Mendeleev Communications Electronic Version, Issue 4, 1999 (pp. 129–170) Synthesis and stereochemical features of 2-oxo-3-cyano-1,2-thiaphosphorinanes Irina L. Odinets,* Natalya M. Vinogradova, Oleg I. Artyushin, Pavel V. Petrovskii, Konstantin A. Lyssenko, Michail Yu. Antipin and Tatyana A. Mastryukova A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 117813 Moscow, Russian Federation.Fax: +7 095 135 5085; e-mail mastr@ineos.ac.ru The intramolecular Pishchimuka rearrangement of 3-halopropyl-substituted thiophosphorylacetonitriles results in the corresponding 2-oxo-3-cyano-1,2-thiaphosphorinanes as a statistical mixture of two diastereomers, which transforms to an individual diastereomer with time; in benzene solution, the latter turns again into an equilibrium mixture of diastereomers.It is well known that 3- and 4-chloro-substituted O,O-diethylthiophosphonates on heating with sodium iodide in acetone form corresponding iodo derivatives, which undergo the intramolecular Pishchimuka rearrangement to yield 2-O-ethyl-2-oxo- 1,2-thiaphosphacyclanes (so-called thiolphostones).1,2 We prepared 3-chloropropyl-substituted thiophosphorylacetonitriles 1 by alkylation of thiophosphorylacetonitriles with 1,3- bromochloropropane under phase-transfer catalysis conditions.3 Unlike non-functionalised O,O-diethyl-w-chloroalkylthiophosphonates, these compounds are rather reactive.They partially undergo the intramolecular Pishchimuka rearrangement to corresponding 2-oxo-3-cyano-1,2-thiaphosphorinanes 3 under vacuum distillation (Scheme 1).Apparently, the formation of compounds 3 proceeds via corresponding phosphonium salts similarly to the previously suggested intramolecular S-alkylation in the series of non-functionalised w-haloalkyl-substituted thiophosphoryl compounds.2 The fact that for the 3-chloropropylsubstituted thiophosphorylacetonitriles with a diphenylthiophosphoryl group we detected (by NMR spectroscopy) the formation of the corresponding phosphonium salt (dP 39.4 ppm) in a MeCN solution at room temperature supports this assumption.Using different 3-chloropropyl-substituted methyl(alkoxy)- thiophosphorylacetonitriles 1b–d as an example, we found that the yield of thiophosphorinane 3b obtained by distillation depends on the radical R1 in the alkoxy group at the phosphorus atom.As should be expected, this yield decreased with increasing volume of the radical and especially when going to the compounds in which R1 is a secondary alkyl (the yield was about 50% at R1 = Et, about 32% at R1 = Bui and as low as 7% at R1 = Pri). Although thiaphosphorinanes 3a,b are sparingly soluble in usual organic solvents and can be recovered from distillates by precipitation, nevertheless it is much more suitable to prepare compounds 3 through corresponding iodo derivatives 2 (Scheme 1).On heating a MeCN solution of 1 with NaI, the cyclization was completed in 6–8 h.† The formation of 2 during the reaction and the structure of the compound were confirmed by NMR spectroscopy (31P and 1H). Note that in a MeCN solution the cyclization of iodopropyl-substituted thiophosphorylacetonitriles 2 proceeds slowly even at room temperature (the yield of 3 was 60–65% after 6 months).This cyclization is not stereoselective, and compounds 3 are formed as a statistical mixture of two diastereomers A and B,‡ which exhibit two closely located signals in the 31P NMR spectra. 1,2-Thiaphosphorinanes 3a,b were precipitated as solids with the same ratio between diastereomers on addition of diethyl ether to distillates (Hal = Cl) or to reaction mixtures (Hal = I).At the same time, in the absence of the solvent in distillates or in concentrated reaction mixtures, the slow transformation of equilibrium mixtures to the preferable individual diastereomers was observed. The relative configuration of chiral atoms in the diastereomers was determined by X-ray diffraction.For 2-ethoxy-substituted 1,2-thiaphosphorinane 3a, the configuration of asymmetric centres was found to be identical, while it was opposite for compound 3b with a methyl group at the phosphorus atom. A comparison of 31P NMR and X-ray diffraction data allows us to conclude that diastereomer † General procedure for the synthesis of 3a,b.Compounds 1 (obtained according to ref. 3) were heated with a 10% molar excess of NaI in a MeCN solution. After 1.5 h, the NaCl precipitate was filtered off, and heating was continued for 5–6 h. The mixture was evaporated, CHCl3 was added to the residue, and the mixture was filtered once again. The filtrate was evaporated under reduced pressure, the residue was either crystallised from Et2O (diastereomer mixture) or allowed to stand for spontaneous crystallization (individual diastereomer) followed by washing with benzene.The yield of 3a,b separated was about 73–78%. Compounds 3a,b had the satisfactory elemental analysis regardless of the isolation procedure. Selected data for 3a. D = 160–190 (1 mmHg), mp 65–70 °C (Et2O, A:B = 1:1).Diastereomer A: 1HNMR (CDCl3) d: 1.05 (t, 3H, MeCH2OP, 3JHH 7.0 Hz), 1.75–1.95 and 2.12–2.23 (2m, 1H + 1H, SCH2CH2), 2.24– 2.33 and 2.43–2.60 [2m, 1H + 1H, C(CN)CH2], 2.92–3.06 (m, 2H, SCH2), 3.02 (ddd, CHCN, 3JHH 4.0 Hz, 3JHH 10.4 Hz, 2JPH 19.0 Hz). 13C NMR (CDCl3) d: 15.7 (Me, 3JPC 7.0 Hz), 23.1 [C(5), 3JPC 6.1 Hz], 29.1 [C(6), 2JPC 5.8 Hz], 30.2 [C(4), 2JPC 3.6 Hz], 31.7 [C(3), 1JPC 100.8 Hz], 62.4 (OCH2, 2JPC 6.7 Hz), 115.2 (CN, 3JPC 4.5 Hz). 31P NMR, d: 36.6 (CDCl3), 34.9 (C6D6). Diastereomer B: mp 116–118 °C. 1H NMR (CDCl3) d: 1.13 (t, 3H, MeCH2OP, 3JHH 7.0 Hz), 1.86–1.90 and 2.15–2.20 (2m, 1H + 1H, SCH2CH2), 2.26–2.32 and 2.50–2.54 [2m, 1H + 1H, C(CN)CH2], 2.92–3.06 (m, 2H, SCH2), 3.16 (ddd, CHCN, 3JHH 3.8 Hz, 3JHH 10.0 Hz, 2JPH 18.4 Hz). 13C NMR (CDCl3) d: 15.9 (Me, 3JPC 6.2 Hz), 25.6 [C(5), 3JPC 4.5 Hz], 29.7 [C(6), 2JPC 5.8 Hz], 30.2 [C(4), 2JPC 3.6 Hz], 32.2 [C(3), 1JPC 96.8 Hz], 62.8 (OCH2, 2JPC 7.1 Hz), 114.9 (CN, 3JPC 11.2 Hz). 31P NMR, d: 36.2 (CDCl3), 34.0 (C6D6). For 3b: D = 170–190 °C (1 mmHg). Diastereomer A: mp 136–137 °C; 1H NMR (CDCl3) d: 1.98 (d, 3H, MeP, 2JPH 13.4 Hz), 2.12–2.19 (m, 2H, SCH2CH2), 2.25–2.39 and 2.52–2.56 [2m, 1H + 1H, C(CN)CH2], 2.87–2.92 and 3.36–3.28 (2m, 1H + 1H, SCH2), 3.25 (dt, CHCN, 3JHH 3.88 Hz, 2JPH 16.66 Hz). 31P NMR, d: 42.5 (CDCl3), 39.4 (C6D6). Diastereomer B: 31P NMR, d: 40.01 (CDCl3), 37.4 (C6D6). ‡ The diastereomer having a downfield signal in the 31P NMR spectra was designated as diastereomer A. P(S)CHCN R1O R (CH2)3Cl P R1O R S NC Cl P(S)CHCN R1O R (CH2)3I P R1O R S NC I NaI/MeCN reflux 1a–d 2a–d D MeCN P O R S NC 3a,b – R1Cl – R1I 1,2: a R = OEt, R1 = Et b R = Me, R1 = Et c R = Me, R1 = Bui d R = Me, R1 = Pri 3: a R = OEt b R = Me Scheme 1 The synthesis of 2-oxo-3-cyano-1,2-thiaphosphorinanes.Mendeleev Communications Electronic Version, Issue 4, 1999 (pp. 129–170) A is characterised by the configuration (2S*,3R*) with the fully staggered disposition of the cyano group and the oxygen atom of the P=O group, while the identical configuration of asymmetric centres, i.e.(2R*,3R*), with the skew arrangement of the above groups corresponds to isomer B. Note that in spite of different surroundings at the phosphorus atom (phosphonate and phosphinate structures in 3a and 3b, respectively) the signals in the 31P NMR spectra of these compounds are close to one another and upfield shifted with respect to the signals of linear compounds with similar surroundings at the phosphorus.Thus the chemical shift primarily depend on the presence of a 1,2-thiaphosphorinane ring in the molecule. According to X-ray diffraction data,§ bond lengths and angles in both molecules (Figures 1 and 2) exhibit expected values.4,5 The phosphorus atoms are characterised by a slightly distorted tetrahedral configuration with the endocyclic angles 105.1(1)° and 103.9(1)° in the structures of 3a(B) and 3b(A), respectively.In both molecules, six-membered rings exhibit a slightly distorted chair conformation. In both structures, the CN group occupies an axial position, while the positions of oxygen atoms of the phosphoryl group are different.In 1,2-thiaphosphorinane 3a(B) (R = OEt), it occupies an equatorial position with the torsion angle O(1)–P(1)– C(4)–C(5) equal to 48.9°, while it is in an axial position in 3b(A) (R = Me) and is fully staggered to the CN group with the torsion angle equal to 170.6°. Evidently, the strength of the possible stereoelectronic n–s* interaction between the lone electron pair of sulfur and the antibonded orbital of the axial group at the phosphorus atom [P(1)–O(2) in 3a(B) and § Crystallographic data for 3a and 3b at –80 °C: crystals of C7H12N2PS 3a are monoclinic, space group C2/c, a = 21.034(9) Å, b = 6.076(4) Å, c = 18.015(9) Å, b = 118.16(2)°, V = 2030(2) Å3, Z = 8, M= 205.21, dcalc = 1.343 g cm–3, m(MoKa) = 4.39 cm–1, F(000) = 864; crystals of C6H10NOPS 3b are triclinic, space group P , a = 6.978(7) Å, b = = 7.132(3) Å, c = 9.813(6) Å, V = 414.7(5) Å3, a = 101.72(4)°, b = = 101.79(6)°, g = 113.77(5)°, Z = 2, M= 175.17, dcalc = 1.403 g cm–3, m(MoKa) = 5.16 cm–1, F(000) = 184.Intensities of 3049 reflections for 3a and 1445 reflections for 3b were measured with a Syntex P21 diffractometer at –80 °C (l MoKa radiation, q/2q scan technique, 2qmax < 60° for 3a and 50° for 3b) and 2977 for 3a and 980 for 3b independent reflections were used in further calculations and refinement.The structures were solved by a direct method and refined by a fullmatrix least-squares against F2 in the anisotropic-isotropic approximation. Hydrogen atoms were located from the difference Fourier synthesis and refined in the isotropic approximation. The refinement converged to wR2 = 0.2615 and COF = 0.869 for all independent reflections [R1 = = 0.0736 for 1102 observed reflections with I > 2s(I)] for structure 3a and to wR2 = 0.1629 and COF = 1.059 for all independent reflections [R1 = 0.0437 for 880 observed reflections with I > 2s(I)] for structure 3b.All calculations were performed using the SHELXTL PLUS 5.0 program on an IBM PC/AT.Atomic coordinates, bond lengths, bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details, see ‘Notice to Authors’, Mendeleev Commun., 1999, Issue 1. Any request to the CCDC should quote the full literature citation and the reference number 1135/51.P(1)=O(1) in 3b(A)] is different in these two cases.6 This n–s* interaction will result in shortening the P(1)–S(1) bond. Taking into account that the P(1)–S(1) bond in 3a(B) is significantly shorter [2.044(2) Å] than that in 3b(A) [2.062(2) Å], we can conclude that the above interaction is more pronounced in the case of the P(1)–O(2) antibonded orbital in diastereomer B of 1,2-thiaphosphorinane 3a.The appreciable shortening of the P(1)=O(1) bond length up to 1.456(2) Å in the above structure in comparison with 3b(A) [1.488(2) Å] is not only due to the difference in the n–s* interaction, but also due to the alteration of the coordination sphere of the phosphorus atom (replacement of OEt with Me).7 Note that P–S bond lengths in cyano-substituted 1,2-thiaphosphorinanes 3 are similar to those [2.048(2)–2.068(2) Å] in the series of 2,2-diphenyl-1,2l4-thiaphospholanium and 2,2-diphenyl- 1,2l4-thiaphosphorinanium salts.2 Furthermore, the S(1)– C(1) bond in the crystal structure of 3b(A) is significantly elongated up to 1.835(1) Å as compared with that in 3a(B) [1.807(5) Å] and also is very similar to the corresponding bond in the above thiaphosphorinanium salts [1.837(5) Å].The P(1)– C(4) bonds in 1,2-thiaphosphorinanes 3a,b are significantly longer [1.817(4) Å]. Thus, the phosphorus atom in the crystal structures of 3a,b possesses a significant positive charge which is larger in 3b(A), where the n–s* interaction is less pronounced. In both of the crystal structures of 3, molecules are assembled by the C(4)–H(4)···O(1)=P(1) H-bonds in two centrosymmetric dimers, which in turn are interlinked by the C–H···O=P bonds in double H-bonded layers (Figures 3 and 4).Note that, from the geometrical point of view (C···O and H···O distances), the C–H···O=P H-bonds in 3b(2S*,3R*) molecules are significantly stronger than those in the crystal structure of 3a(2R*,3R*). This Figure 1 The general view of diastereomer B (2R*,3R*) of 3a.Selected bond lengths (Å): P(1)–O(1) 1.456(3), P(1)–O(2) 1.573(3), P(1)–C(4) 1.817(4), P(1)–S(1) 2.044(2), S(1)–C(1) 1.807(6); selected bond angles (°): O(1)–P(1)–O(2), 116.7(2), O(1)–P(1)–C(4) 117.0(2), O(2)–P(1)–C(4) 98.2(2), O(1)–P(1)–S(1) 109.4(2), O(2)–P(1)–S(1) 109.0(1), C(4)–P(1)– S(1) 105.5(1), C(1)–S(1)–P(1) 99.2(2), C(6)–O(2)–P(1) 119.0(3), C(2)– C(1)–S(1) 114.3(3), C(5)–C(4)–P(1) 109.5(3), C(3)–C(4)–P(1) 113.2(3).C(7) C(6) O(2) P(1) O(1) S(1) C(1) C(2) C(3) C(4) C(5) N(1) 1 Figure 2 The general view of diastereomer A (2S*,3R*) of 3b. Selected bond lengths (Å): P(1)–O(1) 1.488(2), P(1)–C(6) 1.785(3), P(1)–C(4) 1.838(4), P(1)–S(1) 2.062(2), S(1)–C(1) 1.835(3); selected bond angles (°): O(1)–P(1)–C(6) 114.6(1), O(1)–P(1)–C(4) 108.3(1), C(6)–P(1)–C(4) 109.1(2), O(1)–P(1)–S(1) 116.4(1), C(6)–P(1)–S(1) 103.8(1), C(4)–P(1)– S(1) 103.9(1), C(1)–S(1)–P(1) 97.9(2), C(2)–C(1)–S(1) 113.7(3), C(5)– C(4)–P(1) 112.1(2), C(3)–C(4)–P(1) 108.7(3).S(1) P(1) C(6) C(1) C(2) C(3) C(4) C(5) N(1) O(1) Figure 3 The doubly bonded layers in the crystal structure of 3a(B). The shortened contacts are: C(4)–H(4)···O(1') (–x, 1 – y, –z) [H(4)···O(1') 2.31 Å, C(4)···O(1') 3.266(4) Å, C(4)–H(4)···O(1') 147°]; C(3)–H(3A)···O(1'') (x, –1 + y, z) [H(3A)···O(1'') 2.36 Å, C(3)···O(1'') 3.345(4) Å, C(3)– H(3A)···O(1'') 153°].P(1'') O(1'') Et O(2) C(2) C(1) S(1) P(1) O(1) N(1) C(5) C(4) H(4) C(3) H(3A) H(4') C(4') P(1') O(1')Mendeleev Communications Electronic Version, Issue 4, 1999 (pp. 129–170) can be due to additional accumulation of the negative charge at the phosphoryl oxygen atom O(1). These O···H contacts, according to Desiraju,8 can be considered as medium-strength contacts, which play an important role in the crystal packing. It is likely that the formation of these contacts in the crystals of preferential individual diastereomers of 1,2-thiaphosphorinanes 3a,b resulted in the crystallization from concentrated reaction mixtures.At the same time, an equilibrium mixture of both diastereomers is formed in solutions where these contacts are impossible. In benzene solutions, slow reverse transformation of individual diastereomers 3a(B) and 3b(A) to the corresponding equilibrium mixtures, where the ratio A:B = 1:1 was achieved in about 3 months, was observed.Evidently, mutual transformations of the diastereomers proceed through opening of the six-membered ring (at either a P–S or S–C bond), inversion of the configuration of one of the asymmetric centres and subsequent recyclization. This work was supported by the Russian Foundation for Basic Research (grant nos. 96-03-32992a and 96-15-97367). References 1 O.V. Bykhovskaya, I. M. Aladzheva, D. I. Lobanov, P. V. Petrovskii, T. A. Mastryukova and M. I. Kabachnik, Abstratcs of the XI International Conference on Chemistry of Phosphorus Compounds (ICCPC-XI), Kazan, 1996, p. 155. 2 I. M. Aladzheva, O. V. Bykhovskaya, D. I. Lobanov, P. V. Petrovskii, K. A. Lyssenko, T. A. Mastryukova and M. I. Kabachnik, Zh. Obshch. Khim., 1998, 68, 1421 (Russ. J.Gen. Chem., 1998, 68, 1356). 3 N. M. Vinogradova, I. L. Odinets, O. I. Artyushin, P. V. Petrovskii, K. A. Lyssenko, M. Yu. Antipin and T. A. Mastryukova, Zh. Obshch. Khim., 1998, 68, 1434 (Russ. J. Gen. Chem., 1998, 68, 1368). 4 D. G. Gilheany, The Chemistry of Organophosphorus Compounds, ed. F. R. Harley, Wiley–Interscience, Chichester, 1992, vol. 2, p. 1. 5 Cambridge structural database, release 1998. 6 D. G. Gorenstein, Chem. Rev., 1987, 37, 1047. 7 I. L. Odinets, O. I. Artyushin, R. M. Kalyanova, A. G. Matveeva, P. V. Petrovskii, K. A. Lyssenko, M. Yu. Antipin, T. A. Mastryukova and M. I. Kabachnik, Zh. Obshch. Khim., 1997, 67, 922 (Russ. J. Gen. Chem., 1997, 67, 862) and references therein. 8 G. R. Desiarju, Acc. Chem. Res., 1996, 29, 441. Figure 4 The doubly bonded layers in the crystal structure of 3b(A). The shortened contacts are: C(4)–H(4)···O(1') (–x, 1 – y, 1 – z) [H(4)···O(1') 2.22 Å, C(4)···O(1') 3.246(4) Å, C(4)–H(4)···O(1') 161°]; C(6)–H(6B)···O(1'') (1 – x, 1 – y, 1 – z) [H(6B)···O(1'') 2.42 Å, C(3)···O(1'') 3.469(4) Å, C(3)– H(3A)···O(1'') 167°]. P(1'') O(1'') C(2) C(1) S(1) P(1) O(1) N(1) C(5) C(4) H(4) C(3) H(4') C(4') P(1') O(1') C(6) H(6B) C(6'') H(6B'') Received: 24th March 1999; Com. 99/1468