Full text of DOI:10.14233/ajchem.2018.21184

Asian Journal of Chemistry; Vol. 30, No. 5 (2018), 1075-1077
A
SIAN
J
OURNAL OF HEMISTRY
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https://doi.org/10.14233/ajchem.2018.21184
Reactions of Huisgen Zwitterions with Diphenyl Cyclopropenone:
A Novel Strategy for the Synthesis of Oxazinone Derivatives
2
R. DIVYA MOHAN1,* and ANU JOSE
1Department of Chemistry, Amrita School of Arts and Sciences, Amrita Vishwa Vidyapeetham, Amritapuri-690 525, India
2Department of Chemistry, Providence Women's College, Calicut-673 009, India
*Corresponding author: E-mail: divyamohanr@hotmail.com
Received: 15 December 2017;
Accepted: 15 February 2018;
Published online: 29 March 2018;
AJC-18843
A facile and novel route for the synthesis of diphenyl oxazinones in good yield was developed using diphenyl cyclopropenone and dialkyl
azodicarboxylate with triphenyl phosphine as catalyst at room temperature and are well characterized using spectroscopic studies.
Keywords: Oxazinones, Diphenyl cyclopropenone, Dialkyl azodicarboxylate.
system as cyclopropenone has also led to the incorporation of
phosphine azoester into the cyclopropenone system.
INTRODUCTION
In synthetic organic chemistry carbon hetero-atom and
carbon carbon bond forming reactions are of prior importance.
Generally polar and pericyclic reaction strategies are used for
this which utilize reactive intermediates like carbanions, enols,
radicals, carbenes, zwitterions, etc. Although potentially
very useful, zwitterions have received less attention from this
perspective. The present work is concerned with the use of a
less well-known reactive intermediate viz., zwitterion. Neutral
nucleophiles like triphenyl phosphine, nucleophilic carbenes,
and isocyanides can form zwitterionic intermediates with
azodicarboxylates and activated acetylenes [1-4].
Although, phosphine-azoester zwitterion generally known
as the Huisgen zwitterion [5], has been known in the literature
for almost five decades, barring its use as nucleophilic trigger
in the Mitsunobu reaction [6-8]. The chemistry of these powerful
reactive intermediates remained largely unexplored. In recent
years, our research group has explored the synthetic potential
of these zwiterionic intermediates with a view to synthesize
a variety of heterocycles [1,2] and uncovered the interesting
reactivity patterns of the zwitterions generated from triphenyl
phosphine and dialkyl azodicarboxylate. In continuation these
studies, presently, we investigated the reactions of Huisgen
zwitterions derived from triphenylphosphine-azodicarboxylate
with diphenyl cyclopropenones leading to the formation of
oxazinones. Cyclopropenones are an important class of com-
pounds because of their application in a wide range of reactions
such as decarbonylation, addition, oxidation, substitution
reactions, etc. Further, the variety of reactions for such a simple
EXPERIMENTAL
1H NMR spectra are recorded at 300 and 500 MHz, respec-
tively and 13C spectrum at 125 MHz using BrukerAvance DPX-
500 MHz NMR Spectrometer. Chemical shift values (δ) are
reported with respect to TMS (1H) and CDCl3 (12C) as internal
standards while coupling constant values (J) are reported in
hertz (Hz). IR spectra are recorded with Bomem MB Series FT-
IR spectrophotometer. Mass spectra are recorded with FAB/
LRMS and EI/HRMS using JEOL mass spectrometer. Diethyl
azodicarboxylate, diisopropyl azodicaboxylate and dibenzyl
azodicarboxylate are purchased from Lancaster Chemical Co.
and are used as such. Triphenylphosphine is purchased from
Merck. Organic solvents are distilled before use. Thin layer chro-
matography is done using glass plates with silica gel coating
having calcium sulfate as binder material. Column chromato-
graphy is performed with silica gel (100-200 mesh) using hexane-
ethyl acetate mixture for elution.
Diphenyl cyclopropenone was prepared by employing known
procedures [9]. 3,3′-Dinitrodiphenyl cyclopropenone and 3,3′-
dibromodiphenyl cyclopropenone were obtained from diphenyl-
cyclopropenone by aromatic electrophilic substitution reactions
[10,11]. 4,4′-Dichlorodiphenyl cyclopropenones are prepared
starting from their corresponding para substituted phenyl
acetic acids [12].
General procedure for the synthesis of 2-alkoxy-4,5-diaryl-
6H-1,3-oxazin-6-one: These were obtained from the reaction
of the corresponding diaryl cyclopropenone (0.25 mmol) with

1076 Mohan et al.
Asian J. Chem.
dialkyl azodicaboxylate (4 mmol) in dichloromethane (DCM) in
the presence of triphenylphosphine (4 mmol) at room tempera-
ture for 15 min under argon atmosphere (Scheme-I). The product
was isolated from the mixture with the help of column chromato-
graphy using hexane and ethyl acetate (95:5) as eluent. The
reaction was found general for a number of diphenyl cyclpropen-
ones prepared from dibenzyl ketones as shown in Table-1.
2-Ethoxy-4,5-bis(4-chlorophenyl)-6H-1,3-oxazin-6-one
(5): White solid; IR (KBr, νmax, cm-1): 1753, 1611, 1311 and
1091; 1H NMR (500 MHz, CDCl3): δ 7.11-7.31 (m, 8H), 4.53-
4.60 (q, 2H, J = 7.5 Hz), 1.47-1.5 (t, 3H, J = 7.5 Hz); 13C NMR
(75.47 MHz, CDCl3): δ159.7, 157.7, 136.5, 134.5, 134.2, 132.1,
131.2, 128.9, 128.4, 112.3, 66.6, 14.1 ppm. LRMS (+FAB) m/z
calcd for C18H13NO3Cl2 (M+H)+: 362.03; Found: 362.38.
2-(Benzyloxy)-4,5-bis(4-chlorophenyl)-6H-1,3-oxazin-
6-one (6): White solid; IR (KBr, νmax, cm-1): 1741and 1611;
1H NMR (500 MHz, CDCl3): δ 7.41-7.10 (m, 13H), 5.50 (s, 2H);
13C NMR (75.47 MHz, CDCl3): δ 161.0, 160.1, 157.4,136.3,
134.3, 132.8, 130.8, 130, 129.9, 129, 128.5, 127.9, 113.5, 71.5
ppm. LRMS (+FAB) m/z calcd for C23H15NO3Cl2 (M+H)+: 425.28;
Found: 425.69.
O
O
O
Ar
Ar
DCM; Argon
O
N
N
OR
15 min,
Room temp. RO
RO
N
Ar
Ar
O
Scheme-I
2-Isopropoxy-4,5-bis(3-nitrophenyl)- 6H-1,3-oxazin-6-
one (7): White solid; IR (KBr, νmax, cm-1): 1759, 1609, 1096
and 1295; 1H NMR (300 MHz, CDCl3): δ 7.8-7.2 (m, 10H),
5.18-5.14 (m, 1H), 1.35 (d, 6H, J = 6.5 Hz); 13C NMR (125 MHz,
CDCl3): δ 162, 150, 148, 147.9, 136, 129.7, 125, 120, 72.4, 21.6,
21.5 ppm. LRMS (+FAB) m/z calcd for C19H17N3O5 (M+H)+:
397.09; Found: 397.5.
2-Ethoxy-4,5-bis(3-nitrophenyl)- 6H-1,3-oxazin-6-one
(8): White solid; IR (KBr, νmax, cm-1): 1761, 1614, 1311 and
1091; 1H NMR (500 MHz, CDCl3): δ 7.64-7.15 (m, 8H), 4.2-4.02
(q, 2H, J = 7 Hz), 1.27-1.22 (t, 3H, J = 7 Hz); 13C NMR (75.47
MHz, CDCl3): δ162.2, 133.1, 132.8, 132.3, 132.1, 129.8, 128.7,
128.6, 123.3, 61.2, 61.1, 14.7 ppm. LRMS (+FAB) m/z calcd
for C18H13N3O5 (M+H)+: 383.08; Found: 383.51.
TABLE-1
REACTIONS OF DIARYL CYCLOPROPENONES
WITH DIALKYL AZODICARBOXYLATES
Compound
Ar group
Phenyl
Phenyl
R group
Yield (%)
1
2
3
4
5
6
7
8
9
Isopropyl
Ethyl
63
68
65
56
65
85
75
50
75
70
Phenyl
Benzyl
Isopropyl
Ethyl
Isopropyl
Ethyl
Benzyl
Ethyl
Isopropyl
m-Nitro phenyl
m-Nitro phenyl
p-Chloro phenyl
p-Chloro phenyl
p-Chloro phenyl
m-Bromo phenyl
m-Bromo phenyl
10
2-(Isopropoxy)-4,5-bis(3-bromophenyl)-6H-1,3-
oxazin-6-one (9): White solid; IR (KBr, νmax, cm-1): 1759 and
1609; 1H NMR (300 MHz, CDCl3): δ 7.92-7.18 (m, 8H), 5.180-
5.091 (m, 1H), 1.35 (d, 6H, J = 6.5 Hz); 13C NMR (125 MHz,
CDCl3): δ 162.4, 150, 139, 131, 130, 125, 124.6, 120.6, 64, 23
ppm. LRMS (+FAB) m/z calcd for C19H15NO3Br2 (M+H)+: 462.94;
Found: 462.85.
2-Ethoxy-4,5-bis(3-bromophenyl)- 6H-1,3-oxazin-6-
one (10): White solid; IR (KBr, νmax, cm-1): 1759, 1609 and
1611; 1H NMR (500 MHz, CDCl3): δ 7.8-7.2 (m, 8H), 5.180-5.14
(m, 1H, J= 6 Hz), 1.35 (d, 6H, J = 6.5 Hz); 13C NMR (75.47 MHz,
CDCl3): δ162.4, 149, 139, 131, 125, 123, 120, 55.16 ppm. LRMS
(+FAB) m/z calcd for C18H13NO3Br2 (M+H)+: 448.93; Found:
448.34.
Spectral data
2-Isopropoxy-4,5-diphenyl-6H-1,3-oxazin-6-one (1):
White solid; IR (KBr, νmax, cm-1): 1746, 1607, 1096 and 1295;
1H NMR (500 MHz CDCl3): δ 7.17-7.27 (m, 10H), 5.37-5.39
(m, 1H, J = 6 Hz), 1.47-1.48 (d, 6H, J = 6.5 Hz); 13C NMR (75.47
MHz,CDCl3): δ 161.2, 160.3, 157.1, 136.5, 133.0, 130.8, 128.3,
127.8, 113, 74.7, 21.6 ppm. LRMS (+FAB) m/z calcd for
C19H17NO3 (M+H)+: 308.12; Found: 308.58.
2-Ethoxy-4,5-diphenyl-6H-1,3-oxazin-6-one (2):White
solid; IR (KBr, νmax, cm-1): 1754, 1614, 1319 and 1096; H
1
NMR (500 MHz CDCl3): δ 7.18-7.33 (m, 10H), 4.56-4.57(q,
2H, J = 7 Hz), 1.47-1.5 (t, 3H, J = 6.5 Hz); 13C NMR (75.47
MHz, CDCl3): δ 161.11, 160.1, 157.5, 136.4, 132.9, 130.8, 130,
128.3, 127.9, 127.8, 66.3, 14.1 ppm. LRMS (+FAB) m/z calcd
for C18H15NO3 (M+H)+: 294.11; Found: 294.50.
RESULTS AND DISCUSSION
2-(Benzyloxy)-4,5-diphenyl-6H-1,3-oxazin-6-one (3):
White solid; IR (KBr, νmax, cm-1): 1752, 1612, 1305 and 1115;
1H NMR (500 MHz, CDCl3): δ 7.17-7.47 (m, 15H), 5.51 (s, 2H);
13C NMR (75.47 MHz, CDCl3): δ 160.9, 160.0, 157.5, 136.3,
134.3,132.8,130.8,130,129.9,129, 127.9,113.5,71.5 ppm.
LRMS (+FAB) m/z calcd for C23H17NO3 (M+H)+: 356.12; Found:
356.67.
2-Isopropoxy-4,5-bis(4-chlorophenyl)- 6H-1,3-oxazin-
6-one (4): White solid; IR (KBr, νmax, cm-1): 1759, 1608, 1091
and 1309; 1H NMR (300 MHz, CDCl3): δ 7.91-7.11 (m, 8H), 5.4-
5.25 (m, 1H, J = 6.3 Hz), 1.46-1.450 (d, 6H, J = 6.3 Hz); 13C NMR
(125 MHz, CDCl3): δ 160.3, 159.8, 157.3, 136.4, 134.6, 134.1,
1.32.1, 128.9, 128.3, 112, 21.59 ppm. LRMS (+FAB) m/z calcd
for C19H15NO3Cl2 (M+H)+: 376.04; Found: 376.34.
Despite their potential utility, zwitterions are rarely used
in synthetic organic chemistry when compared with other
reactive intermediates. However, we have employed the utility
of Huisgen zwitterion for the synthesis of various oxazinones
(1-10).
The mechanism of the reaction is explained by the nucleo-
philic attack of Huisgen zwitterion on cyclopropenone followed
by internal cyclization to yield corresponding oxazinone
(Scheme-II).
Conclusion
We have unravelled a facile and novel route for the synthesis
of oxazinones and successfully employed it for a series of diaryl
cyclopropenones with various dialkyl azodicarboxylates. It is

Vol. 30, No. 5 (2018)
Reactions of Huisgen Zwitterions with Diphenyl Cyclopropenone 1077
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