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Crystallography Reports, Vol. 49, No. 6, 2004, pp. 9981009. Translated from Kristallografiya, Vol. 49, No. 6, 2004, pp. 10951106. Original Russian Text Copyright © 2004 by Mazina, Rybakov, Chernyshev, Babaev, Aslanov.

STRUCTURE OF ORGANIC COMPOUNDS

X-ray Mapping in Heterocyclic Design: XIV. Tricyclic Heterocycles Based on 2-Oxo-1,2,5,6,7,8-Hexahydroquinoline-3-Carbonitrile
O. S. Mazina, V. B. Rybakov, V. V. Chernyshev, E. V. Babaev, and L. A. Aslanov
Moscow State University, Vorob'evy gory, Moscow, 119992 Russia e-mail: rybakov@biocryst.phys.msu.su
Received November 11, 2003

Abstract--The structures of four compounds are studied using single-crystal X-ray diffraction: 1-[2-(4-chlorophenyl)-2-oxoethyl]-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carbonitrile [a = 4.908(4) е, b = 11.644(10) е, c = 13.587(2) е, = 94.31(5)°, Z = 2, space group P21]; 2-[2-(4-chlorophenyl)-2-oxoethoxy]-5,6,7,8-tetrahydroquinoline-3-carbonitrile [a = 7.6142(8) е, b = 14.778(2) е, c = 14.132(2) е, = 100.38(1)°, Z = 4, space group P21/c]; 4-(aminocarbonyl)-2-(chlorophenyl)-6,7,8,9-tetrahydro[1.3]oxazolo[3,2-a]quinolin-3-ium perchlorate [a = 5.589(7) е, b = 24.724(15) е, c = 13.727(5) е, = 97.66(9)°, Z = 4, space group P21/n]; and (3amino-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-2-yl)-(4-chlorophenyl) methanone [a = 7.150(2) е, b = 7.4288(10) е, c = 15.314(3) е, = 98.030(10)°, = 99.21(2)°, = 105.34(2)°, Z = 2, space group P 1 ]. The structures are solved by direct methods and refined by the full-matrix least-squares procedure in the anisotropic approximation to R = 0.0728, 0.0439, 0.1228, and 0.0541, respectively. The structure of 1-(4-chlorophenyl)-4piperidin-1-yl-8,9-dihydro-7H-pyrrolo[3.2.1-ij]quinoline-5-carboxamide [a = 23.9895(9) е, b = 5.1557(3) е, c = 17.0959(9) е, = 106.43°, Z = 4, space group P1/c] is investigated by X-ray powder diffraction. This structure is solved using the grid search procedure and refined by the Rietveld method to Rwp = 0.0773, Rexp = 0.0540, Rp = 0.0585, Rb = 0.1107, and 2 = 1.78. © 2004 MAIK "Nauka / Interperiodica".

INTRODUCTION Readily available derivatives of 6-methyl-cyanopyridones-2 are promising substances as precursors of complex condensed heterocyclic compounds. For example, it is known that the phenacylation of these

pyridones results the formation of N and O alkylation products. It should be noted that, in alkaline media, O isomers easily enter into cyclization reactions with the formation of furo[2,3-b]pyridine derivatives, whereas N isomers are cyclized to form 5-indolizinones [1, 2] (see Scheme 1):

CH3 CN H3C N O O R H3C NC O N R H3C

CH3 CN N H O H3C

CH3 CN N O O R CH3 NH2 O H3C N O R

Scheme 1
1063-7745/04/4906-0998$26.00 © 2004 MAIK "Nauka / Interperiodica"

X-RAY MAPPING IN HETEROCYCLIC DESIGN

999

In the present work, we demonstrated that the possible heterocyclization reactions of 6-methyl-cyanopyridones-2 are not exhausted by the above processes. The
CN N I O O N

synthesis of the studied compounds was performed according to the following scheme:

CN + O IIa IIb N

CN O O

Cl O NH2 N III O
+
ClO4

Cl O NH2 NH2 O N V O

N IV Cl

N

Cl

Cl

Scheme 2

By using compound I as an example, we found one more direction of the heterocyclization of N-phenyl derivatives of the aforementioned pyridones, namely, the transformation of N isomer IIa into compound III, which, in turn, can be recyclized into the poorly investigated compound IV.

Earlier, the phenacylation of compound I was not described. We revealed that this reaction results in the formation of N and O isomers (in the ratio 1 : 1); in this case, it is possible to separate the mixture of isomers. As could be expected, compound IIb is cyclized with the formation of compound V.

Table 1. Physicochemical characteristics of the compounds synthesized Melting Compound temperature Tm, °C IIa IIb 233 247
1H

NMR* (DMSO-d6)

III

283

IV

262

V

278

8.10 and 7.69 (d, 8.3 Hz, 2H, 14-CH + 15-CH and 17-CH + 18-CH)**; 8.03 (s, 1H, 4-CH); 5.66 (s, 2H, 11-CH2); 2.57 (m, 4H, 6-CH2 + 9-CH2); 1.73 and 1.64 (m, 2H, 7-CH2 and 8-CH2)*** 8.01 and 7.64 (d, 8.6 Hz, 2H, 14-CH + 15-CH and 17-CH + 18-CH)**; 7.98 (s, 1H, 4-CH); 5.97 (s, 2H, 11-CH2); 2.66 and 2.56 (t, 5.8 Hz and 6.0 Hz, 2H, 6-CH2 and 9-CH2)***; 1.70 (m, 4H, 7-CH2 + 8-CH2) 9.52 (s, 1H, 11-CH); 8.59 (s, 1H, 4-CH), 8.32 and 8.24 (s, 1H, 31-NH2); 8.12 and 7.8 (d, 8.6 Hz, 2H, 14-CH + 15-CH and 17-CH + 18-CH)**; 3.14 and 2.98 (t, 5.9 Hz and 5.6 Hz, 2H, 6-CH2 and 9-CH2)***; 2.02 and 1.86 (m, 2H, 7-CH2 and 8-CH2)*** 7.78 and 6.41 (s, 1H, 31-NH2); 7.66 and 7.47 (d, 8.5 Hz, 2H, 17-CH + 18-CH and 14-CH + 15-CH)**; 7.53 (s, 1H, 4-CH); 6.41 (s, 1H, 11-CH); 3.17 and 3.05 (s, 2H, 19-CH2 and 23-CH2)***; 2.96 and 2.78 (t, 2H, 5.6 Hz, 8-CH2 and 6-CH2)***; 1.95 (m, 2H, 7-CH2); 1.82 and 1.70 and 1.40 (m, 6H, Pip (CH2CH2CH2)) 8.16 (s, 1H, 4-CH); 8.11 and 7.63 (d, 8.3 Hz, 2H, 14-CH + 15-CH and 17-CH + 18-CH)**; 7.56 (s, 2H, 31-NH2); 2.91 and 2.86 (t, 6.4 Hz and 6.1 Hz, 2H, 6-CH2 and 9-CH2)***; 1.82 (m, 4H, 7-CH2 + 8-CH2)

* The assignment of the signals is given in accordance with the atomic numbering used in X-ray diffraction analysis (Figs. 26). ** The reverse assignment of CH2 groups is possible. *** The reverse assignment of CH groups is possible. CRYSTALLOGRAPHY REPORTS Vol. 49 No. 6 2004

1000 3500 в7

MAZINA et al.

0

0

10

20

30

40

50

60

70 2

Fig. 1. Experimental and difference X-ray powder diffraction patterns (after the final Rietveld refinement) for structure IV.

N(31)

In this work, we did not analyze the possibility of cyclizing compound IIa into indolizine. It is known [3] that, under the action of acids, N-phenacylpyridones-2 are able to undergo cyclocondensation with the formation of bicyclic oxazolopyridinium salts. In [3], it was shown that oxazolopyridinium salts with a methyl group in the fifth position can be recyclized to form 5-substituted indolizines. In the case of compound IIa, a similar cyclization proceeds with the formation of tricyclic compound III. It is worth noting that the cyclization is accompanied by the hydrolysis of the nitrile group and the formation of the amide group in the system. Compound III also contains the methylene group in the position appropriate for recyclization. It turned out that, under the action of the secondary amine, the tricyclic system of oxazolopyridinium undergoes previously unknown recyclization into a poorly studied tricyclic system of compound IV. Note that the topological feature of the observed recyclization is the transformation of a partially hydrogenated cata-condensed tricyclic system (in which each fusion atom is shared only by two rings) into a peri-condensed system (involving the atom shared by three rings). EXPERIMENTAL

C(4) C(6) C(7) C(8) C(9) O(12) C(12) C(13) C(18) C(17) C(14) C(11) C(5) C(3) C(2) C(10) N(1) O(2)

C(31)

C(16)

C(15)

Cl(16)
Fig. 2. Molecular structure and atomic numbering for compound IIa.

Compounds IV were synthesized according to Scheme 2. Compound 2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carbonitrile (I) was prepared using the procedure described in [4] and was investigated in our previous work [5]. The physicochemical characteristics of the compounds synthesized are presented in Table 1. 1-[2-(4-Chlorophenyl)-2-oxoethyl]-2-1,2,5,6,7,8hexahydroquinoline-3-carbonitrile (IIa) and 2-[2(4-chlorophenyl)-2-oxoethoxy]-5,6,7,8-tetrahydroquinoline-3-carbonitrile (IIb). These compounds were synthesized according to a procedure similar to that proposed in [1]. Potassium hydroxide (0.0057 mol) and ethanol (5 ml) were placed in a round-bottomed flask. Compound I (0.0057 mol) was added portionwise with stirring to the prepared solution. The mixture was allowed to stand in an ultrasonic bath for 40 min, and then the alcohol was evaporated with a rotary evaporator. Dimethylformamide (10 ml) and phenacyl bromide (0.0057 mol) were added to the dry residue. The mixture was allowed to stand at an elevated temperature (T ~ 50°C) for 18 h with stirring. After completing the reaction (controlled by thin-layer chromatography indicating the absence of compound I), the reaction mixture was cooled and poured into water. The precipitate was filtered off and dried in air. The mixture of N and O isomers was separated using a column (sorbent, SiO2; chloroform : hexane = 1 : 1). The yields of compounds IIa and IIb were equal to 43 and 47%, respectively. 4-(Aminocarbonyl)-2-(chlorophenyl)-6,7,8,9-tetrahydro[1.3]oxazolo[3,2-a]quinolin-3-ium perchlorate (III). Compound III was prepared from comCRYSTALLOGRAPHY REPORTS Vol. 49 No. 6 2004

X-RAY MAPPING IN HETEROCYCLIC DESIGN Table 2. Crystal data, data collection, and refinement parameters for structures IIa, IIb, III, IV, and V Empirical formula Molecular weight Crystal system Space group a, е b, е c, е , deg , deg , deg V, е3 Z calcd, g/cm3 cm1 µ(CuK), 774.3(10) 2 1.401 2.28 3.26-54.98 0.3 в 0.3 в 0.3 1576 1433 (Rint = 0.074) 209 0.0728/0.1399 0.233/ 0.180 1564.2(4) 4 1.388 2.26 4.37-69.97 0.3 в 0.3 в 0.3 3083 2958 (Rint = 0.028) 209 0.0439/0.1099 0.175/ 0.256 1881(3) 4 1.508 3.46 3.58-49.97 0.3 в 0.3 в 0.3 2030 1936 (Rint = 0.244) 254 0.1228/0.2983 0.776/ 0.518 0.0773 0.0540 0.0585 0.1107 1.78 2028.18(2) 4 1.290 1.80 1.92-35.00 Powder 94.31(5) 100.38(1) 97.66(9) 106.43(3) C18H15ClN2O2 (IIa) 326.79 Monoclinic P2
1

1001

C18H15ClN2O (IIb) 326.79 Monoclinic P21/c 7.6142(8) 14.778(2) 14.132(2)

2

C18H16ClN2O2 · ClO4 (III) 427.24 Monoclinic P21/n 5.589(7) 24.724(15) 13.727(5)

C23H24ClN3 (IV) 393.92 Monoclinic P21/c 23.9895(9) 5.1557(3) 17.0959(9)

C18H15ClN2O2 (V) 326.79 Triclinic P1 7.150(2) 7.4288(10) 15.314(3) 98.030(10) 99.21(2) 105.34(2) 760.0(3) 2 1.428 2.32 2.98-69.92 0.3 в 0.3 в 0.3 2900 2791 (Rint = 0.079) 217 0.0541/0.1379 0.597/ 0.531

4.908(4) 11.644(10) 13.587(8)

range, deg Crystal size, mm Number of reflections measured Number of unique reflections Number of reflections refined R factor [I 2(I)] R1/wR2 max/min, Rwp Rexp Rp Rb 2 e/е3

pound IIa according to a procedure similar to that described in [3]. Compound IIa (1 g) was dissolved in 96% H2SO4 (2 ml) and left to stand for a night. 70% HClO4 (5 ml) was added to water (50 ml), and the H2SO4 mixture was poured into the prepared solution. The precipitate was filtered off, washed on a filter with water, and dried. The yield of compound III was 98%. 1-(4-Chlorophenyl)-4-piperidin-1-yl-8,9-dihydro7H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide (IV). This compound was synthesized according to a procedure similar to that described in [3]. Compound III (0.5 g) and piperidine (5 ml) were boiled in acetonitrile (15 ml) to the formation of a yellowish green thick solution. The solution was poured into water, and the precipitate was filtered off and recrystallized from acetonitrile. The yield of compound IV was 87%.
CRYSTALLOGRAPHY REPORTS Vol. 49 No. 6 2004

Table 3. Selected bond lengths d (е) in structure IIa Bond N(1)C(2) N(1)C(10) N(1)C(11) C(2)O(2) C(2)C(3) C(3)C(4) C(3)C(31) C(4)C(5) C(5)C(10) C(5)C(6) d 1.355(19) 1.41(2) 1.472(18) 1.21(2) 1.44(2) 1.361(11) 1.43(2) 1.499(11) 1.38(2) 1.482(19) Bond C(6)C(7) C(7)C(8) C(8)C(9) C(9)C(10) C(11)C(12) C(12)O(12) C(12)C(13) Cl(16)C(16) C(31)N(31) d 1.50(2) 1.36(2) 1.48(2) 1.479(18) 1.499(18) 1.168(17) 1.55(2) 1.781(17) 1.13(2)

1002 C(6) C(5) C(4) C(3) O(2) C(11) N(31) C(31) C(8) C(9) C(10) N(1) C(2)

MAZINA et al.
O(31) C(6) C(5) C(4) C(3) C(2) C(9) C(10) N(1) C(11) C(13) C(18) C(16) O(2) C(12) C(14) C(15) C(31) N(31)

C(7)

O(12)

O(14)

C(7) C(8)

Cl(1) O(12) C(12) C(13) C(14) O(11) O(13)

C(17) Cl(16)

C(18) C(17)

C(15) C(16) Cl(16)

Fig. 4. Molecular structure and atomic numbering for compound III.

Fig. 3. Molecular structure and atomic numbering for compound IIb.

(3-Amino-5,6,7,8-tetrahydrofuro[2,3-b]quinolin2-yl)-(4-chlorophenyl)-methanone (V). Compound V was prepared using a procedure similar to that proposed by Gewald [1]. Compound IIb was boiled in absolute methanol with a threefold excess of sodium methylate for 16 h. The precipitate was filtered off, washed on a filter with methanol, and dried. The yield of compound V was 68%.
Table 4. Selected bond angles (deg) in structure IIa Angle C(2)N(1)C(10) C(2)N(1)C(11) C(10)N(1)C(11) O(2)C(2)N(1) O(2)C(2)C(3) N(1)C(2)C(3) C(4)C(3)C(31) C(4)C(3)C(2) C(31)C(3)C(2) C(3)C(4)C(5) C(10)C(5)C(4) C(10)C(5)C(6) C(4)C(5)C(6) C(5)C(6)C(7) 123.7(16) 114.6(16) 121.7(15) 122(2) 122(2) 115.8(18) 118.7(19) 122.4(16) 118.9(19) 119.7(16) 119.7(17) 120.3(15) 120.0(17) 107.6(14)

The experimental intensities of diffraction reflections for single crystals of compounds IIa, IIb, III, and V were measured on a CAD4 automated diffractometer [6] (CuK radiation, graphite monochromator, scan mode) at room temperature. The unit cell parameters were determined and refined using 25 reflections in the ranges 24°26.5°, 30°35°, 21°25°, and 25°29°, respectively. No correction for absorption was introduced because of the small linear absorption coefficients of the compounds studied and the small sizes of their crystals. The primary processing of the sets of diffraction data was performed with the WinGX program package [7]. All the subsequent calculations were carried out with the SHELX97 program package [8]. The

Angle C(8)C(7)C(6) C(7)C(8)C(9) C(10)C(9)C(8) C(5)C(10)N(1) C(5)C(10)C(9) N(1)C(10)C(9) N(1)C(11)C(12) O(12)C(12)C(11) O(12)C(12)C(13) C(11)C(12)C(13) C(17)C(16)Cl(16) C(15)C(16)Cl(16) N(31)C(31)C(3)

121(2) 118.8(18) 112.5(16) 118.6(14) 124.5(19) 116.8(17) 111.0(10) 121.8(16) 127.3(16) 110.9(17) 122.4(16) 113.6(19) 179(3)

CRYSTALLOGRAPHY REPORTS

Vol. 49

No. 6

2004

X-RAY MAPPING IN HETEROCYCLIC DESIGN Table 5. Selected bond lengths d (е) in structure IIb Bond N(1)C(2) N(1)C(10) C(2)O(2) C(2)C(3) O(2)C(11) C(3)C(4) C(3)C(31) C(31)N(31) C(4)C(5) C(5)C(10) d 1.312(2) 1.353(2) 1.350(2) 1.409(2) 1.426(2) 1.375(3) 1.436(3) 1.136(3) 1.390(3) 1.394(2) Bond C(5)C(6) C(6)C(7) C(7)C(8) C(8)C(9) C(9)C(10) C(11)C(12) C(12)O(12) C(12)C(13) C(16)Cl(16) d 1.505(3) 1.514(3) 1.508(3) 1.524(3) 1.502(3) 1.499(3) 1.211(2) 1.488(3) 1.739(2)

1003

For compound III, the R factor is rather large due to the low quality of crystals. The diffraction experiments for compound IV (available only in the form of a finely crystalline powder) were performed on a DRON-3 automated powder diffractometer (NPO Burevestnik) (CuK radiation; Ge monochromator; step width, 0.02° in 2) at room temperature. The unit cell parameters were determined with the ITO indexing program [9]. Preliminary information on the molecular structure of compound IV was obtained from the NMR spectroscopic data. The initial geometrical model was constructed using semiempirical and empirical methods with the MOPAC 6.0 [10] and PCMODEL [11] programs. The structure was solved by the grid search procedure [12] based on the preassigned molecular fragments. The Rietveld fullprofile refinement of the structure was carried out according to the MRIA program [13]. The pseudoVoigt function was used as a profile function, and the background was approximated by Chebyshev fifthdegree polynomials. The thermal parameters of the non-hydrogen atoms of the molecular skeleton were averaged in the course of refinement. The hydrogen atoms were placed at calculated positions. The experimental and difference X-ray powder diffraction patterns after the final refinement are shown in Fig. 1. The tick marks indicate the calculated positions of reflections. The main parameters of the X-ray diffraction experiments and crystal data for compounds IIa, IIb, III, IV, and V are summarized in Table 2. The spatial arrangement of atoms in molecules and their numbering are depicted in Figs. 26 obtained with the ORTEP-3 graphic program package [14, 15]. The interatomic dis-

crystal structures were determined by direct methods. The positional and thermal parameters for all the nonhydrogen atoms were refined in the anisotropic approximation. The hydrogen atoms, except for the hydrogen atoms involved in the formation of hydrogen bonds, were located from geometric considerations and refined as riding atoms together with the corresponding carbon atoms. The thermal parameters of these hydrogen atoms were calculated from those of the carbon atoms [Uiso(H) = 1.2Ueq(C) for the aromatic hydrogen atoms and Uiso(H) = 1.5Ueq(C) for the aliphatic hydrogen atoms]. The hydrogen atoms involved in the formation of hydrogen bonds were located from electron-density difference syntheses and independently refined in the isotropic approximation.
Table 6. Selected bond angles (deg) in structure IIb Angle C(2)N(1)C(10) N(1)C(2)O(2) N(1)C(2)C(3) O(2)C(2)C(3) C(2)O(2)C(11) C(4)C(3)C(2) C(4)C(3)C(31) C(2)C(3)C(31) N(31)C(31)C(3) C(3)C(4)C(5) C(4)C(5)C(10) C(4)C(5)C(6) C(10)C(5)C(6)
CRYSTALLOGRAPHY REPORTS

118.20(16) 121.31(16) 123.41(17) 115.28(16) 117.73(14) 117.49(17) 121.24(17) 121.25(17) 177.7(2) 120.65(17) 117.12(17) 120.19(17) 122.67(17)
Vol. 49 No. 6 2004

Angle C(5)C(6)C(7) C(8)C(7)C(6) C(7)C(8)C(9) C(10)C(9)C(8) N(1)C(10)C(5) N(1)C(10)C(9) C(5)C(10)C(9) O(2)C(11)C(12) O(12)C(12)C(13) O(12)C(12)C(11) C(13)C(12)C(11) C(15)C(16)Cl(16) C(17)C(16)Cl(16)

112.84(17) 110.87(18) 111.29(18) 113.22(17) 123.10(17) 115.89(16) 121.02(17) 107.73(15) 120.78(18) 120.60(18) 118.61(16) 119.27(17) 119.49(18)

1004 Table 7. Selected bond lengths d (е) in structure III Bond N(1)C(11) N(1)C(10) N(1)C(2) C(2)O(2) C(2)C(3) O(2)C(12) d 1.390(15) 1.367(16) 1.371(16) 1.361(15) 1.374(18) 1.388(15) Bond C(3)C(4) C(3)C(31) C(31)O(31) C(31)N(31) C(4)C(5) C(5)C(10) d

MAZINA et al.

Bond C(5)C(6) C(6)C(7) C(7)C(8) C(8)C(9) C(9)C(10) C(11)C(12)

d 1.501(18) 1.48(2) 1.51(2) 1.534(18) 1.464(18) 1.343(18)

Bond C(12)C(13) C(16)C(16) Cl(1)O(14) Cl(1)O(11) Cl(1)O(12) Cl(1)O(13)

d 1.459(18) 1.710(15) 1.3644(14) 1.3648(12) 1.3650(13) 1.365(2)

1.381(18) 1.540(19) 1.198(15) 1.330(18) 1.392(18) 1.367(18)

tances and bond angles in the structures are presented in Tables 312. The crystal data for the structures studied (CIF files) have been deposited with the Cambridge Structural Database (deposits CCDC nos. 24-984124-9845). RESULTS AND DISCUSSION In structure IIa (Fig. 2), the O(2), C(6), C(9), C(31), and N(31) atoms lie in the plane of the six-membered heterocycle, whereas the C(7) and C(8) atoms in the cyclohexene fragment deviate from its plane by 0.58 and 0.21 е, respectively. The n-chlorobenzoyl group of the molecule is nearly perpendicular to the plane of the heterocyclic fragment of the molecule: the corresponding dihedral angle between the planes is equal to 78.76(1)°. The C(7)C(8) distance (Table 3) is considerably shorter than the distances between the other atoms forming the six-membered aliphatic ring due to strong anisotropy of thermal vibrations of these atoms. However, by introducing the correction for anisotropy of thermal vibrations [16], this distance (1.61 е) can be considered to correspond to the CC single bond between sp3-hybridized carbon atoms. A comparison of the C(3)C(4)C(5)C(10) fragment with a similar fragment in the 2-oxo-1,2,5,6,7,8hexahydroquinoline-3-carbonitrile molecule [5] indicates a quasi-diene character of the fragments under
O NH2 O N
+

consideration and a similar structure of the bicyclic fragments of the studied compounds. In molecule IIb (Fig. 3), the C(6), C(9), O(2), C(31), and N(31) atoms lie in the plane of the pyridine ring, whereas the C(7) and C(8) atoms of the cyclohexene fragment deviate from the ring plane by 0.35 and 0.39 е, respectively. The dihedral angle between the planes of the heterocyclic fragment and the benzoyl group of the molecule is equal to 2.75(7)°; i.e., the phenacyloxy group virtually lies in the plane of the heterocyclic fragment. In structure III (Fig. 4), the C(6) and C(9) atoms lie in the plane of the oxazolopyridine bicycle, and the C(7) and C(8) atoms deviate from the plane by 0.53 and 0.24 е, respectively. The C(31)O(31)N(31)H(31A)H(31B) amide group is rotated with respect to the plane of the bicycle by 18.83° and forms the intramolecular hydrogen bond with the O(2) atom. The hydrogen atoms of the amide group and the oxygen atoms of the perchlorate anion are involved in the formation of the intermolecular hydrogen bonds N(31)H(31A)···O(12) and N(31) H(31B)···O(13), which link molecules into chains. The parameters of the hydrogen bonds are listed in Table 13, and their spatial arrangement is shown in Fig. 7. The dihedral angle between the planes of the heterocyclic and phenyl rings is equal to 5.3(7)°. The structure of the oxazolopyridinium cation can be represented by three resonance structures (see Scheme 3):
O NH2 O+ Cl N C Cl

O

NH2 O

Cl

N

+

A

B Scheme 3

The bond lengths in the C(3)C(4)C(5)C(10) fragment (Table 7) indicate its quasi-diene structure.

Consequently, the resonance form A should make the least contribution and the structure of the molecule
CRYSTALLOGRAPHY REPORTS Vol. 49 No. 6 2004

X-RAY MAPPING IN HETEROCYCLIC DESIGN Table 8. Selected bond angles (deg) in structure III Angle C(11)N(1)C(10) C(11)N(1)C(2) C(10)N(1)C(2) O(2)C(2)C(3) O(2)C(2)N(1) C(3)C(2)N(1) C(2)O(2)C(12) C(4)C(3)C(2) C(4)C(3)C(31) C(2)C(3)C(31) O(31)C(31)N(31) O(31)C(31)C(3) N(31)C(31)C(3) C(3)C(4)C(5) C(10)C(5)C(4) C(10)C(5)C(6) C(4)C(5)C(6) C(7)C(6)C(5) 129.9(11) 106.7(10) 123.3(11) 129.4(12) 109.3(10) 121.3(12) 106.8(10) 115.3(12) 119.5(12) 125.0(12) 126.0(13) 117.7(13) 116.1(12) 123.2(12) 120.2(11) 118.6(13) 121.1(12) 113.2(12) Angle C(6)C(7)C(8) C(7)C(8)C(9) C(10)C(9)C(8) C(5)C(10)N(1) C(5)C(10)C(9) N(1)C(10)C(9) C(12)C(11)N(1) C(11)C(12)O(2) C(11)C(12)C(13) O(2)C(12)C(13) C(17)C(16)Cl(16) C(15)C(16)Cl(16) O(14)Cl(1)O(11) O(14)Cl(1)O(12) O(11)Cl(1)O(12) O(14)Cl(1)O(13) O(11)Cl(1)O(13) O(12)Cl(1)O(13) 111.2(13) 110.7(12) 112.2(11) 116.4(12) 126.4(11) 117.1(12) 108.3(11) 108.9(11) 133.8(13) 117.3(12) 119.0(14) 120.7(14) 109.51(10) 109.49(11) 109.46(9) 109.48(10) 109.46(11) 109.44(9)

1005

Table 9. Selected bond lengths d (е) in structure IV Bond N(1)C(11) N(1)C(10) N(1)C(2) C(2)C(3) C(2)N(2) C(3)C(4) C(3)C(31) d 1.379(4) 1.395(4) 1.461(4) 1.390(5) 1.442(4) 1.458(5) 1.506(4) Bond C(31)O(31) C(31)N(31) N(31)H(31A) N(31)H(31B) C(4)C(5) C(5)C(6) C(5)C(10) d 1.226(4) 1.376(5) 0.86 0.86 1.390(8) 1.456(6) 1.478(8) Bond C(6)C(7) C(7)C(8) C(8)C(9) C(9)C(10) C(9)C(12) C(11)C(12) C(12)C(13) d 1.465(4) 1.500(5) 1.488(4) 1.372(5) 1.431(4) 1.380(4) 1.486(5) Bond C(16)Cl(16) C(19)C(20) C(19)N(2) C(20)C(21) C(21)C(22) C(22)C(23) C(23)N(2) d 1.736(4) 1.469(4) 1.523(4) 1.480(4) 1.538(3) 1.516(3) 1.482(4)

under investigation is more adequately described by a superposition of resonance forms B and C (see Scheme 4):
O NH2 O N
+

Cl

Scheme 4
CRYSTALLOGRAPHY REPORTS Vol. 49 No. 6 2004

One more structural feature of molecule III is that the N(1)C(10) bond is shortened compared to the C-N single bond. This feature can be associated with the conjugation of a lone electron pair of the bridging nitrogen atom with the exocyclic amide group through the diene fragment. In molecule IV (Fig. 5), the C(31), C(13), and N(2) atoms lie in the plane of the cycloannelated tricyclic fragment. The amide group of the molecule is rotated with respect to this plane through 57.3(1)°. It can be seen from Table 9 that, in the indolizine fragment of the molecule, the formally single CC

1006

MAZINA et al.

Table 10. Selected bond angles (deg) in structure IV Angle C(11)N(1)C(10) C(11)N(1)C(2) C(10)N(1)C(2) C(3)C(2)N(2) C(3)C(2)N(1) N(2)C(2)N(1) C(2)C(3)C(4) C(2)C(3)C(31) C(4)C(3)C(31) O(31)C(31)N(31) O(31)C(31)C(3) N(31)C(31)C(3) C(5)C(4)C(3) C(4)C(5)C(6) C(4)C(5)C(10) C(6)C(5)C(10) C(5)C(6)C(7) C(6)C(7)C(8) C(9)C(8)C(7) C(10)C(9)C(12) 105.6(2) 134.1(2) 120.2(3) 133.3(3) 116.7(3) 109.5(3) 122.6(3) 125.8(3) 111.5(3) 120.6(3) 120.7(3) 118.0(3) 122.0(5) 131.1(6) 115.1(5) 113.9(5) 121.6(4) 122.1(3) 113.5(3) 106.5(3) Angle C(10)C(9)C(8) C(12)C(9)C(8) C(9)C(10)N(1) C(9)C(10)C(5) N(1)C(10)C(5) N(1)C(11)C(12) C(11)C(12)C(9) C(11)C(12)C(13) C(9)C(12)C(13) C(17)C(16)Cl(16) C(15)C(16)Cl(16) C(20)C(19)N(2) C(19)C(20)C(21) C(20)C(21)C(22) C(23)C(22)C(21) N(2)C(23)C(22) C(2)N(2)C(23) C(2)N(2)C(19) C(23)N(2)C(19) 122.1(3) 131.4(3) 110.6(3) 126.1(4) 123.3(4) 110.7(3) 106.3(3) 125.4(3) 127.8(2) 120.3(12) 120.2(3) 112.7(3) 108.6(3) 110.7(2) 112.5(2) 113.4(2) 132.1(2) 110.3(2) 114.5(2)

Table 11. Selected bond lengths d (е) in structure V Bond N(1)C(2) N(1)C(10) C(2)O(2) C(2)C(3) C(3)C(4) C(3)C(31) d 1.334(6) 1.346(6) 1.355(5) 1.388(6) 1.389(6) 1.435(7) Bond C(4)C(5) C(5)C(10) C(5)C(6) C(6)C(7) C(7)C(8) C(8)C(9) d 1.392(7) 1.399(6) 1.507(6) 1.469(9) 1.429(10) 1.507(7) Bond C(9)C(10) C(11)C(31) C(11)C(12) C(11)O(2) C(12)O(12) d 1.512(7) 1.389(6) 1.415(7) 1.416(6) 1.255(6) Bond C(12)C(13) C(16)Cl(16) C(31)N(31) N(31)H(31A) N(31)H(31B) d 1.496(6) 1.729(5) 1.345(7) 0.95(7) 0.79(6)

bonds are substantially shortened and the formally double CC bonds are significantly lengthened. However, it is possible to distinguish the bond chain [C(2) C(3), C(4)C(5), C(9)C(10), C(11)C(12) bonds]

that corresponds to a tetraene structure typical of indolizine. The piperidine fragment of the molecule adopts a chair conformation: the plane passes through the C(19),
CRYSTALLOGRAPHY REPORTS Vol. 49 No. 6 2004

X-RAY MAPPING IN HETEROCYCLIC DESIGN Table 12. Selected bond angles (deg) in structure V Angle C(2)N(1)C(10) N(1)C(2)O(2) N(1)C(2)C(3) O(2)C(2)C(3) C(2)C(3)C(4) C(2)C(3)C(31) C(4)C(3)C(31) C(3)C(4)C(5) C(4)C(5)C(10) C(4)C(5)C(6) C(10)C(5)C(6) C(7)C(6)C(5) C(8)C(7)C(6) C(7)C(8)C(9) C(8)C(9)C(10) N(1)C(10)C(5) N(1)C(10)C(9) 114.4(4) 121.3(4) 126.7(4) 112.0(4) 117.4(5) 106.0(4) 136.5(5) 118.4(4) 118.6(4) 119.9(4) 121.4(4) 114.0(4) 117.7(7) 115.5(6) 115.1(5) 124.4(5) 114.7(4) Angle C(5)C(10)C(9) C(31)C(11)C(12) C(31)C(11)O(2) C(12)C(11)O(2) O(12)C(12)C(11) O(12)C(12)C(13) C(11)C(12)C(13) C(17)C(16)Cl(16) C(15)C(16)Cl(16) C(2)O(2)C(11) N(31)C(31)C(11) N(31)C(31)C(3) C(11)C(31)C(3) C(31)N(31)H(31A) C(31)N(31)H(31B) H(31A)N(31)H(31B) 120.8(4) 126.7(4) 109.9(4) 123.2(4) 117.4(4) 118.6(4) 124.0(5) 118.9(4) 120.0(4) 105.6(3) 126.2(5) 127.5(4) 106.3(4) 118(4) 123(5) 119(7)

1007

Table 13. Parameters of interatomic contacts in the studied structures DH d(DH) d(H···A) DHA III N(31)H(31A) N(31)H(31B) N(31)H(31B) 0.86(1) 0.86(1) 0.86(1) 2.06(1) 2.24(1) 2.54(1) 164.6(8) 130.9(7) 120.9(7) IV N(31)H(31A) N(31)H(31B) 0.86 0.86 2.22 2.13 138 159 V N(31)H(31A) N(31)H(31B) 0.95(7) 0.79(6) 2.10(7) 2.47(7)
Vol. 49 No. 6

d(D···A)

A

2.90(2) 2.87(2) 3.07(2)

O(12) [x + 3/2, y + 1/2, z + 3/2] O(2) O(13) [x + 1/2, y + 1/2, z + 3/2]

2.92 2.95

O(31) [x + 1, y + 1, z] O(31) [x, y 1, z]

124(5) 150(6)
2004

2.750(7) 3.176(7)

O(12) N(1) [x + 1, y, z]

CRYSTALLOGRAPHY REPORTS

1008 N(31) C(4) C(3) C(31) C(10) C(9) C(12) C(18) C(13) C(14) C(17) C(15) C(16) Cl(16) N(1) C(2) C(19)

MAZINA et al. N(31) C(4) C(31) C(3)

C(6) C(5) C(7) C(8)

O(31) C(7)

C(6) C(5)

O(2) C(12) C(13)

C(11) C(20) C(21) C(8) C(10) C(9) N(1) C(2) O(2) C(18) C(17)

C(14)

N(2) C(11) C(23)

C(15) C(16) Cl(16)

C(22)

Fig. 6. Molecular structure and atomic numbering for compound V.

Fig. 5. Molecular structure and atomic numbering for compound IV.
H(31B) H(31A) N(31) C(31)

Cl(1)
O(31)

H(31A) N(31) O(2) H(31B)

O(12)

O(13) Cl(1)

Fig. 8. Spatial arrangement of hydrogen bonds in structure IV.

O(12) H(31A) N(31) H(31B) O(2)

The amide group of the molecule forms a system of hydrogen bonds in which the hydrogen atoms of the NH2 group simultaneously interact with the oxygen atoms of the amide fragments of two different molecules. The parameters of the hydrogen bonds are presented in Table 13, and their spatial arrangement is given in Fig. 8. In molecule V, the C(6) and C(9) atoms and the exocyclic amine group are located in the plane of the heterocyclic bicycle, whereas the C(7) and C(8) atoms deviate from this plane by 0.28 and 0.23 е, respectively. As in molecule IIa, the C(7)C(8) distance is shortened as a result of strong anisotropy of thermal vibrations of these atoms. However, taking into account the correction for anisotropy of thermal vibrations [16], this distance corresponds to the CC single bond between the sp3-hybridized carbon atoms. The dihedral angle between the planes of the phenyl ring and the heterocyclic bicycle is equal to 20.0(2)°. This suggests a weak conjugation of the phenyl ring with the heterocyclic fragment. The hydrogen atoms of the amino group and the nitrogen atom of the pyridine ring of the molecule form
CRYSTALLOGRAPHY REPORTS Vol. 49 No. 6 2004

Fig. 7. Spatial arrangement of hydrogen bonds in structure III.

C(20), C(22), and C(23) atoms, and the C(21) and N(2) atoms deviate from the plane by 0.70 and 0.47 е, respectively. The piperidine ring is rotated with respect to the plane of the heterocyclic fragment by 58.3(1)°. The plane of the phenyl ring is rotated with respect to the plane of the heterocyclic fragment by 17.6(5)°.

X-RAY MAPPING IN HETEROCYCLIC DESIGN

1009

ACKNOWLEDGMENTS This work was supported by the Russian Foundation for Basic Research, project no. 04-03-32823a. We also acknowledge the support of the Russian Foundation for Basic Research in the payment of the license for using the Cambridge Structural Database, project no. 02-0790322.
N(1)

REFERENCES
H(31B) N(31) C(31) O(12) C(12) N(1) H(31B) N(31) C(31) C(12) H(31A)

H(31A)

Fig. 9. Spatial arrangement of hydrogen bonds in structure V.

intermolecular hydrogen bonds that link molecules into chains. The amino group also participates in the formation of the N(31)H(31A)O(12) intramolecular hydrogen bond and is responsible for the planar structure of the N(31)H2C(31)=C(11)C(12)=O(12) fragment with the maximum deviation (by 0.03 е) from the plane. The parameters of the hydrogen bonds are listed in Table 13, and their spatial arrangement is shown in Fig. 9.

1. K. Gewald, J. Prakt. Chem. 318, 313 (1976). 2. C.-F. Lin, Y.-F. Lin, Y.-C. Lo, et al., Heterocycles 53, 15 (2000). 3. E. V. Babaev, A. V. Efimov, D. A. Maiboroda, and K. Jug, Eur. J. Org. Chem., 193 (1998). 4. J. B. Paine, J. Heterocycl. Chem. 24, 351 (1987). 5. D. V. Al'bov, O. S. Mazina, V. B. Rybakov, E. V. Babaev, V. V. Chernyshev, and L. A. Aslanov, Kristallografiya 49 (2), 208 (2004) [Crystallogr. Rep. 49, 158 (2004)]. 6. EnrafNonius CAD4 Software: Version 5.0 (EnrafNonius, Delft, Netherlands, 1989). 7. L. J. Farrugia, WinGX: X-ray Crystallographic Programs for Windows (Univ. of Glasgow, UK, 2003). 8. G. M. Sheldrick, SHELX97: Program for the Solution and Refinement of Crystal Structures (Univ. of GЖttingen, Germany, 1997). 9. J. W. Visser, J. Appl. Crystallogr. 2, 80 (1969). 10. J. J. P. Stewart, MOPAC 6.0: QCPE Program No. 455 (Department of Chemistry, Indiana Univ., Bloomington, USA, 1990). 11. PCMODEL 7.0: Molecular Modelling Software for the Windows 95/NT. Sarena Software (Bloomington, USA, 1999). 12. V. V. Chernyshev and H. Schenk, Z. Kristallogr. 213, 1 (1998). 13. V. B. Zlokazov and V. V. Chernyshev, J. Appl. Crystallogr. 25, 447 (1992). 14. M. N. Burnett and C. K. Johnson, ORTEP. Report ORNL 6895 (Oak Ridge National Laboratory, Tennessee, USA, 1996). 15. L. J. Farrugia, ORTEP-3 for Windows (Univ. of Glasgow, UK, 2003). 16. W. R. Busing and H. A. Levy, Acta Crystallogr. 17, 142 (1964).

Translated by O. Borovik-Romanova

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No. 6

2004