19,20 was ob-
tained in this oxidation. In conclusion, although it is
known that the dehydration or desulfurization of ureas
andthioureasaffordsthecorrespondingcarbodiimide,11-14,20,21
few reports have been made on the preparation method
N-n -Bu tyl-N′-4-tolylselen ou r ea 3b. IR (neat): 3371, 3196,
1545, 1513 cm-1. 1H NMR (400 MHz, CDCl3): δ 0.91 (3H, t, J )
7.2 Hz), 1.30 (2H, dt, J ) 7.2 Hz), 1.55 (2H, quintet, J ) 7.2
Hz), 2.35 (3H, s), 3.67 (2H, q, J ) 6.4 Hz), 6.26 (1H, br s), 7.11
(2H, d, J ) 8.0 Hz), 7.23 (2H, d, J ) 8.0 Hz), 8.93 (1H, br s). 13
C
NMR (100 MHz, CDCl3): δ 13.3, 19.5, 20.6, 30.6, 47.2, 124.8,
130.2, 132.8, 137.0, 177.7 (CdSe). 77Se NMR (76 MHz, CDCl3):
δ 193.3. HRMS: m/z ) 269.24832, calcd for C12H18N2Se, found
269.24841.
N-Isobu tyl-N′-4-tolylselen ou r ea 3c. Mp: 76.0-77.9 °C. IR
(KBr): 3375, 3180, 1543, 1522 cm-1 1H NMR (400 MHz,
.
CDCl3): δ 0.89 (6H, t, J ) 6.4 Hz), 1.86-2.00 (1H, m), 2.35 (3H,
s), 3.51 (2H, t, J ) 5.7 Hz), 6.35 (1H, br s), 7.12 (2H, d, J ) 8.0
Hz), 7.23 (2H, d, J ) 8.0 Hz), 8.92 (1H, br s). 13C NMR (100
MHz, CDCl3): δ 19.8, 20.8, 27.8, 54.9, 125.1, 131.6, 132.9, 137.5,
178.1(CdSe). 77Se NMR (76 MHz, CDCl3): δ 196.6. MS (EI): m/z
) 270. Anal. Calcd for C12H18N2Se: C, 53.53; H, 6.74; N, 10.40.
Found: C, 53.74; H, 6.66; N, 10.25.
N-ter t-Bu tyl-N′-4-tolylselen ou r ea 3d . Mp: 128.8-131.8 °C.
IR (KBr): 3166, 3006, 1558, 1537 cm-1 1H NMR (400 MHz,
.
CDCl3): δ 1.54 (9H, s), 2.34 (3H, s), 6.39 (1H, br s), 7.09 (2H, d,
J ) 8.2 Hz), 7.21 (2H, d, J ) 8.2 Hz), 8.50 (1H, br s). 13C NMR
(100 MHz, CDCl3): δ 20.8, 28.9, 54.6, 125.0, 128.8, 130.4, 137.2,
175.5 (CdSe). 77Se NMR (76 MHz, CDCl3): δ 255.2. HRMS: m/z
) 269.24832, calcd for C12H18N2Se, found 269.24828.
N-Ben zyl-N′-4-tolylselen ou r ea 3e. Mp: 98.9-101.3 °C. IR
(KBr): 3325, 3211, 1556, 1518 cm-1 1H NMR (400 MHz,
.
CDCl3): δ 2.31 (3H, s), 4.93 (2H, s), 6.50 (1H, br s), 7.11 (2H, d,
J ) 8.2 Hz), 7.17 (2H, d, J ) 8.2 Hz), 7.26-7.33 (5H, m), 8.83
(1H, br s). 13C NMR (100 MHz, CDCl3): δ 20.9, 51.9, 125.3, 126.8,
127.6, 128.6, 129.0, 130.7, 132.8, 136.7, 179.0 (CdSe). 77Se NMR
(16) Duus, F. In Comprehensive Organic Chemistry; The synthesis
and reactions of organic compounds; Barton, D., Ollis, W. D, Eds.;
Pergamon Press: Oxford, 1979; Vol. 3, pp 373-487.
(17) Middleton, W. J . J . Org. Chem. 1965, 30, 1390.
(18) J ae, N. K.; Eung, K. R. Tetrahedron Lett. 1993, 34, 8283.
(19) Preisler, P. W.; Scortia, T. N. J . Am. Chem. Soc. 1958, 80, 2309.
(20) Treppendahl, S. Acta Chem. Scand. B. 1975, B29, 385.
(21) Andrew, W.; Ibrahim, T. I. Chem. Rev. 1981, 81, 589.
(22) Ishihara, H.; Yoshimura, K.; Koketsu, M. Chem. Lett. 1998,
1287.

Notes
J . Org. Chem., Vol. 64, No. 17, 1999 6475
(76 MHz, CDCl3): δ 202.2. HRMS: m/z ) 303.26544, calcd for
C15H16N2Se, found 303.26549.
J ) 7.8 Hz), 7.06 (2H, d, J ) 7.8 Hz). 13C NMR (100 MHz,
CDCl3): δ 13.4, 19.8, 20.7, 33.3, 46.4, 123.1, 129.8, 134.0, 136.5,
137.7. HRMS: m/z ) 188.27244, calcd for C12H16N2, found
188.27248.
N-2-Tolyl-N′-4-tolylselen ou r ea 3f. Mp: 141.8-143.7 °C. IR
(KBr): 3351, 3146, 1548, 1508 cm-1 1H NMR (400 MHz,
.
CDCl3): δ 2.21 (3H, s), 2.22 (3H, s), 7.02-7.22 (8H, m), 8.34 (2H,
br s). 13C NMR (100 MHz, CDCl3): δ 18.0, 21.0, 125.9, 127.1,
127.9, 128.6, 130.0, 130.1, 131.3, 135.3, 179.3 (CdSe). HRMS:
m/z ) 303.26544, calcd for C15H16N2Se, found 303.26536.
N-P h en yl-N′-4-tolylselen ou r ea 3g. Mp: 140.0-142.8 °C. IR
N-sec-Bu t yl-N′-4-t olylca r b od iim id e 4c. Yellow oil. IR
(neat): 2132 (NdCdN) cm-1. 1H NMR (400 MHz, CDCl3): δ 1.00
(3H, t, J ) 7.2 Hz), 1.32 (3H, d, J ) 6.8 Hz), 1.53-1.66 (2H, m),
3.55 (1H, dt, J ) 6.8 Hz), 6.98 (2H, d, J ) 8.0 Hz), 7.09 (2H, d,
J ) 8.0 Hz). 13C NMR (100 MHz, CDCl3): δ 10.7, 20.9, 22.5,
31.5, 56.0, 123.1, 130.0, 134.2, 136.6, 138.0. HRMS: m/z )
188.27244, calcd for C12H16N2, found 188.27238.
N-ter t-Bu tyl-N′-4-tolylca r bod iim id e 4d . Yellow oil. IR
(neat): 2109 (NdCdN) cm-1. 1H NMR (400 MHz, CDCl3): δ 1.39
(9H, s), 2.31 (3H, s), 6.98 (d, J ) 8.4 Hz, 2H), 7.08 (d, J ) 8.4
Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 20.9, 31.6, 57.2, 123.0,
129.9, 134.3, 138.0. HRMS: m/z ) 188.27244, calcd for C12H16N2,
found 188.27236.
N-2-Tolyl-N′-4-tolylca r bod iim id e 4e. Yellow oil. IR
(neat): 2137 (NdCdN) cm-1. 1H NMR (400 MHz, CDCl3): δ 2.33
(3H, s), 2.37 (3H, s), 7.04-7.19 (8H, m). 13C NMR (100 MHz,
CDCl3): δ 18.3, 20.9, 123.8, 124.6, 125.4, 126.8, 130.1, 130.8,
132.6, 134.6, 135.1, 136.1, 137.1. HRMS: m/z ) 222.28956, calcd
for C15H14N2, found 222.28961.
(KBr): 3352, 3149, 1551, 1509 cm-1 1H NMR (400 MHz,
.
CDCl3): δ 2.34 (3H, s), 6.50 (1H, br s), 7.16-7.39 (9H, m), 8.45
(1H, br s). 13C NMR (100 MHz, CDCl3): δ 21.0, 119.5, 125.6,
125.7, 127.4, 129.5, 130.2, 137.7, 178.6 (CdSe). 77Se NMR (76
MHz, CDCl3): δ 244.2. HRMS: m/z ) 289.23856, calcd for
C14H14N2Se, found 289.23850.
Syn th esis of N-n -P r op yl-N′-4-tolylca r bod iim id e 4a . To
a refluxing DMF solution of NaIO4 (1.1 equiv) was added a DMF
solution of 3a (1.0 equiv) under an argon atmosphere. The
reaction mixture was refluxed for 1 min. After cooling with ice
water immediately, the mixture was washed with saturated
NaCl solution, and the organic layer was separated, dried over
Na2SO4, and evaporated. The residue was subjected to column
chromatography on silica gel using n-hexane:Et2O (50:1) as
eluent system, affording 4a (90%) as a yellow oil. IR (neat): 2138
N-P h en yl-N′-4-tolylca r bod iim id e 4f. Yellow oil. IR (neat):
1
1
(NdCdN) cm-1. H NMR (400 MHz, CDCl3): δ 1.01 (3H, t, J )
2130 (NdCdN) cm-1. H NMR (400 MHz, CDCl3): δ 2.33 (3H,
7.2 Hz), 1.67 (2H, dt, J ) 7.2 Hz), 2.31 (3H, s), 3.36 (2H, t, J )
6.8 Hz), 6.97 (2H, d, J ) 8.1 Hz), 7.08 (2H, d, J ) 8.1 Hz). 13C
NMR (100 MHz, CDCl3): δ 11.4, 20.9, 24.7, 48.6, 123.2, 129.9,
134.2, 136.6, 137.8. MS (EI): m/z ) 174. Anal. Calcd for
C11H14N2: C, 75.82; H, 8.10; N, 16.08. Found: C, 75.69; H, 8.30;
N, 16.06.
s), 7.06-7.34 (9H, m). 13C NMR (100 MHz, CDCl3): δ 21.0, 124.0,
124.1, 125.5, 129.5, 130.1, 135.4, 138.8. HRMS: m/z ) 208.26268,
calcd for C14H12N2, found 208.26260.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
N-n -Bu tyl-N′-4-tolylca r bod iim id e 4b. Yellow oil. IR
(neat): 2128 (NdCdN) cm-1. 1H NMR (400 MHz, CDCl3): δ 0.93
(3H, t, J ) 7.3 Hz), 1.43 (2H, dt, J ) 7.3 Hz), 1.64 (2H, quintet,
J ) 6.8 Hz), 2.29 (3H, s), 3.37 (2H, t, J ) 6.8 Hz), 6.97 (2H, d,
J O990096J