Intramolecular cyclization of azides by iminium species. A novel method for the construction of nitrogen heterocycles under vilsmeier conditions

Article abstract of DOI:10.1021/jo971745z

An unprecedented attack of the azide functionality by iminium species, generated in situ under Vilsmeier conditions, provided a novel route for the construction of nitrogen heterocycles. Thus, the treatment of 2-azidoacetophenones with Vilsmeier reagent under reflux conditions gave 5-aryloxazole-4-carboxaldehydes. One-pot synthesis of oxazole carboxaldehydes from 2-bromoacetophenones by dehaloazidation-Vilsmeier cyclization reaction sequence provided better yields. The susceptibility of the carbonyl group to undergo chloroformylation at room temperature without affecting the azide function was exploited to provide an attractive scheme for the synthesis of α-azidoβ-chlorovinyl azides from phenacyl azides. The synthesis of a series of N-aryl 5-chloro-2-(dimethylamino)imidazole-4-carboxaldehydes was accomplished by the Vilsmeier cyclization of N-aryl-2-azidoacetamides. The possible mechanisms for the reactions are also discussed.

Full text of DOI:10.1021/jo971745z

7136
J . Org. Chem. 1998, 63, 7136-7142
Articles
In tr a m olecu la r Cycliza tion of Azid es by Im in iu m Sp ecies. A Novel
Meth od for th e Con str u ction of Nitr ogen Heter ocycles u n d er
Vilsm eier Con d ition s
Vattoly J . Majo and Paramasivan T. Perumal*
Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai - 600 020, India
Received September 17, 1997
An unprecedented attack of the azide functionality by iminium species, generated in situ under
Vilsmeier conditions, provided a novel route for the construction of nitrogen heterocycles. Thus,
the treatment of 2-azidoacetophenones with Vilsmeier reagent under reflux conditions gave
5-aryloxazole-4-carboxaldehydes. One-pot synthesis of oxazole carboxaldehydes from 2-bromo-
acetophenones by dehaloazidation-Vilsmeier cyclization reaction sequence provided better yields.
The susceptibility of the carbonyl group to undergo chloroformylation at room temperature without
affecting the azide function was exploited to provide an attractive scheme for the synthesis of R-azido-
â-chlorovinyl azides from phenacyl azides. The synthesis of a series of N-aryl 5-chloro-2-
(dimethylamino)imidazole-4-carboxaldehydes was accomplished by the Vilsmeier cyclization of
N-aryl-2-azidoacetamides. The possible mechanisms for the reactions are also discussed.
In tr od u ction
attack of the vinyl azide can either occur at the â-vinyl
carbon15 or at the R-nitrogen atom of the azide.16
A
In recent times, there has been a growing interest in
the area of application of azides in organic synthesis
which could be attributed to the broad spectrum of
reactivity of these versatile reagents.1 The common types
of reactions of azides which lead to the synthesis of
heterocycles in which only one azide nitrogen is retained
are reductive cyclization,2 Staudinger reaction,3 Curtius
rearrangement,4 Schmidt rearrangement,5 nitrene inser-
tion,6 and radical cyclization.7
The cycloaddition of azides across a double bond
provides a general synthetic approach to triazolines,8
aziridines,9 and other related heterocycles. The vinyl
azides are highly reactive and are susceptible to pho-
tolysis,10 pyrolysis,11 cycloadditions,12 and attack by nu-
cleophiles13 as well as by electrophiles.14 The electrophilic
survey of literature revealed that the electrophilic attack
of the azides by iminium species is not explored to date.
Toward this end, we analyzed a synthetic strategy for
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S0022-3263(97)01745-3 CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/01/1998

Electrophilic Substitution of Azides by Iminium Species
J . Org. Chem., Vol. 63, No. 21, 1998 7137
Sch em e 1
the construction of nitrogen heterocycles by the Vilsmeier
cyclization of azides which consists of the following steps.
(i) The in situ generation of iminium salt from a Vils-
meier-active functional group which is strategically
located from the azide. (ii) The intramolecular cyclization
of the azide by the iminium species followed by elimina-
tion of nitrogen.
systems.24 Recently, we have been focusing attention on
exploiting the cyclization potential of this reagent.25
We began our investigations by examining some of the
general principles underlying the synthetic design of
oxazolecarboxaldehydes from the corresponding 2-azido-
acetophenones.26 A one-pot synthetic strategy starting
from the corresponding 2-bromoacetophenones involving
a dehaloazidation-Vilsmeier cyclization reaction se-
quence also proved successful. The success of our strat-
egy prompted us to extend the potential of Vilsmeier
cyclization of azides for the synthesis of other nitrogen
heterocycles.
The novelty of the entire process lies in the Vilsmeier
cyclization of the azide, which, to the best of our knowl-
edge, is unprecedented. A detailed account of our studies
on the construction of nitrogen heterocycles and the
possible reaction pathways are discussed in this paper.
The capability of Vilsmeier reagent to generate a broad
spectrum of iminium species provides considerable scope
and versatility for the intramolecular cyclization of azides
by iminium species under Vilsmeier conditions. The
reactive intermediates involved in the Vilsmeier-Haack-
Arnold reaction are the halomethyleniminium salts
derived from the action of acid chlorides on N,N-disub-
stituted formamides.17 The classical Vilsmeier-Haack
reaction involves electrophilic substitution of an activated
aromatic ring with a halomethyleniminium salt to yield
the corresponding iminium species.18 However, the scope
of the reagent is not restricted to aromatic formylation.
A wide variety of alkene derivatives,19 carbonyl com-
pounds,20 activated methyl and methylene groups,21 and
oxygen22 and nitrogen nucleophiles23 react with Vilsmeier
reagent to yield the corresponding iminium salts. The
cyclization of iminium species under Vilsmeier conditions
is an important synthetic tool of organic chemistry which
provides a facile entry into large number of heterocyclic
Resu lts a n d Discu ssion
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Syn th esis of Oxa zoles. We envisaged that the Vils-
meier cyclization of 2-azidoacetophenones 1 would pro-
vide an efficient route for the preparation of 5-aryloxazole-
4-carboxaldehydes 3. The reaction was carried out at
80-90 °C for 2-3 h using 3 equiv of Vilsmeier reagent.
Indeed, the reaction proceeded uneventfully, and the
anticipated oxazoles were obtained in 36-45% yield
(Scheme 1 and Table 1).
The prerequisite azidoacetophenones necessary for the
oxazole synthesis were prepared in high yields from the
corresponding 2-bromoacetophenones. The conversion
was carried out in DMF using 2 equiv of NaN3 at 15-20
°C for 20 min.
Sha et al.27 have reported that alkyl azides generated
in situ from the corresponding bromides undergo intra-
molecular cycloaddition to enones in DMF to provide a
one-step synthesis of heterocycles. To enhance the utility
of Vilsmeier cyclization, we examined a one-pot synthetic
strategy of oxazolecarboxaldehydes directly from 2-bro-
moacetophenones 2. This dehaloazidation-Vilsmeier
cyclization protocol was prompted by the facile conversion
of bromoacetophenones to the corresponding azido-
acetophenones under mild conditions in DMF. The
conversion was carried out using 1.1 equiv of NaN3 and
6 equiv of POCl3 in DMF. As expected the one-pot
(16) Thakore, A. N.; Buchshriber, J .; Oehlschlager, A. C. Can. J .
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Burn, D. Chem. Ind. (London) 1973, 870.
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Khoshtariya, T. E.; Kurkovskaya, L. N.; Suvorov, N. N. Khim.
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1 1984, 1173. (b) Barton, D. H. R.; Dressaire, G.; Willis, B. J .; Barret,
A. G. M.; Pfeffer, M. J . Chem. Soc., Perkin Trans. 1 1982, 665. (c) Raju,
B.; Rao, G. S. K. Synthesis 1985, 779. (d) Reddy, M. P.; Rao, G. S. K.
J . Org. Chem. 1981, 46, 5371.
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Trust, R.; Albright, J . D.; Powell, D. W. J . Org. Chem. 1995, 60, 3750.
(c) Katritzky, A. R.; Marson, C. M. J . Am. Chem. Soc. 1983, 105, 3279.
(d) Katritzky, A. R.; Marson, C. M. J . Org. Chem. 1987, 52, 2726. (e)
Katritzky, A. R.; Marson, C. M.; Wang, Z. J . Org. Chem. 1987, 52,
2730. (f) Al-Awar, R. S.; J oseph, S. P.; Comins, D.; L. J . Org. Chem.
1993, 58, 7732.
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1021. (b) Barnela, S. B.; Seshadri, S. Indian J . Chem. Sect. B. 1986,
25, 709. (c) Horvath, S.; Hermecz, I.; Podanyi, B.; Meszaros, Z. J .
Heterocycl. Chem. 1985, 22, 593.
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3553. (b) Hirota, K.; Kitade, Y.; Iwami, F.; Senda, S. Chem. Pharm.
Bull. 1984, 32 2591. (c) Kira, M. A.; Gadalla, K. Z. Egypt. J . Chem.
1978, 21, 395; Chem. Abstr. 1981, 94, 139556v. (d) Purnaprajana, V.;
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R.; Perumal, P. T. Tetrahedron Lett. 1995, 36, 7287. (f) Venugopal,
M.; Umarani, R.; Perumal, P. T.; Rajadurai, S. Tetrahedron Lett. 1991,
32, 3235.
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Perkin Trans. 1, 1982, 2085. (b) Brehme, R.; Nikolajewski, H. E.
Tetrahedron Lett. 1982, 23, 1131. (c) Anderson, D. J . J . Org. Chem.
1986, 51, 945. (d) Kallury, R. K. M. R.; Devi, P. S. U. Tetrahedron
Lett. 1986, 27, 627.
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31, 207. (b) Meth-Cohn, O. Heterocycles 1993, 35, 539. (c) Meth-Cohn,
O.; Taylor, D. L. Tetrahedron Lett. 1993, 34, 3629. (d) J ackson, A.;
Meth-Cohn, O. J . Chem. Soc., Chem. Commun. 1995, 1319. (e) Meth-
Cohn, O.; Taylor, D. L. J . Chem. Soc., Chem. Commun. 1995, 1463. (f)
Megati, S.; Rao. K. G. S. Tetrahedron Lett. 1995, 36, 5819. (g) Meth-
Cohn, O.; Goon, S. J . Chem. Soc., Perkin Trans. 1 1997, 85.
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566.

7138 J . Org. Chem., Vol. 63, No. 21, 1998
Majo and Perumal
Ta ble 1. Syn th esis of Oxa zoles fr om
2-Azid oa cetop h en on es a n d 2-Br om oa cetop h en on es Usin g
Vilsm eier Rea gen t
Sch em e 3
Ta ble 2. Syn th esis of r-Azid o-â-ch lor ovin yla ld eh yd es
fr om 2-Azid oa cetop h en on es Usin g Vilsm eier Rea gen t
entry
product
R1
R2
yield (%)
mp, °C
1
2
3
4
5
8a
8b
8c
8d
8e
Me
Cl
Br
Ph
H
H
H
H
H
70
62
65
80
64
70
98
104
103
95
Me
indefinitely without any apparent sign of decomposition
below 5 °C.
Thus, the treatment of 2-azidoacetophenones with
Vilsmeier reagent at room temperature provided a mild
method for the generation of vinyl azides, and the results
are summarized in Scheme 3 and Table 2. The chemical
manipulation of various functional groups in the presence
of an azide group is a field of current interest.28
Mech a n istic Con sid er a tion s. Vinyl azides upon
pyrolysis normally decompose by loss of nitrogen from
the azide with the formation of 2H-azirines. The azirine
formation is followed by reversible thermal carbon-
nitrogen bond cleavage to give the corresponding vinyl
nitrenes, and hence the stereochemistry about the double
bond of the azide is lost.29 However, the mechanism for
the interaction of azides with iminium species is not
likely to involve the vinyl nitrene intermediate, first
because the temperature employed in the reaction is too
low to generate the nitrene and second the singlet nitrene
is electrophilic in nature and is unlikely to attack an
iminium species in preference to the azide.
Sch em e 2
Intramolecular cycloaddition of azide to a nitrile is
reported to furnish tetrazole derivatives.30 Imidoyl azides,
usually generated in situ by the treatment of the corre-
sponding chloride with azide, also undergo spontaneous
cyclization to tetrazoles.31 Taking into account all these
considerations, a possible pathway for the thermal
decomposition of 2-azidoacetophenones on treatment with
Vilsmeier reagent is shown in Scheme 4. The chloro-
methyleniminium salt generated from DMF and POCl3
reacts with the carbonyl group of 1 to yield the O-
formylated species 9 which is in equilibrium with the
chlorovinyl azide precursor 10. The reaction at room
temperature followed by aqueous workup yields the vinyl
azide 8. At 80-90 °C, the intermediate 9 undergoes a
[3 + 2] dipolar cycloaddition of azide with the iminium
ion to give the corresponding tetrazole intermediate 11.
Presumably, the intermediate 11 decomposes via loss of
methyl proton to give nitrogen, MeNdCH2, and oxazole
carboxaldehyde 3. Although the cyclization of azides by
iminium species is unprecedented, a few reports are
available on the cyclization of azides by imines.32
strategy provided a convenient route to aryl oxazole
carboxaldehydes, and the results are summarized in
Scheme 1 and Table 1.
Th w a r ted Attem p ts a t Cycliza tion . The attempted
cyclization of 2-azidotetralone(4) and 2-azidopropiophe-
none(5) were thwarted by the formation of a complex
mixture of products which could not be characterized by
the conventional analytical techniques. Thus, the scope
of the cyclization seems to be limited to 2-azidoacetophe-
nones which are unsubstituted at 2-position.
2-(Azidoacetyl)thiophene (6) gave a resinous mass
probably due to the competitive formylation of the active
aromatic ring. Attempted cyclization of 2-bromocamphor
(7) with 2 equiv of sodium azide and 6 equiv of Vilsmeier
reagent under reflux conditions on a water bath for 10 h
resulted only in the complete recovery of the starting
material. These attempted cyclizations are represented
in Scheme 2.
Syn th esis of Vin yl Azid es. Studies on the effect of
temperature on cyclization provided some interesting
results. The treatment of 2-azidoacetophenones with 6
equiv of Vilsmeier reagent at room-temperature resulted
in the exclusive formation of products which exhibited
strong IR absorption characteristic of azido group in the
region ∼2100 cm-1. The products were confirmed to be
2-azido-3-chloro-3-aryl-2-propenals 8 by spectral data and
elemental analysis. These vinyl azides could be stored
(28) (a) Card, P. J .; Hitz, W. D.; J . Org. Chem. 1985, 50, 891. (b)
Fleet, G. W. J .; Gough, M. J .; Shing, T. K. M. Tetrahedron Lett. 1984,
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Trans. 1 1986, 1119.
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1984, 913.

Electrophilic Substitution of Azides by Iminium Species
J . Org. Chem., Vol. 63, No. 21, 1998 7139
Sch em e 4
Sch em e 6
Ta ble 3. Th e F or m a tion of Im id a zoles fr om
2-Azid oa ceta n ilid es Usin g Vilsm eier Rea gen t
mp, yield
entry product
R1
R2
R3
°C
(%)a
1
2
3
4
5
6
7
8
15a
15b
15c
15d
15e
15f
15g
15h
H
H
H
H
H
H
H
H
Cl
H
H
H
Cl
OCH3
H
CH3
H
93
45
48
58
39
62
36
51
41
100
108
119
123
b
CH2CH3
H
CH3
-CHdCHsCHdCH- 151
79
H
H
a
The values represent isolated yield of the pure compounds
after column separation. b The product 15f separated out as highly
viscous liquid.
Sch em e 7
Sch em e 5
N-aryl-2-azidoacetamides and the results are summa-
rized in the Scheme 6 and Table 3.
The synthesis of quinoline framework from acylanilides
is reported to be favored by employing POCl3 and DMF
in a ratio of 7:3.35 However, we observed that the nature
of the cyclization product of N-aryl-2-azidoacetamides
was not influenced by varying the ratio of reagent
mixture. In general, better yields were obtained when
3 equiv of POCl3 and 6 equiv of DMF were employed. No
products bearing quinoline framework could be isolated
under any of the reaction conditions adopted by us.
2-Azido-N-(phenylmethyl)acetamide 16a and 2-azido-N-
(2-phenylethyl)acetamide 16b had also undergone cy-
clization on treatment with Vilsmeier reagent to yield
the corresponding imidazoles 17a ,b in low yields (Scheme
7).
Syn th esis of Im id a zoles. The treatment of acyl
anilides with Vilsmeier reagent is reported to provide an
efficient route to the synthesis of 2-chloro-3-substituted
quinolines by formylation of the side chain.33 We have
made an attempt to combine this feature with the
Vilsmeier cyclization of azides to accomplish the synthe-
sis of oxazole-fused quinolines 14 from N-aryl-2-azido-
acetamides 12 as represented in the Scheme 5. Our
synthetic strategy was prompted by the expectation that
the major product might arise from the cascade cycliza-
tion of the intermediate 13.
Mech a n istic Con sid er a tion s. The imidazole forma-
tion seems to proceed through the N-formylation ac-
However, the reaction did not proceed as anticipated
and instead gave 1-aryl-5-chloro-2-(dimethylamino)-1H-
imidazole-4-carboxaldehydes 15 in good yields. Imidazole
derivatives exhibit a broad spectrum of biological activi-
ties which include antimicrobial,34a antitumor,34b anti-
ulcer,34c and antiaggregant properties34d and are used for
asthma treatment.34e Imidazole derivatives also find
applications as inhibitors of HIV virus,34f cytokine,34g and
aldosterone.34h This prompted us to extend the reaction
conditions further for the synthesis of various substituted
imidazole chlorovinyl aldehydes from the corresponding
(34) (a) For a recent review on imidazoles, see Grimmett, M. R. In
Comprehensive Heterocyclic Chemistry II; Shinkai, I. Ed.; Elsevier:
Oxford, UK, 1996; Vol. 3, p 77. (a) Hua, D. Y.; Zhang, F.; Chen, J . J .
Org. Chem. 1994, 59, 5084. (b) Frei, J .; Stanek, J . PCT Int. Appl. WO
96 22, 979, 1996, 89 pp; Chem. Abstr. 1996, 125, 221842c. (c) Arakawa,
E.; Kato, T.; Takamura, T.; Imai, K.; Segami, T.; Nakamura, Y. Eur.
Pat. Appl. EP 728, 747, 1996, 53 pp; Chem. Abstr. 1996, 125, 221843d.
(d) Linz, G.; Himmelsbach, F.; Pieper, H.; Austel, V.; Guth, B.;
Weisenberger, J . PCT Int. Appl. WO 97 15, 567, 1997; Chem. Abstr.
1997, 127, 17681m. (e) Miller, S. C.; J acobs, R. T.; Shenvi, A. B. Eur.
Pat. Appl. EP 739, 831, 1996, 38 pp; Chem. Abstr. 1997, 126, 47220g.
(f) Sugimoto, H.; Fujiwara, T. PCT Int. Appl. WO 96 10, 019, 1996,
396 pp; Chem. Abstr. 1996, 125, 114616k. (g) Adams, J . L.; Gallagher,
T. F.; Sisko, J .; Peng, Z.-Q.; Osifo, I. K.; Boehm, J . C. PCT Int. Appl.
WO 96 40, 143, 1996, 96 pp; Chem. Abstr. 1997, 126, 144274k. (h)
Kawanami, E.; Okada, M.; Seki, N.; Naya, H.; Kudo, M. J pn. Kokai
Tokkyo Koho J P 09 71, 586, 1997; Chem. Abstr. 1997, 127, 5093h.
(35) (a) Meth-Cohn, O.; Narine, B.; Tarnowski, B. J . Chem. Soc.,
Perkin Trans 1 1981, 1531. (b) Meth-Cohn, O.; Narine, B.; Tarnowski,
B. Synthesis 1980, 133. (c) Meth-Cohn, O.; Rhouati, S.; Tarnowski, B.
J . Chem. Soc., Perkin Trans 1 1981, 1537.
(32) (a) Ardakani, M. A.; Smalley, R. K. Smith, R. H. Synthesis 1979,
308. (b) Ardakani, M. A.; Smalley, R. K. Tetrahedron Lett. 1979, 4769.
(c) Darwen, S. P.; Smalley, R. K. Tetrahedron Lett. 1985, 26, 5707. (d)
Smalley, R. K.; Stocker, A. W. Chem. Ind. (London) 1984, 222.
(33) Meth-Cohn, O.; Narine, B.; Tarnowski, B. J . Chem. Soc., Perkin
Trans. 1 1981, 1520.

7140 J . Org. Chem., Vol. 63, No. 21, 1998
Majo and Perumal
the workup. After pouring onto crushed ice, these azides were
extracted with CH2Cl2 and dried (Na2SO4), and the solvent was
evaporated in a vacuum.
Sch em e 8
2-Br om o-1-a r yleth a n on es.36 These compounds were con-
veniently prepared by the dropwise addition of liquid bromine
at 0-5 °C to a mechanically stirred solution of the correspond-
ing acetophenone in ether or glacial acetic acid in the presence
of catalytic amount of anhyd AlCl3.
Typ ica l Exp er im en ta l P r oced u r e for th e Syn th esis of
Oxa zole-4-ca r boxa ld eh yd es (3a -d ). Meth od A. A solu-
tion of 1-aryl-2-azidoethanone (5 mmol) in DMF (2 mL) was
added dropwise to an ice-cooled magnetically stirred mixture
of Vilsmeier reagent prepared from DMF (3 equiv) and POCl3
(3 equiv). The reaction mixture was gradually allowed to
attain room temperature and maintained at 80-90 °C for 3
h. The residual solution was poured into crushed ice, stirred
for 1 h, extracted with CHCl3 (3 × 50 mL), concentrated, and
column chromatographed (petroleum ether: EtAc) to yield the
oxazolecarboxaldehydes in moderate yields.
Meth od B. NaN3 (1.1 equiv) was added in one portion to
an ice-cooled, stirred solution of 1-aryl-2-bromoethanone (10
mmol) in DMF (10 mL). After stirring the suspension for 10-
20 min, 3 equiv of POCl3 was added dropwise. The temper-
ature was gradually allowed to attain 80-90 °C and main-
tained at this temperature for 4-6 h. The crude product was
worked up as in method A.
5-(4-Meth ylph en yl)oxazole-4-car boxaldeh yde (3a). Pre-
pared by following method A from 2-azido-1-(4-methylphenyl)-
ethanone (1a , 0.88 g, 5 mmol). The crude product was purified
by chromatography (10% EtAc in petroleum ether as eluant)
to afford pure 3a (0.34 g, 1.82 mmol) as colorless needles in
36% yield.
companied by chloroformylation at the carbonyl group
to yield the iminium species 18 (Scheme 8). This imin-
ium ion is readily transformed into its resonance struc-
ture 19 where the iminium nitrogen is on the aromatic
ring. The [3 + 2] cycloaddition of the iminium ion 19 by
the azide moiety is not possible, and therefore the
reaction follows a different pathway. The intramolecular
attack of the resultant iminium species by the azide
proceeds and subsequent proton abstraction and elimina-
tion of nitrogen yields the corresponding imidazole-4-
carboxaldehyde 15 on hydrolysis.
Prepared from 2-bromo-1-(4-methylphenyl)ethanone (2a ,
2.13 g, 10 mmol) following method B. The crude product was
chromatographed (10% EtAc in petroleum ether) to afford pure
3a (0.84 g, 4.51 mmol) as colorless needles in 45% yield: mp
90 °C; Rf (25% ethyl acetate/petroleum ether) ) 0.75; MS m/e
187 (M+);1H NMR (300 MHz) δ 9.97 (s, 1H), 8.27 (s, 1H), 7.96
(d, J ) 8.2 Hz, 2H), 7.27 (d, J ) 8.2 Hz, 2H), 2.39 (s, 3H); 13
C
In conclusion, the azide group attached to the active
methylene group of carbonyl compounds acts as a source
for the generation of vinyl azides under Vilsmeier condi-
tions. These vinyl azides could be cyclized in situ at
higher temperatures by the intramolecular attack of the
azide functionality by iminium species. Further studies
are in progress to extend the scope of the reaction for
the synthesis of more nitrogen heterocycles by replacing
the carbonyl group with other active functional groups.
NMR (75 MHz) δ 184.08, 163.24, 144.26, 142.00, 130.15,
129.57, 126.87, 123.35, 21.56. Anal. Calcd for C11H9NO2: C,
70.58; H, 4.85; N, 7.48. Found: C, 70.85; H, 4.87; N, 7.53.
5-(4-Ch lor oph en yl)oxazole-4-car boxaldeh yde (3b). Pre-
pared from 2-azido-1-(4-chlorophenyl)ethanone (1b, 0.98 g, 5
mmol) following the method A. The crude product was
chromatographed (10% EtAc in petroleum ether) to afford pure
3b (0.84 g, 4.51 mmol) as colorless solid in 36% yield.
Prepared from 2-bromo-1-(4-chlorophenyl)ethanone (2b, 2.34
g, 10 mmol) following method B. The crude product was
chromatographed (10% EtAc in petroleum ether) to afford pure
3b (0.84 g, 4.51 mmol) as colorless solid in 48% yield: mp 130
°C; Rf (25% ethyl acetate/petroleum ether) ) 0.74; GCMS m/e
(rel intensity) 209 (M + 2, 28), 207 (M+, 85), 179 (24), 140 (33),
138 (100), 137 (26), 124 (24), 123 (20), 89 (50), 75 (23); 1H NMR
(300 MHz) δ 9.98 (s, 1H), 8.31 (s, 1H), 8.02 (d, J ) 8.4 Hz,
2H), 7.46 (d, J ) 8.7 Hz, 2H); 13C NMR (75 MHz) δ 183.60,
162.31, 144.20, 141.55, 137.48, 129.04, 127.90, 124.26; IR (KBr)
Exp er im en ta l Section
Melting points were measured in capillary tubes and are
uncorrected. Analytical thin-layer chromatography was per-
formed on precoated sheets of silica gel with a 0.25 mm
thickness containing PF254 indicator (Merck, Darmstadt).
Column chromatography was performed with silica gel (60-
120 mesh; SD fine, Boisar, India).
2842, 1696, 1118, 796, 733 cm-1
. Anal. Calcd for C10H6-
2-Azid o-1-a r yleth a n on es. To an ice-cooled magnetically
stirred solution of 2-bromo-1-arylethanone (1 equiv) in DMF
was added 2 equiv of NaN3 in one portion. The suspension
was stirred for 10-30 min. The completion of the reaction
was followed by TLC (20% EtAc in petroleum ether as eluant).
The reaction mixture was poured onto crushed ice to yield the
corresponding azides in good yield.
ClNO2: C, 57.85; H, 2.91; N, 6.75. Found: C, 58.08; H, 2.94;
N, 6.78.
5-(4-Br om oph en yl)oxazole-4-car boxaldeh yde (3c). Pre-
pared from 2-azido-1-(4-bromophenyl)ethanone (1c, 1.2 g, 5
mmol) following method A. The crude product was chromato-
graphed (10% EtAc in petroleum ether) to afford pure 3c (0.53
g, 2.09 mmol) as colorless solid in 42% yield.
N-Su bstitu ted 2-Azid oa ceta m id es. NaN3 (2 equiv) was
added in one portion to a stirred solution of N-substituted
2-chloroacetamide in DMF. The suspension was stirred for
6-10 h at room temperature. The completion of the reaction
was followed by TLC (30% EtAc in petroleum ether as eluant).
The reaction mixture was poured onto crushed ice, and the
solid product was filtered and dried to yield the corresponding
azides in considerable yield.
Prepared from 2-bromo-1-(4-bromophenyl)ethanone (2c, 2.78
g, 10 mmol) following method B. The crude product was
chromatographed (10% EtAc in petroleum ether) to afford pure
3c (1.42 g, 5.63 mmol) as colorless solid in 56% yield: mp 135
°C; Rf (25% ethyl acetate/petroleum ether) ) 0.78; GCMS m/e
(rel intensity) 253 (M + 2, 93), 251 (M+, 95), 223 (28), 200 (68),
(36) (a) Vogel’s Textbook of Practical Organic Chemistry, 4th ed.;
Longman: UK, 1978; p 815. (b) Cowper, R. M.; Davidson, L. H. Organic
Syntheses; Wiley: New York, 1943; Coll. Vol. II., p 480.
2-Azido-N-(2-phenylethyl)acetamide and 2-azido-N-(phenyl-
methyl)acetamide were prepared by a slight modification in

Electrophilic Substitution of Azides by Iminium Species
183 (88), 182 (86), 157 (33), 155 (34), 126 (18), 116 (38), 102
J . Org. Chem., Vol. 63, No. 21, 1998 7141
2-Azido-3-[(1,1′-biph en yl)-4-yl]-3-ch lor o-2-pr open al (8d).
The general procedure was followed by use of 2-azido-1-[(1,1′-
biphenyl)-4-yl]ethanone (1d , 1.19 g, 5 mmol). The crude
product was purified by chromatography (5% EtAc in petro-
leum ether as eluant) to give colorless crystals of 8d (1.13 g,
3.98 mmol) in 80% yield: mp 103 °C; Rf (10% ethyl acetate/
petroleum ether) ) 0.86; MS m/e 255 (M - 28); 1H NMR (300
MHz) δ 9.48 (s, 1H), 7.65 (d, J ) 8.1 Hz, 2H), 7.61-7.40
(several peaks, 7H); 13C NMR (75 MHz) δ 184.31, 143.95,
139.32, 134.74, 132.61, 130.98, 129.02, 128.29, 127.29, 127.11.
IR (KBr) 2903, 2862, 2106, 1679, 1334, 810, 767 cm-1. Anal.
Calcd for C15H10ClN3O: C, 63.50; H, 3.55; N, 14.81. Found:
C, 63.79; H, 3.61; N, 15.03.
2-Azid o-3-ch lor o-3-(3-m eth ylp h en yl)-2-p r op en a l (8e).
The general procedure was followed by use of 2-azido-1-(3-
methylphenyl)ethanone (1e, 1.75 g, 10 mmol). The crude
product was purified by passing through a column of silica gel
using 2% EtAc in petroleum ether as eluant. Recrystallization
from petroleum ether gave colorless crystals of 8e (1.42 g, 6.43
mmol) in 64% yield: mp 95 °C; MS m/e 193 (M - 28); 1H NMR
(300 MHz) δ 9.40 (s, 1H), 7.31-7.23 (several peaks, 4H), 2.38
(s, 3H); 13C NMR (75 MHz) δ 184.38, 140.66, 138.61, 134.45,
133.47, 131.74, 130.84, 128.44, 127.55, 21.14; IR (KBr) 2922,
2892, 2102, 1663, 1333, 835, 799 cm-1. Anal. Calcd for C10H8-
ClN3O: C, 54.19; H, 3.64; N, 18.96. Found: C, 54.25; H, 3.65;
N, 18.99.
Typ ica l Exp er im en ta l P r oced u r e for th e Syn th esis of
N-Su bstitu ted 5-Ch lor o-2-(d im eth yla m in o)im id a zole-4-
ca r boxa ld eh yd es (15a -h ). N-Substituted 2-azidoacetamide
(10 mmol) was dissolved in DMF (5 mL) and cooled to 0-5
°C. To the stirred solution was added POCl3 (30 mmol, 2.5
mL) dropwise, and the temperature was gradually allowed to
attain 80-90 °C and maintained at this temperature for 5 h.
The reaction mixture was then poured cautiously into water
(40 mL), stirred for 1 h, extracted with dichloromethane (3 ×
50 mL), dried (Na2SO4), and concentrated. The crude product
was column chromatographed (petroleum ether: EtAc) to yield
the imidazolecarboxaldehydes in varying yields.
1
(24), 89 (88); H NMR (300 MHz) δ 9.64 (s, 1H), 8.22 (s, 1H),
7.54 (d, J ) 8.1 Hz, 2H), 7.21 (d, J ) 8.0 Hz, 2H); 13C NMR
(75 MHz) δ 183.38, 161.83, 146.11, 141.86, 131.94, 131.19,
131.02, 128.10; IR (KBr) 2873, 1689, 1398, 804 cm-1. Anal.
Calcd for C10H6BrNO2: C, 47.65; H, 2.40; N, 5.56. Found: C,
47.40; H, 2.39; N, 5.58.
5-[(1,1′-Bip h en yl)-4-yl]oxa zole-4-ca r boxa ld eh yd e (3d ).
Prepared from 2-azido-1-[(1,1′-biphenyl)-4-yl]ethanone (1d ,
1.19 g, 5 mmol) following method A. The crude product was
chromatographed (15% EtAc in petroleum ether) to afford pure
3d (0.56 g, 2.24 mmol) as colorless solid in 45% yield.
Prepared from 1-[(1,1′-biphenyl)-4-yl]-2-bromoethanone (2d ,
2.75 g, 10 mmol) following method B. The crude product was
chromatographed (15% EtAc in petroleum ether) to afford pure
3d (1.51 g, 6.06 mmol) as colorless solid in 61% yield: mp 160
°C; Rf (25% ethyl acetate/petroleum ether) ) 0.77; MS m/e 249
(M+); 1H NMR (300 MHz) δ 9.61 (s, 1H), 8.21 (s, 1H), 7.78 (d,
J ) 7.8 Hz, 2H), 7.35 (d, J ) 8.1 Hz, 2H), 7.09-6.99 (m, 5H);
13C NMR (75 MHz) 183.54, 167.72, 144.83, 143.56, 129.91,
128.62, 127.78, 127.14, 127.09, 126.82, 126.69, 126.51; IR (KBr)
2923, 2834, 1681, 1316, 746 cm-1
. Anal. Calcd for C16H11-
NO2: C, 77.10; H, 4.45; N, 5.62. Found: C, 76.80; H, 4.46; N,
5.59.
Typ ica l Exp er im en ta l P r oced u r e for th e Syn th esis of
r-Azid o-â-ch lor ovin yl Azid es (8a -e). A solution of 1-aryl-
2-azidoethanone (5 mmol) in DMF (5 mL) was added dropwise
to an ice-cooled magnetically stirred mixture of Vilsmeier
reagent prepared from DMF (5 mL) and POCl3 (3 equiv). The
reaction mixture was gradually allowed to attain room tem-
perature and maintained at this temperature for 6 h. The
residue was then poured into crushed ice, stirred for 1 h,
filtered, dried, and column chromatographed to yield R-azido-
â-chlorovinyl azides in necessary yield.
2-Azid o-3-ch lor o-3-(4-m eth ylp h en yl)-2-p r op en a l (8a ).
The general procedure was followed by use of 2-azido-1-(4-
methylphenyl)ethanone (1a , 0.88 g, 5 mmol). The crude
product was purified by passing through a column of silica gel
using petroleum ether as eluant. Recrystallization from
petroleum ether gave colorless crystals of 8a (0.77 g, 3.48
mmol) in 70% yield: mp 70 °C; Rf (10% ethyl acetate/petroleum
ether) ) 0.86; MS m/e 193 (M - 28); 1H NMR (300 MHz) δ
9.39 (s, 1H), 7.32-7.23 (several peaks, 4H), 2.39 (s, 3H); 13C
NMR (75 MHz) δ 184.44, 141.74, 141.03, 134.12, 130.78,
130.41, 129.39, 21.38; IR (KBr) 2895, 2861, 2107, 1669, 1338,
5-Ch lor o-2-(d im eth yla m in o)-1-p h en yl-1H-im id a zole-4-
ca r boxa ld eh yd e (15a ). The general procedure was followed
by use of 2-azido-N-phenylacetamide (12a , 1.75 g, 10 mmol),
DMF (5 mL, 65 mmol), and POCl3 (2.5 mL, 27 mmol). The
reaction mixture was worked up, and the residue was purified
by chromatography (30% EtAc in petroleum ether as eluant)
to give pure 15a (1.12 g, 4.49 mmol) as a pale yellow solid in
45% yield: mp 93 °C; Rf (40% ethyl acetate/petroleum ether)
813, cm-1
. Anal. Calcd for C10H8ClN3O: C, 54.19; H, 3.64;
1
) 0.54; MS m/e 249 (M+); H NMR (300 MHz) δ 9.65 (s, 1H),
N, 18.96. Found: C, 54.36; H, 3.66; N, 19.03.
7.40-7.38 (m, 3H), 7.20 (d, J ) 6.3 Hz, 2H), 2.51 (s, 6H); 13C
NMR (75 MHz) 182.15, 153.42, 135.68, 132.54, 132.28, 130.06,
128.70, 124.91, 40.89. IR (KBr) 3044, 2818, 1675, 1576, 1400,
2-Azid o-3-ch lor o-3-(4-ch lor op h en yl)-2-p r op en a l (8b ).
The general procedure was followed by use of 2-azido-1-(4-
chlorophenyl)ethanone (1b, 0.98 g, 5 mmol). The crude
product was purified by passing through a column of silica gel
using petroleum ether as eluant. Recrystallization from
petroleum ether gave colorless crystals of 8b (0.75 g, 3.09
mmol) in 62% yield: mp 98 °C; Rf (10% ethyl acetate/petroleum
ether) ) 0.91; GCMS m/e (rel intensity) 215([(M + 2) - 28],
65), 213([M - 28], 100), 185 (31), 158 (28), 150 (56), 138 (46),
123 (46), 113 (39), 111 (92), 75 (87); 1H NMR (300 MHz) δ 9.38
825, 702 cm-1
. Anal. Calcd for C12H12ClN3O: C, 57.72; H,
4.84; N, 16.83. Found: C, 57.97; H, 4.87; N, 16.89.
5-Chlor o-1-(4-chlor ophen yl)-2-(dim ethylam ino)-1H-im id-
a zole-4-ca r boxa ld eh yd e (15b). Prepared by following the
general procedure from 2-azido-N-(4-chlorophenyl)acetamide
(12b, 2.10 g, 10 mmol). The reaction mixture was worked up,
and the residue was purified by chromatography (30% EtAc
in petroleum ether as eluant) to give pure 15b (1.36 g, 4.78
mmol) as a pale yellow solid in 48% yield: mp 100 °C; Rf (40%
(s, 1H), 7.41 (d, J ) 8.7 Hz, 2H), 7.36 (d, J ) 8.5 Hz, 2H); 13
C
1
ethyl acetate/petroleum ether) ) 0.57; MS m/e 279 (M+); H
NMR (75 MHz) δ 183.85, 138.73, 137.44, 135.10, 132.10,
131.62, 129.09; IR (KBr) 2930, 2842, 2108, 1669, 1333, 1094,
816 cm-1. Anal. Calcd for C9H5Cl2N3O: C, 44.66; H, 2.08; N,
17.36. Found: C, 44.83; H, 2.09; N, 17.47.
NMR (300 MHz) δ 9.78 (s, 1H), 7.48 (d, J ) 7.8 Hz, 2H), 7.27
(d, J ) 7.2 Hz, 2H), 2.63 (s, 6H); 13C NMR (75 MHz) 182.12,
153.32, 135.65, 132.51, 132.25, 130.02, 128.67, 124.82, 40.86.
IR (KBr) 2881, 2835, 1677, 1590, 1247, 849, 821 cm-1. Anal.
Calcd for C12H11Cl2N3O: C, 50.72; H, 3.90; N, 14.79. Found:
C, 50.89; H, 3.92; N, 14.83.
2-Azid o-3-(4-b r om op h en yl)-3-ch lor o-2-p r op en a l (8c).
The general procedure was followed by use of 2-azido-1-(4-
bromophenyl)ethanone (1c, 1.2 g, 5 mmol). The crude product
was purified by chromatography (5% EtAc in petroleum ether
as eluant). Recrystallization from petroleum ether gave
colorless crystals of 8c (0.94 g, 3.27 mmol) in 65% yield: mp
104 °C; Rf (10% ethyl acetate/petroleum ether) ) 0.87; MS m/e
257 (M - 28); 1H NMR (300 MHz) δ 9.38 (s, 1H), 7.75 (d, J )
8.4 Hz, 2H), 7.29 (d, J ) 8.4 Hz, 2H); 13C NMR (75 MHz) δ
183.83, 138.53, 134.82, 132.54, 132.06, 131.79, 122.27. Anal.
Calcd for C9H5BrClN3O: C, 37.73; H, 1.76; N, 14.67. Found:
C, 37.89; H, 1.79; N, 14.89.
5-Ch lor o-2-(d im eth yla m in o)-1-(4-m eth oxyp h en yl)-1H-
im id a zole-4-ca r boxa ld eh yd e (15c). Prepared by following
the general procedure from 2-azido-N-(4-methoxyphenyl)-
acetamide (12c, 2.05 g, 10 mmol). The reaction mixture was
worked up, and the residue was purified by chromatography
(30% EtAc in petroleum ether as eluant) to give pure 15c (1.62
g, 5.79 mmol) as a pale yellow solid in 58% yield: mp 108 °C;
Rf (40% ethyl acetate/petroleum ether) ) 0.43; MS m/e 277
1
(M+); H NMR (300 MHz) δ 9.72 (s, 1H), 7.17 (d, J ) 8.1 Hz,

7142 J . Org. Chem., Vol. 63, No. 21, 1998
Majo and Perumal
2H), 6.95 (d, J ) 8.1 Hz, 2H), 3.79 (s, 3H), 2.58 (s, 6H); 13C
NMR (75 MHz) 182.18, 160.15, 153.59, 131.92, 129.35, 127.88,
125.74, 114.04, 54.76, 40.12. Anal. Calcd for C13H14ClN3O2:
C, 55.82; H, 5.04; N, 15.02. Found: C, 56.04, H, 5.08; N, 15.13.
5-Chlor o-1-(3-chlor ophen yl)-2-(dim eth ylam ino)-1H-im id-
a zole-4-ca r boxa ld eh yd e (15d ). Prepared by following the
general procedure from 2-azido-N-(3-chlorophenyl)acetamide
(12d , 2.10 g, 10 mmol). The reaction mixture was worked up,
and the residue was purified by chromatography (30% EtAc
in petroleum ether as eluant) to give pure 15d (1.10 g, 3.87
mmol) as a pale yellow solid in 39% yield: mp 119 °C; Rf (40%
131.46, 129.93, 128.20, 127.91, 127.68, 127.34, 126.58, 125.46,
124.43, 40.88. IR (KBr) 2822, 1674, 1583, 1258, 817, 752 cm-1
.
Anal. Calcd for C16H14ClN3O: C, 64.11; H, 4.71; N, 14.02.
Found: C, 64.37; H, 4.78; N, 14.23.
5-Ch lor o-2-(d im et h yla m in o)-1-(2-m et h ylp h en yl)-1H -
im id a zole-4-ca r boxa ld eh yd e (15h ). Prepared by following
the general procedure from 2-azido-N-(2-methylphenyl)acet-
amide (12h , 1.89 g, 10 mmol). The reaction mixture was
worked up, and the residue was purified by chromatography
(30% EtAc in petroleum ether as eluant) to give pure 15h (1.07
g, 4.06 mmol) as a pale yellow solid in 41% yield: mp 79 °C;
Rf (40% ethyl acetate/petroleum ether) ) 0.57; MS m/e 263
1
ethyl acetate/petroleum ether) ) 0.55; MS m/e 283 (M+); H
1
(M+); H NMR (300 MHz) δ 9.79 (s, 1H), 7.42-7.31 (several
NMR (300 MHz) δ 9.78 (s, 1H), 7.24 (s, 1H), 7.33 (s, 1H), 7.46
(m, 2H), 2.62 (s, 6H); 13C NMR (75 MHz) 182.21, 153.30,
135.39, 135.17, 132.36, 130.77, 129.96, 127.63, 125.75, 124.71,
peaks, 3H), 7.17 (m, 1H), 2.62 (s, 6H), 2.05 (s, 3H); 13C NMR
(75 MHz) 182.14, 153.18, 136.34, 133.40, 132.27, 131.48,
130.25, 128.55, 127.27, 125.38, 40.62, 17.43. IR (KBr) 3048,
40.92. IR (KBr) 2878, 2850, 1684, 1577, 833 cm-1
. Anal.
2839, 2769, 1687, 1564, 825, 768 cm-1. Anal. Calcd for C13H14
-
Calcd for C12H11Cl2N3O: C, 50.72; H, 3.90; N, 14.79. Found:
C, 50.51; H, 3.92; N, 14.80.
ClN3O: C, 59.21; H, 5.35; N, 15.93. Found: C, 59.08; H, 5.37;
N, 15.99.
5-Ch lor o-2-(d im et h yla m in o)-1-(4-m et h ylp h en yl)-1H -
im id a zole-4-ca r boxa ld eh yd e (15e). Prepared by following
the general procedure from 2-azido-N-(4-methylphenyl)acet-
amide (12e, 1.89 g, 10 mmol). The reaction mixture was
worked up, and the residue was purified by chromatography
(30% EtAc in petroleum ether as eluant) to give pure 15e (1.62
g, 6.15 mmol) as a pale yellow solid in 62% yield: mp 123 °C;
Rf (40% ethyl acetate/petroleum ether) ) 0.57; GCMS m/e (rel
intensity) 265 (M + 2, 16), 263 (M+, 52), 228 (88), 105 (28), 91
5-Ch lor o-2-(dim eth ylam in o)-1-(ph en ylm eth yl)-1H-im id-
a zole-4-ca r boxa ld eh yd e (17a ). Prepared by following the
general procedure from 2-azido-N-(phenylmethyl)acetamide
(16a , 1.89 g, 10 mmol). The reaction mixture was worked up,
and the residue was purified by chromatography (30% EtAc
in petroleum ether as eluant) to give pure 17a (0.28 g, 0.11
mmol) as a pale yellow solid in 11% yield: mp 93 °C; Rf (40%
1
ethyl acetate/petroleum ether) ) 0.53; MS m/e 263 (M+); H
1
(31), 83 (100), 65 (21), 56 (18); H NMR (300 MHz) δ 9.76 (s,
NMR (300 MHz) δ 9.80 (s, 1H), 7.31 (d, J ) 6.4 Hz, 2H), 7.25
1H), 7.27 (d, J ) 7.2 Hz, 2H), 7.15 (d, J ) 6.9 Hz, 2H), 2.58 (s,
6H), 2.37 (s, 3H); 13C NMR (75 MHz) 182.12, 153.51, 139.88,
132.06, 131.52, 130.34, 127.15, 125.43, 40.80, 21.20. Anal.
Calcd for C13H14ClN3O: C, 59.21; H, 5.35; N, 15.93. Found:
C, 59.41; H, 5.37; N, 16.00.
(s, 1H), 7.08 (d, J ) 6.3 Hz, 2H), 5.11 (s, 2H), 2.71 (s, 6H); 13
C
NMR (75 MHz) 182.41, 154.30, 134.83, 132.42, 128.99, 128.01,
126.07, 47.14, 42.75. IR (KBr) 2855, 2809, 1677, 1565, 848,
749 cm-1. Anal. Calcd for C13H14ClN3O: C, 59.21; H, 5.35;
N, 15.93. Found: C, 59.46; H, 5.36; N, 16.04.
5-Ch lor o-2-(dim eth ylam in o)-1-(2-eth ylph en yl)-1H-im id-
a zole-4-ca r boxa ld eh yd e (15f). Prepared by following the
general procedure from 2-azido-N-(2-ethylphenyl)acetamide
(12f, 2.03 g, 10 mmol). The reaction mixture was worked up,
and the residue was purified by chromatography (30% EtAc
in petroleum ether as eluant) to give pure 15f (1.0 g, 3.60
mmol) as a viscous yellow liquid in 36% yield; Rf (40% ethyl
5-Ch lor o-2-(dim eth ylam in o)-1-(2-ph en yleth yl)-1H-im id-
a zole-4-ca r boxa ld eh yd e (17b). Prepared by following the
general procedure from 2-azido-N-(2-phenylethyl)acetamide
(16b, 2.03 g, 10 mmol). The reaction mixture was worked up,
and the residue was purified by chromatography (30% EtAc
in petroleum ether as eluant) to give pure 17b (0.56 g, 2.03
mmol) as a pale yellow solid in 20% yield: mp 55 °C; Rf (40%
1
acetate/petroleum ether) ) 0.61; MS m/e 277 (M+); H NMR
1
ethyl acetate/petroleum ether) ) 0.51; MS m/e 277 (M+); H
(300 MHz) δ 9.74 (s, 1H), 7.36-7.44 (several peaks, 2H), 7.28
(m, 1H), 7.13 (d, J ) 7.2 Hz, 1H), 2.58 (s, 6H), 2.28 (q, J ) 7.4
Hz, 2H), 1.04 (t, J ) 7.3 Hz, 3H); 13C NMR (75 MHz) 181.88,
153.06, 141.76, 132.55, 131.99, 130.34, 129.49, 128.56, 126.94,
125.52, 40.52, 23.57, 13.36. IR (neat) 2876, 2810, 1686, 1569,
NMR (300 MHz) δ 9.68 (s, 1H), 7.21-7.14 (several peaks, 3H),
7.00 (d, J ) 6.7 Hz, 2H), 4.04 (dd, J ) 7.8, 6.8 Hz, 2H), 2.96
(dd, J ) 7.7, 6.8 Hz, 2H), 2.64 (s, 6H); 13C NMR (75 MHz) 182.
11, 153.89, 136.46, 132.07, 130.73, 128.56, 126.89, 125. 21,
124.15, 45.17, 42.48, 34.98. Anal. Calcd for C14H16ClN3O: C,
60.54; H, 5.81; N, 15.13. Found: C, 60.81; H, 5.85; N, 5.21.
827, 762 cm-1
. Anal. Calcd for C14H16ClN3O: C, 60.54; H,
5.81; N, 15.13. Found: C, 60.80; H, 5.83; N, 15.23.
5-Ch lor o-2-(d im et h yla m in o)-1-(2-n a p h t h yl)-1H -im id -
a zole-4-ca r boxa ld eh yd e (15 g). Prepared by following the
general procedure from 2-azido-N-(2-naphthyl)acetamide (12g,
2.25 g, 10 mmol). The reaction mixture was worked up, and
the residue was purified by chromatography (30% EtAc in
petroleum ether as eluant) to give pure 15g (1.54 g, 5.14 mmol)
as a pale yellow solid in 51% yield: mp 151 °C; Rf (40% ethyl
acetate/petroleum ether) ) 0.56; GCMS m/e (rel intensity) 301
(M + 2, 14), 299 (M+, 41), 264 (75), 141 (23), 127 (47), 111
Ack n ow led gm en t. One of the authors (M.V.J .) is
grateful to CSIR, India, for a fellowship. We thank Dr.
K. Vijayakumaran for his support.
Su p p or tin g In for m a tion Ava ila ble: Copies of NMR
spectra (6 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
1
(15), 83 (100), 56 (28), 42 (41); H NMR (300 MHz) δ 9.78 (s,
1H), 7.91-7.76 (several peaks, 4H), 7.53 (m, 2H), 7.34 (s, 1H),
2.58 (s, 6H); 13C NMR (75 MHz) 182.21, 153.62, 133.04, 132.25,
J O971745Z