An efficient synthesis of cyanamide from amine promoted by a hypervalent iodine(III) reagent

Article abstract of DOI:10.1016/j.tetlet.2009.03.017

In a one-pot strategy we have achieved an efficient method for the synthesis of organic cyanamides starting from dithiocarbamic acid salts/amines. In this strategy the in situ generated alkyl or aryl isothiocyanates, obtained by the desulfurization of dithiocarbamic acid salts with diacetoxyiodobenzene (DIB) react with aqueous ammonia forming alkyl or aryl thiourea which on subsequent oxidative desulfurization with DIB led to the formation of corresponding cyanamide in good yields. Mild reaction conditions, shorter reaction time, an environmentally benign protocol, and easy isolation of the desired product make the present methodology a suitable alternative for the preparation of various organic cyanamides.

Full text of DOI:10.1016/j.tetlet.2009.03.017

Tetrahedron Letters 50 (2009) 2407–2410
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An efficient synthesis of cyanamide from amine promoted by a hypervalent
iodine(III) reagent
*
Harisadhan Ghosh, Ramesh Yella, Abdur Rezzak Ali, Santosh K. Sahoo, Bhisma K. Patel
Department of Chemistry, Indian Institute of Technology Guwahati 781 039, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
In a one-pot strategy we have achieved an efficient method for the synthesis of organic cyanamides start-
ing from dithiocarbamic acid salts/amines. In this strategy the in situ generated alkyl or aryl isothiocya-
nates, obtained by the desulfurization of dithiocarbamic acid salts with diacetoxyiodobenzene (DIB) react
with aqueous ammonia forming alkyl or aryl thiourea which on subsequent oxidative desulfurization
with DIB led to the formation of corresponding cyanamide in good yields. Mild reaction conditions,
shorter reaction time, an environmentally benign protocol, and easy isolation of the desired product
make the present methodology a suitable alternative for the preparation of various organic cyanamides.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 26 January 2009
Revised 21 February 2009
Accepted 4 March 2009
Available online 9 March 2009
Due to its unique reactivity, cyanamide is an important func-
tional group in synthetic organic chemistry. Cyanamides are useful
precursors in the synthesis of pharmaceutically important hetero-
cycles1 and N-alkyl or N-aryl imides.2 Due to the easy removal of
the cyano group from cyanamide,3 they often serves as a useful
protecting groups in the synthesis of secondary and tertiary
amines containing heterocycles.3 Cyanamides are also important
intermediates for the synthesis of many biologically active com-
pounds, such as minoxidil4 and herbicides.5
and expensive reagents, high reaction temperatures giving low
yields, and involving tedious purification procedures. Due to ready
availability, low toxicity, and easy handling, the use of hypervalent
iodine reagents is of current interest.19 Hypervalent iodine(III) has
a mild oxidizing ability similar to mercury, lead, and thallium-
based reagents and hence is a suitable alternative to toxic, heavy
metal-based reagents.20 Recently we have exploited the thiophilic
nature of DIB in the regioselective N-acylation of thiourea to N-acyl
urea.21 Further, the desulfurization ability of DIB has been used for
the preparation of isothiocyanate from the corresponding dithio-
carbamate salt.22 The in situ generated isothiocyanates on reaction
with various bis-nucleophiles gave different heterocycles.22 Taking
cues from this work, we have reasoned that isothiocyanate can be
obtained from dithiocarbamic acid salt and DIB in the presence of
aqueous ammonia without using triethylamine. The in situ gener-
ated isothiocyanate will react further with ammonia giving alkyl or
aryl thiourea, which, on oxidative desulfurization with DIB and
ammonia, would form organic cyanamide. All these processes
can be performed in one pot. Herein, we report a high yielding
‘one-pot’ preparation of cyanamides from dithiocarbamate salts
using the non-metallic, non-toxic, eco-friendly hypervalent iodi-
ne(III) reagent diacetoxyiodobenzene (DIB).
Various dithiocarbamate salts can be prepared easily in high
yields from amines following the literature procedure.11,23 When
a freshly prepared salt of dithiocarbamate salt 1 (2 equiv) in aceto-
nitrile (5 mL) was treated with aqueous ammonia (25%) (2 mL) and
DIB (2 equiv) under ice-cooled conditions, 1-phenylthiourea was
obtained. When DIB (2 equiv) was added to this reaction mixture,
phenylcyanamide (1a) was isolated in 85% yield.24 A plausible
mechanism for the transformation of dithiocarbamic acid salt 1
to cyanamide 1a is shown in Scheme 1.
The most frequently adopted method for the synthesis of cyana-
mides is the cyanation of amine using cyanogen halides,6 or its
synthon (CN+). The reagents capable of delivering electrophilic
cyanogens (CN+) are 2-chlorobenzyl thiocyanate,7 1-cyanoimidaz-
ole,8 2-cyanopyridazin-3-(2H)-ones,9 1-cyanobenzotriazole and
metal cyanide,10 tosylcyanide,11 thiocyanogen,12 and cyanogen
azide.13 In an alternative approach, cyanamides are obtained from
ureas and thioureas.14 The other less commonly adopted method is
the Tiemann rearrangement of amidoximes.15 Recently, they were
prepared from organic isocyanides and trimethylsilyl azide via a
Si–N bond cleavage catalyzed by [{(g
3-C3H5)PdCl}2],16 and in one
pot by reacting isocyanate or isothiocyanate with sodium bis(tri-
methylsilyl)amide as deoxygenating or desulfurizing agent in
THF at room temperature.17 In yet another method, cyanamides
were prepared from N,N0-disubstituted glycylamide using a penta-
valent iodine reagent in the presence of tetraethylammonium bro-
mide at ambient temperature.18
Most of the reported methods use cyano cation (CN+) directly
from highly toxic cyanogen bromide or indirectly from (CN+) syn-
thons which, in turn, are prepared from toxic cyanogen halides. An
other reported method uses extremely alkaline conditions, toxic
The mechanism for the formation of isothiocyanate is expected
* Corresponding author. Tel.: +91 61 582307; fax: +91 61 690762.
E-mail address: patel@iitg.ernet.in (Bhisma K. Patel).
to be similar to the one recently proposed by us.22 The in situ gen-
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.03.017

2408
H. Ghosh et al. / Tetrahedron Letters 50 (2009) 2407–2410
Table 1
OAc
OAc
Preparation of cyanamide from dithiocarbamate salt and DIBa
Ph
I
S
Substrate
Productb
Yieldc (%)
85
S
R
N C S
R
R
DIB
aq. NH3
S–· +NHEt3
N
NH2
N
H
H
N
H
N
+ PhI + S
—
S
·
Et3NH+
1
CN
NH3
H
H3N
1a
S
Ph
I
R
-PhI, S
S
OAc
R
NH
N
R
N
H
N
H
N
H
—
N
S
·
Et3NH+
N
NH2
CN
72
65
78
2
2a
S
S
Scheme 1. Proposed mechanism for the formation of cyanamide.
Me
Me
OMe
OMe
H
N
H
N
—
erated isothiocyanate on reaction with NH3 would give 1-phenyl-
thiourea. The 1-phenylthiourea on oxidative desulfurization leads
to the formation of a carbodiimide intermediate which is con-
verted to its stable cyanamide analogue (1a).
·
Et3NH+
CN
3
3a
S
The precipitation of elemental sulfur supports the mechanism
proposed. The formation of isothiocyanate was confirmed by
recording the IR spectra of the crude reaction mixture, which
shows a strong peak at 2063 cmꢀ1 characteristic of isothiocyanate.
Further, when isolated 1-phenylthiourea in acetonitrile was trea-
ted with DIB in aqueous ammonia, it gave cyanamide (1a) confirm-
ing the intermediacy of phenylisothiocyanate and 1-
phenylthiourea in the reaction mixture. It may be mentioned here
that the reaction of 1-phenylthiourea with DIB in the absence of
any base is reported to give 1,2,4-thiadiazole.25
Irrespective of the mechanism involved, the success of the
method depends on the strong thiophilic nature of the DIB.
Employing this one-pot strategy, we have successfully prepared a
series of cyanamides (Table 1) from both aliphatic and aromatic
amines. Aromatic amines containing various substituents in the
phenyl ring (1–7) gave corresponding cyanamides (1a–7a) in good
yields. Benzylic amines 8 and 9 gave a satisfactory yield of corre-
sponding cyanamides 8a and 9a respectively. This method was also
extremely successful in the preparation of cyclohexyl (10a), cyclo-
propyl (11a), and n-butyl (12a) cyanamides starting from their par-
ent amine/dithiocarbamate salt.
This method is compatible with a number of other functional
groups such as –OH, –NO2, and –COR as was tested in substrates
13, 14, and 15 giving their corresponding cyanamides 13a, 14a,
and 15a, respectively, (Table 2). The stability of other functional
groups containing substrates such as alkenes 16 and esters 17 were
also found to be compatible in the second stage of the reaction giv-
ing, respectively, products 16a and 17a.
It was difficult to get suitable thiocarbamate salts having these
functionalities. Hence, their compatibility was tested from isothio-
cyanates 16 and 17 having these functionalities. It is heartening to
know that both these functionalities survived under the reaction
condition giving cyanamides 16a and 17a, respectively, in good
yields. However in the case of 16a and 17a, 0.5 mL of aq NH3
was used per mmol of the substrate instead of 1 mL of the aq
NH3 used when the reaction started from thiocarbamate salt.
In an attempt to synthesize cyanamide of secondary amines
such as pyrrolidine, no traces of cyanamide could be detected.
Rather, it underwent oxidative dimerization. This is possible be-
cause of the inability of the secondary amine to form isothiocya-
nate, thereby further supporting our mechanism. Thus, by this
method, cyanamide of a secondary amine cannot be prepared
and this is perhaps the only draw back of the method.
Me
Me
H
N
H
N
—
S
·
Et3NH+
CN
4a
S
S
4
Me
Me
Cl
Cl
H
N
H
N
—
—
Et3NH+
CN
·
68
71
5a
5
S
S
H
N
H
N
S
·
Et3NH+
CN
6
6a
Cl
Cl
H
N
H
N
—
Et3NH+
CN
S
·
60
76
78
77
S
7a
7
Cl
Cl
S
N
H
CN
—
N
S
8
·
Et3NH+
8a
H
S
O
O
N
H
CN
O
O
—
N
S
9
·
Et3NH+
9a
H
H
H
—
N
S
·
Et3NH+
N CN
10a
10
S
H
N
H
—
S
·
Et3NH+
N
CN
63
67
11
11a
S
H
H
N
—
·
Et3NH+
CN
N
S
12
S
12a
In conclusion, hypervalent iodine reagent DIB serves as an effi-
cient desulfurizing agent for the conversion of dithiocarbamic acid
salts to cyanamides. Organic cyanamide in the past was prepared
by an arduous method involving toxic and expensive reagents.
Although the isolated yield looks moderate considering three steps
a
Reactions were monitored by TLC.
Confirmed by IR, 1H, and 13C NMR.31
Isolated yield.
b
c

H. Ghosh et al. / Tetrahedron Letters 50 (2009) 2407–2410
2409
Table 2
5. (a) Hu, L. Y.; Guo, J.; Magar, S.; Fischer, J. B.; Burkehowie, K. J.; Durant, G. J. J.
Med. Chem. 1997, 40, 4281; (b) Robinson, J. R.; Brown, W. H. Can. J. Chem. 1951,
29, 1069.
6. (a) Van Barun, J. Ber. Dtsch. Chem. Ges. 1900, 33, 1468; (b) Kaupp, G.; Schmeyers,
J.; Boy, J. Chem. Eur. J. 1998, 4, 2467.
7. Wheland, R. C.; Martin, E. L. J. Org. Chem. 1975, 40, 3101.
8. Wu, Y.-Q.; Limburg, D. C.; Wilkinson, D. E.; Hamilton, G. S. Org. Lett. 2000, 2,
795.
Preparation of cyanamide from dithiocarbamate salt and DIBa
Substrate
Productb
Yieldc (%)
72
H
N
H
N
—
S
·
Et3NH+
CN
13a
13
S
9. Kim, J.-J.; Kweon, D. -H.; Cho, S.-D.; Kim, H.-K.; Jung, E.-Y.; Lee, S.-G.; Falck, J. R.;
Yoon, Y.-J. Tetrahedron 2005, 61, 5889.
HO
HO
10. Hughes, T. V.; Hammond, S. D.; Cava, M. P. J. Org. Chem. 1998, 63, 401.
11. (a) Davis, W. A.; Cava, M. P. J. Org. Chem. 1983, 48, 2774; (b) Kahne, D.; Collum,
D. Tetrahedron Lett. 1981, 22, 5011.
12. Boltz, K. H.; Dell, H. D. Justus Liebigs Ann. Chem. 1967, 709, 63.
13. Hermes, M. E.; Marsh, F. D. J. Org. Chem. 1972, 37, 2969.
14. (a) Takahiro, S.; Toshihiro, I.; Kenya, K.; Katsuro, M. Tetrahedron Lett. 1973, 14,
2121; (b) Mai, K.; Patil, G. Synth. Commun. 1986, 16, 1823; (c) Hu, N. X.; Aso, Y.;
Otsubo, T.; Ogura, F. Chem. Lett. 1985, 603; (d) Sato, R.; Itoh, K.; Itoh, K.;
Nishina, H.; Goto, T.; Saito, M. Chem. Lett. 1984, 1913.
15. Bakunov, S. A.; Rukavishnikov, A. V.; Tkachev, A. V. Synthesis 2000, 1148.
16. Kamijo, S.; Jin, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2002, 41, 1780.
17. (a) Wong, F. F.; Chen, C.-Y.; Yeh, M.-Y. Synlett 2006, 559; (b) Chen, C.-Y.; Wong,
F. F.; Huang, J.-J.; Lin, S.-K.; Yeh, M.-Y. Tetrahedron Lett. 2008, 49, 6505.
18. Chaudhuri, K. H.; Mahajan, U. S.; Bhalerao, D. S.; Akamanchi, K. G. Synlett 2007,
2815.
19. (a) Wirth, T.; Ochiai, M.; Zhdankin, V. V.; Koser, G. F.; Tohma, H.; Kita, Y. Topics
in Current Chemistry: Hypervalent Iodine Chemistry-Modern Developments in
Organic Synthesis; Springer: Berlin, 2002; (b) Varvoglis, A. Hypervalent Iodine in
Organic Synthesis; Academic Press: London, 1997; (c) Zhdankin, V. V.; Stang, P.
Chem. Rev. 1996, 96, 1123; (d) Varvoglis, A. Tetrahedron 1997, 53, 1179; (e)
Zhdankin, V. V.; Stang, P. Chem. Rev. 2002, 102, 2523; (f) Zhdankin, V. V.; Stang,
P. Chem. Rev. 2008, 108, 5299.
20. (a) Kitamura, T.; Fujiwara, Y. Org. Prep. Proced. Int. 1997, 29, 409; (b) Wirth, T.
Angew. Chem., Int. Ed. 2005, 44, 3656; (c) Wirth, T. J. Org. Chem. 2005, 70, 2893;
(d) Ochiai, M. In Chemistry of Hypervalent Compounds; Akiba, K., Ed.; VCH: New
York, 1999; pp 359–387. Chapter 13.
H
H
—
O2N
N
S
·
Et3NH+
O2N
N
CN
65
83
14a
14
S
H
H
—
N
S
·
Et3NH+
N
CN
15
15a
S
O
O
O
NCS
H
N
CN
16a
16
76
83
O
NCS
H
N
CN
17
17a
O
O
O
O
21. Singh, C. B.; Ghosh, H.; Murru, S.; Patel, B. K. J. Org. Chem. 2008, 73, 2924.
22. Ghosh, H.; Yella, R.; Nath, J.; Patel, B. K. Eur. J. Org. Chem. 2008, 6189.
23. (a) Emami, S.; Foroumadi, A. Chin. J. Chem. 2006, 24, 791; (b) Sattigeri, V. J.;
Soni, A.; Singhal, S.; Khan, S.; Pandya, M.; Bhateja, P.; Mathur, T.; Rattan, A.;
Khanna, J. M.; Mehta, A. Arkivoc 2005, ii, 46.
24. General procedure for preparation of phenyl cyanamide (1a) from dithiocarbamate
salt (1): Aqueous ammonia (25%, 2 mL) was added to a stirred and ice-cooled
suspension of dithiocarbamate 1 (540 mg, 2 mmol) in acetonitrile (5 mL). DIB
(644 mg, 2 mmol) was added portion-wise over a period of 15 min. A light-
yellow precipitate of sulfur started to separate out during this period. After the
complete addition of DIB, it was kept stirring for 15 min and conversion to the
corresponding 1-phenylthiourea was confirmed by TLC. To the reaction
a
b
c
Reactions were monitored by TLC.
Confirmed by IR, 1H, and 13C NMR.31
Isolated yield.
in one pot, the yields are, in fact, good to excellent. Thus, this is
perhaps the most efficient method reported so far for the prepara-
tion of organic cyanamides.
mixture DIB (644 mg, 2 mmol) was added portion-wise over
a period of
15 min during which further precipitation of elemental sulfur was observed.
The conversion of the 1-phenylthiourea to phenylcyanamide (1a) was
observed within 10 min of the complete addition of DIB. The reaction
mixture was allowed to stand, and the precipitated sulfur was filtered. The
organic layer was concentrated and admixed with ethyl acetate (15 mL). The
ethyl acetate layer was washed with water (25 mL). The organic layer was
dried over anhydrous Na2SO4, concentrated under reduced pressure, and
purified through a short column of silica gel to give the pure product 1a9
(201 mg, 85%). Oily Liquid: 1H NMR (400 MHz, CDCl3): d 7.02–7.07 (m, 3H),
7.28–7.33 (m, 2H), 7.64 (br s, 1H). 13C NMR (100 MHz, CDCl3): d 112.2, 115.5,
123.6, 129.8, 137.4. IR (KBr): 3175, 2919, 2227, 1600, 1501, 1249, 748,
689 cmꢀ1. C7H6N2 (118.13): calcd C, 71.17; H, 5.12; N, 23.71. Found: C, 71.27;
H, 5.09; N, 23.67.
Acknowledgments
B.K.P. acknowledges support of this research from DST New
Delhi (SR/S1/OC-15/2006) and CSIR 01(2270)/08/EMR-II. H.G.
thanks the CSIR for fellowships. Thanks are due to CIF IIT Guwahati
for NMR spectra.
Supplementary data
25. Mamaeva, E. A.; Bakibaev, A. A. Tetrahedron 2003, 59, 7521.
26. Singh, G. R.; Mehra, S. C. Asian J. Chem. 2006, 18, 3132.
27. Bunnett, J. F.; Hrutfiord, B. F. J. Am. Chem. Soc. 1961, 83, 1691–1697.
28. Niwa, R.; Kamada, H.; Shitara, E.; Horiuchi, J.; Kibushi, N.; Kato, T. Chem. Pharm.
Bull. 1996, 44, 2314.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.03.017.
References and notes
29. Lee, Y.; Martasek, P.; Roman, L. J.; Silverman, R. B. Bioorg. Med. Chem. Lett. 2000,
10, 2771.
30. Jacobsen, G. B.; Westernberg, G.; Markides, K. E.; Laangstoem, B. J. Am. Chem.
Soc. 1996, 118, 6868.
1. (a) Sandler, S. R.; Karo, W.. In Organic Functional Group Preparations; Academic:
New York, 1972; Vol. 3; (b) Sandler, S. R.; Karo, W.. In Organic Functional Group
Preparations; Academic: New York, 1972; Vol. 2; (c) Nickon, A.; Fieser, L. F. J.
Am. Chem. Soc. 1952, 74, 5566; (d) Jia, Q.; Cai, T.; Haung, M.; Li, H.; Xian, M.;
Poulos, T. L.; Wang, P. G. J. Med. Chem. 2003, 46, 2271; (e) Cai, T.; Xian, M.;
Wang, P. G. Bioorg. Med. Chem. Lett. 2002, 12, 1507; (f) Kumar, V.; Kaushik, M.
P.; Mazumdar, A. Eur. J. Org. Chem. 2008, 1910; (g) Saneyoshi, M.; Tokuzen, R.;
Maeda, M.; Fukuoka, F. Chem. Pharm. Bull. 1968, 16, 505; (h) Gilman, A. G.;
Goodman, L. S.; Rall, T. W.; Murad, F. Goodman and Gilman’s The Pharmacological
Basis of Therapeutics, 7th ed.; Pergmon Press: New York, 1990; (i) La Mattina, J.
L. J. Heterocycl. Chem. 1983, 20, 533.
2. Stephens, R. W.; Domeier, L. A.; Todd, M. G.; Nelson, V. A. Tetrahedron Lett.
1992, 33, 733.
3. (a) Donetti, A.; Omodei-Sale, A.; Mantegani, A.; Zugna, E. Tetrahedron Lett. 1969,
39, 3327; (b) Pala, G.; Mantegani, A.; Zugna, E. Tetrahedron 1970, 26, 1275; (c)
Currie, A. C.; Newbold, G. T.; Spring, F. S. J. Chem. Soc. 1961, 4693.
4. McCall, J. M.; Tenbrink, R. E.; Ursprung, J. J. J. Org. Chem. 1975, 40, 3304.
31. Spectral data of compounds: p-Tolyl cyanamide 2a:1f Gummy: 1H NMR
(400 MHz, CDCl3):
d 2.28 (s, 3H. CH3), 6.91 (d, J = 8.4 Hz, 2H), 7.10 (d,
J = 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3): d 20.7, 112.4, 115.5, 130.3, 133.2,
134.9. IR (KBr): 3165, 2950, 2228, 1620, 1515, 1249 cmꢀ1. C8H8N2 (132.17):
calcd C, 72.70; H, 6.10; N, 21.20. Found: C, 72.73; H, 6.08; N, 21.15. 2-Methoxy-
phenyl cyanamide 3a:26 Gummy: 1H NMR (400 MHz, CDCl3): d 3.87 (s, 3H,
OCH3), 6.88 (m, 1H), 6.95–7.05 (m, 2H), 7.18 (m, 1H). 13C NMR (100 MHz,
CDCl3): d 55.9, 110.8, 111.0, 114.9, 121.5, 123.8, 126.8, 146.9. IR (KBr): 3219,
2939, 2839, 2224, 1603, 1509, 1454, 1259, 1026 cmꢀ1. C8H8N2O (148.17): calcd
C, 64.85; H, 5.44; N, 18.91. Found: C, 64.81; H, 5.40; N, 18.88. 2,4-Dimethyl-
phenyl cyanamide 4a: mp 115–119 °C. 1H NMR (400 MHz, CDCl3): d 2.18 (s, 3H,
CH3), 2.26 (s, 3H, CH3), 6.74 (br s, 1H, NH), 6.93 (s, 1H), 6.99 (d, J = 8.0 Hz, 1H),
7.05 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3): d 17.3, 20.7, 112.8, 115.7,
124.7, 127.9, 131.8, 133.2, 133.3. IR (KBr): 3186, 2915, 2233, 1599, 1512, 1433,
1271, 1031 cmꢀ1. C9H10N2 (146.19): calcd C, 73.94; H, 6.89; N, 19.16. Found: C,

2410
H. Ghosh et al. / Tetrahedron Letters 50 (2009) 2407–2410
73.87; H, 6.86; N, 19.14. MS (ESI): 146 (M+). 2-Chloro-phenyl cyanamide 5a:27
Gummy. 1H NMR (400 MHz, CDCl3): d 0.94 (t, J = 7.6 Hz, 3H, CH3), 1.40 (m, 2H,
CH2), 1.58 (m, 2H, CH2), 3.06 (m, 2H, CH2), 4.61 (br s, 1H). 13C NMR (100 MHz,
CDCl3): d 13.6, 19.5, 31.7, 45.7, 117.2. IR (KBr): 3207, 2961, 2875, 2221, 1614,
1463, 1373, 1171 cmꢀ1. C5H10N2 (98.15): calcd C, 61.19; H, 10.27; N, 28.54.
Found: C, 61.22; H, 10.23; N, 28.48. 4-Hydroxy-phenyl cyanamide 13a.9 mp
259–261 °C. 1H NMR (400 MHz, CDCl3 + DMSO): d 5.67 (br s, 1H), 6.77 (d,
J = 8.8 Hz, 2H), 6.83 (d, J = 8.8 Hz, 2H), 8.98 (br s, 1H, OH). 13C NMR (100 MHz,
CDCl3 + DMSO): d 112.8, 115.6, 115.8, 129.5, 152.2. IR (KBr): 3213, 2992, 2230,
1613, 1519, 1444, 1258, 1224 cmꢀ1. C7H6N2O (134.14): calcd C, 62.68; H, 4.51;
N, 20.88. Found: C, 62.72; H, 4.55; N, 20.83. 3-Nitro-phenyl cyanamide 14a.17a
Yellow Solid. Mp 133–135 °C. 1H NMR (400 MHz, CDCl3 + DMSO): d 7.38 (d,
J = 8.4 Hz, 1H), 7.52 (t, J = 8.4 Hz, 1H), 7.85 (m, 2H). 13C NMR (100 MHz,
CDCl3 + DMSO): d 109.6, 110.7, 116.8, 120.8, 130.1, 139.9, 148.4. IR (KBr): 3147,
2919, 2241, 1621, 1531, 1354, 1260, 1071, 937, 871 cmꢀ1. C7H5N3O2 (163.14):
calcd C, 51.54; H, 3.09; N, 25.76. Found: C, 51.58; H, 3.12; N, 25.71; MS (ESI):
163 (M+). 4-Acetyl-phenylcyanamide 15a.30 mp 153–157 °C. 1H NMR (400 MHz,
CDCl3 + DMSO): d 2.56 (s, 3H, CH3), 7.08 (d, J = 8.8 Hz, 2H), 7.91 (d, J = 8.8 Hz,
2H). 13C NMR (100 MHz, CDCl3 + DMSO): d 25.9, 110.9, 114.5, 129.8, 131.2,
142.9, 196.2. IR (KBr): 3188, 2966, 2228, 1666, 1599, 1585, 1411, 1362, 1278,
1176, 962 cmꢀ1. C9H8N2O (160.18): calcd C, 67.49; H, 5.03; N, 17.48. Found: C,
67.53; H, 5.08; N, 17.44. MS (ESI): 160 (M+). 4-(Allyloxy)-phenyl cyanamide 16a:
mp 66–70 °C. 1H NMR (400 MHz, CDCl3): d 4.49 (d, J = 4.4 Hz, 2H), 5.29 (d,
J = 10.8 Hz, 1H), 5.40 (d, J = 17.2 Hz, 1H), 6.02 (m, 1H), 6.87 (d, J = 8.4 Hz, 2H),
6.93 (d, J = 8.8 Hz, 2H). 13C NMR (100 MHz, CDCl3): d 69.5, 112.4, 116.1, 116.9,
118.1, 130.7, 133.2, 155.0. IR (KBr): 3148, 3079, 2954, 2887, 2214, 1510, 1240,
1172, 1108, 1014, 994 cmꢀ1. C10H10N2O (174.20): calcd C, 68.95; H, 5.79; N,
16.08. Found: C, 68.91; H, 5.77; N, 16.00. MS (ESI): 174 (M+). 4-Cyanamide-
phenylacetate 17a: mp 95–97 °C. 1H NMR (400 MHz, CDCl3): d 2.32 (s, 3H), 6.93
(d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 7.08 (br s, 1H). 13C NMR (100 MHz,
CDCl3): d 21.3, 111.5, 116.5, 122.9, 135.4, 146.4, 170.7. IR (KBr): 3168, 3100,
2974, 2233, 1754, 1610, 1512, 1374, 1226, 1202, 1164, 1014 cmꢀ1. C9H8N2O2
(176.18): calcd C, 61.36; H, 4.58; N, 15.90. Found: C, 61.40; H, 4.61; N, 15.8.
mp 101–103 °C. 1H NMR (400 MHz, CDCl3): d 6.56 (br s, 1H), 7.05 (m, 1H), 7.31
(m, 2H), 7.35 (m, 1H). 13C NMR (100 MHz, CDCl3): d 110.0, 116.2, 120.4, 124.5,
128.6, 129.9, 134.3. IR (KBr): 3163, 2921, 2243, 1598, 1500, 1426, 1295,
1049 cmꢀ1. C7H5ClN2 (152.58): calcd C, 55.10; H, 3.30; N, 18.36. Found: C,
55.11; H, 3.32; N, 18.29. 3-Chloro-phenyl cyanamide 6a:17a mp 93–95 °C. 1H
NMR (400 MHz, CDCl3) d 6.92 (m, 1H), 7.03 (m, 2H), 7.26 (t, J = 8.0 Hz, 1H). 13
C
NMR (100 MHz, CDCl3) d 111.1, 113.8, 115.9, 124.0, 130.9, 135.7, 138.7. IR
(KBr): 3154, 2910, 2237, 1602, 1513, 1423, 1256 cmꢀ1. C7H5ClN2 (152.58):
calcd C, 55.10; H, 3.30; N, 18.36. Found: C, 55.10; H, 3.29; N, 18.29. MS (ESI):
152 (M+). 4-Chloro-phenyl cyanamide 7a:26 mp 95 °C. 1H NMR (400 MHz,
CDCl3): d 6.91 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H). 13C NMR (100 MHz,
CDCl3): d 111.4, 116.9, 128.9, 129.9, 136.2. IR (KBr): 3166, 2954, 2234, 1600,
1494, 1251, 1091 cmꢀ1. C7H5ClN2 (152.58): calcd C, 55.10; H, 3.30; N, 18.36.
Found: C, 55.09; H, 3.33; N, 18.32. Benzyl cyanamide 8a:9 Gummy. 1H NMR
(400 MHz, CDCl3): d 4.11 (d, J = 5.2 Hz, 2H, CH2), 4.66 (br s, 1H), 7.27–7.37 (m,
5H). 13C NMR (100 MHz, CDCl3): d 49.9, 116.7, 127.9, 128.4, 128.9, 136.4. IR
(KBr): 3207, 2925, 2220, 1455, 1359, 1155, 1014 cmꢀ1. C8H8N2 (132.17): calcd
C, 72.70; H, 6.10; N, 21.19. Found: C, 72.66; H, 6.13; N, 21.11. Benzo[1,3]dioxol-
5-ylmethyl-cyanamide 9a:28 mp 82–84 °C. 1H NMR (400 MHz, CDCl3): d 4.05 (d,
J = 5.2 Hz, 2H, CH2), 4.57 (br s, 1H), 5.94 (s, 2H, OCH2), 6.77 (m, 3H). 13C NMR
(100 MHz, CDCl3): d 49.9, 101.4, 108.46, 108.54, 116.5, 121.7, 130.1, 147.8,
148.2. IR (KBr): 3233, 2952, 2897, 2220, 1500, 1445, 1038, 925, 809 cmꢀ1
.
C9H8N2O2 (176.18): calcd C, 61.36; H, 4.58; N, 15.90. Found: C, 61.41; H, 4.61;
N, 15.85. Cyclohexyl-cyanamide 10a:9 Gummy. 1H NMR (400 MHz, CDCl3): d
1.31 (m, 5H), 1.61 (m, 1H), 1.78 (m, 2H), 1.95 (m, 2H), 3.09 (m, 1H), 3.91 (br s,
1H). 13C NMR (100 MHz, CDCl3) d 24.3, 25.1, 32.6, 54.3, 115.9. IR (KBr): 3196,
2933, 2857, 2217, 1453, 1367, 1167 cmꢀ1. C7H12N2 (124.19): calcd C, 67.70; H,
9.74; N, 22.56. Found: C, 67.67; H, 9.70; N, 22.50. Cyclopropyl-cyanamide 11a:29
Gummy. 1H NMR (400 MHz, CDCl3): d 0.71 (m, 4H, 2 ꢁ CH2), 2.71 (m, 1H, CH),
5.10 (br s, 1H). 13C NMR (100 MHz, CDCl3): d 7.1, 26.9, 116.3. IR (KBr): 3206,
2224, 1571, 1471, 1358, 1238, 1014 cmꢀ1. C4H6N2 (88.11): calcd C, 58.52; H,
7.37; N, 34.12. Found: C, 58.49; H, 7.40; N, 34.06. n-Butyl-cyanamide 12a:9