2-Benzotriazolylaziridines and their reactions with diethyl acetylenedicarboxylate

Article abstract of DOI:10.1021/jo980082y

1-Alkyl-2-benzotriazolylaziridines (3a,b and 8a-g) are synthesized by two routes utilizing a novel benzotriazolyl-substituted carbenoid or 1,2- dibromoethylbenzotriazole. Lithiation of 3b and 8e at the position a to benzotriazole and subsequent trapping with alkyl halides leads to the 1,2- dialkyl-2-benzotriazolylaziridine analogues 12 and 20. Compounds 3a and 3b react with acetylenedicarboxylic ester by C-C bond breaking to give pyrrole- 3,4-dicarboxylic esters (14a,b). By contrast, compounds 8a-d and 20 react with acetylenedicarboxylic ester by C-N bond breaking and form pyrrole-2,3- dicarboxylic esters 18a-d and 21. Structures of each type of pyrroledicarboxylic ester are established by X-ray analysis.

Full text of DOI:10.1021/jo980082y

346
J . Org. Chem. 1999, 64, 346-350
Articles
2-Ben zotr ia zolyla zir id in es a n d Th eir Rea ction s w ith Dieth yl
Acetylen ed ica r boxyla te
Alan R. Katritzky,*,‡ J iangchao Yao,‡ Weiliang Bao,‡ Ming Qi,‡ and Peter J . Steel§
Center for Heterocyclic Compounds,
Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200, and Department of
Chemistry, University of Canterbury,
Christchurch, New Zealand
Received J anuary 16, 1998
1-Alkyl-2-benzotriazolylaziridines (3a ,b and 8a -g) are synthesized by two routes utilizing a novel
benzotriazolyl-substituted carbenoid or 1,2-dibromoethylbenzotriazole. Lithiation of 3b and 8e at
the position a to benzotriazole and subsequent trapping with alkyl halides leads to the 1,2-dialkyl-
2-benzotriazolylaziridine analogues 12 and 20. Compounds 3a and 3b react with acetylenedicar-
boxylic ester by C-C bond breaking to give pyrrole-3,4-dicarboxylic esters (14a ,b). By contrast,
compounds 8a -d and 20 react with acetylenedicarboxylic ester by C-N bond breaking and form
pyrrole-2,3-dicarboxylic esters 18a -d and 21. Structures of each type of pyrroledicarboxylic ester
are established by X-ray analysis.
Sch em e 1
Aziridines are of importance as natural products and
as versatile synthetic intermediates.1 They are used as
chiral auxiliaries, reagents, and ligands2 and as mono-
mers for polymer synthesis;3 their synthesis and trans-
formations are actively studied. Many preparative meth-
ods for aziridines involve a two-component reaction,1 such
as the aza-Darzens,4 utilization of carbenes5 or ylides,6
and the 1,2-dihalide route.7 Meanwhile, benzotriazole has
emerged as a versatile synthetic auxiliary, capable of
stabilizing both R-carbocations and R-carbanions.8 As a
leaving group, benzotriazole can generate a carbocation,8
radical,9 or carbanion.10 Therefore, the preparation of
benzotriazolyl-substituted aziridines could enable several
different types of reactivity. Herein, we describe our
preparation of 2-benzotriazolylaziridines and their utility
in the synthesis of a variety of pyrroles.
Resu lts a n d Discu ssion
Syn th eses of 2-Ben zotr iazolylazir idin es. Two meth-
ods were developed for the preparation of benzotriazolyl-
substituted aziridines 3a ,b and 8a -g (Schemes 1 and
2), one involving a novel carbenoid intermediate 2 and
the 1,2-dihalide route via 5.
Attempts to lithiate 1-chloromethylbenzotriazole (1)
and trap intermediate 2 were modeled on previous
generations of carbenoids.11 As a result of the electron-
donating ability of the benzotriazolyl group, carbenoid 2
(Scheme 1) is not expected to be long-lived and needs to
be rapidly trapped by an appropriate electrophile; to our
knowledge, there are no reports on R-nitrogen substituted
carbenoids.12 However, we now find that 1-chlorometh-
ylbenzotriazole (1) can be lithiated in the presence of a
diaryl imine and intermediate 2 can be captured to form
aziridines 3a ,b in high yields (Scheme 1). For the
‡ University of Florida.
§ University of Canterbury.
(1) (a) Pearson, W. H.; Lian, B. W.; Bergmeier, S. C. In Compre-
hensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven,
E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 1A, p 1. (b) Evans, D. A.;
Faul, M. M.; Bilodeau, M. T. J . Am. Chem. Soc. 1994, 116, 2742.
(2) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599.
(3) Goethals, E. J . In Comprehensive Polymer Science; Allen, G.,
Bevington, J . C., Eds.; Pergamon: Oxford, 1989; Vol 3, p 837.
(4) (a) Reutrakul, V.; Prapansiri, V.; Panyachotipun, C. Tetrahedron
Lett. 1984, 25, 1949. (b) Satoh, T.; Sato, T.; Oohara, T.; Yamakawa, K.
J . Org. Chem. 1989, 54, 3973.
(5) Casarrubios, L.; Pe´rez, J . A.; Brookhart, M.; Templeton, J . L. J .
Org. Chem. 1996, 61, 8358.
(6) Wang, D.-K.; Dai, L.-X.; Hou, X.-L. Chem. Commun. 1997, 1231
and references therein.
(7) (a) Carlier, P.; Gelas-Mialhe, Y.; Vessiere, R. Can. J . Chem. 1977,
55, 3190. (b) Saoudi, A.; Hamelin, J .; Benhaoua, H. J . Chem. Res. (S)
1996, 492.
(8) Katritzky, A. R.; Lan, X.; Yang, J . Z.; Denisko, O. V. Chem. Rev.
1998, 98, 409.
(9) Aurrecoechea, J . M.; Lo´pez, B.; Ferna´ndez, A.; Arrieta, A.; Coss´ıo,
F. P. J . Org. Chem. 1997, 62, 1125 and references therein.
(10) (a) Katritzky, A. R.; Qi, M. J . Org. Chem. 1997, 62, 4116. (b)
Katritzky, A. R.; Qi, M.; Feng, D.; Nichols, D. A. J . Org. Chem. 1997,
62, 4121.
(11) (a) Siegel, H. Top. Curr. Chem. 1982, 106, 55. (b) Kobrich, G.
Angew. Chem., Int. Ed. Engl. 1972, 11, 473.
(12) Boche, G.; Lohrenz, J . C. W.; Opel, A. In Lithium Chemistry, A
Theroretical and Experimental Overview; Sapse, A.-M., Schleyer, P.
V. R., Eds.; J ohn Wiley & Sons: New York, 1995; p195.
10.1021/jo980082y CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/31/1998

2-Benzotriazolylaziridines
Sch em e 2
J . Org. Chem., Vol. 64, No. 2, 1999 347
Sch em e 3
Sch em e 4
conversion of 1 f 3, lithium bis(trimethylsilyl)amide
(LiHMDS) is superior to s-butyllithium. As the reaction
medium, either THF-HMPA or DME-HMPA can be
used. However, only imines derived from aromatic alde-
hydes and aniline reacted satisfactorily with the car-
benoid 2 formed in situ; this limited aziridines 3 made
in this way to 1,3-diaryl substituted derivatives.
As 1-chloromethylbenzotriazole (1), but not its benzo-
triazol-2-yl isomer, is available, only 2-(benzotriazol-1-
yl)aziridines 3a ,b were obtained by this method, but as
mixtures of cis and trans isomers. The diastereomers of
3a were separated by column chromatography. The
methine groups (NCHBt) of the cis and trans isomers
resonate as doublets at 5.28 (δH) and 5.48 ppm, respec-
tively. The isomer with a coupling constant of 4.9 Hz was
assigned as cis, and the isomer with 1.9 Hz as trans,
following literature analogies.7a
Like most alkenes, we found that 2-vinylbenzotriazole
(4a ) was easily brominated to give 2-(1,2-dibromoethyl)-
benzotriazole (5a ) in 93% yield. The reaction of 2-(1,2-
dibromoethyl)benzotriazole (5a ) with alkylamines in the
presence of sodium hydroxide affords 2-(benzotriazol-2-
yl)aziridines (8a -g) (Scheme 2). The reaction evidently
involves amine substitution of the terminal bromide of
compound 5a to give 7a -g, which is followed by intramo-
lecular cyclization. The first substitution product 7 can
be detected in the early stage of the reaction by 1H NMR.
In contrast, reactions of amines and 1,2-dihalo com-
pounds containing stronger electron-withdrawing groups
(e.g., ester7b or sulfone7a) usually involve vinyl bromide
intermediates (cf. 6), Michael addition, and cyclization.
In the present case, we excluded this latter possible route
by preparing vinyl bromide 6a from 5a and triethyl-
amine. No reaction was observed when vinyl bromide 6a
was treated with propylamine, reflecting the relatively
weak electron-withdrawing ability of the benzotriazolyl
group.
Similarly to 2-vinylbenzotriazole (4a ), 2-(1-propenyl)-
benzotriazole (4b) was brominated to give 2-(1,2-dibro-
mopropyl)benzotriazole (5b) in high yield. Also, when 5b
was reacted with propylamine, only propenyl benzotri-
azole 6b was detected by NMR; this means that the
formation of 6b is faster than the substitution of a
secondary alkyl bromide 5b by amine (Scheme 2).
By contrast, 1-vinylbenzotriazole (9) reacted with
bromine to form 1-(1,2-dibromoethyl)benzotriazole (10)
in low yield (22%), and compound 10 gave only 1-(1-
bromovinyl)benzotriazole (11) when it was treated with
alkylamines (Scheme 3). The rapid formation of 1-(1-
bromovinyl)benzotriazole can be attributed to the higher
acidity of the R-proton of the benzotriazol-1-yl isomer (vs
that of Bt2),8,13 which suppressed the cyclization.
Lith ia tion of 2-Ben zotr ia zolyla zir id in es. Gener-
ally, direct lithiation at the R-CH position of an amine is
difficult.14 Indeed, attempted lithiation of several N-(R-
aminoalkyl)benzotriazoles failed. However, the combined
effect of the benzotriazolyl group and the three-membered
ring in the 2-benzotriazolylaziridines 3b and 8e has now
been demonstrated to allow lithiation at the methine
position (NCHBt, Schemes 4 & 6). Accordingly, N-phenyl-
2-(benzotriazol-1-yl)-3-(4-chlorophenyl)aziridine (3b) and
N-cyclohexyl-2-(benzotriazol-2-yl)aziridine (8e) were
treated with n-BuLi to form the carbanion intermediates,
which were quenched with alkyl bromides to give N-phen-
yl-2-butyl-2-(benzotriazol-1-yl)-3-(4-chlorophenyl)aziri-
dine (12, 80%, Scheme 4) and N-cyclohexyl-2-methyl-2-
(benzotriazol-2-yl)aziridine (20, 71%, Scheme 6), respec-
tively.
[2 + 3] Cycloa d d ition Rea ction s. Pyrroles constitute
one of the most important types of heterocycles, with
extensive applications as medicinal agents, polymers, and
other materials.15 Syntheses of pyrroles from aziridines
have been reported.4a,16 In particular, aziridines with a
2-sulfonyl4a or 2-cyano16b group reacted with acetylenes
to give pyrroles via [2 + 3] cyclization of azomethine
ylides and loss of the sulfonyl or cyano group. In all these
reactions, the C2-C3 bond underwent scission and the
acetylene component provided C3 and C4 of the pyrrole
ring.
Reactions between compounds 3a ,b and dialkyl acet-
ylenedicarboxylates at 100 °C similarly gave pyrroles
(13) (a) Katritzky, A. R.; Wu, J .; Kuzmierkiewicz, W.; Rachwal, S.
Liebigs Ann. Chem. 1994, 1. (b) Katritzky, A. R.; Wu, J .; Kuz-
mierkiewicz, W.; Rachwal, S.; Balasubramanian, M.; Steel, P. J . Liebigs
Ann. Chem. 1994, 7.
(14) (a) Ahlbrecht, H.; Dollinger, H. Tetrahedron Lett. 1984, 25,
1353. (b) Kessar, S. V.; Singh, P. Chem. Rev. 1997, 97, 721. (c)
Katritzky, A. R.; Qi, M. Tetrahedron 1998, 54, 2647.
(15) Gribble, G. W. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon:
Oxford, 1996; Vol. 2, p 207.
(16) (a) Sundberg, R. J . In Comprehensive Heterocyclic Chemistry
II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon:
Oxford, 1996; Vol. 2, p 119. (b) Porta, P. L.; Capuzzi, L.; Bettarini, F.
Synthesis 1994, 287. (c) DeShong, P.; Kell, D. A.; Sidler, D. R. J . Org.
Chem. 1985, 50, 2309.

348 J . Org. Chem., Vol. 64, No. 2, 1999
Katritzky et al.
Sch em e 5
F igu r e 1. Perspective view of one of the two independent
molecules in the unit cell of the X-ray crystal structure of 14b.
Ta ble 1. Selected 13C a n d 1H NMR Ch em ica l Sh ifts
(p p m ) of P r od u cts 14a ,b, 21, a n d 18a -d
14a
14b
21
18a
18b
18c
18d
C2
C3
C4
C5
CO 163.6
165.5
123.1
119.7
119.5
120.3
162.0
166.2
128.5
120.8
110.0
124.9
161.8
164.3
120.9
118.9
109.7
125.5
161.9
165.0
124.3
120.7
110.0
124.8
161.5
164.8
124.9
120.7
109.9
124.2
161.5
164.8
Sch em e 6
163.5
165.4
H5 7.51(s) 7.47(s) 6.69(s) 6.69(d) 6.69(d) 6.69(d) 6.68(d)
H4 6.46(d) 6.47(d) 6.47(d) 6.46(d)
now with the methoxycarbonyl groups at the 2 and 3
positions (18a -d , Scheme 5). The 1H and 13C NMR
spectra of each of compounds 18a -d show two non-
equivalent methoxycarbonyl groups and two nonequiva-
lent pyrrole-ring protons signals (Table 1). For example,
for compound 18d , the 1H NMR spectrum had two
different ring protons (δH 6.46 ppm, d, 1H, J ) 2.4 Hz
and 6.68 ppm, d, 1H, J ) 2.4 Hz); the 13C NMR spectrum
showed the presence of two carbonyl groups (δc 161.5 and
164.8 ppm) and four different peaks of the pyrrole ring
carbon (δc 109.9, 120.7, 124.2, 124.9 ppm). If the carboxyl
groups were at the 3 and 4 positions, symmetrical 1H and
13C NMR patterns would be expected for compounds
18a -d ; thus, the reaction of 8a -d is demonstrated to
proceed in a different orientation from the reaction of
3a ,b.
The structure of pyrrole 18d was established by the
hydrolysis of 18d to give the crystalline acid 19; X-ray
crystallography of 19 (Figure 2) showed the 2,3-orienta-
tion of the carboxyl groups. Compound 19 also crystallizes
with two independent molecules in the asymmetric unit,
which have different conformations of the N-butyl group.
In the unit cell molecule of 19 shown in Figure 2, the
N-butyl substituent has a 1-anti, 2-gauche conformation,
whereas in the other unit cell molecule of 19, the N-butyl
has a 1-gauche, 2-anti conformation. In each of the
molecules in the unit cell of 19, an intramolecular
hydrogen bond exists between the two carboxylate groups,
with the result that all the carboxyl groups are coplanar
with the attached pyrrole ring. The remaining OH
hydrogens of 19 are involved in intermolecular hydrogen
bonds to the carbonyl oxygens of adjacent molecules.
The assignment of pyrrole-ring 1H and 13C NMR
features of compounds 18a -d were based on literature
14a ,b in good yields (Scheme 4), presumably via forma-
tion of an azomethine ylide (13) followed by a polar [2 +
3] cyclization and aromatization by loss of benzotriazole.
The structure of the diester 14b was confirmed by X-ray
crystallography (Figure 1), thereby unambiguously locat-
ing the positions of the two methoxycarbonyl substituents
in the 3 and 4 positions of the pyrrole ring. Compound
14b crystallizes with two independent molecules in the
asymmetric unit, which show significant differences in
the conformations of the various substituents attached
to the pyrrole ring (for details, see supporting materials).
1
Because the pyrrole-ring H5 and the H and 13C signals
of each of the two methoxycarbonyl groups of 14a and
14b appeared in similar positions in the NMR spectra
(Table 1), we deduced that compound 14a has the same
type of structure as 14b.
1-Alkyl-2-(benzotriazol-2-yl)aziridines (8a -d ) required
a higher temperature (140 °C) and longer times for
complete reaction with diethyl acetylenedicarboxylate;
these reactions also form pyrrole-dicarboxylic esters, but

2-Benzotriazolylaziridines
J . Org. Chem., Vol. 64, No. 2, 1999 349
ary amines.16 However, to our knowledge, no previous
examples of [2 + 3] cycloadditions are known in which
the aziridine provides a N-C-C component.17,19
To summarize, we have developed two routes for the
synthesis of 2-benzotriazolylaziridines. These aziridines
possess multiple reaction centers and have interesting
synthetic potential, as exemplified by our preliminary
studies of their utility in the preparation of polysubsti-
tuted pyrroles.
Exp er im en ta l Section
Gen er a l Com m en ts. Melting points were measured on a
hot-stage microscope and are uncorrected. 1H and 13C NMR
data were collected on a 300 MHz NMR spectrometer (300 and
75 MHz, respectively) using CDCl3 as solvent. Compounds 1,20
4,21 and 921 were prepared by the literature methods quoted.
Gen er a l P r oced u r e for th e Syn th esis of 1,3-Dia r yl-2-
(ben zotr ia zol-1-yl)a zir id in es (3). A mixture of 1-(chloro-
methyl)benzotriazole (1, 1.0 g, 6 mmol) and an imine (6 mmol)
in THF-HMPA (4:1) was cooled to -20 °C, and lithium bis-
(trimethylsilyl)amide (7.2 mmol, 1.0 M in THF) was added over
15 min. The mixture was stirred at room temperature for
another 12 h. Water was added, and the mixture was extracted
with ether. After the organic layers were dried and concen-
trated, the crude product was purified by chromatography on
silica gel (eluent: hexanes-EtOAc-Et3N, 100:3:1) to give 3.
1,3-Dip h en yl-2-(ben zotr ia zol-1-yl)a zir id in e (3a ). The cis
and trans isomers (cis/trans ) 57/43) were separated by
column chromatography. cis-1,3-Diphenyl-2-(benzotriazol-1-yl)-
aziridine, white solid, mp 129-131 °C; 1H NMR δH 3.92 (d,
1H, J ) 4.9 Hz), 5.28 (d, 1H, J ) 4.9 Hz), 6.67-7.48 (m, 12H),
7.83 (d, 1H, J ) 8.3 Hz), 7.96 (d, 1H, J ) 8.4 Hz); 13C NMR δC
47.9, 56.8, 111.1, 114.7, 119.6, 119.8, 123.9, 124.1, 127.2, 127.6,
128.1, 128.2, 129.2, 129.7, 149.3, 150.7. Anal. Calcd for
F igu r e 2. Perspective view of one of the two independent
molecules in the unit cell of the X-ray crystal structure of 19.
analogies.4,16 The four ring carbons have two types of 13
C
NMR signals: (i) C2, C3 and (ii) C4, C5 signals. C2 and
C5 (linked directly to nitrogen) appeared downfield (i.e.,
at higher ppm) relative to those for C3 and C4, and thus
we assign the 13C NMR peaks as in Table 1. The ring
protons H5 appear at higher ppm than proton H4, as also
shown in Table 1.
The formation of pyrroles 18a -d probably involves the
pathway in Scheme 5. In contrast to aziridines 3a ,b,
aziridines 8a -d have no aryl group at the C3 position
to stabilize the azomethine ylide intermediate (cf. 13,
Scheme 4).17 Evidently, at a higher temperature, the
electronic effects of the amino and Bt moieties of 8a -d
can combine to break either the C-N bond or the C-Bt
bond, which would form species 15 and 16, respectively.18
Whereas 15 is expected to simply equilibrate with aziri-
dine 8a -d , 16 should react with acetylene to give
pyrrolines 17, which can aromatize to afford pyrroles
18a -d by the loss of benzotriazole.
C
20H16N4: C, 76.90; H, 5.16; N, 17.94. Found: C, 76.92; H,
5.17; N, 17.47. trans-1,3-Diphenyl-2-(benzotriazol-1-yl)aziri-
dine: viscous colorless oil; 1H NMR δH 4.76 (d, 1H, J ) 1.9
Hz), 5.48 (d, 1H, J ) 1.9 Hz), 6.82-7.58 (m, 12H), 7.86 (d, 1H,
J ) 9.0 Hz), 8.06 (d, 1H, J ) 8.7 Hz); 13C NMR δC 45.5, 56.6,
109.9, 113.4, 120.3, 120.6, 123.3, 124.3, 127.7, 128.1, 128.5,
129.0, 133.2, 133.5, 145.4, 146.2.
2-(1,2-Dibr om oeth yl)ben zotr ia zole (5a ). Br2 (4 g, 25
mmol) was added to a solution of 2-vinylbenzotriazole (2.0 g,
13.8 mmol) in CCl4 (100 mL) at room temperature, and the
mixture was stirred for 45 min. The reaction mixture was
poured into ice water and ether; the organic layer was washed
with saturated NaHCO3 and concentrated to afford 5a (93%)
1
as a white solid, mp 62-65 °C; H NMR δH 4.28 (dd, 1H, J )
The reaction of 20 with dimethyl acetylenedicarboxyl-
ate could take two paths (C-C or C-N scission) to form
21 or 22, however, we only obtained one product. Com-
3.7, 11.2 Hz), 4.88 (dd, 1H, J ) 11.2 Hz), 6.98 (dd, 1H, J )
3.7, 11.2 Hz), 7.46-7.49 (m, 2H), 7.90-7.94 (m, 2H); 13C NMR
δC 31.8, 60.7, 118.7, 128.0, 144.9. Anal. Calcd for C8H7Br2N3:
C, 31.93; H, 2.31; N, 13.51. Found: C, 31.97; H, 2.25; N, 13.73.
Gen er a l P r oced u r e for th e Syn th esis of 1-Alk yl-2-
(ben zotr ia zol-2-yl)a zir id in es (8). A mixture of 2-(1,2-dibro-
moethyl)benzotriazole (5a , 1.3 g, 4.0 mmol), an appropriate
alkylamine (10 mmol), NaOH (0.5 g, 12 mmol), ether (6 mL),
and HMPA (4 mL) was stirred at room temperature for 24 h
under nitrogen. Water was added, and the mixture was
extracted with ether. After the organic layer was dried and
concentrated, the crude product was purified by column
chromatography on neutral Al2O3 (eluent: hexanes-EtOAc,
100:3) to afford 8.
1
parison of the chemical shift of the H5 signal in the H
NMR spectrum of this product with the corresponding
values for 18a -d (Table 1) suggested structure 21. This
was confirmed by the observation of an NOE enhance-
ment of the methyl group signal upon irradiation of the
signal for H5. Thus the reaction between 20 and dimethyl
acetylenedicarboxylate proceeded by the same pathway
as the reaction between 8a -d and diethyl acetylenedi-
carboxylate through the C-N scission as shown in
Scheme 5.
The scission of a C-N bond is of course the normal
reaction of aziridines with diverse nucleophiles (R2CuLi,
NaN3, KSCN, NaI, KCN, allylsilane, RMgBr, RLi, amine,
alchol, phosphite, ylide, et al.) to form primary or second-
(19) The scission of both C-N and C2-C3 bonds of aziridines and
its cyclization with isothiocyanates have been reported; see (a) Nomura,
R.; Nakano, T.; Nishio, Y.; Ogawa, S.; Ninagawa, A.; Matsuda, H.
Chem. Ber. 1989, 122, 2407. (b) Lown, J . W.; Matsumoto, K. Can. J .
Chem. 1970, 48, 3399. (c) Lown, J . W.; Dallas, G.; Malony, T. W. Can.
J . Chem. 1969, 47, 3557.
(17) In the transformation of aziridines to pyrroles, most literature
(see ref 4a and 16) only reported the reaction between phenyl-
substituted aziridines and diethyl acetylenedicarboxylate.
(20) Burckhalter, J . H.; Stephens, V. C.; Hall, L. A. R. J . Am. Chem.
Soc. 1952, 74, 3868.
(18) We have observed for open-chain compounds of type Bt-C-N
similar competition between C-N and C-Bt bond scission; see ref 10b.
(21) Katritzky, A. R.; Li, J .; Malhotra, N. Liebigs Ann. Chem. 1992,
843.

350 J . Org. Chem., Vol. 64, No. 2, 1999
Katritzky et al.
1-P en t yl-2-(b en zot r ia zol-2-yl)a zir id in e (8a ). Colorless
oil; H NMR δH 0.89 (t, 3H, J ) 6.7 Hz), 1.33-1.35 (m, 4H),
Dim eth yl 1-cycloh exyl-4-m eth yl-1H-p yr r ole-2,3-d ica r -
boxyla te (21). Prepared from 20 and dimethyl acetylenedi-
carboxylate at 130 °C for 72 h in 30% yield, colorless oil; H
1
1
1.68-1.70 (m, 2H), 1.96 (d, 1H, J ) 5.4 Hz), 2.44-2.48 (m,
1H), 2.65-2.68 (m, 1H), 2.97 (d, 1H, J ) 1.7 Hz), 4.58-4.65
(m, 1H), 7.35-7.38 (m, 2H), 7.83-7.86 (m, 2H); 13C NMR δC
13.9, 22.4, 28.8, 29.3, 34.5, 57.0, 59.5, 118.1, 126.5, 144.2. Anal.
Calcd for C13H18N4: C, 67.78; H, 7.88; N, 24.34. Found: C,
67.33; H, 7.66; N, 24.53.
NMR δH 1.18-1.26 (m, 1H), 1.36-1.61 (m, 4H), 1.74 (d, 1H, J
) 13.2 Hz), 1.88 (d, 2H, J ) 12.6 Hz), 2.06 (d, 2H, J ) 12.0
Hz), 2.15 (s, 3H), 3.84 (s, 3H), 3.85 (s, 3H), 4.47-4.55 (m, 1H),
6.69 (s, 1H); 13C NMR δC 10.8, 25.4, 25.7, 34.4, 51.5, 51.8, 56.7,
119.5, 119.7, 120.3, 123.1, 162.0, 166.2. Anal. Calcd for C15H21
-
Gen er a l P r oced u r e for th e Syn th esis of Azir id in es 12
a n d 20. To a solution of 3b or 8e (1.0 mmol) in THF (20 mL,
-78 °C) was added n-BuLi (1.1 mmol), and the mixture was
then stirred for 20 min. 1-Bromobutane or iodomethane (1.0
equiv) was added to the reaction mixture, which was kept
overnight. The reaction mixture was treated with saturated
NaHCO3 solution and extracted with ether. After column
chromatography on neutral alumina (eluent: hexanes-EtOAc,
100:3), the pure product was obtained.
NO4: C, 64.50; H, 7.58; N, 5.01. Found: C, 64.75; H, 7.45; N,
5.91.
1-Bu tyl-1H-p yr r ole-2,3-d ica r boxylic a cid (19). Com-
pound 18d (0.1 g) in methanol (1 mL) and aqueous NaOH (2
N, 1 mL) were stirred at room temperature for 24 h. The
reaction mixture was acidified to pH ) 2 with aqueous
saturated HCl solution and extracted with EtOAc (3 × 20 mL).
The organic layer was washed with aqueous saturated NaCl
solution and dried over MgSO4. Removal of the solvent under
vacuum afforded 19; mp 120-123 °C; 1H NMR δH 0.95 (t, 3H,
J ) 5.6 Hz), 1.35-1.37 (m, 2H), 1.78-1.81 (m, 2H), 4.50 (t,
2H, J ) 6.6 Hz), 6.88 (br, 2H); 13C NMR δC 13.6, 19.8, 33.4,
51.1, 113.2, 118.2, 128.4, 170.7.
X-r a y Cr ysta llogr a p h y. Data were collected with a Si-
emens SMART CCD area detector, using graphite monochro-
matized Mo KR radiation (λ ) 0.71073 Å). The structures were
solved by direct methods and refined on F2 using all data by
full-matrix least-squares procedures. Hydrogen atoms were
included in calculated positions, except for the OH hydrogens
which were located from a difference map.
1-P h en yl-2-bu tyl-2-(ben zotr ia zol-1-yl)-3-(4-ch lor op h e-
1
n yl)a zir id in e (12). White solid, mp 60-61 °C; H NMR δH
0.76 (t, 3H, J ) 6.9 Hz), 1.19-1.35 (m, 3H), 1.56-1.60 (m, 1H),
1.88-1.93 (m, 1H), 2.13-2.18 (m, 1H), 3.78 (s, 1H), 7.05 (br s,
5H), 7.20 (t, 1H, J ) 7.2 Hz), 7.27 (d, 2H, J ) 7.5 Hz), 7.34 (t,
1H, J ) 7.5 Hz), 7.46 (t, 2H, J ) 7.5 Hz), 7.80 (d, 1H, J ) 8.4
Hz), 8.01 (d, 1H, J ) 8.1 Hz); 13C NMR δC 13.7, 22.4, 27.7,
33.8, 50.3, 64.1, 110.7, 119.9, 120.1, 123.7, 127.5, 128.0, 128.3,
128.7, 129.5, 132.7, 133.2, 133.7, 145.0, 146.8. Anal. Calcd for
C
24H23ClN4: C, 71.54; H, 5.75. Found: C, 71.67; H, 5.98.
Gen er a l P r oced u r e for th e Syn th esis of Su bstitu ted
P yr r oles 14. A mixture of an appropriate benzotriazolylaziri-
dine (3a or 3b, 2.2 mmol) and dialkyl acetylenedicarboxylate
(2.8 mmol) was stirred at 100 °C for 48 h. Then the mixture
was purified by column chromatography on silica gel (eluent:
hexanes-EtOAc-Et3N, 100:3:1) to afford pure 14.
Crystal Data for 14b at -110 °C: C20H16ClNO4, M ) 369.79,
monoclinic, space group P21/c; a ) 11.4672(6), b ) 38.103(2),
c ) 8.1776(4) Å; â ) 103.718(1); V ) 3471.1(3), Z ) 8, F(000)
) 1536, Dx ) 1.415 g cm-3; colorless block, 0.64 × 0.52 × 0.11
mm; µ, 0.246 mm-1, 2θmax 53°; 6767 unique reflections, 473
parameters, wR ) 0.0943 for all data, R ) 0.0377 for 5415
data with I > 2σ(I).
Dieth yl 2-(4-ch lor op h en yl)-1-p h en yl-1H-p yr r ole-3,4-d i-
1
ca r boxyla te (14b).4a White solid, mp 120-121 °C; H NMR
δH 3.75 (s, 3H), 3.82 (s, 3H), 7.04-7.06 (m, 2H), 7.12 (d, 2H, J
) 8.6 Hz), 7.18 (d, 2H, J ) 8.6 Hz), 7.28-7.30 (m, 3H), 7.47
(s, 1H); 13C NMR δC 51.3, 51.8, 115.4, 116.8, 125.7, 127.9, 128.0,
128.1, 129.2, 131.4, 131.5, 133.9, 134.2, 138.0, 163.5, 165.4.
Anal. Calcd for C20H16ClNO4: C, 64.96; H, 4.36; N, 3.79.
Found: C, 64.71; H, 4.23; N, 3.93.
Crystal Data for 19 at -115 °C: C10H13NO4, M ) 211.21,
triclinic, space group P-1; a ) 7.767(2), b ) 11.193(3), c )
13.039(4) Å, R ) 75.336(5), â ) 86.921(4), γ ) 80.660(4)°; V )
1081.9(5), Z ) 4, F(000) ) 448, Dx ) 1.297 g cm-3; colorless
plate, 0.62 × 0.38 × 0.02 mm, µ, 0.101 mm-1, 2θmax 47°; 3124
unique reflections, 271 parameters, wR ) 0.1620 for all data,
R ) 0.0586 for 1728 data with I > 2σ(I).
Gen er a l P r oced u r e for th e Syn th esis of Su bstitu ted
P yr r oles 18. A mixture of an appropriate benzotriazolylaziri-
dine (8, 2.2 mmol) and diethyl acetylenedicarboxylate (2.8
mmol) was stirred at 140 °C for 72 h. Then the mixture was
purified by column chromatography on silica gel (eluent:
hexanes-EtOAc-Et3N, 100:1:1) to afford pure 18.
Ack n ow led gm en t . We thank the referees of this
manuscript for helpful comments.
Su p p or tin g In for m a tion Ava ila ble: Text providing de-
tailed analysis data (1H, and 13C NMR and microanalysis) of
compounds 3b, 8b-g, 10, 11, 14a , 18b-d , and 20 and eight
tables of crystal data for compounds 14b and 19 (17 pages).
This material is contained in libraries on microfiche, im-
mediately 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.
Dieth yl 1-p en tyl-1H-p yr r ole-2,3-d ica r boxyla te (18a ).
1
Colorless oil; H NMR δH 0.89 (t, 3H, J ) 6.9 Hz), 1.22-1.39
(m, 10H), 1.72-1.77 (m, 2H), 4.14 (t, 2H, J ) 7.1 Hz), 4.25-
4.36 (m, 4H), 6.46 (d, 1H, J ) 2.7 Hz), 6.69 (d, 1H, J ) 2.7
Hz); 13C NMR δC 13.9, 14.1, 14.3, 22.2, 28.7, 31.2, 49.2, 60.4,
61.1, 110.0, 120.8, 124.9, 128.5, 161.8, 164.3. Anal. Calcd for
C
15H23NO4: C, 64.04; H, 8.24; N, 4.98. Found: C, 63.73; H,
8.70; N, 5.38.
J O980082Y