A Novel Approach to Substituted 2H-Azirines

Article abstract of DOI:10.1021/jo034472i

2-(Benzotriazol-1-yl)-2H-azirines 4a-c, obtained by treatment of oximes 2a-c with tosyl chloride and aqueous KOH, were reacted with benzylmagnesium bromide or 4-methylbenzylmagnesium bromide in the presence of zinc chloride to give 2-benzyl-2H-azirines 5a

Full text of DOI:10.1021/jo034472i

SCHEME 1
A Novel Ap p r oa ch to Su bstitu ted
2H-Azir in es
Alan R. Katritzky,* Mingyi Wang,
Chavon R. Wilkerson, and Hongfang Yang
Department of Chemistry, Center for Heterocyclic
Compounds, University of Florida,
Gainesville, Florida 32611-7200
katritzky@chem.ufl.edu
Received April 14, 2003
Abstr a ct: 2-(Benzotriazol-1-yl)-2H-azirines 4a -c, obtained
by treatment of oximes 2a -c with tosyl chloride and aque-
ous KOH, were reacted with benzylmagnesium bromide
or 4-methylbenzylmagnesium bromide in the presence of
zinc chloride to give 2-benzyl-2H-azirines 5a -f. Potas-
sium phthalimide and sodium salt of benzenethiol con-
verted 2-(benzotriazol-1-yl)-2H-azirines 4a -c into novel
2H-azirines 6a -c and 7 in good yields.
azirines containing a carboxylic ester group3c or a phos-
phorus substituent3d,7 by this methodology have been
reported.
Recently, 2-halo-2H-azirines8 have been used for halide
displacement by reacting with nucleophiles. However,
reported successful halide displacements of 2-halo-2H-
azirines are limited to some N-nucleophiles, specifically
potassium phthalimide. A reaction with aniline gave the
expected substitution product in 11% yield.
2H-Azirines are important for their versatile chemical
and biological behavior.1 2H-Azirines are naturally oc-
curring antibiotics.2 Substituted and functionalized azir-
ines are versatile precursors for the preparation of
functionalized aziridines.1a,3 Azirines with phosphorus
substituents regulate many important biological func-
tions.4
Benzotriazole can be used in place of a halogen as a
leaving group in many reactions;9 indeed, the combina-
tion of a 2H-azirine ring and a benzotriazole group can
enhance 2H-azirine chemistry as is now demonstrated.
Syn t h esis of 2-(Ben zot r ia zol-1-yl)-2H -a zir in es
4a -c. Starting N-acylmethylbenzotriazoles 1a -c were
obtained either by reaction of 1-(trimethylsilylmethyl)-
benzotriazole and acyl chlorides10 or by treatment of
benzotriazole with 2-chloroacetophenone in toluene under
reflux.11 Compounds 1a -c with hydroxylamine hydro-
chloride provided oximes 2a -c (g90%) as single isomers,
which with tosyl chloride and aqueous KOH in a mix-
ture of chloroform and ethyl ether at 0 °C in the pres-
ence of tetra-n-butylammonium hydrogen sulfate (as a
phase-transfer catalyst) provided 2-(benzotriazol-1-yl)-
2H-azirines 4a -c (Scheme 2, Table 1). The concentration
and amount of aqueous KOH and the reaction time
significantly affected product yields. Optimal conditions
were found to be 10 equiv of 10% aqueous KOH and 5-6
h of reaction time at 0 °C; this avoided any isolation of
oxime tosylates 3. NMR spectra and elementary analysis
supported the structures of 4a -c (Table 1). The 13C NMR
spectra of 4a -c displayed the expected signals charac-
2H-Azirines were first reported by Neber et al.5 Exist-
ing synthetic protocols can be categorized6 as the follow-
ing: (i) intramolecular reactions of N-functionalized
imines, vinyl azides, isoxazoles, and oxazaphospholes
(routes a, b, and c of Scheme 1) and (ii) intermolecular
reactions between nitriles and carbenes or nitrenes and
acetylenes (routes d and e of Scheme 1). The Neber
reaction (route a), the most extensively used, is facilitated
by electron-withdrawing groups at the R-position to
N-functionalized imines. Asymmetric syntheses of 2H-
(1) (a) Padwa, A.; Woolhouse, A. D. In Comprehensive Heterocyclic
Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon Press:
Oxford, UK, 1984; Vol. 7, pp 47-93. (b) Nair, V. In Heterocyclic
Compounds; Hassner, A., Ed.; J ohn Wiley and Sons: New York, 1983;
Vol. 42, Part I, pp 215-332.
(2) (a) Stapley, E. O.; Hendlin, D.; J ackson, M.; Miller, A. K. J .
Antibiot. 1971, 24, 42. (b) Miller, T. W.; Tristram, E. W.; Wolf, F. J . J .
Antibiot. 1971, 24, 48. (c) Molinski, T. F.; Ireland, C. M. J . Org. Chem.
1988, 53, 2103. (d) Salomon, C. E.; Williams, D. H.; Faulkner, D. J . J .
Nat. Prod. 1995, 58, 1463.
(3) (a) Osborn, H. M. I.; Sweeney, J . Tetrahedron: Asymmetry 1997,
8, 1693. (b) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599. (c)
Verstappen, M. M. H.; Ariaans, G. J . A.; Zwanenburg, B. J . Am. Chem.
Soc. 1996, 118, 8491. (d) Palacios, F.; Ochoa de Retana, A. M.; Gil, J .
I.; Ezpeleta, J . M. J . Org. Chem. 2000, 65, 3213.
(4) Kafarski, P.; Lejezak, B. Phosphorus Sulfur 1991, 63, 193.
(5) (a) Neber, P. W.; Burgard, A. J ustus Liebigs Ann. Chem. 1932,
493, 281. (b) Neber, P. W.; Huh, G. J ustus Liebigs Ann. Chem. 1935,
515, 283.
(6) (a) Palacios, F.; Ochoa de Retana, A. M.; de Marigorta, E. M.; de
los Santos, J . M. Eur. J . Org. Chem. 2001, 2401. (b) Palacios, F.; Ochoa
de Retana, A. M.; de Marigorta, E. M.; de los Santos, J . M. Org. Prep.
Proc. Int. 2002, 34, 219.
(7) (a) Palacios, F.; Ochoa de Retana, A. M.; Gil, J . I. Tetrahedron
Lett. 2000, 41, 5363. (b) Palacios, F.; Aparicio, D.; Ochoa de Retana,
A. M.; de los Santos, J . M.; Gil, J . I.; Alonso, J . M. J . Org. Chem. 2002,
67, 7283.
(8) (a) Pinho e Melo, T. M. V. D.; Lopes, C. S. J .; Rocha Gonsalves,
A. M. d’A. Tetrahedron Lett. 2000, 41, 7217. (b) Pinho e Melo, T. M. V.
D.; Lopes, C. S. J .; Rocha Gonsalves, A. M. d’A.; Beja, A. M.; Paixa˜o,
J . A.; Silva, M. R.; da Veiga, L. A. J . Org. Chem. 2002, 67, 66.
(9) Katritzky, A. R.; Lan, X.; Yang, J . Z.; Denisko, O. V. Chem. Rev.
1998, 98, 409.
(10) Katritzky, A. R.; Zhang, S.; Fang, Y. Org. Lett. 2000, 2, 3789.
(11) Katritzky, A. R.; Wu, J . Synthesis 1994, 597.
10.1021/jo034472i CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/23/2003
J . Org. Chem. 2003, 68, 9105-9108
9105

SCHEME 2
In conclusion, we have developed a methodology for the
synthesis of 2-(benzotriazol-1-yl)-2H-azirines under mild
conditions, and have disclosed the first example of
nucleophilic substitution reactions of 2H-azirines with
organometallic reagents. Novel 2H-azirine derivatives
were thus obtained.
Exp er im en ta l Section
Gen er a l. Melting points were determined on a MEL-TEMP
capillary melting point apparatus equipped with a Fluke 51
digital thermometer. NMR spectra were taken in CDCl3 (unless
stated otherwise) with tetramethylsilane as the internal stan-
dard for 1H (300 MHz) or a solvent as the internal standard for
13C (75 MHz). All anhydrous solvents were distilled from sodium
under nitrogen immediately prior to use. All reactions with air-
sensitive compounds were carried out under an argon or nitrogen
atmosphere.
teristic of benzotriazolyl at δ ca. 146 and 110, and of the
sp3 carbon (C-2) and the sp2 carbon (C-3) of the 2H-azirine
ring at δ ca. 42 and 164, respectively.
Gen er a l P r oced u r e for th e Oxim es 2a -c. To a solution
of hydroxylamine hydrochloride (30 mmol) in water (50 mL) was
added a solution of benzotriazolylmethyl ketone 1 (15 mmol) in
ethanol (50 mL) followed by dropwise addition of 10% NaOH
(30 mmol) solution at room temperature. After addition, the
yellow or off-white colored mixture was stirred under reflux
overnight. Upon cooling to room temperature, white crystals of
the product formed and were collected by filtration with no
further purification necessary.
2-(1H -1,2,3-Be n zot r ia zol-1-yl)-1-p h e n yl-1-e t h a n on e -
oxim e (2a ). White prisms (93%), mp 234-236 °C (lit.14 mp 223-
225 °C, 56%); 1H NMR (DMSO-d6) 12.2 (s, 1H), 8.00 (d, J ) 8.4
Hz, 1H), 7.83 (d, J ) 8.2 Hz, 1H), 7.73-7.70 (m, 2H), 7.55 (dd,
J ) 7.2, 7.9 Hz, 1H), 7.40-7.32 (m, 4H), 6.09 (s, 2H); 13C NMR
(DMSO-d6) 151.2, 145.3, 134.4, 133.3, 129.6, 128.8, 127.9, 126.7,
124.5, 119.6, 110.9, 41.5.
2-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-(4-ch lor op h en yl)-1-eth a -
n on eoxim e (2b). White needles (91%), mp 226-227 °C; 1H
NMR (DMSO-d6) 12.33 (s, 1H), 8.01 (d, J ) 8.2 Hz, 1H), 7.83 (d,
J ) 8.2 Hz, 1H), 7.74 (d, J ) 8.4 Hz, 2H), 7.58 (dd, J ) 7.8, 7.0
Hz, 1H), 7.43-7.37 (m, 3H), 6.10 (s, 2H); 13C NMR (DMSO-d6)
149.9, 144.8, 134.0, 132.8, 128.4, 128.0, 127.4, 124.0, 119.1, 110.4,
41.0. Anal. Calcd for C15H14N4O: C, 67.65; H, 5.31; N, 21.04.
Found: C, 67.43; H, 5.47; N, 21.02.
Su bstitu tion Rea ction s of 2-(Ben zotr ia zol-1-yl)-
2H-a zir in es. Most documented reactions of 2H-azirines
with nucleophiles involve nucleophilic addition to the
imine bond.1,12 No previous nucleophilic replacement of
a 2-substituent of 2H-azirines with a C-nucleophile has
been documented. Reported successful halide displace-
ments of 2-halo-2H-azirines with nucleophiles have all
involved an additional electron-withdrawing group, e.g.
carboxylate, at the 2-position.8
We studied the reactivity of 2-(benzotriazol-1-yl)-2H-
azirines using organometallic reagents, phthalimide
anion, and benzenethiol anion as nucleophiles. Treatment
of 2-(benzotriazol-1-yl)-2H-azirines 4a-c with benzylmag-
nesium chloride or 4-methylbenzylmagnesium bromide
in the presence of zinc chloride gave the desired products
5a -f in moderate to good yields (Scheme 2, Table 1).
Except for 5a -f, no other products were observed in each
case. Compared with 2H-azirines 4a -c, the 13C NMR
spectra of 5a -f displayed the disappearance of benzo-
triazole moiety signals, and the appearance of signals
characteristic of benzyl at δ ca. 33.2-33.6. The spectra
data of 5a are also consistent with those reported.13 In
the presence of zinc chloride, unfortunately, reactions of
4a -c with other Grignard reagents, both aryl (e.g.
phenyl, p-chlorophenyl, p-tolyl) and alkyl (e.g. phenyl-
ethyl, pentyl), failed. In some cases, the reactions did not
proceed but allowed for the recovery of the starting
2-(benzotriazol-1-yl)-2H-azirines, while in other cases, the
disappearance of the starting 2-(benzotriazol-1-yl)-2H-
azirines resulted in a complicated mixture.
2-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-(4-m eth ylp h en yl)-1-eth a -
n on eoxim e (2c). White microcrystals (92%), mp 185-188 °C;
1H NMR (DMSO-d6) 12.11 (s, 1H), 7.99 (d, J ) 8.4 Hz, 1H), 7.82
(d, J ) 8.4 Hz, 1H), 7.62-7.53 (m, 3H), 7.37 (dd, J ) 8.0, 7.3
Hz, 1H), 7.12 (d, J ) 8.0 Hz, 2H), 6.07 (s, 2H), 2.24 (s, 3H); 13
C
NMR (DMSO-d6) 150.6, 144.9, 138.8, 132.8, 131.1, 128.9, 127.4,
126.2, 124.0, 119.1, 110.4, 41.0, 20.7. Anal. Calcd for C14H11
-
ClN4O: C, 58.65; H, 3.87; N, 19.54. Found: C, 58.47; H, 3.92;
N, 19.49.
Gen er a l P r oced u r e for 2-(Ben zotr ia zol-1-yl)-2H-a zir in es
4a -c. To a solution of oxime 2 (20 mmol) in a mixture of ethyl
ether (150 mL) and chloroform (50 mL) was added dropwise
aqueous KOH (11.2 g of KOH dissolved in 50 mL of water) at 0
°C. After the addition of the base solution, the mixture was
stirred vigorously at this temperature for 30 min, and then a
catalytic amount of Bu4NHSO4 was added. A solution of p-
toluenesulfonyl chloride (TsCl) in Et2O (50 mL) was added
dropwise at 0 °C. After this addition, the final mixture was
stirred at 0-5 °C for 6 h until the solid reactants disappeared.
The reaction mixture was transferred into a separatory funnel
and extracted with ethyl ether. The combined organic layer was
washed with water and dried over MgSO4. The residue on
removal of solvents was purified by column (hexanes-ethyl
acetate) to give the desired products 4a -c.
Following a procedure previously used for substitution
of 2-halo-2H-azirines,8b treatment of 2-(benzotriazol-1-
yl)-2H-azirines 4a -c with potassium phthalimide at
room temperature in DMF led to the synthesis of novel
2H-azirine derivatives 6a -c in good yield (Scheme 2,
Table 1). Reaction with the sodium salt of benzenethiol
was less successful: 4a gave an oil that consisted largely
of 7, a compound that decomposed at 20 °C and could
not be completely purified.
1-(3-P h en yl-2H-a zir en -2-yl)-1H-1,2,3-ben zotr ia zole (4a ).
White needles (40%), mp 99-100 °C; 1H NMR δ 8.15 (d, J ) 6.7
(12) (a) Alves, M. J .; Gilchrist, T. L.; Sousa, J . H. J . Chem. Soc.,
Perkin Trans. 1 1999, 1305. (b) Gilchrist, T. L.; Mendonca, R. Synlett
2000, 1843.
(13) Banert, K.; Hagedorn, M.; Liedtke, C.; Melzer, A.; Scho¨ffler, C.
Eur. J . Org. Chem. 2000, 257.
(14) Katritzky, A. R.; Wu, J .; Wrobel, L.; Rachwal, S.; Steel, P. J .
Acta Chem. Scand. 1993, 47, 167.
9106 J . Org. Chem., Vol. 68, No. 23, 2003

TABLE 1. 2H-Azir in es 4 a n d Th eir Der iva tives 5, 6, a n d 7
entry
R
R′
yield (%)
mp (°C)
99-100
158-160
101-102
oil
oil
oil
93-95
oil
13C NMR
4a
4b
4c
5a
5b
5c
5d
5e
5f
6a
6b
6c
7
Ph
60
58
66
66
53
44
66
71
50
71
57
79
60
42.6 (C-2)
42.4 (C-2)
42.6 (C-2)
40.1 (C-2)
39.7 (C-2)
40.0 (C-2)
39.6 (C-2)
40.2 (C-2)
39.9 (C-2)
35.6 (C-2)
35.7 (C-2)
35.5 (C-2)
37.6 (C-2)
164.6 (C-3)
163.8 (C-3)
164.1 (C-3)
171.6 (C-3)
171.3 (C-3)
170.9 (C-3)
171.0 (C-3)
171.1 (C-3)
171.3 (C-3)
165.3 (C-3)
164.7 (C-3)
164.8 (C-3)
166.4 (C-3)
4-ClC6H4
4-MeC6H4
Ph
C6H5CH2
4-MeC6H4CH2
C6H5CH2
4-MeC6H4CH2
C6H5CH2
4-MeC6H4CH2
phthalimido
phthalimido
phthalimido
PhS
Ph
4-ClC6H4
4-ClC6H4
4-MeC6H4
4-MeC6H4
Ph
4-ClC6H4
4-MeC6H4
Ph
oil
139-140
182.5-184.5
145-146
oil
Hz, 2H), 8.05 (d, J ) 8.4 Hz, 1H), 7.73-7.62 (m, 4H), 7.50 (t, J
) 7.6 Hz, 1H), 7.37 (dd, J ) 7.9, 7.3 Hz, 1H), 5.19 (s, 1H); 13C
NMR δ 164.6, 146.1, 134.4, 132.8, 130.5, 129.5, 127.8, 124.2,
123.0, 120.1, 109.8, 42.7. Anal. Calcd for C14H10N4: C, 71.78;
H, 4.30; N, 23.92. Found: C, 71.81; H, 4.39; N, 23.92.
1-[3-(4-Ch lor op h en yl)-2H -a zir en -2-yl]-1H -1,2,3-b en zo-
tr ia zole (4b). Yellow prism (58%), mp 158-160 °C; 1H NMR δ
8.10 (d, J ) 8.5 Hz, 2H), 8.06 (d, J ) 8.7 Hz, 1H), 7.75 (d, J )
8.4 Hz, 1H), 7.63 (d, J ) 8.5 Hz, 2H), 7.52 (t, J ) 7.6 Hz, 1H),
7.39 (dd, J ) 8.0, 7.3 Hz, 1H), 5.17 (s, 1H); 13C NMR δ 163.8,
146.2, 140.9, 132.9, 131.7, 130.0, 127.9, 124.3, 121.6, 120.2, 109.7,
42.4. Anal. Calcd for C14H9ClN4: C, 62.58; H, 3.38; N, 20.85.
Found: C, 62.81; H, 3.34; N, 20.84.
3-(4-Ch lor op h en yl)-2-(4-m eth ylben zyl)-2H-a zir in e (5d ).
White prism (80%), mp 93-95 °C; 1H NMR δ 7.69 (d, J ) 8.5
Hz, 2H), 7.49 (d, J ) 8.4 Hz, 2H), 7.17-7.09 (m, 4H), 3.05 (dd,
J ) 14.6, 4.8 Hz, 1H), 2.68 (dd, J ) 14.6, 5.4 Hz, 1H), 2.51 (dd,
J ) 5.1, 4.8 Hz, 1H), 2.33 (s, 3H); 13C NMR δ 171.0, 139.0, 136.0,
135.9, 130.5, 129.5, 129.2, 128.8, 124.1, 39.6, 33.6, 21.0. Anal.
Calcd for C16H14ClN: C, 75.14; H, 5.52; N, 5.48. Found: C, 75.18;
H, 5.65; N, 5.32.
2-Ben zyl-3-(4-m eth ylp h en yl)-2H-a zir in e (5e). Oil (71%);
1H NMR δ 7.57 (d, J ) 7.8 Hz, 2H), 7.24-7.14 (m, 7H), 2.97
(dd, J ) 14.6, 5.1 Hz, 1H), 2.65 (dd, J ) 14.6, 5.1 Hz, 1H), 2.40
(t, J ) 5.1 Hz, 1H), 2.35 (s, 3H). 13C NMR δ 171.1, 143.6, 139.5,
129.7, 129.4, 128.9, 128.5, 126.2, 122.7, 40.2, 32.9, 21.8. Anal.
Calcd for C16H15N: C, 86.84; H, 6.83; N, 6.33. Found: C, 86.67;
H, 7.23; N, 6.02.
1-[3-(4-Met h ylp h en yl)-2H -a zir en -2-yl]-1H -1,2,3-b en zo-
1
tr ia zole (4c). Yellow microcrystals (66%), mp 101-102 °C; H
NMR δ 8.07-8.02 (m, 3H), 7.69 (d, J ) 8.2 Hz, 1H), 7.50-7.44
(m, 3H), 7.37 (dd, J ) 7.8, 7.4 Hz, 1H), 5.18 (s, 1H), 2.5 (s, 3H);
13C NMR δ 164.1, 146.1, 145.6, 132.8, 130.6, 130.2, 127.7, 124.2,
120.3, 120.1, 109.9, 42.6, 22.0. Anal. Calcd for C15H12N4: C,
72.56; H, 4.87; N, 22.57. Found: C, 72.63; H, 4.96; N, 24.46.
Gen er a l P r oced u r e for 2H-Azir in es 5a -f. Under N2,
activated Mg powder (2 mmol) was added into a dried two-
necked flask equipped with a condenser and magnetic stirrer.
Then 5 mL of Et2O was added. With the starting of the stirrer,
3-4 drops of a solution of the bromide (2 mmol) in 5 mL of Et2O
was added by syringe, and several minutes later, the remaining
bromide solution was added dropwise. The mixture was heated
and refluxed slowly for 1h. Upon cooling to -18 °C (ice-salt
bath), ZnCl2 solution (1.0 M, 2.0 mL) was added, and 30-40 min
later, a solution of starting 2H-azirine 4 (0.5 mmol) in 5 mL of
toluene was added at this temperature. After these additions,
the final mixture was stirred at -18 °C to room temperature
overnight (around 24 h). TLC showed almost no starting
material. The reaction was quenched with water, and the
reaction mixture was diluted with Et2O, washed with water, and
dried over MgSO4. The residue on removal of solvents was
purified by column (hexanes-ethyl acetate) to give the desired
products 5a -f.
2-(4-Meth ylben zyl)-3-(4-m eth ylp h en yl)-2H-a zir in e (5f).
1
Oil (50%); H NMR δ 7.67 (d, J ) 8.0 Hz, 2H), 7.32 (d, J ) 8.0
Hz, 2H), 7.18 (d, J ) 8.0 Hz, 2H), 7.12 (d, J ) 8.0 Hz, 2H), 3.01
(dd, J ) 14.6, 4.9 Hz, 1H), 2.68 (dd, J ) 14.6, 5.4 Hz, 1H), 2.46-
2.44 (m, 4H), 2.34 (s, 3H); 13C NMR δ 171.3, 143.6, 136.4, 135.7,
129.8, 129.4, 129.2, 128.8, 122.9, 39.9, 33.1, 21.8, 21.0. HRMS
(FAB) Calcd for C17H17N1 [M+] 235.1361. Found 235.1359.
Gen er a l P r oced u r e for 2H-Azir in es 6a -c. To a solution
of potassium phthalimide (0.5 mmol) in DMF (5 mL) was added
dropwise a solution of starting 2H-azirine 4 (0.5 mmol) in DMF
(5 mL) at room temperature. After addition, the reaction mixture
was stirred at room temperature overnight (around 18 h).
Crushed ice was added to quench the reaction, then the mixture
was transferred to a separatory funnel and extracted with ether.
The organic layer was washed with water and dried over MgSO4.
The residue on the removal of Et2O was purified by column to
give a yellow oil. Recrystallization was carried out in hexane/
ethyl acetate.
2-(3-P h en yl-2H-a zir en -2-yl)-1H-isoin d ole-1,3(2H)-d ion e
(6a ). Yellow microcrystals (70%), mp 139-140 °C; 1H NMR
8.10-8.07 (m, 2H), 7.82-7.80 (m, 2H), 7.72-7.70 (m, 2H), 7.66-
7.58 (m, 3H), 4.27 (s, 1H); 13C NMR 167.9, 165.3, 134.3,
133.4, 131.7, 130.2, 128.9, 124.7, 123.3, 35.6. Anal. Calcd for
C16H10N2O: C, 73.27; H, 3.84; N, 10.68. Found: C, 73.16; H,
3.83; N, 10.58.
2-[3-(4-Ch lor op h en yl)-2H-a zir en -2-yl]-1H-isoin d ole-1,3-
(2H)-d ion e (6b). Yellow needles (57%), mp 182.5-184.5 °C; 1H
NMR δ 8.03 (d, J ) 8.4 Hz, 2H), 7.85-7.81 (m, 2H), 7.75-7.72
(m, 2H), 7.60 (d, J ) 8.4 Hz, 2H), 4.27 (s, 1H). 13C NMR δ 167.9,
164.7, 139.9, 134.4, 131.8, 131.5, 129.5, 123.5, 123.3, 35.7. HRMS
(FAB) calcd for C16H9N2O2 [M+] 296.0353. Found 296.0351.
2-[3-(4-Meth ylp h en yl)-2H-a zir en -2-yl]-1H-isoin d ole-1,3-
(2H)-d ion e (6c). Yellow needles (79%), mp 145-146 °C; 1H
NMR δ 7.97 (d, J ) 8.1 Hz, 2H), 7.83-7.79 (m, 2H), 7.72-7.70
(m, 2H), 7.41 (d, J ) 8.0 Hz, 2H), 4.24 (s, 1H), 2.48 (s. 3H); 13C
NMR δ 168.0, 164.8, 144.4, 134.3, 131.8, 130.3, 129.7, 123.4,
122.0, 35.5, 21.9. Anal. Calcd for C17H12N2O2: C, 73.90; H, 4.38;
N, 10.14. Found: C, 73.79; H, 4.21; N, 10.10.
2-Ben zyl-3-p h en yl-2H-a zir in e (5a ). Oil (70%);13 1H NMR
δ 7.77-7.75 (m, 2H), 7.55-7.47 (m, 3H), 7.31-7.21 (m, 5H), 3.06
(dd, J ) 14.6, 5.1, 1H), 2.76 (dd, J ) 14.6, 5.1 Hz, 1H), 2.51 (t,
J ) 5.1 Hz, 1H); 13C NMR δ 171.6, 139.3, 132.8, 129.3, 129.0,
128.9, 128.5, 126.3, 125.5, 40.1, 33.2.
2-(4-Meth ylben zyl)-3-p h en yl-2H-a zir in e (5b). Oil (70%);
1H NMR δ 7.86-7.83 (m, 2H), 7.65-7.55 (m, 3H), 7.25 (d, J )
8.0 Hz, 2H), 7.18 (d, J ) 8.0 Hz, 2H), 3.08 (dd, J ) 14.6 4.9 Hz,
1H), 2.77 (dd, J ) 14.6, 5.3 Hz, 1H), 2.55 (t, J ) 5.1 Hz, 1H),
2.40 (s, 3H); 13C NMR δ 171.7, 136.2, 135.8, 132.8, 129.4, 129.2,
129.0, 128.8, 125.6, 39.7, 33.4, 21.0. Anal. Calcd for C16H15N:
C, 86.84; H, 6.83; N, 6.33. Found: C, 86.53; H, 7.24; N, 6.20.
2-Ben zyl-3-(4-ch lor op h en yl)-2H-a zir in e (5c). Oil (70%); 1H
NMR δ 7.67 (d, J ) 8.5 Hz, 2H), 7.48 (d, J ) 8.4 Hz, 2H), 7.33-
7.20 (m, 5H), 3.09 (dd, J ) 14.6, 4.9 Hz, 1H), 2.73 (dd, J ) 14.6,
5.1 Hz, 1H), 2.54 (t, J ) 5.1 Hz, 1H); 13C NMR δ 170.9, 139.1,
139.0, 130.5, 129.5, 128.9, 128.6, 126.4, 124.0, 40.0, 33.5. Anal.
Calcd for C15H12ClN: C, 74.53; H, 5.00; N, 5.79. Found: C, 74.55;
H, 5.37; N, 5.76.
Th e P r oced u r e for 2H-Azir in e 7. To a solution of the
sodium salt of benzenethiol (0.5 mmol) in DMF (5 mL), cooled
at 0 °C, was added dropwise a solution of starting 2H-azirine
4a (0.5 mmol) in DMF (5 mL). After addition, the reaction
J . Org. Chem, Vol. 68, No. 23, 2003 9107

mixture quickly turned purple and was stirred at 0 °C for 1 h.
Crushed ice was added to quench the reaction, then the mixture
was transferred to a separatory funnel and extracted with ether.
The organic layer was washed with water and dried over MgSO4.
The residue on the removal of Et2O was purified by column to
give green oil. This compound is not stable at room temperature.
P h en yl 3-P h en yl-2H -a zir en -2-ylsu lfid e (7). Green oil
(70%); 1H NMR 7.87 (d, J ) 8.4 Hz, 2H), 7.67-7.55 (m, 5H),
7.36-7.24 (m, 3H), 3.84 (s, 1H); 13C NMR 166.4, 136.3, 133.6,
130.1, 129.8, 129.2, 129.0, 126.8, 124.0, 37.6. HRMS (FAB) calcd
for C14H11NS [M + 2H] 227.0769. Found 227.0764.
Su p p or tin g In for m a tion Ava ila ble: General procedure
and characterization data for compounds 2a -c, 4a -c, 5a -f,
6a -c, and 7. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O034472I
9108 J . Org. Chem., Vol. 68, No. 23, 2003