Introduction

Azomethine imines, R–N+–N−R = CHR/, are 1,3-dipoles of the aza-allyl type. Much use has been made in organic syntheses of their cycloaddition reactions, in particular [3 + 2] additions [1,2,3]. While many are transient intermediates and are used in situ, others have been found to be stable and isolatable. Cyclic derivatives with additional carbonyl substituents are more stable, due to increased conjugation. Further stabilization may arise from the presence of a benzylidene derivative.

Various preparations of azomethine imide derivatives have been reported with more accessible routes involving reactions of pyrazolidin-3-ones with substituted benzaldehydes or using substituted acylhydrazines, RCONHNHR as precursors [4,5,6,7].

In studies of the cyclisation reactions of alkyl (S)-2-[2-(benzylidene)hydrazine]-1-(hydroxymethyl)-2-oxocarbamates, 1, prepared from L-serine, 2 [8], see Scheme 1, we have found that their treatment with mesityl chloride and triethylamine generates chiral azomethine imines derivatives (Z)-(4S)-4-(alkyloxycarbonylamino)-3-oxo-1-(benzylidene)-pyrazolidinium inner salts, 3, see Scheme 1. We now wish to report the structure determination of (Z)-(4S)-4-(tert-butyloxycarbonylamino)-3-oxo-1-(2-methoxybenzylidene)-pyrazolidinium inner salt, also named (Z)-(S)-4-(tert-butylcarbonylamino)-2-(2-methoxybenzylidene)-5-oxopyrazolidin-2-ium-1-ide, (3a: R = tert-Bu, X = 2-MeO) The chirality of the compounds is derived from that of the (l)-serine precursor. The kinetic resolutions of 5-oxopyrazolidin-2-ium-1-ides using copper catalysts has been carried out [9].

Scheme 1
scheme 1

Reagents and conditions: (i) MeOH, SOCl2, rt; (ii) PhCH2Cl, NaHCO3, H2O, rt or (ButOC)2O, Et3N, THF, rt; (iii) N2H4.H2O (80%), EtOH, rt; (iv) EtOH, XC6H4CHO, reflux, (v) MeSO2Cl, Et3N, CH2Cl2

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The stability of compound 3a is considered to be due, partially at least, to the presence of the 2-methoxybenzylidenyl substituent and its near planarity with the core of the oxo-1-(benzylidene)-pyrazolidinium unit, which allows a very extensive conjugation to be set up, see Fig. 1.

Fig. 1
figure 1

Canonical forms for a (2-methoxybenzylidene)-pyrazolidinium inner salt

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The crystal structure of 3a is compared to the reported structures of of other 3-oxo-1-pyrazolidinium inner salts.

General

Melting points were determined on a Buchi apparatus and are uncorrected. Infrared spectra were recorded on a Thermo Nicolet Nexus 670 spectrometer in potassium bromide discs. Mass spectra (ESI assay in solution of ammonium chloride) were recorded on a Micromass ZQ Waters mass spectrometer. Microanalysis data were obtained using a Perkin–Elmer 240 analyser, using a Perkin–Elmer AD-4 balance. NMR spectra were recorded on a Bruker Avance 500 spectrometer at room temperature. TLC was carried out on plates coated with silica gel, using ultraviolet light or ninhydrine (0.2% p/v in ethanol) to develop the plates.

Formation of 3a

tert-Butyl (S)-2-[2-(methoxybenzylidene)hydrazine]-1-(hydroxymethyl)-2-oxocarbamate, (1a: R = tert-Bu, X = 2-MeO) was prepared as previously reported [8]. A reaction mixture of 1a (0.30 g, 0.9 mmol), methanesulfonyl chloride (0.1 mL, 1.35 mmol) and Et3N (3.7 mL, 27 mmol) in dichloromethane (10 mL) was stirred at room temperature for 24 h. To the reaction mixture was added water (10 mL), the organic phase was collected and successively washed with aqueous hydrochloric acid (10%v/v, 2 × 20 mL) and water (2 × 20 mL), and dried over sodium sulfate. The residue, after rotary evaporation, was column chromatographed. The desired compound 3a was obtained in 80% yield, 230 mg, mp 165-6 °C.

1H NMR (500 MHz, DMSO-d6) δ (ppm): 8.97 (1H, d; J = 7.8 Hz, NHCH), 7.76 (1H. s, N = CH), 7.52 (1H, t, J = 7.8 Hz, H3), 7.29 (1H, d, J = 7.8 Hz; H5), 7.16 (1H, d, J = 7.8 Hz, H2), 7.10 (1H, t, J = 7.8 Hz, H4), 4.81 (1H, m, CH), 4.40–4.25 (2H, m, CH2), 3.90 (3H, s, CH3), 1.39 (9H, s, (CH3)3C).

13C NMR (125 MHz, DMSO-d6) δ (ppm): 182.4 (COCH), 158.5 (C1), 155.8 (COO), 133.8 (N = CH), 131.8 (C3 or C5), 127.7 (C3 or C5), 121.0 (C4), 118.4 (C6), 111.8 (C2), 78.8 ((CH3)3C−), 62.4 (CH); 56.5 (CH3), 50.2 (CH2), 28.6 ((CH3)3C−).

ir (cm−1; KBr): 1705 (COCH), 1662 (COO).

ms/esi: [M + Na]: 342.

Calcd. for C16H21N3O4: C: 60.18; H: 6.62; N: 13.15. Found: C: 60.31; H: 6.68; N: 13.03.

Crystal Structure Determination

Intensity data were obtained at 120(2) K with Mo-Kα radiation by means of a Bruker-Nonius Roper CCD on kappa-goniostat by the National Crystallographic Service, UK, based at the University of Southampton. Data collection was carried out under the control of the program COLLECT [10] and data reduction and unit cell refinement were achieved with the COLLECT [10] and DENZO [11] programs. Correction for absorption was achieved in each case by a semi-empirical method based upon the variation of equivalent reflections with the program SADABS 2007/2 [12]. The program MERCURY [13] was used in the preparation of the Figures. The structures were solved by direct methods using SHELXS-97 [14] and fully refined by means of the program SHELXL-97 [14]. The refinement was carried out as a 2-component inversion twin. The programs, SHELXL97 [14] and PLATON [15], were used in the calculation of molecular geometry. All hydrogen atoms were placed in calculated positions. Crystal data and structure refinement details are listed in Table 1.

Table 1 Crystal data and structure refinement for 3a
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Results and Discussion

As found for various acylhydrazone derivatives [16, 17], compound (1a: R = tert-Bu, X = 2-MeO) in solution is a mixture of (E)/(Z) isomers about the C=N bond, as shown by the doubling of certain NMR signals. In contrast, the 1H and 13C NMR spectra of 3a indicated a single isomer in solution: considering the results of the X-ray structure determination, see below, this is shown to be the (Z)-isomer. As the formation of the five-membered ring does not involve reaction at the chiral cente in 1, the stereochemistry is maintained in the product 3a. The role of MeSO2Cl is to form a more effective leaving group on reaction with the hydroxyl group.

Crystal Structure of 3a

The crystals of 3a used in the structure determination were grown by slow evaporation of a solution in methanol at room temperature. The betaine compound crystallizes in the chiral orthorhombic space group P212121, with one molecule in the asymmetric unit. Figure 2a shows the numbering scheme and the atom arrangements, with a (S)-configuration at C4 and a (Z) arrangement about the exocyclic C=N bond. There are four weak intramolecular hydrogen bonds in five as listed in Table 1.

Fig. 2
figure 2

a Atom numbering scheme and atom connectivity for 3a. Probability ellipsoids are drawn at the 50% level, b view of the molecular conformation, looking along the edge of the phenyl and pyrazolyl rings

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As indicated by the Puckering parameters [18], [Q(2) = 0.083(4) Å and Φ(2) = 147(3)°], the pyrazolyl ring exhibits a slight envelope shape, with the flap at C5. The displacement of C5 from the best plane through the ring, however, is only 0.053(5) Å, which for all intents and purposes indicates a very near planar ring. Sush a light deviation from planarity has been reported for other 5-oxopyrazolidin-2-ium-1-ides [19,20,21,22] The dihedral angle between the phenyl group and the complete oxopyrazolidinyl ring is 12.14(16)°: dihedral angle between the phenyl group and the N–N–C=O fragment of the oxopyrazolidinyl moiety moiety involved in the conjugation is just a little smaller at 10.82(16)°. A view of the conformation of 3a, looking along the edge of the combined phenyl and pyrazolyl rings, is shown in Fig. 2b. There are four intramolecular hydrogen bonds in 3a: two of which, C17–H17A···O1 and C18–H18B···O1, involve the tert-butyloxycarbonylamino substiuent and the other two, C6–H6···O4 and C18–H18C···N2, involve the 2-anisyl substiuent and the oxopyrazolidinyl ring. The latter two must be influential in keeping the dihedral angle small between the two components, thereby possibly aiding conconjugation between the two fragments.

The pyrazolyl ring has a betaine character with opposite charges on N1 and N2 atoms. The bond lengths and angles in the betaine ring are within the regions found for related compounds [4,5,6, 18,19,20,21]. The C7–C12 bond length, 1.429(6) Å, is noticeably longer than the other C–C bond lengths, 1.377(6)–1.399(6) Å, in the phenyl ring, which indicates a degree of bond fixation arising.

The PLATON analysis [15] indicated that the supramolecular arrangement is created from one classical N–H···O and weaker C–H···X (X = O, N) intermolecular hydrogen bonds [23], see Table 2 for symmetry operations. The strongest intermolecular interaction, the N3–H3···O2 hydrogen bond, generates zig-zag chains, C(5) [24], of molecules formed in the direction of the a axis, as illustrated in Fig. 3a. These chains are augmented by C3=O2···π(pyrazole) interactions. The four weaker intermolecular hydrogen bonds individually generate chains of molecules [23]: the C19–H19···O1 and the C15–H15A···N2 hydrogen bonds generate C(6) and C(8) chains, respectively, in the direction of the a axis, and the C11–H11···O2 and C18–H18B···O1 hydrogen bonds form C(9) and C(6) chains, respectively, in the direction of the b axis. Combinations of pairs of these individual hydrogen bonds create more elaborate structural sub-sets. Thus combinations (i) of the C19–H19A···O1 and C11–H11···O2 hydrogen bonds generate sheets of molecules in the ab plane, containing R44(40) rings [24], as illustrated in Fig. 3b, (ii) of the C18–H18C···O1 and C11–H11···O2 hydrogen bonds produce a two molecule wide column, containing R33(26) rings, propagated in the ac plane, see Fig. 3c, and (iii) of the C19–H19A···O1 and C15–H15A···N2 hydrogen bonds generate another two molecule wide column, containing R33(26) rings, propagated in the ab plane, see Fig. 3d. Overall, a 3-dimensional arrangement is formed.

Table 2 Geometric parameters (Å, °) for intra- and intermolecular interactions
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Fig. 3
figure 3

a A part of a chain, C(5), of molecules generated from N3–H3···O2 intermolecular hydrogen bonds, augmented by C3–O2···π(pyrazole) interactions, b a sheet of molecules, with a network of rings, R44(40), obtained from C19–H19A···O1 and C11–H11···O2 intermolecular hydrogen bonds, c part of a two-molecule wide column of molecules, containing R33(26) rings, generated from C18–H18B···O1 and C11–H11···O2 intermolecular hydrogen bonds, d part of another two-molecular wide column, also containing rings, obtained from C19–H19A···O1 and C15–H15A···N2 intermolecular hydrogen bonds. Table 2 contains the symmetry operations. Intermolecular interactions are drawn as thin dashed lines

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Comparison of the structures

In Table 3, selected data are provided for a number of 5-oxopyrazolidin-2-ium-1-ide derivatives, 12 of which contained an arylidene sbstituent [4, 6, 19, 21, 25,26,27,28,29]. Featured are the C3 = O and N+=CC5,C6 bond distances, which are taken as indicators of the conjugation of the N+–N− bond with the carbonyl group of the 5-oxopyrazolidin-2-ium-1-ide derivative and the R5, R6CH = fragment, respectively: the values of the two bond lengths ranges for all 13 compounds are narrow being 1.226(2) to 1.242(11) (C–O) and 1.289(3) to 1.324(12) Å (C–N). No clear cut pattern w.r.t. to substituent effects emerges from these data regarding the interplanar angle between the aryl unit at R5 and the 5-oxopyrazolidin-2-yl ring in compounds 3a, 4–15. It is argued that the smaller this angle the greater possibilitythere will be for conjugation between the two fragments. It is apparent that the smallest angles are found for compounds having both electron releasing substituents in the benzylidene moiety and the absence of steric hindrance, arising from R1 and R2 substituents. Thus compound 5, with a 4-methoxyphenyl substituent and only hydrogens at R1 and R2, has a zero interplanar angle, while compounds 9 and 10, each with 2,6-dichlorobenzylidene substituents and alkyl groups at R1 and /or R2 have large interplanar angles > 58°. Interestingly the presence of polynuclear aryl groups such as pyren-1-yl in 12, anthracen-9-yl in 13 and 2-hydroxynaphenylen-1-yl in 4, result in large interplanar angles, even in the absence of bulky substituents. In other cases, the lack of steric hindrance, even wth poorly electron releasing aryl substituents, e.g. 4-chlorophenyl in compounds 7 and 8, can result in small interplanar angles, but on the contrary, a strong electronwithdrawing group, such as the 4-nitrophenyl group in 11, even in the absence of steric effects, produces a significant interplanar angle of 19.4°.

Table 3 Selected geometric parameters for 5-oxopyrazolidin-2-ium-1-ides (Å, °)
figure b
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Other Cyclization Reactions of 1

In earlier articles [8, 30], we have reported on the formation of 2-oxo-1,3-oxazolidine 4-carbohydrazide derivatives from cyclization reactions of (1: PhCH2 or But), see Scheme 2. Thus, reaction of 1 with NaH lead to the formation of 2-oxo-1,3-oxazolidine 4-carbohydrazide derivatives, 16 [8], while treatment with the weaker base, potassium carbonate, in the presence of methyl iodide, only the more reactive compounds 1 underwent cyclizations to N-methylated 2-oxo-1,3-oxazolidine 4-carbohydrazide derivatives, 17 [30, 31]. The tert-butyl esters, proved to be generally less susceptible to cyclizations and just provided the methylated products, alkyl N-[(E)-1-(2-benzylidene-1-methylhydrazinyl)-3-hydroxy-1-oxopropan-2-yl]carbamates, 18, [30, 32]. The presence of the basic reaction media leads to racemisations in some cases.

Scheme 2
scheme 2

Reagents : (i) NaH, THF; (ii) MeI, K2CO3, Me2CO, 50 °C, 24–48 h

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Conclusions

The crystal structure determination of the title compound revealed similiarities with published structures of related compounds. A small interplanar angle between the 2-methoxyphenyl and the pyrazolidinyl ring allows extensive conjugation in the molecule. Compounds, (S)-ROCH2CONHCH(CH2OH)CONHN = Ar are versatile precursors of different cyclized products, such as (Z)-(S)-4-(tert-butylcarbonylamino)-2-(benzylidene)-5-oxopyrazolidin-2-ium-1-ides as well as 2-oxo-1,3-oxazolidine 4-carbohydrazides, N-methylated 2-oxo-1,3-oxazolidine 4-carbohydrazides derivatives and alkyl N-[(E)-1-(2-benzylidene-1-methylhydrazinyl)-3-hydroxy-1-oxopropan-2-yl]carbamates.

Supplementary Material

Full details of the crystal structure determination in cif format are available in the online version, at doi: (to be inserted), and have also been deposited with the Cambridge Crystallographic Data Centre with deposition number 1426424. Copies can be obtained free of charge on written application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax: +44 1223 336033); on request by e-mail to deposit@ccdc.cam.ac.uk or by access to http://www.ccdc.cam.ac.uk.