Microwave Assisted Aza-Wittig Reactions of N-Imidoyliminophosphorane with Aldehydes: A Convenient and Selective Route to Quinazolines

Article abstract of DOI:10.1081/SCC-120027237

A novel synthetic strategy for the selective synthesis of biologically important quinazolines with shorter reaction times, better yields, lower energy inputs and hassle free work up using a domestic microwave oven is reported.

Full text of DOI:10.1081/SCC-120027237

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Microwave Assisted Aza‐Wittig Reactions of
N‐Imidoyliminophosphorane with Aldehydes: A
Convenient and Selective Route to Quinazolines
Vipan Kumar a , Ashwini Sharma a & Mohinder P. Mahajan a
a Department of Applied Chemistry , Guru Nanak Dev University , Amritsar, 143005,
Punjab, India
Published online: 16 Aug 2006.
To cite this article: Vipan Kumar , Ashwini Sharma & Mohinder P. Mahajan (2004) Microwave Assisted Aza‐Wittig
Reactions of N‐Imidoyliminophosphorane with Aldehydes: A Convenient and Selective Route to Quinazolines, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 34:1, 49-53, DOI:
10.1081/SCC-120027237
To link to this article: http://dx.doi.org/10.1081/SCC-120027237
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 1, pp. 49–53, 2004
Microwave Assisted Aza-Wittig Reactions
of N-Imidoyliminophosphorane with
Aldehydes: A Convenient and
Selective Route to Quinazolines
*
Vipan Kumar, Ashwini Sharma, and Mohinder P. Mahajan
Department of Applied Chemistry, Guru Nanak Dev University,
Amritsar, Punjab, India
ABSTRACT
A novel synthetic strategy for the selective synthesis of biologically
important quinazolines with shorter reaction times, better yields, lower
energy inputs and hassle free work up using a domestic microwave oven
is reported.
Key Words: Aza-Wittig; Microwave; N-Imidoyliminophosphoranes;
Quinazolines.
*
Correspondence: Mohinder P. Mahajan, Department of Applied Chemistry, Guru
Nanak Dev University, Amritsar 143005, Punjab, India; E-mail: mohinderpmahajan@
angelfire.com.
49
DOI: 10.1081/SCC-120027237
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

50
Kumar, Sharma, and Mahajan
Phosphazenes[1] represent an important class of compounds and play a
significant role in modern armoury of organic synthesis. These organophos-
phorus compounds have attracted a great deal of attention in recent years
because of their broad range of application in the construction of carbon-
nitrogen double bonds,[2–4] synthesis of azadienes[5–7] and heterocumulene
associated azadienes.[8,9] Their utility in the preparation of various hetero-
cycles including pyridine derivatives,[10,11] polycyclic compounds,[12]
benzodiazepines[13] and pharmacologically active alkaloids[14] has also been
well documented. However the reports on aza-Wittig reactions of N-
imidoyliminophosphoranes are very rare.[15–18] Rossi et al.[15–17] have
reported that the reactions of N-imidoyliminophosphoranes with various
aldehydes resulted in a mixture of quinazoline and dihydroquinazoline
derivatives in a ratio which was found to depend upon the nature of aldehydes
as well as the employed thermal conditions. The reaction apparently suffers
from disadvantages such as longer reaction periods (25–90 hrs), lower yields,
lack of selectivity often leading to a mixture of products and cumbersome
workup procedure.
Quinazolines being biologically and medicinally potent neoplasm
inhibitors,[11] diuretics,[20] antimalarials,[21] antithrombics[22] and antico-
agulants,[23] the development of a simple non-conventional route for their
synthesis in improved yields was considered to be of immense significance. In
recent years microwave heating[24] together with high pressure[25] and
ultrasound[26] have been reported as important non-conventional techniques
for accelerating the reaction rates and improving yields.[27,28] Seijas et al. have
also reported the enhanced synthesis of quinazoline derivatives using
microwave radiations.[29] Because of these potential advantages, we report
herein a simple and convenient version of the aza-Wittig reaction of
N-imidoyliminophosphoranes with aldehydes using a domestic microwave
oven. Several experiments were performed at various power levels in order to
establish the optimum reaction conditions. In a typical experiment,
N-imidoyliminophosphorane 1 was mixed with 1.5 equivalents of aldehyde
2 and the mixture was exposed to microwave radiation at a power of 300 watts
for a period of 3–4 minutes. The purification of the reaction mixture by flash
chromatography resulted in the exclusive isolation of quinazolines 3 in good
yields (65–80%) (Sch. 1).[21] Interestingly, the formation of dihydroquinazo-
line derivatives was not observed even in aza-Wittig reactions of 1 with para
substituted aromatic aldehydes possessing strong electron donating groups
viz. –OCH3 and –N(CH3)2. This is in contrast to the earlier reports wherein
the formation of dihydroquinazoline and their aromatisation was shown to
depend on electronic factors. The observed absence of dihydroquinazolines in
the present case suggests that the thermal conditions also play a predominant
role in aromatisation of dihydroquinazolines to quinazolines. In conclusion, a

Microwave Assisted Aza-Wittig Reactions
51
Scheme 1.
very simple, convenient, accelerated, less expensive and high yielding method
for the selective synthesis of quinazolines is reported and further work is in
progress.
6-Methyl-2,4-diphenylquinazoline (3a). Yield-72%, m.p. 2266–
2278C; 2.58 (s, 3H, –CH3); 7.34–7.81(m, 11H, ArH); 8.01–8.05(d, 2H,
ArH): dc (50.4 MHz) 21.5, 112.5, 118.0, 119.2, 124.0, 125.7, 127.2, 128.0,
128.5, 129.0, 130.1, 134.0, 137.8, 138.2, 144.8, 161.4, 162.8 m/z-296 (Mþ).
6-Methyl-4-(40-nitrophenyl)-2-phenylquinazoline (3b). Yield-73%,
m.p. 2189–1908C dH (200 MHz): 2.58 (s, 3H, –CH3); 7.50–7.53 (m, 3H,
ArH); 7.74–7.78 (d, 2H, J ¼ 8.0 Hz, ArH); 8.02–8.08 (m, 3H, ArH); 8.44–
8.48 (d, 2H, J ¼ 8.1 Hz, ArH); 8.61–8.66 (m, 2H, ArH); dc (50.4 MHz) 21.9,
121.2, 123.7, 124.2, 128.4, 128.5, 129.2, 130.4, 130.6, 131.0, 136.3, 137.7,
137.9, 143.9, 148.5, 159.5, 165.0 m/z-341 (Mþ).
6-Methyl-4-(40-methoxyphenyl)-2-phenylquinazoline
(3c). Yield-
77%, m.p. 2160–1618C, dH (200 MHz): 2.51 (s, 3H, –CH3); 3.92 (s, 3H,
–OCH3); 7.09–7.13 (d, 2H, J ¼ 8.7 Hz, ArH); 7.46–7.54 (m, 3H, ArH);
7.66–7.71 (d, 1H, J ¼ 10.0 Hz, ArH); 7.85–7.90 (m, 3H, ArH); 8.00–8.05 (d,
1H, J ¼ 10.2 Hz, ArH) 8.64–8.68 (m, 2H, ArH): dc (50.4 MHz) 21.8, 55.3,
113.9, 115.5, 121.5, 123.9, 125.6, 126.6, 127.2, 128.4, 128.8, 130.1, 130.5,
135.4, 136.8, 150.6, 159.4, 160.9.m/z-326 (Mþ).
6-Methyl-4-(40-dimethy1aminophenyl)-2-phenylquinazoline
(3d).
Yield-78%, m.p. 2213–2158C, dH (200 MHz): 2.56 (s, 3H, –CH3); 3.14 (s,
6H, –N(CH3)2); 6.91–6.96 (d, 2H, J ¼ 10.0 Hz, ArH); 7.52–7.55 (m, 3H,
ArH); 7.74–7.79 (m, 1H, ArH); 7.90–7.95 (d, 2H, J ¼ 10.0 Hz, ArH); 8.03–
8.07 (m, 2H, ArH); 8.68–8.73(m, 2H, ArH); dc (50.4 MHz) 20.9, 44.0 (–
N(CH3)2), 114.2, 116.7, 120.6, 124.0, 125.9, 127.0, 127.2, 128.0, 128.8, 130.0,
130.9, 135.9, 137.5, 144.5, 160.7, 161.8 m/z-339 (Mþ).

52
Kumar, Sharma, and Mahajan
6-Methy1-4-(40-chlorophenyl)-2-phenylquinazoline (3e). Yield-72%,
m.p. 2180–1828C, dH (200 MHz): 2.57 (s, 3H, –CH3); 7.12–7.16 (d, 2H,
J ¼ 8.2 Hz, ArH); 7.42–7.46 (d, 2H, J ¼ 8.2 Hz, ArH); 7.53–7.56 (m, 3H,
ArH); 7.75–7.79 (m, 1H, ArH); 7.83–7.88 (d, 1H, J ¼ 10.0 Hz, ArH); 7.89–
7.93 (d, 1H, J ¼ 10.0 Hz, ArH); 8.65–8.69 (m, 2H, ArH): dc (50.4 MHz) 21.2,
112.3, 117.7, 119.5, 123.8, 126.0, 127.2, 127.8, 128.1, 129.0, 129.7, 130.7,
133.8, 137.9, 144.0, 161.2, 162.5 m/z-330.5 (Mþ).
ACKNOWLEDGMENT
Vipan Kumar is grateful to CSIR, New Delhi for a Junior Research
Fellowship and the financial assistance by CSIR, New Delhi, under grant No.
01(1590)/99/EMR-II is gratefully acknowledged.
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Received in the USA July 30, 2003