664
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 4, April, 2001
Gataullin et al.
ing effect in the latter case. The 13C NMR spectroscopy
was also used to confirm either cis- or trans-configura-
tion of the double bond. In the case of trans-configura-
tion (compound 25), the signals for the C atoms of the
methyl group at C(1´) and of the methylene group shift
upfield due to the 1,2-syn-interaction: δ 21.6 and 17.2
for compound 25 and δ 22.5 and 24.6 for compound 24
(see Table 2). The other signals are in accord with the
values calculated using additive parameters.16
CH2Cl2 until the initial amide disappeared (TLC). The solvent
was evaporated in vacuo and the residue was dried in vacuo.
(α-Bromoalkyl)-3,1-benzooxazine hydrobromides 13, 14,
31, and 32. A solution of Br2 (0.1 mL, 1.9 mmol) in 5 mL of
CCl4 was added dropwise with stirring to a solution of com-
pound 5, 12,9 26, or 27 (1.86 mmol) in 20 mL of dry CCl4. The
precipitate of the hydrobromide was filtered off and washed
with 10 mL of CCl4.
Preparation of 3,1-benzooxazines 1520, 30, 33 and 34
(bases). The hydrohalide of the corresponding benzooxazine
(5 mmol) was dissolved in 50 mL of CH2Cl2 and treated with
10 mL of a 5% solution of NaHCO3. The organic phase was
washed with water (10 mL), dried with MgSO4, and concen-
trated in vacuo.
In the 13C NMR spectra of α-bromopropyl-substi-
tuted benzooxazine hydrobromides 31 and 32, the chemi-
cal shifts of the C atoms are different.
Thus, N-acylated î-(cyclopent-1-enyl)- and î-(cyclo-
hex-1-enyl)anilines or î-((E)- and (Z)-1-methylbut-1-
enyl)anilines react with HCl or Br2 to give the corre-
sponding 3,1-benzooxazine as the only product, irre-
spective of the geometry of the double bond, the size of
the ring in the alkenyl group, and the nature of the
carboxylic acid fragment in N-acylaniline.
References
1. K. R. Rajender and R. M. Satyanarayana, Synth. Commun.,
1992, 22, 2499.
2. F. A. Vassin, A. M. F. Eissa, and A. A. F. Wasfy, Ind. J.
Chem., Sec. B, 1994, 33, 1193.
3. I. V. Ukrainets, S. G. Taran, O. V. Gorokhova, P. A.
Bezuglyi, and A. V. Turov, Khimiya Geterotsikl. Soedinen.,
1994, 225 [Chem. Heterocycl. Compd., 1994, No. 2 (Engl.
Transl.)].
4. A. A. Maksimenko, P. I. Gadzhieva, and I. D. Sadekov,
Zh. Org. Khim., 1996, 32, 317 [Russ. J. Org. Chem., 1996, 32
(Engl. Transl.)].
5. Eur. Pat. 0510235.
6. US Pat. 5652237.
7. P. D. Williams, B. V. Clineschmidt, J. M. Erb, R. M.
Freidinger, M. T. Guidotti, E. V. Lis, J. M. Pawluczyk,
D. I. Pettibone, D. R. Ress, D. F. Veber, and C. J. Woyden,
J. Med. Chem., 1995, 38, 4634.
Experimental
1
H and 13C NMR spectra were recorded on a Bruker
AM-300 spectrometer operating at 300.13 and 75.47 MHz,
respectively (Må4Si was used as the internal standard), IR
spectra were measured on a UR-20 spectrometer. The purity of
the products was checked by GLC on a Chrom-5 chromato-
graph (SE-30 on Chromaton, a 1.2 m ½ 3.5 mm column, a
flame ionization detector, 12 deg min1, helium as the carrier
gas) and by TLC on Silufol UV-254 plates with CH2Cl2 (À) and
CH2Cl2MåOH, 95 : 5 (B) solvent systems.
Amines 24 and 25. The starting amine 23 13 (40 mmol) was
refluxed with solid ÊOH (150 mmol) at 300 °C for 1 h. After
cooling the reaction mixture, the liquid was decanted from the
solid ÊOH and distilled using a distillation column in vacuo.
Amides 26 and 27. Acetic anhydride (2.04 g, 20 mmol) was
added to a solution of amine 24 or 25 (10 mmol) in 10 mL of
CH2Cl2 and the mixture was left for 18 h. Then water was
added to the reaction mixture, the aqueous layer was extracted
with 100 mL of CH2Cl2, and the extract was washed with a 5%
solution of NaHCO3 until CO2 evolution ceased and with water
(20 mL) and dried with MgSO4. The solvent was evaporated to
give amide 26 or 27.
Amides 2, 3, 4, and 28. Benzoyl, chloroacetyl, methacryloyl,
or pentanoyl chloride (0.9 mmol) and Ê2CO3 (1.6 g, 12 mmol)
were added with stirring at 20 °C to a solution of amine 1 9, 6,10
or 24 (0.6 mmol) in 20 mL of dry CH2Cl2. The reaction
mixture was stirred for 1.5 h with TLC monitoring. The precipi-
tate was filtered off and washed with 10 mL of CH2Cl2. The
filtrate was washed with water and a 10% solution of NaHCO3
(2½25 mL), dried with MgSO4, and concentrated in vacuo.
N-Formyl-2-(cyclohex-1-enyl)aniline (5). Amine 6 (1 g,
5.8 mmol) was refluxed for 40 min in 10 mL of anhydrous
formic acid and excess acid was evaporated in vacuo. The residue
was twice dissolved in 5 mL of toluene with subsequent evapora-
tion of the toluene in vacuo and recrystallized from hexane.
Anilide 21. Hydrogen chloride was passed for 10 min through
a solution of amide 3 in CH2Cl2. The solvent was decanted
from the resinous precipitate and evaporated in vacuo at 30 °C.
3,1-Benzooxazine hydrochlorides 7, 8, 10, 11, 22, and 29.
Hydrogen chloride was passed through a solution of the corre-
sponding anilide 2, 4, 5, 9,10 21, or 28 (1 mmol) in 10 mL of
8. Comprehensive Organic Chemistry, Eds. D. Barton and W. D.
Ollis, Pergamon Press, OxfordNew YorkToronto
SydnayParisFrankfurt, 1979, 4.
9. R. R. Gataullin, I. S. Afon'kin, I. V. Pavlova, I. B.
Abdrakhmanov, and G. A. Tolstikov, Izv. Akad. Nauk, Ser.
Khim., 1999, 398 [Russ. Chem. Bull., 1999, 48, 396 (Engl.
Transl.)].
10. R. R. Gataullin, I. S. Afon'kin, A. A. Fatykhov, L. V.
Spirikhin, and I. B. Abdrakhmanov, Izv. Akad. Nauk, Ser.
Khim., 2000, 118 [Russ. Chem. Bull., Int. Ed., 2000, 49, 122].
11. C. Cardillo and M. Orena, Tetrahedron, 1990, 46, 3321.
12. B. I. Ionin, B. A. Ershov, and A. I. Kol'tsov, YaMR
spektroskopiya v organicheskoi khimii [NMR Spectroscopy in
Organic Chemistry], Nauka, Leningrad, 1983, 170 pp. (in
Russan).
13. I. B. Abdrakhmanov, V. M. Sharafutdinov, and G. A.
Tolstikov, Izv. Akad. Nauk SSSR, Ser. Khim., 1982, 2160
[Bull. Acad. Sci. USSR, Div. Chem. Sci., 1982, 31 (Engl.
Transl.)].
14. I. B. Abdrakhmanov, A. G. Mustafin, L. M. Khalilov, and
G. A. Tolstikov, Izv. Akad. Nauk SSSR, Ser. Khim., 1983,
2171 [Bull. Acad. Sci. USSR, Div. Chem. Sci., 1983, 32,
1964 (Engl. Transl.)].
15. A. Zschunke, Kernmagnetische Resonanzspektroskopie in der
Organischen Chemie, Academie Verlag, Berlin, 1971.
16. S. Pretch and S. Saibl, Tables of Spectral Data for Structure
Determination of Organic Compounds, Springer-Verlag, New
York, 1990, 630 pp.
Received October 7, 1999;
in revised form March 2, 2001