Cyclization of N-(2-cyclopent-1-en-1-ylphenyl)benzamides in solution and under mass-spectrometric conditions

Article abstract of DOI:10.1007/s10593-011-0764-6

The cyclization has been studied of N-(2-cyclopent-1-en-1-ylphenyl) benzamides into the corresponding 3,1-benzoxazines by the action of gaseous hydrogen chloride, trifluoroacetic acid, or bromine, and also under conditions of electron impact in the gas ph

Full text of DOI:10.1007/s10593-011-0764-6

Chemistry of Heterocyclic Compounds, Vol. 47, No. 3, June, 2011 (Russian Original Vol. 47, No. 3, March, 2011)
CYCLIZATION OF N-(2-CYCLOPENT-1-EN-
1-YLPHENYL)BENZAMIDES IN SOLUTION AND
UNDER MASS-SPECTROMETRIC CONDITIONS
S. A. Kazaryants1*, A. S. Erastov2, E. G. Galkin2, E. M. Vyrypaev2,
Sh. M. Salikhov2, and I. B. Abdrakhmanov2
The cyclization has been studied of N-(2-cyclopent-1-en-1-ylphenyl)benzamides into the corresponding
3,1-benzoxazines by the action of gaseous hydrogen chloride, trifluoroacetic acid, or bromine, and also
under conditions of electron impact in the gas phase. A scheme is proposed for the fragmentation of the
molecular ions of the products obtained.
Keywords: 3,1-benzoxazines, N-(2-cyclopent-1-en-1-ylphenyl)benzamides, mass spectra of 2-arylspiro-
[3,1-benzoxazin-4,1'-cyclopentanes] and N-(2-cyclopentenyl)benzamides, cyclization.
It is known that 3,1-benzoxazines possess marked biological activity so it seemed of interest to
synthesize new compounds of this class and study their properties [1]. It should be noted that at the present time
there are no general and efficient methods of obtaining heterocycles of this type. According to data of mass
spectrometry the formation of 3,1-benzoxazines is possible if there is a fragment in the starting substrate from
which a carbenium center of the benzyl type may be generated, and in the position adjoining it there is a triad of
NH-C(R)=O with a oxygen atom capable of displaying nucleophilic properties [2]. It was shown in the same
study that certain reactions of charged particles, observed under gas phase conditions, are like the reactions in
solution. Occasionally it is possible to establish a similarity in behavior of particles under mass-spectrometric
conditions and in solution.
For the synthesis of new 3,1-benzoxazines we studied the cyclization under various conditions of the
products of interaction of (cyclopent-1-en-1-yl)aniline (1) and acid chlorides of carboxylic acids 2a-g, the
amides 3a-g, satisfying the structural requirements given above.
In searches for an optimum variant of carrying out the indicated reaction we used the following
cyclization initiators: gaseous hydrogen chloride, liquid bromine, trifluoroacetic acid, acetic acid, 30% aqueous
hydrochloric acid solution, concentrated sulfuric acid, KU-2-8 catalyst, and UV irradiation.
_______
*To whom correspondence should be addressed, e-mail: ksa.85@mail.ru.
1Bashkir State University, 32 Zaki Validi, St., Ufa 450074, Republic of Bashkortostan, Russia.
2Institute of Organic Chemistry, Ufa Scientific Center of the Russian Academy of Sciences, 71 Oktyabrya
Prospect, Ufa 450054, Republic of Bashkortostan, Russia; e-mail: chemorg@anrb.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 432-440, March, 2011. Original
article submitted July 27, 2010; revision submitted December 20, 2010.
0009-3122/11/4703-0355©2011 Springer Science+Business Media, Inc.
355

Cyclization was unsuccessful under the action of acetic acid, 30% aqueous hydrochloric acid solution,
concentrated sulfuric acid, catalyst KU-2-8, and UV irradiation and the starting amide was resinified.
On catalysis with trifluoroacetic acid the, cyclization of amide 3a was effected after 18 h, and the yield
of product 4a was 43%. In the case of gaseous HCl, the duration of the same reaction was 5 h, but the yield of
compound 4a was increased to 80%. Consequently compounds 4b-g were also synthesized under these
conditions.
+

O
O
+
–
Cl
–
Cl
Ar
N
H
N
H
Ar
4'

A
B
3'
4'
5'
1'
2'
3'
5'
3
4
3
5
4a
2'
6
O
HCl (gas)
ArCOCl
+
2
1
N
5
7
NH2
NHCOAr
Ar
8a
8
1
2a–g
3a–g
4a–g
2–4 Ar = C6H4R, a R = H; b R = m-Br; с R = p-Cl; d R = p-NO2; e R = p-Me; f R = o-OMe;
g R = m-OMe
To carry out the cyclization, gaseous hydrogen chloride was bubbled through a solution of amide 3a-g
in methylene chloride. Subsequent treatment of the reaction mixture with 10% aqueous NaHCO3 solution led to
the appropriate benzoxazine 4a-g (52-94% yield).
The reaction is probably initiated by the addition of proton at the double bond of the cyclopentenyl
fragment and the generation of a carbenium ion of the benzyl type A, subsequent intramolecular stabilization of
which by the nucleophilic oxygen atom of the amide fragment led to the heterocyclic ion B, the precursor of
product 4. It is known that carbocations of type A are also formed under conditions of mass spectrometry [3]
(the direction of the conversion of the molecular ions and the structure of the resulting ions for the initial amides
3 and products 4 are considered by us below).
It was established that base 4a is unstable and on extended storage (more than 3 months from the
moment of its preparation without access to oxygen), with one action of high temperatures (above 200oC) or
maintaining for 1 h at 250oC in an atmosphere of argon it is quantitatively converted into the starting amide 3a.
The most effective initiator of cyclization proved to be bromine in CCl4. The reaction proceeded for
20 min and the yield of 5 hydrobromide was 97%.
Br
Br2
CCl4
O
3a
N
.
HBr
5
The composition and structure of amides 3a-g, synthesized for the first time, were confirmed by results
of elemental analysis, and also by data of 1H, 13C NMR, and mass spectra (see Experimental).
356

Analysis of the mass spectra of compounds 3a-g and 4a-g enabled the characteristic fragment ions to be
made apparent, common for amides 3 ([Ar]+, [ArCO]+, [M-ArCO]+) and specific for benzoxazines 4
([M-C2H5]+).
+
+
[ArCO]
[Ar]
+
.
.
O
.
+
O
O
.
+
N
H
.
.
.
Ar
N
H
Ar
N
Ar
+
M+
M
4a–g
C
3a–g
+
H
+
O
O
+
NH
[M–ArCO]+
N
Ar
N
Ar
–
[M–C2H5]+
D
The total intensity of the three common ions ([Ar]+, [ArCO]+, and [M-ArCO]+) was 40-60% of the total
ion current for amides 3 and 10-27% for benzoxazines 4 (see Table 1). This suggests that the decomposition of
the molecular ions of the indicated compounds proceeds through a common transition state. The high intensity
of the [M-ArCO]+ fragments in the case of the benzoxazines may be explained if it is assumed that this
decomposition is brought about through the intermediate 3,1-benzoxazinium ion D.
Fig. 1. Dependence of log(I[ArCO]+R/I[ArCO]+O) on the Hammett
σ constant of the substituent R for compounds 3b-e,g, y = 0.25 –
1.1x (r = 0.88)
It was shown above that in solution the formation of products 4 is also brought about through
3,1-benzoxazinium ions B, which is in agreement with the results of special investigations on the transformation
of arylamides in solution through stable intermediates [3]. The high intensities of the [ArCO]+ and [M-ArCO]+
357

TABLE 1. Contributions (% of Total Ion Current) of Molecular and
Characteristic Ion Peaks in the Mass Spectra of Compounds 3a-g and 4a-g
Intensity, % of total ion current
∑ [Ar]+,
Com-
[ArCO]+,
M+
[Ar]+
[ArCO]+
[M–ArCO]+
[M–C2H5]+
pound
[M–ArCO]+
10.6
5.0*
9.2*2
10.0
10.7
11.1
10.1
12.7
7.5*
10.1*2
8.8
9.4
4.2*
8.6*2
0.1
17.1
6.3*
25.3*2
4.1
20.1
11.4
24.1
24.0
20.2
18.1
16.2
9.8
46.6
21.9*
58.0*2
28.2
61.6
58.3
56.3
19.8
9.7*
19.7*2
16.5
25.3
25.7
23.5
0.22
0.14*
0.1*2
0.6
3a
3b
3c
3d
3e
3f
11.0
0.1
30.4
40.1
40.0
6.4
0.21
0.04
0.04
14.1
8.4*
11.1*2
8.4
0.1
3g
4a
4b
4c
4d
4e
4f
3.6
1.3*
2.7*2
0.2
2.9*
7.6*2
2.1
5.4
9.4
14.2
9.9
15.5
6.2
3.4
12.0
17.8
16.3
16.9
6.3
0.7
7.2
6.1
0.3
6.9
6.2
4g
_______
*Includes contribution of fragments with 79Br and 81Br.
*2Includes contribution of fragments with 35Cl and 37Cl.
ions in the spectra of compounds 4 are the evidence is, that in the gas phase as also in solution, electrophilic
attack occurs just at the oxygen atom. Consequently the mechanism of cyclization of arylamides under mass
spectrometry conditions and in solution is identical.
A quantitative assessment of the effect of the nature of substituent R on the formation of fragment
[ArCO]+ was carried out with the aid of Hammett constants. In Figure 1 the interdependence of the σ constants
and log(I[ArCO]+R/I[ArCO]+O) is represented, where I [ArCO]+R is the intensity of the peaks of [ArCO]+ ions of para-
and meta-substituted compounds 3b-e,g, and I[ArCO]+O is the intensity of the peaks of the corresponding ions in
the spectrum of compound 3a (R = H). The dependence of the experimentally obtained values of
log(I[ArCO]+R/I[ArCO]+O) on the electronic parameters of substituent R is described satisfactorily by the equation
y = 0.25 – 1.1x, as indicated by the correlation coefficient r = 0.88.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on a Bruker AM 300 spectrometer (at 300 and 75 MHz
respectively) in CDCl3, internal standard was TMS. Melting points were measured on a Kofler hot bench with
modification S 30A/G (GDR). For analytical TLC Sorbfil plates of type PTSKh-AF-A were used (Sorbpolimer,
Krasnodar). Elemental analysis was carried out on a Evro 2000 CHNS(O) analyzer. Preparative separation was
carried out by column chromatography on silica gel 40-100 mesh (Lancaster), eluent was petroleum ether–ethyl
acetate, 6:1. Mass spectra were recorded on a Thermo Finnigan MAT 95 XP by EI, 70 eV, temperature of ion
source 200oC; direct insertion of samples, isotherm 50oC, heating 22oC/min, to temperature 270oC. Precise
determination of mass numbers of ions was carried out in the range 1-1000 D at a resolution of 10000 at a height
of 10%, for all known ions formed in the source, using procedures for combining peaks. Standard was
perfluorokerosene.
358

Acid Chlorides of Arenecarboxylic Acids 2a-g (General Method). Thionyl chloride (15 ml) was
added dropwise to a solution of the appropriate arenecarboxylic acid (54 mmol) in absolute toluene (25 ml) and
absolute DMF (2 ml). The mixture was maintained at 70oC for 3 h. The excess of thionyl chloride and toluene
was then removed at reduced pressure and the residue, acid chloride 2, was used for the synthesis of amides 3
without purification.
Arenecarboxylic Acid Amides 3a-g (General Method). Amine 1 (7.7 mmol) and K2CO3 (13 mmol)
were added to a solution of acid chloride 2 (10 mmol) in absolute CH2Cl2 with stirring at room temperature. The
reaction mixture was stirred for 24 h (check by TLC). The solid was then filtered off, the filtrate washed with
water, with 10% Na2CO3 solution, dried over MgSO4, and the solvent removed at reduced pressure. Amide 3
was isolated from the residue by column chromatography in an analytically pure state.
N-(2-Cyclopent-1-en-1-ylphenyl)benzamide (3a). Yield 70%, white needles, crystallizing as spheres,
mp 85-87oC. 1H NMR spectrum δ, ppm (J, Hz): 2.05 (2H, m, H-4'); 2.61 (2H, m, H-5'); 2.70 (2H, m, H-3'); 5.95
(1H, t, J = 2.0, H-2'); 7.15 (1H, t, J = 7.1, H-4); 7.28 (2H, m, H-3,5); 7.51 (3H, m, H m,m',p-Ar); 7.87 (2H, d, J =
7.0, H o,o'-Ar); 8.45 (1H, d, J = 8.1, H-6); 8.57 (1H, br. s, NH). 13C NMR spectrum, δ, ppm: 23.21 (C-4'); 33.66
(C-5'); 36.66 (C-3'); 121.03 (C-2'); 123.87, 126.70, 127.54, 127.58, 127.95, 128.09, 128.62 (C-1'); 130.42,
131.52, 134.56, 134.78, 140.81, 164.80 (C=O). Mass spectrum, m/z (Irel, %): 263 [M]+ (52.6), 246 [M-OH]+
(7.2), 158 [M-PhCO]+ (100), 130 (22.3), 105 [PhC≡O]+ (84.9), 77 [Ph]+ (46.5). Found, %: C 82.00; H 5.99;
N 5.49. C18H17NO. Calculated, %: C 82.10; H 6.51; N 5.32.
3-Bromo-N-(2-cyclopent-1-en-1-ylphenyl)benzamide (3b). Yield 79%, yellow oil. 1H NMR spectrum,
δ, ppm (J, Hz): 2.0 (2H, m, H-4'); 2.62 (2H, m, H-5'); 2.75 (2H, m, H-3'); 6.0 (1H, t, J = 1.9, H-2'); 7.10 (1H,
ddd, J1 = 7.6, J2 = 1.1, J3 = 1.1, H-4); 7.20 (1H, dd, J1 = 7.6, J2 = 1.1, H-6); 7.23 (2H, m, H-5,3); 7.33 (1H, t,
J = 7.6, H m-Ar); 7.62 (1H, dt, J1 = 7.6, J2 = 1.1, H p-Ar); 7.68 (1H, dt, J1 = 7.6, J2 = 1.1, H o-Ar); 7.92 (1H, t,
J = 1.1, H o'-Ar); 8.45 (1H, br. s, NH). 13C NMR spectrum, δ, ppm: 23.02 (C-4'); 33.74 (C-5'); 36.14 (C-3');
115.64 (C-2'); 117.98, 122.91, 125.22, 127.39, 127.70, 127.98 (C-1'); 130.23, 130.65, 134.29, 134.48, 136.86,
140.91, 143.67, 163.23 (C=O). Mass spectrum, m/z (Irel, %): 343 [M+2]+ (21.8), 341 [M]+ (22.2), 324 [M-OH]+
(5.3), 183 [BrPhCO]+ (28.4), 158 [M-BrPhCO]+ (100), 155 [M-PhBr]+ (18.9), 130 (23.8), 77 (5.2), 76 (8.1).
Found, %: C 63.10; H 4.85; Br 22.95; N 4.15. C18H16BrNO. Calculated, %: C 63.17; H 4.71; Br 23.35; N 4.09.
4-Chloro-N-(2-cyclopent-1-en-1-ylphenyl)benzamide (3c). Yield 45%, white needles, crytstallizing as
spheres, mp 105-107oC. 1H NMR spectrum, δ, ppm (J, Hz): 2.05 (2H, m, H-4'); 2.60 (2H, m, H-5'); 2.70 (2H, m,
H-3'); 5.95 (1H, t, J = 1.9, H-2'); 7.15 (1H, ddd, J1 = 6.4, J2 = 1.2, J3 = 1.2, H-4); 7.25 (3H, m, H-3,5,6); 7.43
(2H, d, J = 8.5, H m,m'-Ar); 7.75 (2H, d, J = 8.5, H o,o'-Ar); 8.47 (1H, br. s, NH). 13C NMR spectrum, δ, ppm:
23.34 (C-4'); 33.78 (C-5'); 36.76 (C-3'); 121.26 (C-2'); 124.20, 127.68, 127.73, 128.26, 128.28, 128.88 (C-1');
128.95, 128.96, 130.52, 133.33, 134.43, 137.88, 140.98, 163.84 (C=O). Mass spectrum, m/z (Irel, %): 299
[M+2]+ (12.7), 297 [M]+ (38.1), 280 [M-OH]+ (8.3), 186 [M-PhCl]+ (2.3), 158 [M-ClPhCO]+ (100), 139
[ClPhCO]+ (78.2), 143 (7.2), 130 (24.2), 111 [PhCl]+ (33.3), 75 (8.0). Found, %: C 72.56; H 5.55; Cl 11.85; N
4.42. C18H16ClNO. Calculated, %: C 72.60; H 5.42; Cl 11.91; N 4.70.
1
N-(2-Cyclopent-1-en-ylphenyl)-4-nitrobenzamide (3d). Yield 70%, white powder, mp 120-122oC. H
NMR spectrum, δ, ppm (J, Hz): 2.06 (2H, m, H-4'); 2.62 (2H, m, H-5'); 2.75 (2H, m, H-3'); 6.0 (1H, t, J = 1.9,
H-2'); 7.08 (1H, ddd, J1 = 7.5, J2 = 7.3, J3 = 0.9, H-4); 7.28 (1H, dd, J1 = 7.5, J2 = 0.9, H-3); 7.32 (1H, ddd,
J1 = 7.3, J2 = 7.2, J3 = 0.9, H-5); 8.0 (2H, d, J = 8.7, H o,o'-Ar); 8.33 (2H, d, J = 8.7, H m,m'-Ar); 8.42 (1H, dd,
J1 = 7.2, J2 = 0.9, H-6); 8.51 (1H, br. s, NH). 13C NMR spectrum, δ, ppm: 24.38 (C-4'); 33.52 (C-5'); 37.23
(C-3'); 119.39 (C-2'); 123.13, 124.09, 124.17, 127,47, 128.36, 128.83 (C-1'); 131.85, 132.95, 135.13, 136.68,
137.56, 139.03, 149.14, 161.07 (C=O). Mass spectrum, m/z (Irel, %): 308 [M]+ (62.4), 291 [M-OH]+ (10.4), 279
[M-C2H5]+ (59.4), 278 [M-NO]+ (25.8), 249 (8.6), 224 [M-C5H8O]+ (3.9), 178 (7.3), 158 [M-NO2PhCO]+ (100),
359

150 [NO2PhCO]+ (14.6), 143 (13.0), 130 (33.1), 120 [OPhCO]+ (47.2), 104 [PhCO]+ (18.2), 92 [OPh]+ (7.9),
77 (7.3), 76 (14.2). Found, %: C 70.01; H 5.35; N 8.99. C18H16N2O3. Calculated, %: C 70.12; H 5.23; N 9.09.
N-(2-Cyclopent-1-en-1-ylphenyl)-4-methylbenzamide (3e). Yield 40%, yellow needles, crystalli-zing
as spheres, mp 75-77oC. 1H NMR spectrum, δ, ppm (J, Hz): 2.09 (2H, m, H-4'); 2.50 (3H, s, CH3); 2.65 (2H, m,
H-5'); 2.78 (2H, m, H-3'); 6.0 (1H, t, J = 1.9, H-2'); 7.13 (1H, t, J = 7.2, H-4); 7.30 (3H, m, H-3,5,6); 7.75 (2H,
d, J = 8.1, H m,m'-Ar); 8.15 (2H, d, J = 8.1, H o,o'-Ar); 8.50 (1H, br. s, NH). 13C NMR spectrum, δ, ppm: 21.24
(CH3); 23.26 (C-4'); 33.68 (C-5'); 36.77 (C-3'); 120.71 (C-2'); 123.60, 126.72, 126.75, 127.54, 127.56, 127.63,
128.34 (C-1'); 129.32, 130.41, 132.12, 134.76, 140.94, 142.04, 164.69 (C=O). Mass spectrum, m/z (Irel, %): 277
[M]+ (35.3), 260 [M-OH]+ (3.0), 158 [M-COPhMe]+ (66.6), 130 (12.7), 119 [MePhCO]+ (100), 91 [PhMe]+
(36.2). Found %: C 82.10; H 6.85; N 4.95. C19H19NO. Calculated, %: C 82.28; H 6.90; N 5.05.
1
N-(2-Cyclopent-1-en-1-ylphenyl)-2-methoxybenzamide (3f). Yield 60%, light-yellow oil. H NMR
spectrum, δ, ppm (J, Hz): 2.04 (2H, m, H-4'); 2.59 (2H, m, H-5'); 2.71 (2H, m, H-3'); 3.95 (3H, s, OCH3); 5.97
(1H, t, J = 1.9, H-2'); 7.01 (1H, d, J = 8.3, H m-Ar); 7.10 (2H, m, H m'-Ar, H-4); 7.20 (1H, dd, J1 = 7.7, J2 = 1.6,
H-3); 7.29 (1H, ddd, J1 = 7.6, J2 = 1.6, J3 = 1.6, H-5); 7.48 (1H, td, J1 = 8.3, J2 = 1.8, H p-Ar); 8.32 (1H, dd,
13
J1 = 7.8, J2 = 1.8, H o-Ar); 8.31 (1H, d, J = 7.6, H-6); 10.0 (1H, br. s, NH). C NMR spectrum, δ, ppm: 23.29
(C-4'); 33.68 (C-5'); 36.30 (C-3'); 55.56 (OCH3); 111.23, 121.22, 121.71, 121.83, 123.58 (C-2'); 127.34, 127.78,
129.19 (C-1'); 130.29, 132.31, 132.98, 135.32, 140.68, 156.89, 163.02 (C=O). Mass spectrum, m/z (Irel, %): 293
[M]+ (27.8), 226 [M-C5H7]+ (0.6), 158 [M-COPhMe]+ (45.2), 135 [MeOPhCO]+ (100), 130 (7.2), 92 (8.2), 77
(15.2). Found, %: C 76.98; H 7.01; N 4.70. C19H19NO2. Calculated, %: C 77.79; H 6.53; N 4.77.
1
N-(2-Cyclopent-1-en-1-ylphenyl)-3-methoxybenzamide (3g). Yield 70%, light-yellow oil. H NMR
spectrum, δ, ppm (J, Hz): 2.02 (2H, m, H-4'); 2.60 (2H, m, H-5'); 2.73 (2H, m, H-3'); 3.88 (3H, s, OCH3); 5.97
(1H, t, J = 2.1, H-2'); 7.10 (2H, m, H p-Ar, H-5); 7.40 (6H, m, H o,o'-Ar, H m-Ar, H 3,4,6); 8.45 (1H, br. s, NH).
13C NMR spectrum, δ, ppm: 23.29 (C-4'); 33.77 (C-5'); 36.79 (C-3'); 55.25 (OCH3); 112.22, 117.86, 118.36,
120.81, 123.88, 127.64; 128.53, 129.69 (C-1'); 130.53, 134.63, 136.40, 140.90, 159.89, 164.62 (C=O). Mass
spectrum, m/z (Irel, %): 293 [M]+ (28.1), 292 [M-H]+ (2.0), 226 [M-C5H7]+ (2.0), 158 [M-COPhOMe]+ (40.4),
135 [MeOPhCO]+ (100), 130 (6.4), 92 (8.5), 77 (15.5). Found, %: C 78.00; H 6.47; N 4.83. C19H19NO2.
Calculated, %: C 77.79; H 6.53; N 4.77.
Heterocyclization of Amides 3a-g under the Action of Gaseous Hydrogen Chloride (General
Method). Gaseous HCl was bubbled through a solution of amide 3 (90 mmol) in CH2Cl2 (20 ml). After the end
of the reaction (check by TLC) the solution of benzoxazine 4 hydrochloride was stirred for 1 h with NaHCO3
powder (2 g), then filtered. The filtrate was evaporated under reduced pressure, and benzoxazine 4 was isolated
from the residue by column chromatography.
2-Phenylspiro[3,1-benzoxazine-4,1'-cyclopentane] (4a). Yield 80%, yellow oil. 1H NMR spectrum, δ,
ppm (J, Hz): 1.90 and 2.35 (4H, two m, both 2H, H-2' and H-5'); 2.00 (4H, m, H-3',4'); 7.17 (1H, m, H-6), 7.30
(3H, m, H-5,7,8); 7.48 (3H, m, H m,m',p-Ar); 8.14 (2H, d, J = 7.0, H o,o'-Ar). 13C NMR spectrum, δ, ppm: 23.80
(C-3',4'); 40.08 (C-2',5'); 88.90 (C-4); 122.04, 124.63, 126.43, 127.65, 127.78, 128.15, 128.17, 128.21, 128.33,
129.25, 131.16, 139.65, 156.75 (C-2). Mass spectrum, m/z (Irel, %): 263 [M]+ (89.9), 262 [M-H]+ (4.7), 246
[M-OH]+ (5.2), 234 [M-C2H5]+ (100), 179 [M-C5H8O]+ (23.3), 158 [M-PhCO]+ (69.7), 130 (11.2), 105
[PhCO]+ (45.5), 77 [Ph]+ (25.6). Found, %: C 81.90; H 6.48; N 4.75. C18H17NO. Calculated, %: C 82.10; H 6.51;
N 5.32.
1
2-(m-Bromophenyl)spiro[3,1-benzoxazine-4,1'-cyclopentane] (4b). Yield 55%, yellow oil. H NMR
spectrum, δ, ppm (J, Hz): 1.91 and 2.33 (4H, two m, both 2H, H-2' and H-5'); 2.06 (4H, m, H-3',4'); 7.16 (1H, t,
J = 7.4, H-6); 7.21 (1H, t, J = 7.4, H-7); 7.29 (3H, m, H-5,8, H m-Ar); 7.62 (1H, d, J = 7.9, H p-Ar); 8.05 (1H, d,
J = 7.9, H o-Ar); 8.26 (1H, s, H o'-Ar). 13C NMR spectrum, δ, ppm : 23.94 (C-3',4'); 40.32 (C-2',5');
360

89.34 (C-4); 122.14, 122.40, 125.03, 126.34, 126.87, 128.47, 129.31, 129.71, 130.75, 134.05, 135.34, 139.30,
155.30 (C-2). Mass spectrum, m/z (Irel, %): 341 [M]+ (72.7), 324 [M-OH]+ (8.1), 312 [M-C2H5]+ (73.3), 298
(4.0), 284 (10), 257 [M-C5H8O]+ (5.6), 186 (8.9), 183 [BrPhCO]+ (28.5), 178 (11.5), 151 (10.4), 143 (15.4),
130 (24.0), 77 (13.2), 76 (16.1). Found, %: C 63.25; H 4.52; Br 23.11; N 4.26. C18H16BrNO. Calculated, %:
C 63.17; H 4.71; Br 23.35; N 4.09.
2-(p-Chlorophenyl)spiro[3,1-benzoxazine-4,1'-cyclopentane] (4c). Yield 68%, colorless oil. 1H NMR
spectrum, δ, ppm (J, Hz): 1.81 and 2.23 (4H, two m, both 2H, H-2' and H-5'); 1.97 (4H, m, H-3',4'); 7.09 (2H, m,
H-5,6); 7.21 (2H, m, H-7,8); 7.32 (2H, d, J = 8.5, H o,o'-Ar); 7.97 (2H, d, J = 8.5, H m,m'-Ar). 13C NMR
spectrum, δ, ppm : 23.88 (C-3',4'); 40.23 (C-2',5'); 89.22 (C-4); 122.12, 124.91, 126.71, 128.46, 128.51, 128.64,
129.14, 129.20, 129.23, 131.74, 137.37, 139.45, 155.85 (C-2). Mass spectrum, m/z (Irel, %): 297 [M]+ (80.7),
280 [M-OH]+ (7.4), 268 [M-C2H5]+ (87.8), 240 (9.9), 284 (10.0), 213 [M-C5H8O]+ (12.1), 186 [M-PhCl]+
(3.6), 178 (12.0), 158 [M-ClPhCO]+ (100), 139 [ClPhCO]+ (61.0), 143 (5.8), 130 (16.1), 111 [PhCl]+ (21.1), 77
(8.0), 76 (10.8). Found, %: C 72.43; H 5.37; N 4.85. C18H16ClNO. Calculated, %: C 72.60; H 5.42; Cl 11.91;
N 4.70.
1
2-(p-Nitrophenyl)spiro[3,1-benzoxazine-4,1'-cyclopentane] (4d). Yield 80%, orange oil. H NMR
spectrum, δ, ppm (J, Hz): 1.85 and 2.25 (4H, two m, both 2H, H-2' and H-5'); 1.97 (4H, m, H-3',4'); 2.25 (2H, m,
H-5'); 7.0 (1H, d, J = 7.3, H-5); 7.06-7.21 (3H, H-6,7,8); 8.15 (2H, d, J = 7.2, H o.o'-Ar); 8.21 (2H, d, J = 7.2,
H m,m'-Ar). 13C NMR spectrum, δ, ppm: 26.20 (C-3',4'); 38.40 (C-2',5'); 81.21 (C-4), 121.39, 123.25, 123.90,
127.54, 128.93, 129.89, 130.72, 132.12, 136.88, 139.47, 150.57, 150.91, 160.68 (C-2). Mass spectrum, m/z (Irel,
%): 308 [M]+ (62.4), 291 [M-OH]+ (10.4), 279 [M-C2H5]+ (59.4), 278 [M-NO]+ (25.8), 249 (8.6), 224 [M-
C5H8O]+ (3.6), 178 (7.3), 158 [M-NO2PhCO]+ (100), 150 [NO2PhCO]+ (14.6), 143 (13.0), 130 (33.1), 120
[OPhCO]+ (47.2), 104 [PhCO]+ (18.2), 92 [OPh]+ (7.9), 77 (7.3), 76 (14.2). Found, %: C 70.20; H 5.13; N 9.16.
C18H16N2O3. Calculated, %: C 70.12; H 5.23; N 9.09.
1
2-(p-Methylphenyl)spiro[3,1-benzoxazine-4,1'-cyclopentane] (4e). Yield 69%, light-yellow oil. H
NMR spectrum, δ, ppm (J, Hz): 1.92 and 2.31 (4H, two m, both 2H, H-2' and H-5'); 2.07 (4H, m, H-3',4'); 2.90
(3H, s, CH3); 7.15-7.35 (6H, m, H-5,6,7,8, H m,m'-Ar); 8.02 (2H, d, J = 8.2, H o,o'-Ar). 13C NMR spectrum, δ,
ppm: 21.43 (CH3); 23.76 (C-3',4'); 39.92 (C-2',5'); 88.67 (C-4); 121.91, 124.68, 126.16, 127.75, 127.82, 128.23,
128.31, 128.64, 129.25, 130.43, 139.82, 141.47, 156.60 (C-2). Mass spectrum, m/z (Irel, %): 277 [M]+ (91.9),
246 [M-H]+ (4.8), 260 [M-OH]+ (3.4), 248 [M-C2H5]+ (100), 193 [M-C5H8O]+ (17.4), 192 (12.9), 158 [M-
COPhMe]+ (58.8), 130 (8.0), 119 [MePhCO]+ (71.4), 91 [PhMe]+ (20.4). Found, %: C 82.15; H 6.60; N 5.15.
C19H19NO. Calculated, %: C 82.28; H 6.90; N 5.05.
1
2-(o-Methoxyphenyl)spiro[3,1-benzoxazine-4,1'-cyclopentane] (4f). Yield 52%, light-yellow oil. H
NMR spectrum, δ, ppm (J, Hz): 1.79 and 2.47 (4H, two m, both 2H, H-2' and H-5'); 2.06 (4H, m, H-3',4'); 3.79
(3H, s, OCH3); 6.96 (1H, d, J = 8.3, H m-Ar); 7.01 (1H, t, J = 7.5, H m'-Ar); 7.19 (2H, m, H o,p-Ar); 7.22-7.43
(3H, m, H-5,6,7); 7.67 (1H, dd, J1 = 7.5, J2 = 1.6, H-8). 13C NMR spectrum, δ, ppm (J, Hz): 23.63 (C-3',4');
40.09 (C-2',5'); 59.23 (OCH3); 90.03 (C-4); 111.23, 120.03, 120.11, 121.74, 123.16, 124.48, 126.25, 127.96,
129.05, 130.74, 131.53, 131.91, 158.25 (C-2). Mass spectrum, m/z (Irel, %): 293 [M]+ (34.9), 292 [M-H]+ (8.4),
264 [M-C2H5]+ (35.4), 236 (6.1), 209 [M-C5H8O]+ (4.7), 208 (6.8), 180 (12.5), 159 (39.6), 158 [M-COPhMe]+
(40.5), 135 [MeOPhCO]+ (100), 130 (12.3), 92 (10.0), 77 (22.2). Found, %: C 77.49; H 6.43; N 5.00.
C19H19NO2. Calculated, %: C 77.79; H 6.53; N 4.77.
1
2-(m-Methoxyphenyl)spiro[3,1-benzoxazine-4,1'-cyclopentane] (4g). Yield 94%, light-yellow oil. H
NMR spectrum, δ, ppm (J, Hz); 1.81 and 2.24 (4H, two m, both 2H, H-2' and H-5'): 1.98 (4H, m, H-3',4'); 3.81
(3H, s, OCH3); 6.94-7.30 (7H, m, H-5,6,7, H o,o',m,p-Ar); 7.61 (1H, dd, J1 = 8.9, J2 = 1.1, H-8). 13C NMR
spectrum, δ, ppm: 23.65 (C-3'4'); 39.85 (C-2',5'); 55.09 (OCH3); 88.83 (C-4); 112.50, 117.29, 120.17, 121.90,
124.72, 126.40, 128.22, 129.06, 129.13, 134.46, 139.46, 156.47, 159.32 (C-2). Mass spectrum, m/z (Irel, %): 293
[M]+ (37.6), 292 [M-H]+ (4.9), 264 [M-C2H5]+ (38.2), 236 (5.9), 209 [M-C5H8O]+ (5.9), 208 (7.6),
361

180 (13.6), 159 (47.3), 158 [M-COPhOMe]+ (42.1), 135 [MeOPhCO]+ (100), 130 (12.9), 92 (10.3), 77 (23.0).
Found, %: C 76.95; H 6.77; N 4.61. C19H19NO2. Calculated, %: C 77.79; H 6.53; N 4.77.
2'-Bromo-2-phenylspiro[3,1-benzoxazine-4,1'-cyclopentane] Hydrobromide (5). A solution of Br2
(0.37 g, 2.3 mmol) in CCl4 (5 ml) was added dropwise with stirring to a solution of amide 3a (0.6 g, 2.3 mmol)
in CCl4 (20 ml). The reaction mixture was stirred for a further 15 min, the precipitated solid was filtered off,
washed with CCl4 (10 ml), and dried in vacuum. Product 5 (0.944 g) was obtained, and was recrystallized from
CCl4. Yield was 97%, dark-olive-colored powder, mp 160-162oC. 1H NMR spectrum, δ, ppm (J, Hz): 2.32 (2H,
m, H-4'); 2.55 (2H, m, H-5'); 2.76 (1H, m, H-3'b); 2.97 (1H, m, H-3'a); 4.51 (1H, m, H-2'); 7.50 (5H, m,
H m,m'-Ar, H p-Ar, H-6,7); 7.70 (2H, m, H o,o'-Ar); 8.70 (2H, m, H-5,8). 13C NMR spectrum, δ, ppm: 20.72
(C-4'); 34.46 (C-5'); 34.97 (C-3'); 55.70 (C-2'); 97.87 (C-1'); 120.10, 121.57, 123.21, 126.53, 128.73, 129.58,
129.78, 130.94, 131.00, 137.56, 164.75 (C-2). Found, %: C 50.89; H 4.28; Br 37.52; N 3.39. C18H17Br2NO.
Calculated, %: C 51.09; H 4.05; Br 37.77; N 3.31.
REFERENCES
1.
S. S. Mochalov and R. A. Gazzaeva, Khim. Geterotsikl. Soedin., 1123 (2003). [Chem. Heterocycl.
Comp., 39, 975 (2003)].
2.
3.
V. V. Lobodin and A. T. Lebedev, Mass Spektrom., 91 (2003).
S. S. Mochalov, R. A. Gazzaeva, A. N. Fedotov, Yu. S. Shabarov, and N. S. Zefirov, Khim. Geterotsikl.
Soedin., 922 (2003). [Chem. Heterocycl. Comp., 39, 794 (2003)].
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