Novel synthesis of unsymmetrical azines from semicarbazones and aldehydes

Article abstract of DOI:10.1081/SCC-100000188

A new synthesis of unsymmetrical azines utilizing semicarbazones and aldehyde is described.

Full text of DOI:10.1081/SCC-100000188

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NOVEL SYNTHESIS OF UNSYMMETRICAL AZINES FROM
SEMICARBAZONES AND ALDEHYDES
Ren Zhongjiao a , Cao Weiguo a , Tong Weiqi a & Xi Jiajun a
a Department of Chemistry , Shanghai University , Shanghai, 201800, P.R. China
Published online: 09 Nov 2006.
To cite this article: Ren Zhongjiao , Cao Weiguo , Tong Weiqi & Xi Jiajun (2001) NOVEL SYNTHESIS OF UNSYMMETRICAL
AZINES FROM SEMICARBAZONES AND ALDEHYDES, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:1, 125-129, DOI: 10.1081/SCC-100000188
To link to this article: http://dx.doi.org/10.1081/SCC-100000188
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SYNTHETIC COMMUNICATIONS, 31(1), 125–129 (2001)
NOVEL SYNTHESIS OF UNSYMMETRICAL
AZINES FROM SEMICARBAZONES
AND ALDEHYDES
Ren Zhongjiao,∗ Cao Weiguo, Tong Weiqi, and Xi Jiajun
Department of Chemistry, Shanghai University,
Shanghai 201800, P.R. China
ABSTRACT
A new synthesis of unsymmetrical azines utilizing semicar-
bazones and aldehyde is described.
In general, symmetrical azines are easily prepared by condensation of hy-
drazine with appropriate carbonyl compounds (1). In this manner, it is difficult to
obtain pure unsymmetrical substituted azines in good yield (2). The methods in-
volving synthesis of unsymmetrical azines have received much attention recently.
Some routes, such as the alkylidene group exchange between azines and imines (3),
N-(diethoxyphosphinyl)-hydrazone with carbonyl compounds (4), and Zirconium
“metalloazines” and aldehydes (5), have been proposed. These methods suffer
from the fact that the starting substances are not commercially available. Herein,
we wish to report a new, simple, and convenient process for preparing unsym-
metrical azines from aromatic aldehyde semicarbazones and aromatic aldehydes
(Scheme 1, Table 1).
The reaction was performed with semicarbazones and aldehydes in DMF
under reflux.
∗ To whom correspondence should be addressed.
125
Copyright ꢀ 2001 by Marcel Dekker, Inc.
www.dekker.com
C

ORDER
REPRINTS
126
ZHONGJIAO ET AL.
Scheme 1.
Table 1. Preparation of Unsymmetrical Azines
Compd.
Ar
Arꢁ
Reaction Time (h) Yield (%)
m.p. (◦C)
3a
3b
3c
3d
3e
3f
3g
3h
3i
4-Cl-Ph
4-NO2-Ph
4-F-Ph
2-Cl-Ph
2,4-(Cl)2-Ph 4-OCH3-Ph
4-Cl-Ph
4-NO2-Ph
4-F-Ph
2-Cl-Ph
2,4-(Cl)2-Ph 4-CH3-Ph
4-OCH3-Ph
4-OCH3-Ph
4-OCH3-Ph
4-OCH3-Ph
16
16
16
16
16
16
16
16
16
16
87
87
84
79
78
92
90
80
72
73
130.5–131.5
203.7–204.5
90.0–91.0
74.5–75.2
152.5–153.4
153.0–154.0
193.5–194.0
119.0–120.0
106.0–106.5
178.0–179.0
4-CH3-Ph
4-CH3-Ph
4-CH3-Ph
4-CH3-Ph
3j
RESULTS AND DISCUSSION
Because the formation of NH3 and CO2 has been observed during the reac-
tion, the suggested reaction mechanism is as follows (Scheme 2).
Scheme 2.
At first, the ammonia is released from semicarbazones A under reflux to
form intermediate B. Subsequently, a four-membered cyclic transition state D is
suggested for the cycloaddition reaction of B with the aromatic aldehydes C, and
finally carbon dioxide and unsymmetrical azines E are obtained by fragmentation
of ring D.
A mixture of unsymmetrical and symmetrrical azines is produced when
using aromatic aldehyde semicarbazones with an electron-donating group. The
mechanism for the formation of symmetrical azine is similar to that outlined above
(Scheme 3).

ORDER
REPRINTS
UNSYMMETRICAL AZINES
127
Ar = Ph, 4-CH3Ph, 4-N(CH3)2, 4-OH-Ph; Arꢁ = 4-CH3O-Ph
Scheme 3.
First, unsymmetrical azines E are prepared. Next, the four-membered cyclic
interimediate F is formed by cycloaddition reaction of aldehyde C and the imine
group in azine E with electron-donating group, because the electron charge density
of this imine is higher than one without an electron-donating group. The cleavage
of ring F produces aldehyde H and symmetrical azine G.
When the electron-donating group is replaced by an electron-withdrawing
group, the exchanging reaction between the aldehyde and imine always occurs on
the imine with 4-methoxybenzaldehyde. As a result, the unsymmetrical azines are
retained (Scheme 4).
Scheme 4.
EXPERIMENTAL
Melting points are uncorrected. They were determined on a WRS-1 digital
melting point apparatus made by Shanghai Physical Optical Instrument Factory
(SPOIF), China. IR spectra were measured in KBR on a PE-580B spectrometer.
Elemental analyses were carried out on a Foss Heraeus CHN-O-RAPID element
1
analysis instrument. HNMR were recorded at Bruker AC-100SC, using CDCl3
as solvent and TMS as internal reference.

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128
ZHONGJIAO ET AL.
General Procedure
The mixture of aromatic aldehyde semicarbazones (2.5 mmol) and aromatic
aldehydes (10 mmol) in 20 mL DMF are refluxed for 16 h. After cooling, water
(200 mL) is added to the reaction mixture. The precipitate is allowed to stand
overnight, collected by suction filtration, washed with petroleum ether, and dried
at room temperature.
1
3a: IR, νC
(cm−1), 1654, HNMR, δ (ppm), 3.87 (s, 3H), 6.98 (d, 2H,
=
N
J = 9.0 Hz), 7.42, (d, 2H, J = 8.0 Hz), 7.78 (d, 2H, J = 9.0 Hz), 7.83 (d, 2H,
J = 8.0 Hz), 8.61 (s, 1H), 8.66 (s, 1H). Anal. calcd. for C15H13ClN2O, C, 66.06,
H, 4.80, N, 10.27. Found, C, 66.39, H, 4.80, N, 10.28.
1
3b: IR, νC
(cm−1), 1625, HNMR, δ (ppm), 3.88 (s, 3H), 6.99 (d, 2H,
=
N
J = 8.7 Hz), 7.83 (d, 2H, J = 8.7 Hz), 7.99 (d, 2H, J = 8.6 Hz), 8.31 (d, 2H,
J = 8.6 Hz), 8.65 (s, 1H), 8.71 (s, 1H). Anal. calcd. for C15H13N3O3, C, 63.60, H,
4.63, N, 14.83. Found, C, 63.77, H, 4.46, N, 14.65.
1
3c: IR, νC
(cm−1), 1657, HNMR, δ (ppm), 3.87 (s, 3H), 6.97 (d, 2H,
=
N
J = 8.7 Hz), 7.18 (d, 2H, J = 8.7 Hz), 7.76–7.91 (d, d, 4H, J = 8.7 Hz, J = 8.7 Hz),
8.62–8.64 (d, 2H). Anal. cacld. for C15H13FN2O, C, 70.30, H, 5.11, N, 10.93.
Found, C, 70.26, H, 5.19, N, 10.89.
1
3d: IR, νC
(cm−1), 1619, HNMR, δ (ppm), 3.87 (s, 3H), 6.97 (d, 2H,
=
N
J = 8.5 Hz), 7.25–7.40 (m, 3H), 7.82 (d, 2H, J = 8.5 Hz), 8.14–8.22 (q, 1H), 8.63
(s, 1H), 9.09 (s, 1H). Anal. cacld. for C15H13ClN2O, C, 66.06, H, 4.80, N, 10.27.
Found, C, 66.34, H, 4.78, N, 10.25.
1
3e: IR, νC
(cm−1), 1719, HNMR, δ (ppm), 3.88 (s, 3H), 6.98 (d, 2H,
=
N
J = 8.2 Hz), 7.38 (d, 1H, J = 8.7 Hz), 7.45 (s, 1H), 7.82 (d, 2H, J = 8.2 Hz), 8.14
(d, 1H, J = 8.7 Hz), 8.62 (s, 1H) 9.02 (s, 1H). Anal cacld. for C15H12Cl2N2O, C,
58.65, H, 3.94, N, 9.12. Found, C, 58.19, H, 3.77, N, 9.09.
1
3f: IR, νC
(cm−1), 1654, HNMR, δ (ppm), 2.41 (s, 3H), 7.26 (d, 2H,
=
N
J = 8.0 Hz), 7.41 (d, 2H, J = 8.5 Hz), 7.70–7.82 (d, d, 4H, J = 8.0 Hz, J = 8.5 Hz),
8.61–8.63(d, 2H). Anal. cacld. forC15H13ClN2, C, 70.18, H, 5.10, N, 10.91. Found,
C, 69.80, H, 4.78, N, 10.85.
1
3g: IR, νC
(cm−1), 1628, HNMR, δ (ppm), 2.42 (s, 3H), 7.29 (d, 2H,
=
N
J = 8.0 Hz), 7.76 (d, 2H, J = 8.0 Hz), 7.99 (d, 2H, J = 8.4 Hz), 8.30 (d, 2H,
J = 8.4 Hz), 8.66–8.96 (d, 2H). Anal. calcd. for C15H13N3O2 C, 67.40, H, 4.90,
N, 15.72. Found, C, 67.00, H, 4.69 N, 16.02.
3h: IR, νC
(cm−1), 1654, 1HNMR, δ (ppm), 2.42 (s, 3H), 7.14–7.30 (q,
=
N
4H), 7.70–7.83 (q, 4H), 8.64 (d, 2H). Anal. cacld. for C15H13FN2, C, 74.98, H,
5.45, N, 11.66. Found, C, 74.93, H, 5.75, N, 11.64.
3i: IR, νC
(cm−1), 1654, 1HNMR, δ (ppm), 2.42 (s, 3H), 7.23–7.40 (m,
=
N
5H), 7.72–7.80 (d, 2H), 8.17–8.22 (q, 1H), 8.64 (s, 1H), 9.09 (s, 1H). Anal. cacld.,
for C15H13ClN2, C, 70.18, H, 5.10 N, 10.91. Found, C, 70.13, H, 4.99, N, 10.89.

ORDER
REPRINTS
UNSYMMETRICAL AZINES
129
3j: IR, νC N (cm−1), 1718, 1HNMR, δ (ppm), 2.42 (s, 3H), 7.24–7.36 (d,d,
=
3H, J = 8.0 Hz, J = 8.5 Hz), 7.45 (s, 1H), 7.75 (d, 2H, J = 8.0 Hz), 8.14 (d, 1H,
J = 8.5 Hz), 8.63 (s, 1H), 9.01 (s, 1H). Anal. calcd. for C15H12Cl2N2, C, 61.87,
H, 4.15, N, 9.62. Found, C, 61.89, H, 3.97, N, 9.75.
REFERENCES
1. Tennam, G. Comprehensive Organic Chemistry; Sutherland, I. O., Ed.;
Pergamon Press: Oxford, 1979; Vol. 2, 455.
2. Ugriumov, P.G. Zh Obshch. Khim. 1959, 29, 4091.
3. Barluenga, J.; Fustero, S.; Gomez, N.; Gotor, V. Synthesis 1982, 966.
4. Koziara, A.; Turski, K.; Zwierzak A. Synthesis 1986, 298.
5. Georgia, M.A.; Jeffrey, S. Organometallics 1987, 6, 421.
Received March 27, 2000

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