- Email: [email protected]
A structural study of pyrazole-1-carboxamides by X-ray crystallography and 13C CPMAS NMR spectroscopy
Journal of Molecular Structure 478 (1999) 81–91
A structural study of pyrazole-1-carboxamides by X-ray crystallography and 13C CPMAS NMR spectroscopy Antonio L Llamas-Saiz a,*, Concepcio´n Foces-Foces a, Isabel Sobrados b, Nadine Jagerovic c, Jose´ Elguero c a
Departamento de Cristalografia, Instituto de Quı´mica-Fı´sica Rocasolano, CSIC, Serrano 119, E-28006 Madrid, Spain b Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, E-28049 Madrid, Spain c Instituto de Quı´mica Me´dica, CSIC, Juan de Cierva, 3, E-28006 Madrid, Spain Received 27 July 1998; received in revised form 28 September 1998; accepted 28 September 1998
Abstract The crystal structures of the first two pyrazole N-substituted primary amides (3-methyl and 4-bromo) were determined. The amide groups from the R22 (8) hydrogen-bond dimeric pattern in all cases, in accordance with the higher rate found for the formation of this pattern in monosubstituted benzamides (81%) compared with the whole group of primary amide structures (34%). These two compounds and four other N-CONH2 pyrazoles were studied by solid state NMR (CPMAS technique). 䉷 1999 Elsevier Science B.V. All rights reserved. Keywords: Hydrogen bonding; Pyrazoles; X-Ray crystallography; 13C CPMAS NMR
1. Introduction 1H-Pyrazole-1-carboxamides 1 are a class of compounds belonging to the family of azolides 2 [1], which in spite of having been studied through the last century [1–9], their molecular structures have never been determined, not even for the simplest and most common case where R4yR5y-H. The only related structure is that of compound 3 (Cambridge Structural Database [10], CSD hereinafter, refcode:FAGRUA). Regarding the structural aspects of pyrazolecarboxamides, it was established that the CONHR4 group (R5yH) can migrate between positions 1 and 2, the
* Corresponding author.
mechanism involving a dissociation-recombination of pyrazole and isocyanate (OyCyN–R4) [4,7]. Scheme 1 The other relevant structural data is related to the rotational isomerism about the C(O)– NH2 group (R4yR5yH) which was estimated to be 16 kcal mol ⫺1 which corresponds to a typical amide group [5]; moreover, it was established by 1 H NMR, for both 1 and 2, that the oxygen atom is situated anti with regard to the N2 lone pair [5]. Scheme 2 Finally, the 13C NMR spectra in DMSO–d6 solution was determined for a series of pyrazoles bearing at position 1 a CONH2 group 4–9. The most relevant conclusion for the present work is that all these compounds have very similar conformations in solution [8].
0022-2860/99/$ - see front matter 䉷 1999 Elsevier Science B.V. All rights reserved. PII: S0022-286 0(98)00658-9
82
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
2. Experimental Chemistry: The six compounds discussed in the present work were described previously by one of us [4]. In the case of 3(5)-methylpyrazole-1-carboxamide, the synthesis lead to two possible isomers 4 (3-methyl) and 4 0 (5-methyl) but it was established
that the 5-methyl isomer 4 0 isomerizes thermally to the 3-methyl one 4 [4,6]. The compound studied in this work is the most stable isomer, 4. X-Ray structure determination: Details of data collection and refinement procedure for 4 and 7 are gathered in Table 1. Both samples were enclosed in Lindemann capillaries to prevent decomposition. As the extremely anisotropic unit cell dimensions of 7, the orientation matrix had to be carefully refined in order to predict the reciprocal lattice directions with enough accuracy for data collection (mainly at high resolution angles and along the largest reciprocal axis vector). To achieve this, an appropriate set of reflections was chosen, containing 24 reflections evenly distributed through the reciprocal space. The structures were solved by direct methods using the SIR92 program [12] and refined by full matrix least squares procedures on Fo using the XTAL 3.2 System [13]. The hydrogen atoms were located in the difference Fourier synthesis and were included in the refinement
Scheme 1.
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
83
Scheme 2.
as isotropic, although the thermal factor of all of them had to be kept fixed for 7. The weighting scheme was obtained (PESOS [14]) in an empirical way as to give no trends in 具wD 2Fo典 vs. 具Fo典 or 具sin u/l典. The atomic scattering factors were taken from the International Tables for X-Ray Crystallography, [15]. The final atomic coordinates and equivalent displacement parameters for 4 and 7 are reported in Table 2. Crystallographic data (excluding structure factors) for the structures reported in this article was deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-111913 and CCDC-111914. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: int. code ⫹ (1223)-336-033, e-mail: [email protected]). Solid state NMR spectroscopy. The 13C CPMAS NMR spectra were recorded at 100 MHz with the spectrometer and the conditions used in previous publications [16,17].
3. Results and discussion 3.1. Molecular structure Selected geometrical parameters [18] for 4 and 7 are reported in Table 3 according to the numbering scheme displayed in Fig. 1. The three crystallographically independent molecules in 4 (4A, 4B and 4C hereinafter) are not significantly different in terms of bond distances and angles after comparison using half-normal probability plots [19]. As far as the torsion angles are concerned, the only differences are at the angles defining the coplanarity of the
substituents in 4B (carboxamide and methyl groups, Table 3) with regard to the pyrazole ring. The highest distortion from planarity of the pyrazole ring is also presented by 4B (x 2 values of 1.73, 7.94 and 3.31 for 4A, 4B and 4C respectively versus a tabulated one of 5.99 at 95% probability level) [6]. In 7, the molecule as a whole is more planar than in 4 as measured by the torsion angle around the N(1)– C(6) bond (significantly different to that observed in 4B and 4C) and by the planarity of the pyrazole ring (x 2 0.30 versus 5.99 at 95% probability level). When the methyl substituent at C(3) in 4 is replaced by the Br at C(4) in 7, the differences in the pyrazole ring geometry are not significant in terms of the achieved precision, indicating the opposite effects of the Me and Br substituents in the deformation of the intra-anular ipso and ortho angles in a similar way to that reported for benzene derivatives [20]. The molecules (4A and 7), which present lower distortion from planarity, are both forming a hydrogen bonded R22 (8) dimer [21] around a crystallographic symmetry centre (R stands for ring, subscript and superscript indicate the number of donor and acceptor atoms respectively and 8 is the total number of atoms involved in the ring. See Ref. [22] for a detailed description). However, molecules 4B and 4C are hydrogen bonded one with the other forming the same type of dimer, but around a pseudosymmetry centre located at (0.150(3), 0.216(12), 0.170(1)) [18] and the P-1 symmetry related positions. In all molecules the NH2 group present a planar conformation, the sum being of bond angles around the N atom 359(4)⬚, 360(4)⬚, 360(4)⬚ and 359(22)⬚ for 4A, 4B, 4C and 7, respectively. The crystal structure of an azolide derived from 4bromopyrazole has already been reported [23] (CSD
84
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
Table 1 Crystal analysis parameters for compounds 4 and 7 Crystal data
4
7
Formula Crystal habit Crystal size (mm) Symmetry Unit cell determination
C5H7ON3 Colourless, plate 0.67 × 0.37 × 0.13 Triclinic, P-1 Least-squares fit[11] from 65 and 35 reflections (u ⬍ 45⬚) a 7.7347(7) b 10.5644(11) c 12.3134(17) 108.665(10), 100.324(12), 94.745(12) 927.2(2), 6 1.345, 125.13, 396 8.265 298
C4H2ON3Br Colourless, prism 0.70 × 0.33 × 0.13 Monoclinic, P2/c
˚ ,⬚); Unit cell dimension (A
˚ 3),Z Packing: V(A Dc(g/cm 3), M, F(000) m(cm ⫺1) T(K) Experimental data Technique
Scan width (⬚) Number of reflections Measured Independent Observed (2s(I)) Standard reflections Absorption correction Transmission (max–min) Solution and refinement Solution Refinement Parameters Number of variables Degrees of freedom Ratio of freedom H atoms Weighting-scheme ˚ 2) Max. thermal value (A ˚ 3) Final DF peaks (eA Final R and Rw
a 3.9305(5) b 30.6119(32) c 5.4767(10) 90, 110.328(13), 90 617.9(2), 4 2.042, 190.00, 368 84.058 298
Four circle diffractomet: Seifert XRD3000-S diffractometer. Bisecting geometry. Graphite oriented monochromator. v/2u scans. Detector apertures 1 × 1⬚. 1 min/reflex., CuKa, umax 65⬚ 1.5 ⫹ 0.15 tan (u) 3107 2882 2260 2 reflections every 90 min. No decay. None ⫺
1103 938 857 Psi-scan method 1.000-0.390
Direct methods: Sir92 Least Squares on Fobs, Full matrix 328 1932 6.9 From difference synthesis Empirical as to give no trends in 具wD 2F典 vs. 具兩Fobs兩典 and 具sinu/l典 U22[N(8C)] 0.088(1) ⫺ 0.26/0.25 0.040, 0.045
[10], refcode: ABPZOL) where an acetyl group replaces the carboxamide one present in 7. Only two significant differences were found when both molecules are compared [19] the C(6)– N(8)/C(8) bond ˚ in ABPZOL) and the N(1)– distance (1.486(11) A
94 763 9.1
U22[C(3)] 0.049(6) ⫺ 1.19/1.26 near Br atom 0.067, 0.076
C(6)– N(8)/C(8) bond angle (117.4(6)⬚inABPZOL), which is smaller in 7 probably owing to the stronger N(8)– H(8a) … N(2) intramolecular interaction ˚ ), Fig. 1b, compared with the C(8)– (2.67(13) A ˚ ). … H(8a) N(2) one (2.800(9) A
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
85
Table 2 Final atomic coordinates and equivalent displacement parameters. Atom
x/a
y/b
z/c
U(eq) (1/3) ˚2 S[Uij.ai*.aj*.ai.aj.cos(ai,aj)] A
Compound 4 N(11) N(12) C(13) C(14) C(15) C(16) C(17) N(18) C(19) N(21) N(22) C(23) C(24) C(25) C(26) O(27) N(28) C(29) N(31) N(32) C(33) C(34) C(35) C(36) O(37) N(38) C(39)
0.1793(2) 0.1554(2) 0.2370(2) 0.3132(3) 0.2751(3) 0.1095(2) 0.1441(2) 0.0128(3) 0.2442(4) 0.5369(2) 0.5358(2) 0.7051(3) 0.8145(3) 0.7047(3) 0.3783(3) 0.3874(2) 0.2314(3) 0.7599(4) ⫺ 0.2365(2) ⫺ 0.2309(2) ⫺ 0.3995(3) ⫺ 0.5127(3) ⫺ 0.4061(3) ⫺ 0.0809(3) ⫺ 0.0962(2) 0.0701(2) ⫺ 0.4507(4)
0.2985(2) 0.3235(2) 0.4487(2) 0.5036(2) 0.4063(2) 0.1743(2) 0.1565(1) 0.0869(2) 0.5136(3) 0.2904(2) 0.3349(2) 0.3667(2) 0.3418(3) 0.2934(3) 0.2499(2) 0.2326(2) 0.2346(2) 0.4219(3) 0.1378(2) 0.1178(2) 0.0964(2) 0.1036(2) 0.1297(2) 0.1627(2) 0.1663(2) 0.1801(2) 0.0670(3)
⫺ 0.2770(1) ⫺ 0.1652(1) ⫺ 0.1068(2) ⫺ 0.1807(2) ⫺ 0.2879(2) ⫺ 0.3681(2) ⫺ 0.4647(1) ⫺ 0.3389(2) 0.0207(2) 0.3832(1) 0.5001(1) 0.5534(2) 0.4722(2) 0.3647(2) 0.2956(2) 0.1939(1) 0.3337(2) 0.6845(2) ⫺ 0.0441(1) ⫺ 0.1585(1) ⫺ 0.2138(2) ⫺ 0.1354(2) ⫺ 0.0286(2) 0.0454(2) 0.1429(1) 0.0123(2) ⫺ 0.3435(2)
0.0408(5) 0.0429(6) 0.0449(7) 0.0545(8) 0.0504(8) 0.0405(7) 0.0494(5) 0.0552(7) 0.0604(9) 0.0451(6) 0.0468(6) 0.0493(8) 0.0593(9) 0.0553(9) 0.0444(7) 0.0558(6) 0.0534(7) 0.0646(11) 0.0430(6) 0.0446(6) 0.0462(7) 0.0535(8) 0.0500(8) 0.0444(7) 0.0604(7) 0.0576(8) 0.0613(11)
Compound 7 Br N(1) N(2) C(3) C(4) C(5) C(6) O(7) N(8)
0.0033(3) 0.130(2) ⫺ 0.129(2) ⫺ 0.193(3) 0.019(2) 0.220(3) 0.287(2) 0.526(2) 0.145(3)
0.21145(3) 0.0997(2) 0.1184(3) 0.1572(4) 0.1623(3) 0.1260(3) 0.0589(3) 0.0449(2) 0.0399(3)
0.3960(2) 0.055(2) ⫺ 0.154(2) ⫺ 0.069(2) 0.190(2) 0.264(2) 0.037(2) 0.225(1) ⫺ 0.191(2)
0.0397(5) 0.025(3) 0.038(3) 0.037(4) 0.024(3) 0.030(4) 0.029(4) 0.044(3) 0.046(4)
3.2. Secondary structure The carboxamide groups in both compounds are involved in the formation of R22 (8) dimers. The tendency of the structures containing an amide fragment to form this cyclic pattern has previously been reported [21]. According to this study, 34% of all structures form the R22 (8) hydrogen-bond pattern, this means that although it is quite common, it is not
the only one formed. No primary amides with the carboxamide group attached to the N(1) pyrazole atom was found in the CSD (October 1997 version). To avoid this, we have done a search at the CSD [10] looking for benzamide derivatives instead (similar to the title compounds) and excluding organometallic derivatives and those with more than one chemical species in the crystal (salts, hydrates, inclusion complexes). The resulting 32 crystal structures can
86
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
Table 3 Selected geometrical parameter and hydrogen bond interactions Compound N(1)–C(6) C(6)–O(7) C(6)–N(8) N(2)–C(3)–C(4) C(3)–C(4)–C(5) N(1)–C(6)–N(8) N(1)–C(6)–O(7) O(7)–C(6)–N(8)
4A
4B 1.412(2) 1.225(3) 1.318(3)
4C 1.413(2) 1.221(3) 1.322(3)
7 1.420(2) 1.216(3) 1.322(3)
1.412(12) 1.206(11) 1.312(14)
111.0(2) 106.2(2) 115.2(2) 118.6(2) 126.1(2)
111.3(2) 106.2(2) 115.1(2) 118.7(2) 126.2(2)
111.0(2) 106.2(2) 114.8(2) 119.0(2) 126.2(2)
109.8(9) 107.3(9) 114.1(8) 119.0(9) 127.0(10)
C(5)–N(1)–C(6)–O(7) N(2)–N(1)–C(6)–N(8) C(6)–N(1)–N(2)–C(3) N(1)–N(2)–C(3)–C(9) N(2)–C(3)–C(4)–Br Br–C(4)–C(5)–N(1)
4.3(3) 3.0(3) ⫺179.3(2) ⫺178.8(2) ⫺ ⫺
⫺10.6(3) ⫺11.8(3) ⫺178.1(2) 179.4(2) ⫺ ⫺
6.6(3) 7.2(3) 179.1(2) ⫺178.7(2) ⫺ ⫺
1.7(18) ⫺l.4(13) ⫺176.0(9) ⫺ ⫺177.2(7) 177.5(7)
Hydrogen bonds
D–H
D…A
H…A
D–H…A
Compound 4 N(8A)–H(8Ab)…O(7A)(⫺x, ⫺y, ⫺z ⫺1) N(8A)–H(8Aa)…N(2C) N(8B)–H(8Bb)…O(7C) N(8B)–H(8Ba)…O(7A)(x, y, z⫹1) N(8C)–H(8Cb)…O(7B) N(8C)–H(8Ca)…N(2A) C(4A)–H(4A)…O(7B)(⫺x⫹1, ⫺y⫹1, ⫺z) C(5A)–H(5A)…N(2B)(x, y, z⫺1) C(9A)–H(9Aa)…N(8C) C(4B)–H(4B)…O(7A)(x⫹1, y, z⫹1) C(5B)–H(5B)…O(7C)(x⫹1, y, z) C(5C)–H(5C)…O(7B)(x⫺1, y, z) C(9C)–H(9Ca)…N(8A)
0.87(3) 0.89(3) 0.87(3) 0.91(3) 0.90(3) 0.89(4) 0.96(3) 0.95(3) 0.92(5) 0.95(4) 0.93(3) 0.97(3) 0.94(5)
2.895(2) 3.120(3) 2.991(2) 3.019(3) 2.889(2) 3.159(3) 3.537(3) 3.511(3) 3.629(4) 3.467(3) 3.338(3) 3.345(3) 3.564(4)
2.03(2) 2.31(3) 2.13(3) 2.24(4) 1.99(3) 2.38(4) 2.65(3) 2.68(3) 2.89(4) 2.80(4) 2.50(3) 2.48(3) 2.77(4)
173(3) 150(3) 171(3) 144(3) 176(3) 146(3) 154(3) 147(2) 138(4) 128(3) 150(2) 149(2) 143(4)
Compound 7 N(8)–H(8a)…O(7)(x⫺1, y, z⫺1) N(8)–H(8b)…O(7)(⫺ x⫹1, ⫺y, ⫺z) C(5)–H(5)…N(2)(x⫹1, y, z⫹1)
0.80(15) 0.73(13) 0.79(11)
3.283(12) 2.934(12) 3.333(12)
2.55(15) 2.22(14) 2.57(11)
154(16) 168(14) 164(12)
be subdivided in two groups: the first one (Table 4) includes the parent compound (benzamide) and 26 monosubstituted benzamides (ortho, meta or para) and the second one is constituted by 5 derivatives with 3 or 5 additional substituents. In the first group 81% of the structures form R22 (8) dimers, while in the second one it is only 40%, which is more similar to the number previously reported. There is a clear tendency towards the formation of the R22 (8) system in the monosubstituted derivatives, that is more
consistent with the structures reported in this article. However, there is still a small difference in the behaviour of compound 4 as all 24 R22 (8) dimers found in the CSD (22 in the first group and 2 in the second) are rigorously centrosymmetric, while in 4 there is a pseudocentrosymmetric one as mentioned above. Considering the geometry of the interaction, the values observed in 4 and 7 are very similar to those obtained from the CSD as far as the mean values are
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
87
Fig. 1. (a) Perspective view of the three crystallographically independent molecules of 4 displaying the numbering system. Dotted lines stand for intermolecular hydrogen bond interactions. Atoms labelled using I, II and III are related by the (⫺x, ⫺y, ⫺z⫺1), (x, y, z⫹1) and (x, y, z⫺1) symmetry operations respectively. (b) perpendicular view to the pyrazole ring of the molecular structure of 7 and a centrosymmetric related molecule. Labels IV to VIII correspond to the (1⫺x, ⫺y, ⫺z), (1⫹x, y, 1⫹z), (2⫺x, ⫺y, 1⫺z), (x⫺1, y, z⫺1) and (⫺x, ⫺y, ⫺z⫺1) symmetry operations respectively. Anisotropic displacement, parameters are plotted at 30% probability level for (a) and (b).
88
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
Table 4 Summary of the packing modes in monosubstituted benzamide derivatives retrieved from the Cambridge Structural Database Substituent/ substituent disposition
H (Yes, T,BZAMID04) (2.937, 173) NH2 OH
Cemtrosymmetric dimer R22(8), Symmetry element, a CSD refcode / N…O distance and ˚ , ⬚) N–H…O angle (A ortho meta para
(⫺) No, b HXBNZM
No, b AMBZAM10 (⫺)
F
No, b JIXCIC Yes, X, SALMID01 2.926, 179 Yes, T, ONBZAM 2.941, 163 Yes, T, NABQEM 3.000, 179 (⫺)
Cl c
(⫺)
Yes, X, JACYOB 2.893, 173 Yes, T, MEBENA 2.993, 158 Yes, T, BENAFM10 2.950, 172 (⫺)
CO–NH2
(⫺)
(⫺)
–NH–COCH3 c
(⫺) (⫺)
(⫺)
(⫺)
(⫺)
(⫺)
(⫺)
–NH–NyN ⫹O ⫺CH3
Yes, X, ACBNZA 2.895, 176 Yes, X, ACBNZA01 2.970, 167 Yes, X, ACSLCA10 2.935, 173 Yes, T, CONYEJ01 2.978, 170 (⫺)
Yes, X, NTBZAM01 2.891, 168 Yes, GP, DABVAD01 2.968, 179 Yes, GP, BENAFP 2.899, 178 Yes, SA, PCBZAM03 3.053, 151 Yes, T, PCBZAM10 2.986, 179 Yes, T, TRPHAM 2.897, 176 (⫺)
(⫺)
–NCH3 –NyN ⫹O ⫺CH3
(⫺)
(⫺)
–N ⫹O ⫺yN–N(CH3)2
(⫺)
(⫺)
–C(Ph)yNOH
(⫺)
–NyN–N(CH3)3
Yes, X, MTZPCX 2.910, 152 No, b ZENTUH
Yes, X, KUGSUA 2.963, 161 (⫺)
Yes, GP, DEFGIE 2.882, 171 Yes, T, FINWOO 2.967, 161 Yes, T. JOLNAZ 2.995, 155 (⫺)
NO2 Me
–O–COCH3 –O–CO–Ph
1, 8-naphthalene-dicarboximido
(⫺)
No, b ZIKQOZ (⫺)
a 2 R2 (8) centrosymmetric dimer linked by N–H…O hydrogen bondsl T, GP, SA stand for translation, glide-plane and screw axis symmetry elements relating dimers in the different packing types. X means dimers no directly connected. b No information about the geometry of the hydrogen bond is given when no dimers are present. c Two polymorphic forms are known.
˚ , 173(2)⬚; concerned (0.88(2), 2.925(47), 2.05(53) A weighted mean values (sample estimated standard ˚, deviation) versus 0.97(9), 2.945(39), 2.00(10) A 170(8)⬚; non-weighted mean value for the CSD retrieved structures (sample estimated standard deviation) for N–H, N…O, H…O and NH…O respectively).
3.3. Packing of R22 (8) dimers The packing arrangement of the centrosymmetric amide pair R22 (8) was described thirty years ago [24] in the case that the dimers directly hydrogen bond with each other. Three possibilities were reported: translation (T), glide plane (GP) and two-fold screw
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
89
Fig. 2. (a) View of the crystal packing of 4 down the c axis. The molecules form two independent R22 (8) dimers[21] that give rise to chains along the c axis. b) View of 7 down the c-axis. Dotted lines represent intermolecular hydrogen bonds. The R22 (8) dimers of molecules form chains via a translation along the a ⫹ c axis. c) same as b) but down the a ⫹ c direction.
90
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
Table 5 13 C NMR chemical shifts of pyrazole-1-carboxamides Compound
Carbon atom
DMSO-d6[8]
CPMAS
4
3-CH3 C3 C4 C5 CONH2 3-CH3 5-CH3 C3 C4 C5 CONH2 3-CH3 4-CH3 5-CH3 C3 C4 C5 CONH2 C3 C4 C5 CONH2 3-CH3 C3 C4 C5 CONH2 3-CH3 -5CH3 C3 C4 C5 CONH2
13.26 150.33 108.58 129.14 151.10 13.51 13.10 148.89 109.48 142.37 151.89 11.67 7.09 11.55 148.69 115.09 138.03 151.10 142.32 95.98 128.80 149.28 11.64 149.29 97.26 129.03 149.53 12.54 11.98 147.32 98.61 139.89 151.04
14.4 152.0 111.5 130.0 154.4 15.2 13.4 150.9 111.6 143.3 153.4 12.9 7.2 12.9 150.9 115.5 139.9 154.4 140.7 96.8 128.0 151.0 12.4 150.5 97.0 129.1 151.6 13.3 13.3 148.0 99.0 138.0 153.2
5
6
7
8
9
axis (SA), which are the same motifs we have found for the monosubstituted benzamide derivatives, Table 4. The most populated set of structures corresponds to type T (10 structures), decreasing in the sequence GP(3) and SA(11), that is the same order found in Ref. [24]. The remaining 8 structures (X on Table 4) containing R22 (8) dimers (36%) present a wide variety of hydrogen bond networks interconnecting the dimers and it is not possible to establish an easy classification. In general, it is observed that the potential hydrogen bond donors and acceptors of the benzamide substituent are involved in the interdimer connections. The crystal packing in 4 is formed by two independent R22 (8) dimers (See the discussion above and Fig.1)
that are hydrogen bonded directly involving molecules 4A and 4B, and through the pyrazole moiety between molecules 4A and 4C. This results in a chain of molecules parallel to the c axis, Fig. 2a. The main interactions between chains are of CH…O type, Table 3. The dimer interconnection in 7 belongs to the translation (T) type, giving rise to chains of R22 (8) dimers along the a ⫹ c direction, Fig. 2b and c, that are further stabilized by CH…N interactions, Table 3. The ‘‘molecular ribbons’’ formed interact with each other via Br…Br short interactions (3.615(2) versus ˚ (sum of van der Waals radii [25])). This kind 3.700 A of short Halogen…Halogen interactions that stabilize the crystal structure was found in all the mono halogen benzamide derivatives found in CSD ˚ (p-F) versus (Fluoride: 2.902 (m-F), 2.825 A ˚ ˚ and Chloride: 3.235 (p-Cl a form), 3.330 A 2.940 A ˚ ). (p-Cl g-form) versus 3.560 A 3.4. 13C CPMAS NMR study We have collected in Table 5 the 13C chemical shifts reported for the DMSO-d6 solution [8] and those that we have determined in the solid state. The first comment is that they are remarkably alike, those in the solid state being generally slightly larger by 1 ppm on average (largest deviations ⫹ 3.3 ppm for the CONH2 of compound 4 and ⫺ 1.9 ppm for the C5 of compound 9). The chemical shifts for the C4 signal of 4-bromo derivatives 7–9 is the centre of a complex signal as a result of the dipolar coupling [17]. The C4 signal of compound 5 is split (110.7 and 112.5 ppm) and its CONH2 signal (153.4 ppm) is broad suggesting some mobility of the amide. The three independent molecules of 4 (A–C) are too similar in terms of geometry to produce observable differences in the corresponding 13C CPMAS spectrum. In conclusion, the X-ray structures of compounds 4 and 7 are representative for all this series of compounds and most probably for other pyrazole-1-carboxamides. 4. Conclusions Monosubstituted pyrazole-1-carboxamides display a similar tendency to form R22 (8) dimers as monosubstituted benzamides; however, only in the first group a situation of pseudosymmetry centre was found. The
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
importance of the weak CH…O and CH…N hydrogen bonds in the stability of the chains of molecules (secondary structure) and in the packing of these chains to form the whole crystal is also evidenced. We have tried to find some relationship between the geometry of the amide fragment and the barrier to rotation about the amide bond. For the following eight compounds (formamide, N-methylformamide, N,N-dimethylformamide, N-methylbenzamide, N,Ndimethylbenzamide, urea, tetramethylurea and pyrazole-1-carboxamide) [4,26,27] there is no relationship with the CyO bond length but there is an acceptable ˚ ) [28,29] relationship with the C–N bond length (in A and with the number R of methyl groups on the nitrogen (from 0 for formamide to 4 for tetramethylurea). Ea(kcal mol) (494 ^ 24) – (364 ^ 18) dC–N ⫹ (3.7 ^ 0.2) R, n 8, r 2 0.988. The sign, but not the actual value, of both coefficients are as expected: first, the longer the C–N bond the lower the barrier and, second, the presence of methyl groups on the nitrogen increases the barrier. Acknowledgements Thanks are given to the DGICYT of Spain for financial support, PB96-0001-C03-02. References [1] H.A. Staab, H. Bauer, K.M. Schneider, K.M. Azolides, Organic Synthesis and Biochemistry, Wiley, New York, 1997. [2] L. Bouveault, Bull. Soc. Chim. Fr. 20 (1898) 77. [3] K. von Auwers, W. Daniels, J. Prakt Chem. 110 (1925) 235. [4] J. Elguero, R. Jacquier, Comp. Rend. Acad. Sci. (Paris) 260 (1965) 606. [5] J. Elguero, C., Marzin, L., Pappalardo, Bull. Soc. Chim. Fr. (1974) 1137. [6] P. Hennings, G. Ka¨stner, M. Klepel, A. Jumar, Z. Chem. 27 (1987) 435.
91
[7] J. Castells, M.A. Merino, M. Moreno-Man˜as, J. Chem. Soc. Chem. Commun. (1972) 709. [8] M. Begtrup, G. Boyer, P. Cabildo, C. Cativiela, R.M. Claramunt, J. Elguero, J.I. Garcı´a, C. Toiron, P. Vedsø, Magn. Reson. Chem. 31 (1993) 107. [9] R.W. Okey, H.D. Stensel, M.C. Martis, Water Sci. Technol. 33 (1996) 101. [10] F.H. Allen, J.E. Davies, J.J. Galloy, O. Johnson, O. Kennard, C.F. Macrae, E.M. Mitchell, G.F. Mitchell, J.M. Smith, D.G. Watson, J. Chem. Info. Comp Sci. 31 (1991) 187. [11] D.E. Appleman, (1984). LSUCRE, Program for least-squares refinement of reticular constants. US Geological Survey, Washington DC, USA. [12] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M.C. Burla, G. Polidori, M. Camalli, SIR92. J. Appl. Cryst. 27 (1994) 435. [13] S.R. Hall, H.D. Flack, J.M. Stewart, Xtal 3.2 (1993). Eds. University of Western Australia. Lamb: Perth. [14] M. Martı´nez-Ripoll, F.H. Cano, unpublished program, 1975. [15] International Tables for X-Ray Crystallography, vol. IV, 1974, Birmingham. Kynoch Press (present distributor D. Reidel, Dordrecht). [16] A.C. Olivieri, J. Elguero, I. Sobrados, P. Cabildo, R.M. Claramunt, J. Phys. Chem. 98 (1994) 5207. [17] C. Foces-Foces, C. Fontenas, J. Elguero, I. Sobrados, An. Quim, Int. Ed. 93 (1997) 219. [18] M. Nardelli, Comp. Chem. 7 (1983) 95. [19] S. Abrahams, E.T. Keve, Acta Crystallogr. A27 (1971) 157. [20] A. Domenicano, P. Murray-Rust, Tetrahedron Lett. 24 (1979) 2283. [21] L. Shimoni, J.P. Glusker, C.W. Bock, J. Phys. Chem. 100 (1996) 2957. [22] M.C. Etter, J.C. MacDonald, J. Bernstein. Acta Crystallogr. B 46 (1990) 256; J. Bernstein, R.E. Davis, L. Shimoni, N.-L. Chang, Angew. Chem., Int. Ed. Engl. 34 (1995) 1555 and references therein. [23] J. Lapasset, A. Escande, J. Falgueirettes, Acta Crystallogr. B28 (1972) 3316. [24] L. Leiserowitz, G.M.J. Schmidt, J. Chem. Soc. A (1969) 2372. [25] B.K. Vainshtein, V.M. Fridkin, V.L. Indenbom in Modern Crystallography II, Springer, Berlin, Heidelberg, New York, 1982, pp. 87. [26] M. Oki, Applications of Dynamic NMR Spectroscopy to organic Chemistry, VCH, Weinheim, 1985. [27] T. Drakenber, S. Forse´n, J. Phys. Chem. 74 (1970) 1. [28] K.B. Wiberg, K.E. Laidig, J. Am. Chem. Soc. 109 (1987) 5935. [29] K.B. Wiberg, C.M. Breneman, J. Am. Chem. Soc. 114 (1992) 831.
A structural study of pyrazole-1-carboxamides by X-ray crystallography and 13C CPMAS NMR spectroscopy Antonio L Llamas-Saiz a,*, Concepcio´n Foces-Foces a, Isabel Sobrados b, Nadine Jagerovic c, Jose´ Elguero c a
Departamento de Cristalografia, Instituto de Quı´mica-Fı´sica Rocasolano, CSIC, Serrano 119, E-28006 Madrid, Spain b Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, E-28049 Madrid, Spain c Instituto de Quı´mica Me´dica, CSIC, Juan de Cierva, 3, E-28006 Madrid, Spain Received 27 July 1998; received in revised form 28 September 1998; accepted 28 September 1998
Abstract The crystal structures of the first two pyrazole N-substituted primary amides (3-methyl and 4-bromo) were determined. The amide groups from the R22 (8) hydrogen-bond dimeric pattern in all cases, in accordance with the higher rate found for the formation of this pattern in monosubstituted benzamides (81%) compared with the whole group of primary amide structures (34%). These two compounds and four other N-CONH2 pyrazoles were studied by solid state NMR (CPMAS technique). 䉷 1999 Elsevier Science B.V. All rights reserved. Keywords: Hydrogen bonding; Pyrazoles; X-Ray crystallography; 13C CPMAS NMR
1. Introduction 1H-Pyrazole-1-carboxamides 1 are a class of compounds belonging to the family of azolides 2 [1], which in spite of having been studied through the last century [1–9], their molecular structures have never been determined, not even for the simplest and most common case where R4yR5y-H. The only related structure is that of compound 3 (Cambridge Structural Database [10], CSD hereinafter, refcode:FAGRUA). Regarding the structural aspects of pyrazolecarboxamides, it was established that the CONHR4 group (R5yH) can migrate between positions 1 and 2, the
* Corresponding author.
mechanism involving a dissociation-recombination of pyrazole and isocyanate (OyCyN–R4) [4,7]. Scheme 1 The other relevant structural data is related to the rotational isomerism about the C(O)– NH2 group (R4yR5yH) which was estimated to be 16 kcal mol ⫺1 which corresponds to a typical amide group [5]; moreover, it was established by 1 H NMR, for both 1 and 2, that the oxygen atom is situated anti with regard to the N2 lone pair [5]. Scheme 2 Finally, the 13C NMR spectra in DMSO–d6 solution was determined for a series of pyrazoles bearing at position 1 a CONH2 group 4–9. The most relevant conclusion for the present work is that all these compounds have very similar conformations in solution [8].
0022-2860/99/$ - see front matter 䉷 1999 Elsevier Science B.V. All rights reserved. PII: S0022-286 0(98)00658-9
82
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
2. Experimental Chemistry: The six compounds discussed in the present work were described previously by one of us [4]. In the case of 3(5)-methylpyrazole-1-carboxamide, the synthesis lead to two possible isomers 4 (3-methyl) and 4 0 (5-methyl) but it was established
that the 5-methyl isomer 4 0 isomerizes thermally to the 3-methyl one 4 [4,6]. The compound studied in this work is the most stable isomer, 4. X-Ray structure determination: Details of data collection and refinement procedure for 4 and 7 are gathered in Table 1. Both samples were enclosed in Lindemann capillaries to prevent decomposition. As the extremely anisotropic unit cell dimensions of 7, the orientation matrix had to be carefully refined in order to predict the reciprocal lattice directions with enough accuracy for data collection (mainly at high resolution angles and along the largest reciprocal axis vector). To achieve this, an appropriate set of reflections was chosen, containing 24 reflections evenly distributed through the reciprocal space. The structures were solved by direct methods using the SIR92 program [12] and refined by full matrix least squares procedures on Fo using the XTAL 3.2 System [13]. The hydrogen atoms were located in the difference Fourier synthesis and were included in the refinement
Scheme 1.
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
83
Scheme 2.
as isotropic, although the thermal factor of all of them had to be kept fixed for 7. The weighting scheme was obtained (PESOS [14]) in an empirical way as to give no trends in 具wD 2Fo典 vs. 具Fo典 or 具sin u/l典. The atomic scattering factors were taken from the International Tables for X-Ray Crystallography, [15]. The final atomic coordinates and equivalent displacement parameters for 4 and 7 are reported in Table 2. Crystallographic data (excluding structure factors) for the structures reported in this article was deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-111913 and CCDC-111914. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: int. code ⫹ (1223)-336-033, e-mail: [email protected]). Solid state NMR spectroscopy. The 13C CPMAS NMR spectra were recorded at 100 MHz with the spectrometer and the conditions used in previous publications [16,17].
3. Results and discussion 3.1. Molecular structure Selected geometrical parameters [18] for 4 and 7 are reported in Table 3 according to the numbering scheme displayed in Fig. 1. The three crystallographically independent molecules in 4 (4A, 4B and 4C hereinafter) are not significantly different in terms of bond distances and angles after comparison using half-normal probability plots [19]. As far as the torsion angles are concerned, the only differences are at the angles defining the coplanarity of the
substituents in 4B (carboxamide and methyl groups, Table 3) with regard to the pyrazole ring. The highest distortion from planarity of the pyrazole ring is also presented by 4B (x 2 values of 1.73, 7.94 and 3.31 for 4A, 4B and 4C respectively versus a tabulated one of 5.99 at 95% probability level) [6]. In 7, the molecule as a whole is more planar than in 4 as measured by the torsion angle around the N(1)– C(6) bond (significantly different to that observed in 4B and 4C) and by the planarity of the pyrazole ring (x 2 0.30 versus 5.99 at 95% probability level). When the methyl substituent at C(3) in 4 is replaced by the Br at C(4) in 7, the differences in the pyrazole ring geometry are not significant in terms of the achieved precision, indicating the opposite effects of the Me and Br substituents in the deformation of the intra-anular ipso and ortho angles in a similar way to that reported for benzene derivatives [20]. The molecules (4A and 7), which present lower distortion from planarity, are both forming a hydrogen bonded R22 (8) dimer [21] around a crystallographic symmetry centre (R stands for ring, subscript and superscript indicate the number of donor and acceptor atoms respectively and 8 is the total number of atoms involved in the ring. See Ref. [22] for a detailed description). However, molecules 4B and 4C are hydrogen bonded one with the other forming the same type of dimer, but around a pseudosymmetry centre located at (0.150(3), 0.216(12), 0.170(1)) [18] and the P-1 symmetry related positions. In all molecules the NH2 group present a planar conformation, the sum being of bond angles around the N atom 359(4)⬚, 360(4)⬚, 360(4)⬚ and 359(22)⬚ for 4A, 4B, 4C and 7, respectively. The crystal structure of an azolide derived from 4bromopyrazole has already been reported [23] (CSD
84
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
Table 1 Crystal analysis parameters for compounds 4 and 7 Crystal data
4
7
Formula Crystal habit Crystal size (mm) Symmetry Unit cell determination
C5H7ON3 Colourless, plate 0.67 × 0.37 × 0.13 Triclinic, P-1 Least-squares fit[11] from 65 and 35 reflections (u ⬍ 45⬚) a 7.7347(7) b 10.5644(11) c 12.3134(17) 108.665(10), 100.324(12), 94.745(12) 927.2(2), 6 1.345, 125.13, 396 8.265 298
C4H2ON3Br Colourless, prism 0.70 × 0.33 × 0.13 Monoclinic, P2/c
˚ ,⬚); Unit cell dimension (A
˚ 3),Z Packing: V(A Dc(g/cm 3), M, F(000) m(cm ⫺1) T(K) Experimental data Technique
Scan width (⬚) Number of reflections Measured Independent Observed (2s(I)) Standard reflections Absorption correction Transmission (max–min) Solution and refinement Solution Refinement Parameters Number of variables Degrees of freedom Ratio of freedom H atoms Weighting-scheme ˚ 2) Max. thermal value (A ˚ 3) Final DF peaks (eA Final R and Rw
a 3.9305(5) b 30.6119(32) c 5.4767(10) 90, 110.328(13), 90 617.9(2), 4 2.042, 190.00, 368 84.058 298
Four circle diffractomet: Seifert XRD3000-S diffractometer. Bisecting geometry. Graphite oriented monochromator. v/2u scans. Detector apertures 1 × 1⬚. 1 min/reflex., CuKa, umax 65⬚ 1.5 ⫹ 0.15 tan (u) 3107 2882 2260 2 reflections every 90 min. No decay. None ⫺
1103 938 857 Psi-scan method 1.000-0.390
Direct methods: Sir92 Least Squares on Fobs, Full matrix 328 1932 6.9 From difference synthesis Empirical as to give no trends in 具wD 2F典 vs. 具兩Fobs兩典 and 具sinu/l典 U22[N(8C)] 0.088(1) ⫺ 0.26/0.25 0.040, 0.045
[10], refcode: ABPZOL) where an acetyl group replaces the carboxamide one present in 7. Only two significant differences were found when both molecules are compared [19] the C(6)– N(8)/C(8) bond ˚ in ABPZOL) and the N(1)– distance (1.486(11) A
94 763 9.1
U22[C(3)] 0.049(6) ⫺ 1.19/1.26 near Br atom 0.067, 0.076
C(6)– N(8)/C(8) bond angle (117.4(6)⬚inABPZOL), which is smaller in 7 probably owing to the stronger N(8)– H(8a) … N(2) intramolecular interaction ˚ ), Fig. 1b, compared with the C(8)– (2.67(13) A ˚ ). … H(8a) N(2) one (2.800(9) A
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
85
Table 2 Final atomic coordinates and equivalent displacement parameters. Atom
x/a
y/b
z/c
U(eq) (1/3) ˚2 S[Uij.ai*.aj*.ai.aj.cos(ai,aj)] A
Compound 4 N(11) N(12) C(13) C(14) C(15) C(16) C(17) N(18) C(19) N(21) N(22) C(23) C(24) C(25) C(26) O(27) N(28) C(29) N(31) N(32) C(33) C(34) C(35) C(36) O(37) N(38) C(39)
0.1793(2) 0.1554(2) 0.2370(2) 0.3132(3) 0.2751(3) 0.1095(2) 0.1441(2) 0.0128(3) 0.2442(4) 0.5369(2) 0.5358(2) 0.7051(3) 0.8145(3) 0.7047(3) 0.3783(3) 0.3874(2) 0.2314(3) 0.7599(4) ⫺ 0.2365(2) ⫺ 0.2309(2) ⫺ 0.3995(3) ⫺ 0.5127(3) ⫺ 0.4061(3) ⫺ 0.0809(3) ⫺ 0.0962(2) 0.0701(2) ⫺ 0.4507(4)
0.2985(2) 0.3235(2) 0.4487(2) 0.5036(2) 0.4063(2) 0.1743(2) 0.1565(1) 0.0869(2) 0.5136(3) 0.2904(2) 0.3349(2) 0.3667(2) 0.3418(3) 0.2934(3) 0.2499(2) 0.2326(2) 0.2346(2) 0.4219(3) 0.1378(2) 0.1178(2) 0.0964(2) 0.1036(2) 0.1297(2) 0.1627(2) 0.1663(2) 0.1801(2) 0.0670(3)
⫺ 0.2770(1) ⫺ 0.1652(1) ⫺ 0.1068(2) ⫺ 0.1807(2) ⫺ 0.2879(2) ⫺ 0.3681(2) ⫺ 0.4647(1) ⫺ 0.3389(2) 0.0207(2) 0.3832(1) 0.5001(1) 0.5534(2) 0.4722(2) 0.3647(2) 0.2956(2) 0.1939(1) 0.3337(2) 0.6845(2) ⫺ 0.0441(1) ⫺ 0.1585(1) ⫺ 0.2138(2) ⫺ 0.1354(2) ⫺ 0.0286(2) 0.0454(2) 0.1429(1) 0.0123(2) ⫺ 0.3435(2)
0.0408(5) 0.0429(6) 0.0449(7) 0.0545(8) 0.0504(8) 0.0405(7) 0.0494(5) 0.0552(7) 0.0604(9) 0.0451(6) 0.0468(6) 0.0493(8) 0.0593(9) 0.0553(9) 0.0444(7) 0.0558(6) 0.0534(7) 0.0646(11) 0.0430(6) 0.0446(6) 0.0462(7) 0.0535(8) 0.0500(8) 0.0444(7) 0.0604(7) 0.0576(8) 0.0613(11)
Compound 7 Br N(1) N(2) C(3) C(4) C(5) C(6) O(7) N(8)
0.0033(3) 0.130(2) ⫺ 0.129(2) ⫺ 0.193(3) 0.019(2) 0.220(3) 0.287(2) 0.526(2) 0.145(3)
0.21145(3) 0.0997(2) 0.1184(3) 0.1572(4) 0.1623(3) 0.1260(3) 0.0589(3) 0.0449(2) 0.0399(3)
0.3960(2) 0.055(2) ⫺ 0.154(2) ⫺ 0.069(2) 0.190(2) 0.264(2) 0.037(2) 0.225(1) ⫺ 0.191(2)
0.0397(5) 0.025(3) 0.038(3) 0.037(4) 0.024(3) 0.030(4) 0.029(4) 0.044(3) 0.046(4)
3.2. Secondary structure The carboxamide groups in both compounds are involved in the formation of R22 (8) dimers. The tendency of the structures containing an amide fragment to form this cyclic pattern has previously been reported [21]. According to this study, 34% of all structures form the R22 (8) hydrogen-bond pattern, this means that although it is quite common, it is not
the only one formed. No primary amides with the carboxamide group attached to the N(1) pyrazole atom was found in the CSD (October 1997 version). To avoid this, we have done a search at the CSD [10] looking for benzamide derivatives instead (similar to the title compounds) and excluding organometallic derivatives and those with more than one chemical species in the crystal (salts, hydrates, inclusion complexes). The resulting 32 crystal structures can
86
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
Table 3 Selected geometrical parameter and hydrogen bond interactions Compound N(1)–C(6) C(6)–O(7) C(6)–N(8) N(2)–C(3)–C(4) C(3)–C(4)–C(5) N(1)–C(6)–N(8) N(1)–C(6)–O(7) O(7)–C(6)–N(8)
4A
4B 1.412(2) 1.225(3) 1.318(3)
4C 1.413(2) 1.221(3) 1.322(3)
7 1.420(2) 1.216(3) 1.322(3)
1.412(12) 1.206(11) 1.312(14)
111.0(2) 106.2(2) 115.2(2) 118.6(2) 126.1(2)
111.3(2) 106.2(2) 115.1(2) 118.7(2) 126.2(2)
111.0(2) 106.2(2) 114.8(2) 119.0(2) 126.2(2)
109.8(9) 107.3(9) 114.1(8) 119.0(9) 127.0(10)
C(5)–N(1)–C(6)–O(7) N(2)–N(1)–C(6)–N(8) C(6)–N(1)–N(2)–C(3) N(1)–N(2)–C(3)–C(9) N(2)–C(3)–C(4)–Br Br–C(4)–C(5)–N(1)
4.3(3) 3.0(3) ⫺179.3(2) ⫺178.8(2) ⫺ ⫺
⫺10.6(3) ⫺11.8(3) ⫺178.1(2) 179.4(2) ⫺ ⫺
6.6(3) 7.2(3) 179.1(2) ⫺178.7(2) ⫺ ⫺
1.7(18) ⫺l.4(13) ⫺176.0(9) ⫺ ⫺177.2(7) 177.5(7)
Hydrogen bonds
D–H
D…A
H…A
D–H…A
Compound 4 N(8A)–H(8Ab)…O(7A)(⫺x, ⫺y, ⫺z ⫺1) N(8A)–H(8Aa)…N(2C) N(8B)–H(8Bb)…O(7C) N(8B)–H(8Ba)…O(7A)(x, y, z⫹1) N(8C)–H(8Cb)…O(7B) N(8C)–H(8Ca)…N(2A) C(4A)–H(4A)…O(7B)(⫺x⫹1, ⫺y⫹1, ⫺z) C(5A)–H(5A)…N(2B)(x, y, z⫺1) C(9A)–H(9Aa)…N(8C) C(4B)–H(4B)…O(7A)(x⫹1, y, z⫹1) C(5B)–H(5B)…O(7C)(x⫹1, y, z) C(5C)–H(5C)…O(7B)(x⫺1, y, z) C(9C)–H(9Ca)…N(8A)
0.87(3) 0.89(3) 0.87(3) 0.91(3) 0.90(3) 0.89(4) 0.96(3) 0.95(3) 0.92(5) 0.95(4) 0.93(3) 0.97(3) 0.94(5)
2.895(2) 3.120(3) 2.991(2) 3.019(3) 2.889(2) 3.159(3) 3.537(3) 3.511(3) 3.629(4) 3.467(3) 3.338(3) 3.345(3) 3.564(4)
2.03(2) 2.31(3) 2.13(3) 2.24(4) 1.99(3) 2.38(4) 2.65(3) 2.68(3) 2.89(4) 2.80(4) 2.50(3) 2.48(3) 2.77(4)
173(3) 150(3) 171(3) 144(3) 176(3) 146(3) 154(3) 147(2) 138(4) 128(3) 150(2) 149(2) 143(4)
Compound 7 N(8)–H(8a)…O(7)(x⫺1, y, z⫺1) N(8)–H(8b)…O(7)(⫺ x⫹1, ⫺y, ⫺z) C(5)–H(5)…N(2)(x⫹1, y, z⫹1)
0.80(15) 0.73(13) 0.79(11)
3.283(12) 2.934(12) 3.333(12)
2.55(15) 2.22(14) 2.57(11)
154(16) 168(14) 164(12)
be subdivided in two groups: the first one (Table 4) includes the parent compound (benzamide) and 26 monosubstituted benzamides (ortho, meta or para) and the second one is constituted by 5 derivatives with 3 or 5 additional substituents. In the first group 81% of the structures form R22 (8) dimers, while in the second one it is only 40%, which is more similar to the number previously reported. There is a clear tendency towards the formation of the R22 (8) system in the monosubstituted derivatives, that is more
consistent with the structures reported in this article. However, there is still a small difference in the behaviour of compound 4 as all 24 R22 (8) dimers found in the CSD (22 in the first group and 2 in the second) are rigorously centrosymmetric, while in 4 there is a pseudocentrosymmetric one as mentioned above. Considering the geometry of the interaction, the values observed in 4 and 7 are very similar to those obtained from the CSD as far as the mean values are
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
87
Fig. 1. (a) Perspective view of the three crystallographically independent molecules of 4 displaying the numbering system. Dotted lines stand for intermolecular hydrogen bond interactions. Atoms labelled using I, II and III are related by the (⫺x, ⫺y, ⫺z⫺1), (x, y, z⫹1) and (x, y, z⫺1) symmetry operations respectively. (b) perpendicular view to the pyrazole ring of the molecular structure of 7 and a centrosymmetric related molecule. Labels IV to VIII correspond to the (1⫺x, ⫺y, ⫺z), (1⫹x, y, 1⫹z), (2⫺x, ⫺y, 1⫺z), (x⫺1, y, z⫺1) and (⫺x, ⫺y, ⫺z⫺1) symmetry operations respectively. Anisotropic displacement, parameters are plotted at 30% probability level for (a) and (b).
88
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
Table 4 Summary of the packing modes in monosubstituted benzamide derivatives retrieved from the Cambridge Structural Database Substituent/ substituent disposition
H (Yes, T,BZAMID04) (2.937, 173) NH2 OH
Cemtrosymmetric dimer R22(8), Symmetry element, a CSD refcode / N…O distance and ˚ , ⬚) N–H…O angle (A ortho meta para
(⫺) No, b HXBNZM
No, b AMBZAM10 (⫺)
F
No, b JIXCIC Yes, X, SALMID01 2.926, 179 Yes, T, ONBZAM 2.941, 163 Yes, T, NABQEM 3.000, 179 (⫺)
Cl c
(⫺)
Yes, X, JACYOB 2.893, 173 Yes, T, MEBENA 2.993, 158 Yes, T, BENAFM10 2.950, 172 (⫺)
CO–NH2
(⫺)
(⫺)
–NH–COCH3 c
(⫺) (⫺)
(⫺)
(⫺)
(⫺)
(⫺)
(⫺)
–NH–NyN ⫹O ⫺CH3
Yes, X, ACBNZA 2.895, 176 Yes, X, ACBNZA01 2.970, 167 Yes, X, ACSLCA10 2.935, 173 Yes, T, CONYEJ01 2.978, 170 (⫺)
Yes, X, NTBZAM01 2.891, 168 Yes, GP, DABVAD01 2.968, 179 Yes, GP, BENAFP 2.899, 178 Yes, SA, PCBZAM03 3.053, 151 Yes, T, PCBZAM10 2.986, 179 Yes, T, TRPHAM 2.897, 176 (⫺)
(⫺)
–NCH3 –NyN ⫹O ⫺CH3
(⫺)
(⫺)
–N ⫹O ⫺yN–N(CH3)2
(⫺)
(⫺)
–C(Ph)yNOH
(⫺)
–NyN–N(CH3)3
Yes, X, MTZPCX 2.910, 152 No, b ZENTUH
Yes, X, KUGSUA 2.963, 161 (⫺)
Yes, GP, DEFGIE 2.882, 171 Yes, T, FINWOO 2.967, 161 Yes, T. JOLNAZ 2.995, 155 (⫺)
NO2 Me
–O–COCH3 –O–CO–Ph
1, 8-naphthalene-dicarboximido
(⫺)
No, b ZIKQOZ (⫺)
a 2 R2 (8) centrosymmetric dimer linked by N–H…O hydrogen bondsl T, GP, SA stand for translation, glide-plane and screw axis symmetry elements relating dimers in the different packing types. X means dimers no directly connected. b No information about the geometry of the hydrogen bond is given when no dimers are present. c Two polymorphic forms are known.
˚ , 173(2)⬚; concerned (0.88(2), 2.925(47), 2.05(53) A weighted mean values (sample estimated standard ˚, deviation) versus 0.97(9), 2.945(39), 2.00(10) A 170(8)⬚; non-weighted mean value for the CSD retrieved structures (sample estimated standard deviation) for N–H, N…O, H…O and NH…O respectively).
3.3. Packing of R22 (8) dimers The packing arrangement of the centrosymmetric amide pair R22 (8) was described thirty years ago [24] in the case that the dimers directly hydrogen bond with each other. Three possibilities were reported: translation (T), glide plane (GP) and two-fold screw
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
89
Fig. 2. (a) View of the crystal packing of 4 down the c axis. The molecules form two independent R22 (8) dimers[21] that give rise to chains along the c axis. b) View of 7 down the c-axis. Dotted lines represent intermolecular hydrogen bonds. The R22 (8) dimers of molecules form chains via a translation along the a ⫹ c axis. c) same as b) but down the a ⫹ c direction.
90
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
Table 5 13 C NMR chemical shifts of pyrazole-1-carboxamides Compound
Carbon atom
DMSO-d6[8]
CPMAS
4
3-CH3 C3 C4 C5 CONH2 3-CH3 5-CH3 C3 C4 C5 CONH2 3-CH3 4-CH3 5-CH3 C3 C4 C5 CONH2 C3 C4 C5 CONH2 3-CH3 C3 C4 C5 CONH2 3-CH3 -5CH3 C3 C4 C5 CONH2
13.26 150.33 108.58 129.14 151.10 13.51 13.10 148.89 109.48 142.37 151.89 11.67 7.09 11.55 148.69 115.09 138.03 151.10 142.32 95.98 128.80 149.28 11.64 149.29 97.26 129.03 149.53 12.54 11.98 147.32 98.61 139.89 151.04
14.4 152.0 111.5 130.0 154.4 15.2 13.4 150.9 111.6 143.3 153.4 12.9 7.2 12.9 150.9 115.5 139.9 154.4 140.7 96.8 128.0 151.0 12.4 150.5 97.0 129.1 151.6 13.3 13.3 148.0 99.0 138.0 153.2
5
6
7
8
9
axis (SA), which are the same motifs we have found for the monosubstituted benzamide derivatives, Table 4. The most populated set of structures corresponds to type T (10 structures), decreasing in the sequence GP(3) and SA(11), that is the same order found in Ref. [24]. The remaining 8 structures (X on Table 4) containing R22 (8) dimers (36%) present a wide variety of hydrogen bond networks interconnecting the dimers and it is not possible to establish an easy classification. In general, it is observed that the potential hydrogen bond donors and acceptors of the benzamide substituent are involved in the interdimer connections. The crystal packing in 4 is formed by two independent R22 (8) dimers (See the discussion above and Fig.1)
that are hydrogen bonded directly involving molecules 4A and 4B, and through the pyrazole moiety between molecules 4A and 4C. This results in a chain of molecules parallel to the c axis, Fig. 2a. The main interactions between chains are of CH…O type, Table 3. The dimer interconnection in 7 belongs to the translation (T) type, giving rise to chains of R22 (8) dimers along the a ⫹ c direction, Fig. 2b and c, that are further stabilized by CH…N interactions, Table 3. The ‘‘molecular ribbons’’ formed interact with each other via Br…Br short interactions (3.615(2) versus ˚ (sum of van der Waals radii [25])). This kind 3.700 A of short Halogen…Halogen interactions that stabilize the crystal structure was found in all the mono halogen benzamide derivatives found in CSD ˚ (p-F) versus (Fluoride: 2.902 (m-F), 2.825 A ˚ ˚ and Chloride: 3.235 (p-Cl a form), 3.330 A 2.940 A ˚ ). (p-Cl g-form) versus 3.560 A 3.4. 13C CPMAS NMR study We have collected in Table 5 the 13C chemical shifts reported for the DMSO-d6 solution [8] and those that we have determined in the solid state. The first comment is that they are remarkably alike, those in the solid state being generally slightly larger by 1 ppm on average (largest deviations ⫹ 3.3 ppm for the CONH2 of compound 4 and ⫺ 1.9 ppm for the C5 of compound 9). The chemical shifts for the C4 signal of 4-bromo derivatives 7–9 is the centre of a complex signal as a result of the dipolar coupling [17]. The C4 signal of compound 5 is split (110.7 and 112.5 ppm) and its CONH2 signal (153.4 ppm) is broad suggesting some mobility of the amide. The three independent molecules of 4 (A–C) are too similar in terms of geometry to produce observable differences in the corresponding 13C CPMAS spectrum. In conclusion, the X-ray structures of compounds 4 and 7 are representative for all this series of compounds and most probably for other pyrazole-1-carboxamides. 4. Conclusions Monosubstituted pyrazole-1-carboxamides display a similar tendency to form R22 (8) dimers as monosubstituted benzamides; however, only in the first group a situation of pseudosymmetry centre was found. The
A.L. Llamas-Saiz et al. / Journal of Molecular Structure 478 (1999) 81–91
importance of the weak CH…O and CH…N hydrogen bonds in the stability of the chains of molecules (secondary structure) and in the packing of these chains to form the whole crystal is also evidenced. We have tried to find some relationship between the geometry of the amide fragment and the barrier to rotation about the amide bond. For the following eight compounds (formamide, N-methylformamide, N,N-dimethylformamide, N-methylbenzamide, N,Ndimethylbenzamide, urea, tetramethylurea and pyrazole-1-carboxamide) [4,26,27] there is no relationship with the CyO bond length but there is an acceptable ˚ ) [28,29] relationship with the C–N bond length (in A and with the number R of methyl groups on the nitrogen (from 0 for formamide to 4 for tetramethylurea). Ea(kcal mol) (494 ^ 24) – (364 ^ 18) dC–N ⫹ (3.7 ^ 0.2) R, n 8, r 2 0.988. The sign, but not the actual value, of both coefficients are as expected: first, the longer the C–N bond the lower the barrier and, second, the presence of methyl groups on the nitrogen increases the barrier. Acknowledgements Thanks are given to the DGICYT of Spain for financial support, PB96-0001-C03-02. References [1] H.A. Staab, H. Bauer, K.M. Schneider, K.M. Azolides, Organic Synthesis and Biochemistry, Wiley, New York, 1997. [2] L. Bouveault, Bull. Soc. Chim. Fr. 20 (1898) 77. [3] K. von Auwers, W. Daniels, J. Prakt Chem. 110 (1925) 235. [4] J. Elguero, R. Jacquier, Comp. Rend. Acad. Sci. (Paris) 260 (1965) 606. [5] J. Elguero, C., Marzin, L., Pappalardo, Bull. Soc. Chim. Fr. (1974) 1137. [6] P. Hennings, G. Ka¨stner, M. Klepel, A. Jumar, Z. Chem. 27 (1987) 435.
91
[7] J. Castells, M.A. Merino, M. Moreno-Man˜as, J. Chem. Soc. Chem. Commun. (1972) 709. [8] M. Begtrup, G. Boyer, P. Cabildo, C. Cativiela, R.M. Claramunt, J. Elguero, J.I. Garcı´a, C. Toiron, P. Vedsø, Magn. Reson. Chem. 31 (1993) 107. [9] R.W. Okey, H.D. Stensel, M.C. Martis, Water Sci. Technol. 33 (1996) 101. [10] F.H. Allen, J.E. Davies, J.J. Galloy, O. Johnson, O. Kennard, C.F. Macrae, E.M. Mitchell, G.F. Mitchell, J.M. Smith, D.G. Watson, J. Chem. Info. Comp Sci. 31 (1991) 187. [11] D.E. Appleman, (1984). LSUCRE, Program for least-squares refinement of reticular constants. US Geological Survey, Washington DC, USA. [12] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M.C. Burla, G. Polidori, M. Camalli, SIR92. J. Appl. Cryst. 27 (1994) 435. [13] S.R. Hall, H.D. Flack, J.M. Stewart, Xtal 3.2 (1993). Eds. University of Western Australia. Lamb: Perth. [14] M. Martı´nez-Ripoll, F.H. Cano, unpublished program, 1975. [15] International Tables for X-Ray Crystallography, vol. IV, 1974, Birmingham. Kynoch Press (present distributor D. Reidel, Dordrecht). [16] A.C. Olivieri, J. Elguero, I. Sobrados, P. Cabildo, R.M. Claramunt, J. Phys. Chem. 98 (1994) 5207. [17] C. Foces-Foces, C. Fontenas, J. Elguero, I. Sobrados, An. Quim, Int. Ed. 93 (1997) 219. [18] M. Nardelli, Comp. Chem. 7 (1983) 95. [19] S. Abrahams, E.T. Keve, Acta Crystallogr. A27 (1971) 157. [20] A. Domenicano, P. Murray-Rust, Tetrahedron Lett. 24 (1979) 2283. [21] L. Shimoni, J.P. Glusker, C.W. Bock, J. Phys. Chem. 100 (1996) 2957. [22] M.C. Etter, J.C. MacDonald, J. Bernstein. Acta Crystallogr. B 46 (1990) 256; J. Bernstein, R.E. Davis, L. Shimoni, N.-L. Chang, Angew. Chem., Int. Ed. Engl. 34 (1995) 1555 and references therein. [23] J. Lapasset, A. Escande, J. Falgueirettes, Acta Crystallogr. B28 (1972) 3316. [24] L. Leiserowitz, G.M.J. Schmidt, J. Chem. Soc. A (1969) 2372. [25] B.K. Vainshtein, V.M. Fridkin, V.L. Indenbom in Modern Crystallography II, Springer, Berlin, Heidelberg, New York, 1982, pp. 87. [26] M. Oki, Applications of Dynamic NMR Spectroscopy to organic Chemistry, VCH, Weinheim, 1985. [27] T. Drakenber, S. Forse´n, J. Phys. Chem. 74 (1970) 1. [28] K.B. Wiberg, K.E. Laidig, J. Am. Chem. Soc. 109 (1987) 5935. [29] K.B. Wiberg, C.M. Breneman, J. Am. Chem. Soc. 114 (1992) 831.