A regiospecific synthesis of 1-heterocyclic substituted 1,2,4-triazoles via addition reaction of 1,2,4-triazole with functionalized carbodiimide

Article abstract of DOI:10.1081/SCC-120012998

The reaction of 1,2,4-triazole with functionalized carbodiimide 2 or 6 under solid K₂CO₃ provide a convenient and regiospecific route to 1-(2-imidazolonyl)-1,2,4-triazole 4 or 1-(2-quinazolonyl)-1,2,4-triazole 8.

Full text of DOI:10.1081/SCC-120012998

This article was downloaded by: [University of California Santa Cruz]
On: 29 November 2014, At: 02:30
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
A REGIOSPECIFIC SYNTHESIS OF 1-HETEROCYCLIC
SUBSTITUTED 1,2,4-TRIAZOLES VIA ADDITION
REACTION OF 1,2,4-TRIAZOLE WITH FUNCTIONALIZED
CARBODIIMIDE
Ming-Wu Ding a , Gui-Ping Zeng a & Zhao-Jie Liu b
a Institute of Organic Synthesis , Central China Normal University , Wuhan, 430079, P.R.
China
b Institute of Organic Synthesis , Central China Normal University , Wuhan, 430079, P.R.
China
Published online: 16 Aug 2006.
To cite this article: Ming-Wu Ding , Gui-Ping Zeng & Zhao-Jie Liu (2002) A REGIOSPECIFIC SYNTHESIS OF 1-HETEROCYCLIC
SUBSTITUTED 1,2,4-TRIAZOLES VIA ADDITION REACTION OF 1,2,4-TRIAZOLE WITH FUNCTIONALIZED CARBODIIMIDE, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:19, 3057-3062, DOI:
10.1081/SCC-120012998
To link to this article: http://dx.doi.org/10.1081/SCC-120012998
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHETIC COMMUNICATIONS
Vol. 32, No. 19, pp. 3057–3062, 2002
A REGIOSPECIFIC SYNTHESIS OF
1-HETEROCYCLIC SUBSTITUTED
1,2,4-TRIAZOLES VIA ADDITION
REACTION OF 1,2,4-TRIAZOLE WITH
FUNCTIONALIZED CARBODIIMIDE
*
Ming-Wu Ding, Gui-Ping Zeng, and Zhao-Jie Liu
Institute of Organic Synthesis, Central China
Normal University, Wuhan, 430079, P.R. China
ABSTRACT
The reaction of 1,2,4-triazole with functionalized carbodi-
imide 2 or 6 under solid K2CO3 provide a convenient and
regiospecific route to 1-(2-imidazolonyl)-1,2,4-triazole 4 or
1-(2-quinazolonyl)-1,2,4-triazole 8.
Key Words: Triazoles; Iminophosphorane; Imidazolinones;
Quinazolinones; Aza-Wittig reaction
Many 1-substituted 1,2,4-triazole compounds show good fungicidal
activities and plant growth regulative activities. They are generally
prepared by N-alkylations of 1,2,4-triazole with alkylating reagents, of
which various types have been used, however, many of these reactions
*Corresponding author. E-mail: ding5229@yahoo.com.cn
3057
DOI: 10.1081/SCC-120012998
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3058
DING, ZENG, AND LIU
are limited by the simultaneous formation of the unwanted and biologically
inactive 4-isomer.[1] It was reported that 1,2,4-triazole derivatives can
be regiospecifically synthesized by addition reactions of 1,2,4-triazole
with aldehydes and this method was successfully utilized to prepare
many novel triazole derivatives.[2–5] However, there is no report about
addition reaction of 1,2,4-triazole with carbodiimide. Recently we
provided a facile synthesis of 2-substituted imidazolinones and quinazoli-
nones via tandem aza-Wittig reaction.[6–8] We now report a new
regiospecific synthesis of 2-heterocyclic substituted 1,2,4-triazoles via
base catalytic addition reaction of 1,2,4-triazole with functionalized
carbodiimide.
The easily accessible vinyliminophosphorane 1 reacted with aro-
matic isocyanates to give carbodiimides 2. The direct reaction of 2
with 1,2,4-triazole at room temperature took place very slow for 2 did
not disappear even after 5 days, however, when the reaction was
carried out under solid K2CO3(s), the reaction mixture was getting red
quickly and then becoming yellow gradually within 15 min. The final
product obtained was verified to be 1-(2-imidazolonyl)-1,2,4-triazole 4.
No 4-isomer of 4 was formed during the reaction process. The struc-
ture of 4 has been characterized spectroscopically. For example, the
1H NMR spectrum data in 4a showed the signals of 3-H in triazole
ring at 7.94 ppm as a single absorption and 5-H at 8.97 ppm as a
single absorption. The use of a 10-fold of excess solid K2CO3(s) gave
better yields of 4. The best reaction time was 15 min, for the reaction
mixture was getting dark gradually after 15 min due to side reactions
(Table 1). The formation of 4 can be rationalized in terms of
an initial nucleophilic addition of 1,2,4-triazole under potassium car-
bonate to give the intermediate 3 which directly cyclized to give 4
(Sch. 1).
The above method was also successively applied to synthesize
1-(2-quinazolonyl)-1,2,4-triazole 8, which having been found to show
fungicidal activities.[9] Iminophosphorane
5 reacted with aromatic
isocyanates to give carbodiimides 6, which was allowed to react with
1,2,4-triazole under solid potassium carbonate to give 8 (Sch. 2). Good
yields of 8 were obtained when catalytic solid potassium carbonate was
used with overnight stirring (Table 1). The structure of 8 has been char-
1
acterized spectroscopically. For example, the H NMR spectrum data in 8a
showed the signals of 3-H in triazole ring at 8.14 ppm as a single absorp-
tion and 5-H at 8.60 ppm as a single absorption. The formation of 8 can
be rationalized in terms of an initial nucleophilic addition of 1,2,4-triazole
under potassium carbonate to give the intermediate 7 which directly
cyclized to give 8.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1-HETEROCYCLIC SUBSTITUTED 1,2,4-TRIAZOLES
3059
Table 1. Preparation of 1-(2-Imidazolonyl)-1,2,4-triazole 4 and 1-(2-Quinazolonyl)-
1,2,4-triazole 8
Reaction
Time (h)
Compds.
Ar1
Ph
Ar2
Ph
Ar
K2CO3(s)
Yield (%)*
4a
0.25
1
24
10 equiv
10 equiv
10 equiv
0.1 equiv
1 equiv
10 equiv
10 equiv
10 equiv
10 equiv
10 equiv
0.1 equiv
0.1 equiv
0.1 equiv
82
38
11
22
45
72
68
87
80
76
74
70
71
0.25
0.25
0.25
0.25
0.25
0.25
0.25
24
4b
4c
4d
4e
4f
Ph
Ph
4-Cl-Ph
3-Cl-Ph
3-Cl-Ph
4-Cl-Ph
3-Cl-Ph
4-Cl-Ph
Ph
4-Cl-Ph
8a
8b
8c
Ph
4-Cl-Ph
3-Cl-Ph
24
24
*isolated yields based on iminophosphoranes.
Scheme 1.
EXPERIMENTAL
Melting points were uncorrected. MS were measured on a HP5988A
spectrometer. IR were recorded on a Shimadzu IR-408 infrared spectrom-
eter. NMR were taken on a Varian XL-200 spectrometer.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3060
DING, ZENG, AND LIU
Scheme 2.
General Preparation of 1-(2-Imidazolonyl)-1,2,4-triazole 4
To a solution of vinyliminophosphorane 1 (5 mmol) in dry methylene
dichloride (15 mL) was added aromatic isocyanate (5 mmol) under nitrogen
at room temperature. After the reaction mixture was stirred for 4 ꢀ 6 h, the
solvent was removed off under reduced pressure and ether/petroleum ether
(1 : 2, 20 mL) was added to precipitate triphenylphosphine oxide. Filtered,
the solvent was removed to give carbodiimide 2, which was used directly
without further purification. To the solution of 2 prepared above in
CH3CN (15 mL) was added 1H-1,2,4-triazole (0.34 g, 5 mmol) and
excess solid K2CO3 (6.9 g, 50 mmol). The mixture was stirred for 15 min
vigorously at room temperature and filtered, the filtrate was condensed
and the residual was recrystallized from methylene dichloride/petroleum
ether or purified by a short silica gel column to give 1-(2-imidazolonyl)-
1,2,4-triazole 4.
4a: yellow crystals, m.p. 160 ꢀ 162ꢁC, H NMR (CDCl3, 200 MHz)
1
ꢀ 8.97 (s, 1H, triazolyl-5-H), 7.94 (s, 1H, triazolyl-3-H), 8.21 ꢀ 7.18
(m, 11H, Ar–H and ¼CH); IR (cmÀ1), 1722, 1640, 1560, 1476; MS (m/z),
315 (Mþ, 100%), 171 (42%), 144 (14%), 117 (76%).
4b: yellow crystals, m.p. 197 ꢀ 199ꢁC, H NMR (CDCl3, 200 MHz)
1
ꢀ 9.06 (s, 1H, triazolyl-5-H), 7.94 (s, 1H, triazolyl-3-H), 8.20 ꢀ 7.12
(m, 10H, Ar–H and ¼CH); IR (cmÀ1), 1728, 1636, 1562, 1474; MS (m/z),
349 (Mþ, 100%), 351 (33%), 205 (25%), 151 (40%), 116 (20%).
4c: yellow crystals, m.p. 152 ꢀ 154ꢁC, H NMR (CDCl3, 200 MHz)
1
ꢀ 9.08 (s, 1H, triazolyl-5-H), 7.94 (s, 1H, triazolyl-3-H), 8.22 ꢀ 7.14

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1-HETEROCYCLIC SUBSTITUTED 1,2,4-TRIAZOLES
3061
(m, 10H, Ar–H and ¼CH); IR (cmÀ1), 1725, 1638, 1558, 1475; MS (m/z),
349 (Mþ, 100%), 351 (34%), 205 (23%), 151 (28%), 116 (19%).
4d: yellow crystals, m.p. 197 ꢀ 199ꢁC, H NMR (CDCl3, 200 MHz)
1
ꢀ 9.10 (s, 1H, triazolyl-5-H), 7.90 (s, 1H, triazolyl-3-H), 8.20 ꢀ 7.10 (m,
9H, Ar–H and ¼CH); IR (cmÀ1), 1730, 1638, 1550, 1478, MS (m/z), 383
(Mþ, 100%), 385 (62%), 387 (11%), 205 (47%), 151 (30%).
4e: yellow crystals, m.p. 176 ꢀ 178ꢁC, H NMR (CDCl3, 200 MHz)
1
ꢀ 9.06 (s, 1H, triazolyl-5-H), 7.92 (s, 1H, triazolyl-3-H), 8.21 ꢀ 7.12
(m, 10H, Ar–H and ¼CH); IR (cmÀ1), 1728, 1640, 1552, 1478; MS (m/z),
349 (Mþ, 100%), 351 (33%), 205 (27%), 151 (36%).
4f: yellow crystals, m.p. 218 ꢀ 220ꢁC, 1H NMR (CDCl3, 200 MHz)
ꢀ 9.02 (s, 1H, triazolyl-5-H), 7.88 (s, 1H, triazolyl-3-H), 8.18 ꢀ 7.03
(m, 9H, Ar–H and ¼CH); IR (cmÀ1), 1735, 1640, 1548, 1478; MS (m/z),
383 (Mþ, 88%), 385 (61%), 387 (11%), 205 (58%), 151 (58%).
General Preparation of 1-(2-Quinazolonyl)-1,2,4-triazole 8
To a solution of iminophosphorane 5 (2.12 g, 5 mmol) in dry methy-
lene dichloride (15 mL) was added aromatic isocyanate (5 mmol) under
nitrogen at 0 ꢀ 5ꢁC. After the reaction mixture was stand for 6 ꢀ 12 h at
0 ꢀ 5ꢁC, the solvent was removed off under reduced pressure and ether/pe-
troleum ether (1 : 2, 20 mL) was added to precipitate triphenylphosphine
oxide. Filtered, the solvent was removed to give carbodiimide 6, which was
used directly without further purification. To the solution of 6 prepared
above in CH3CN (15 mL) was added 1H-1,2,4-triazole (0.34 g, 5 mmol)
and catalytic solid K2CO3 (0.07 g, 0.5 mmol). The mixture was stirred
overnight at room temperature and filtered, the filtrate was
condensed and the residual was recrystallized from methylene dichloride/
petroleum ether or purified by a short silica gel column to give 1-(2-quina-
zolonyl)-1,2,4-triazole 8.
8a: white crystals, m.p. 148 ꢀ 150ꢁC, 1H NMR (CDCl3, 200 MHz)
ꢀ 8.60 (s, 1H, triazolyl-5-H), 8.14 (s, 1H, triazolyl-3-H), 8.32 ꢀ 6.90
(m, 9H, Ar–H); IR (cmÀ1), 1684, 1550, 1300; MS (m/z), 289 (Mþ, 100%),
221 (46%), 144 (14%), 77 (66%).
8b: white crystals, m.p. 156 ꢀ 158ꢁC, 1H NMR (CDCl3, 200 MHz)
ꢀ 8.68 (s, 1H, triazolyl-5-H), 8.16 (s, 1H, triazolyl-3-H), 8.36 ꢀ 6.92
(m, 8H, Ar–H); IR (cmÀ1), 1686, 1552, 1306; MS (m/z), 323 (Mþ, 100%),
325 (32%), 255 (40%), 220 (12%), 144 (16%), 90 (71%).
8c: white crystals, m.p. 150 ꢀ 152ꢁC, 1H NMR (CDCl3, 200 MHz)
ꢀ 8.66 (s, 1H, triazolyl-5-H), 8.16 (s, 1H, triazolyl-3-H), 8.35 ꢀ 6.90

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3062
DING, ZENG, AND LIU
(m, 8H, Ar–H); IR (cmÀ1), 1685, 1550, 1302; MS (m/z), 323 (Mþ, 100%),
325 (33%), 255 (48%), 144 (24%), 90 (56%).
ACKNOWLEDGMENTS
We gratefully acknowledge financial support of this work by the
National Natural Science Foundation of China (Project No. 20102001).
REFERENCES
1. Bentley, T.W.; Jones, R.V.H.; Wareham, P. J. Tetrahedron Lett. 1989,
30, 4013.
2. Smith, K.; Hammond, M.E.W.; James, D.M.; Ellison, I.J.; Hutchings,
Chem. Lett. 1990, 351.
3. Smith, K.; Small, A.; Hutchings, M.G. Synlett. 1991, 485.
4. Seele, R.; Goetz, N.; Brox, W.; Kober, R.; Ammermann, E.; Lorenz, G.
EP449067 (1991).
5. Seele, R.; Goetz, N.; Saupe, T.; Lorenz, G.; Ammermann, E. Ger. Offen.
4034352 (1992).
6. Ding, M.W.; Zeng, G.P.; Wu, T. J. Synth. Commun. 2000, 30, 1599.
7. Ding, M.W.; Xu, Z.F.; Wu, T. J. Synth. Commun. 1999, 29, 1171.
8. Ding, M.W.; Tu, H.Y.; Liu, Z. J. Synth. Commun. 1997, 27, 3657.
9. Green, D.E.; Percival, A. EP183458 (1986).
Received in the Netherlands September 21, 2001