Reaction of oxophosphorane-sulphenyl and -selenenyl chlorides with dialkyl trimethylsilyl phosphites. Novel synthesis of compounds containing a sulphur or selenium bridge between two phosphoryl centres

摘要

J. CHEM. SOC. PERKIN TRANS. I 1988 Reaction of Oxophosphorane-sulphenyl and -selenenyl Chlorides with Dialkyl Trimethylsilyl Phosphites. Novel Synthesis of Compounds Containing a Sulphur or Selenium Bridge Between Two Phosphoryl Centres t Aleksandra Skowronska," Roman Dembinski, Rafal Kaminski, and Jan Michalski Polish Academy of Sciences, Centre of Molecular and Macromolecular Studies, 90-362Lodz, Boczna 5 Poland A novel highly efficient synthesis of sym-tetra-alkyl monothio- and monoseleno-pyrophosphates (RO),P(O)XP(O) (OR'), (X = S,Se) based on the condensation of dialkoxyoxophosphorane-sulphenyl or -selenenyl chlorides (RO),P(O)XCI (X = S,Se) with dialkyl trimethylsilyl phosphites (RO),POSiMe, (9) is described. Remarkably selective reaction of a 0,O'-dialkyl 0"-trimethylsilyl selenophosphate (RO),P(Se)OSiMe, (13) with sulphuryl dichloride in the presence of an equimolar amount of a phosphite (9) leads to the formation of sym-monoselenopyrophosphates in excellent yield. A new rearrangement in phosphorus chemistry, sym-monoselenopyrophosphates (11) to asym-monoseleno-pyrophosphates (12), has been observed.Organic pyrophosphates play a fundamental role in biology. The reaction between oxophosphoranesulphenyl chlorides Their thio analogues have been used in stereochemical studies (3) and trialkyl phosphites (6) proceeds in a complex manner. on nucleophilic displacement reactions at tetraco-ordinate The anhydrides (1) are formed in low yield with a number of phosphorus,2 and more recently in enzymatic ~tudies.~ other products,6 Although the phosphonium salt (7)containing Tetra-alkyl monothiopyrophosphates exist in two isomeric a phosphorus-sulphur-phosphorus bridge is observed as a first structures: symmetrical (RO),P(O)SP(O)(OR'), (1) and asym- intermediate, its decomposition to thiopyrophosphate (1) uia metrical (RO),P(S)OP(O)(OR'), (2).The monothiopyrophos- dialkylation constitutes a minor pathway (path a) (Scheme 3).phates (2) are more readily available and thermodynamically more stable than the isomers (1). The latter undergo thiolo- (RO),P-SCI + (R'O),PII11thiono rearrangement (1) -(2).4 This pronounced tendency for isomerization impedes the synthesis of the thioanhydrides 0 (1). The only feasible approach towards the synthesis of compounds (1) is phosphorylation of dialkyl phosphites with dialkoxyoxophosphoranesulphenyl chlorides (RO),P(O)SCl $.7(1) + RCI (3)5 (Scheme 1). +(RO), P-S-PPOR'), 4. CISN3 "/-C5H,0N*HCl bsol; 0" CI' 'i;k (RO,)P(O)CI + (R'O), P=S L(RO)zP,Go (RO),P-OH (1 1 .=.-H + (3) -HCI Scheme 1. ( RO),P-OII -P(OR'), Methods a and b are satisfactory for the preparation of the anhydrides (1) of relatively high stability. From a preparative point of view method b is more convenient provided that hydrogen chloride is rapidly removed, at below room temper- ature, from the reaction medium. Even with proper precautions, a certain amount of product (1) is lost due to the rearrangement (1) -(2) catalysed by dialkyl hydrogen thiophosphate (4).The latter and dialkyl phosphorochloridate (5) are formed by cleavage of compounds (1) with hydrogen chloride (Scheme 2). (1) + HCl-(RO),P(S)OH + (RO),P(O)CI (4) (5) (1) J (2) Scheme 2. t Preliminary paper concerning sym-monoselenopyrophosphates.' Scheme 1. Nucleophilic attack of the chloride anion on the phosphoryl centre of intermediate (7)(path b), or isomerization of (7)into phosphonium salt (8) (path c), efficiently competes with dealkylation. The intermediate salt (8)also decomposes, usually by dephosphorylation (path e) rather than by dealkylation (path d). We have found that the course of the reaction could be noticeably changed using dialkyl trimethylsilyl phosphites (9). With compounds (9), the only phosphorus products observed are the sym-monothiopyrophosphates(l),resulting from attack of the chloride anion on silicon in the intermediate phos- phonium salts (10) (Scheme 4).The reaction between substrates (3) and (9) can be recom- mended as the method of choice for the preparation of simple (R = R'), mixed (R # R'), and labelled (35S)thioanhydrides 2198 (RO),P-SC1 + (R'O),POSiMe, igz P I1 0 (9) (3) (10) Me,SiCl + (RO),P-S-P(OR'),It It 00 Scheme 4. (1). All compounds (1) have n.m.r. and i.r. spectra consistent with the assigned structures. The reaction is highly exothermic and occurs satisfactorily below -35 "C with intensive stirring. In this manner the thioanhydrides (1) can be obtained in almost quantitative yield and high purity.If the esters (9) are sufficiently pure, and nucleophilic catalysis does not operate, the method does not give any by-products. In these conditions the thioanhydrides (1) are relatively stable. Until recently, access to the seleno analogues of (1) contain-ing the P(O)-Se-P(0): skeleton has been hampered by the lack of preparative methods. Rycroft and White prepared bis- (5,5-dimethyl-2-oxo-1,3,2-dioxaphosphinan-2-y1)selenide (1le Me Me -2H20 + H2SeOj in low yield by condensation of selenious acid with two equiva- lents of 5,5-dimethyl-2-oxo- 1,3,2-dioxaphosphinane 'equation (l). We have found that this procedure leads to a complex mixture of phosphorus-containing products. We can confirm, however, that in exceptional cases like the one described above compound (lle) is formed in low yield.This result is not surprising in the light of our present knowledge on the reactivity of compound (lle) and their analogues (11). Water, which is formed in reaction (l),causes hydrolytic splitting of compound (lle). This splitting promotes a variety of secondary reactions including rearrangement (11) -(12) equation (2). OR' /Robsol; P-Se-P, '-+ Ro, P-0-P OR' (2) RO'll II OR' RO'll 11 'OR' 0 Se 0 (11) (12) The sym-monoselenopyrophosphates (11) are effectiveiy syn- thesized in a similar manner to their sulphur analogues (1) starting from dialkyl trimethylsilyl phosphites (9) and the J. CHEM. SOC. PERKIN TRANS. I 1988 oxophosphoraneselenenyl chlorides (14).The chlorides (14) are extremely unstable, even when prepared from the seleno- phosphates (13) equation (3), and can only be used as reagents if the temperature is sufficiently low.8 Se SeC I4 / + Me,SiCI (3)(RO),Pbsol; OSiMe3 -78 '' In our experience chlorides (14) decompose rapidly even below -40 "C by a chain reaction involving nucleophilic displacement at the phosphoryl centre by chloride anion (Scheme 5). CI-(RO)CI' + (14) P/ + -SeCI 2+ 0 The SeCl group is very readily displaced at both phosphoryl and phosphonium centres. The phosphonium intermediates (15) and (16) are observed at -78 "C by 31 P n.m.r. spectroscopy when elemental chlorine is allowed to react with the silane (13).9 The structure of the phosphonium salt (16) has been con- firmed by its independent synthesis via Arbuzov reaction between triethyl phosphite (17) and elemental chlorine lo (Scheme 6).SeCl C'2 RO, I (13) -/+P-OR Robsol; R = Et P-OR/ RO-(17) Scheme 6. The selenenyl chlorides (14) prepared in situ by chlorination of silanes (13) were allowed to react immediately at -78 "C with the corresponding phosphites (9) to afford the s-vm-monoselenopyrophosphates (1 1) equation (4). Although this -78 "C(RO),P-SeCl + (R'O),POSiMe,It 0 (9) (4)(14) (RO),P-Se-P(OR'), + Me,SiClIt 80 (11) J. CHEM. SOC. PERKIN TRANS. I 1988 procedure is quite satisfactory from a preparative point of view, we have improved it. We have discovered a very selective reaction of silanes (13)with sulphuryl dichloride in the presence of an equimolar amount of phosphites (9),leading to the simple (R = R') and mixed (R # R') sym-monoselenopyrophosphates (11) in excellent yield equation (5).CHZCIZ -78 OC (5)I (11) + SO, + 2Me3SiCI Ia; R= R = Me; b; R= R'= Et; c; R= R'= Pri; ,-d; R= R'= Bu'CH~; f; R =ButCH2, R'R'= Meamp;, CH2-The transformation of silanes (13)into selenopyrophosphates (11)involves two reactions: the formation of selenenyl chlorides (14) from (13)with sulphuryl dichloride equation (3) followed by condensation of chlorides (14) with the ester (9) equation (411.The rates of these reactions seem to be significantly higher than the rate of interaction between the trico-ordinate ester (9) and sulphuryl dichloride, and the rate of decomposition of chlorides (14).This result is somewhat surprising because the tri- co-ordinate phosphorus esters are known to be highly reactive towards elemental chlorine and sulphuryl dichloride.lo In our opinion, an alternative route (Scheme 7) in which the inter- mediate phosphonium salt (18) reacts with the phosphite (9) to give the diphosphonium salt (19) and subsequently compound (19) desilylates to afford the selenoanhydrides (11) is less likely. RO SeCl bsol; +/c'z(13 1 P /bsol;RO OSiMe, CI-(18) (R'O)2POSiMc,I +/P-Se--Pbsol;(11) -OR' 1 -2Me3SiCl RO' ' I OR' OSiMe, OSi Me, Yields of the isolated pure sym-monoselenopyrophosphates (11) are very good. Owing to their relative instability com- pounds (11) are best purified by crystallization crude solid (ll) or chromatography on silanized silica gel crude liquid (1113.If the required sym-selenopyrophosphates (11) contain the same substituents at both phosphorus atoms (R = R'), a simplified procedure can be applied.Two mol equiv. of the phosphite (9) were allowed to react with one mol equiv. of elemental selenium. When the exothermic addition was com- plete the mixture is treated with sulphuryl dichloride. 31PN.m.r. spectra of all the anhydrides obtained were in full agreement with their assigned structure (11). The Jpse coupling constant values (41-25 Hz) are in the range characteristic for compounds containing a bridging selenium atom.' Some preliminary observations illustrate the chemical reactivity of sym-monoselenopyrophosphates (11). They are very reactive towards nucleophiles and can be considered as potent phosphorylating agents. The phosphorylating properties are demonstrated in reactions with water and alcohols equation (6). sym-Selenopyrophosphates(11) when heated to above 60OC, isomerize into asyrn-selenopyrophosphates (12) which are identical with the compounds prepared by the condensation of the dialkyl phosphorochloridates (5) with the corresponding salts of dialkyl hydrogen phosphoroselenoates (20) equation 0 o.bsol; /OR' RO' 'CI + :Y/ pbsol;Se OR' (7)I Robsol; / OR' P-0-P (12) The structure of products (12) was evident from their 31Pn.m.r. spectra which reveal two characteristic doublets, indicating two different phosphorus nuclei, with typical Jme (1 004-1 010 Hz) and ,JPp(23-25 Hz) value^.^.^ This new rearrangement (11) -(12) is analogous to that observed for the sym-monothi~pyrophosphates.~ Experimental Since the sym-monothio- and -monoseleno-pyrophosphates are very sensitive to moisture, all reactions were carried out under strictly anhydrous conditions.Solvents and reagents were purified and dried by conventional methods before use. M.p.s were measured on a Boetius PHMK apparatus and are uncorrected. 'H N.m.r. spectra were recorded on a Tesla BS B47 (80 MHz) instrument and 31Pn.m.r. spectra on a JEOL JNM-FX 60 FT spectrometer operating at 24.3 MHz. Positive chemical shift values (p.p.m.) are reported for compounds absorbing at lower field than 85 H3PO4 and Me,Si, respectively.1.r. spectroscopy was carried out on a Perkin- 2200 Elmer Model 325 spectrophotometer. The purity of products were determined from integrated 31Pn.m.r. spectra. Dialkyl trimethylsilyl phosphites (9) were prepared from the appropriate dialkyl phosphites and trimethylsilyl chloride in the presence of triethylamine.l3 O,O'-Dialkyl 0"-trimethylsilyl selenophosphates (13) and thiophosphates were obtained by addition of elemental selenium or sulphur to the phosphites (9). General Procedure for Preparation of sym-Monothiopyro-phosphates.-A solution of sulphuryl dichloride (10 mmol) in methylene dichloride (5 ml) was added dropwise at -10 "C to a vigorously stirred solution of the appropriate dialkyl trimethylsilyl thiophosphate (10 mmol) in methylene dichloride (6 ml) at -10 "C.After the addition of the sulphuryl dichloride was complete, a solution of the corresponding dialkyl trimethylsilyl phosphite (10 mmol) in methylene dichloride (5 ml) was added dropwise to the mixture at -40 "C. The mixture was then allowed to warm slowly to ambient temperature. The solvent was evaporated off under reduced pressure to afford the product. If purification was necessary, the crude liquid product was chromatographed on silanized silica gel 60 with benzene and chloroform as the eluants; the crude solid product was recrystallized from methylene dichloride-benzene (1 :1). The following compounds were then prepared.Thiopyrophosphate (la) (R = R' = Me) (95); 6, +18.1 p.p.m.; vmax,(film) 542 (P-S-P) and 1289 cm-' (Pa). Thiopyrophosphate (lb) (R = R' = Et) (95); 6, + 14.7 p.p.m.; vmax~(film) 542 (P-S-P) and 1 270 cm-' (Pa). Thiopyrophosphate (lc) (R = R' = Pr') (95); 6, + 12.4 p.p.m.; vmax.(film) 542 (P-S-P) and 1 270 cm-' (Pa). Thiopyrophosphate (Id) (R = R' = Bu'CH,) (96); m.p. 62-63 "C; 6, + 15.2 p.p.m.; v,,,~(film) 542 (P-S-P) and 1 275 cm-' (Pa). /CH,-Thiopyrophosphate (le) (RR = R'R' = Me,ClCH,_). (95); m.p. 113-114 "C; 6, +5.9 p.p.m.; vmax.(film) 542 (P-S-P) and 1 295 cm-' (Pa). ,CH,-Thiopyrophosphate (If) (R = Bu'CH,, R' = Me,C,CH2-) (95); m.p. 186-187 "C; 6, +6.1 and + 14.3 p.p.m. (2Jpp13 Hz); vmax,(film) 534 (P-S-P) and 1297 cm-' (Pa).General Procedure for Preparation of sym-Monoselenopyro- phosphates (11) (R = R') and (R # R').-A solution of sulphuryl dichloride (10 mmol) in methylene dichloride (5 ml) was added dropwise to a vigorously stirred solution of the appropriate dialkyl trimethylsilyl selenophosphate (10 mmol) and dialkyl trimethylsilyl phosphite (10 mmol) in methylene dichloride (10 ml) at -78 "C. The mixture was then allowed to warm slowly to ambient temperature. The solvent was evaporated off under reduced pressure to afford the product. If purification was necessary, crude liquid product was chromato- graphed on silanized silica gel 60 with benzene and chloroform as the eluants; the crude solid product was recrystallized from benzene-light petroleum (b.p.40-60 "C) (1 : 1). The following compounds were thus prepared. Monoselenopyrophosphate (lla) (R = R' = Me) (80); 6,+ 13.1 p.p.m. (.IPSe425 Hz); vmax~(film) 420 (P-Se-P), 1 260 (Pa), and 1 029 cm-' (P-0-C). Monoselenopyrophosphate (llb) (R = R' = Et) (78); 6,+ 12.8 p.p.m. (JMe425 Hz); v,,,~(film) 400 (P-Se-P), 1 264 (Pa), and 1 028 (P-0-C). Monoselenopyrophosphate (llc) (R = R' = Pr') (75); 6, +6.9 p.p.m. (.IPSe414 Hz); vmax,(film) 480 (P-Se-P), 1 250 (Pa), and 1 030 cm-I (P-0-C). Monoselenopyrophosphate (lld) (R = R' = Bu'CH,) (90); m.p. 46-48 "C; 6, + 10.8 p.p.m. (JPSe418.7 Hz); J. CHEM. SOC. PERKIN TRANS. I 1988 vmax.(film)490 (P-Se-P), 1 245 (Pa),and 1 040 cm-' (P-0-C).Monoselenopyrophosphate (lle) (RR = R'R' = /CH -(95); m.p. 162-164 "C; 6, + 1.1 p.p.m. (JMe 415 Hz); vmax,(film) 495 (P-Se-P), 1 292 (Pa), and 1 040 cm-' (P-0-C).Monoselenopyrophosphate (llf) (R = Bu'CH,, R' = Me,C'cH2-) (95); m.p. 100-101 "C; 6, + 1.2 (d) and + 9.8CH2-p.p.m. ('.Ipp19.5 Hz); vmax~(film) 507 (P-Se-P), 1 284 (Pa), and 1 038 cm-' (P-0-C). Monoselenopyrophosphate (0,0'-2,2-dimethyltrimethyleneSe-phenyl-t-butylphosphoryl selenophosphate) (1 lg) R = 0CH2-Me,C ,CH,-, (R'O), = Bu', Ph (82); m.p. 1lamp; 112 "C; 6, +68.3 (d) and + 1.0 (d) p.p.m. (,JPp 14.6 Hz); vmax.(film)498 (P-Se-P), 1 284 (Pa), and 995 cm-' (P-0-C). General Procedure for Preparation of Simple sym-Mono- selenopyrophosphates (R = R').-Anhydrous elemental black selenium (5 mmol) was added to stirred dialkyl trimethylsilyl phosphite (10 mmol).The exothermic reaction was complete after several min. The mixture was diluted with methylene dichloride (5 ml), cooled to -78 "C, and a solution of sulphuryl dichloride (5 mmol) in methylene dichloride (5 ml) was added dropwise. The reaction mixture was worked up as in the preceding procedure. The following compounds were thus prepared. Monoselenopyrophosphate (lla) (R = R' = Me) (80); 6,+ 13.1 p.p.m. (Jpse425 Hz); vmax.(film) 420 (P-Se-P), 1 260 (Pa), and 1 029 cm-' (P-0-C). Monoselenopyrophosphate (llb) (R = R' = Et) (79); 6,+ 12.8 p.p.m. (JMe425 Hz); vmax~(film) 400 (P-Se-P), 1264 (Pa), and 1 028 cm-' (P-0-C). Monoselenopyrophosphate (llc) (R = R' = Pr') (78); 6, +6.9 p.p.m.(Jme 414 Hz); vmax~(film) 480 (P-Se-P), 1250 (Pa), and 1 030cm-' (P-0-C). Monoselenopyrophosphate(lld)(R = R' = Bu'CH,) (90); m.p. 46-48 "C; 6, + 10.8 p.p.m. (Jme418.7 Hz); film) 490 (P-Se-P), 1 245 (Pa), and 1 040 cm-' (P-0-C). Monoselenopyrophosphate (lle) (RR = R'R' = Me,C:EE:I ) (95); m.p. 162-164 "C; 6, + 1.1 p.p.m. (Jme 415 Hz); vmax~(film) 495 and 512 (P-Se-P), 1292 (Pa), and 1 040 cm-' (P-0-C). Reaction of Tetra-0-neopentyl sym-Selenopyrophosphate (1 ld) with Water.-A solution of the selenopyrophosphate (5 mmol) in acetone-water (4: 1) (10 ml) was stirred overnight at ambient temperature. The exclusive products were identified (3 'P n.m.r.) as di-0-neopentyl hydrogen phosphoroselenoate (6, 64.5 p.p.m., Jme 908 Hz) and dineopentyl hydrogen phosphate (6, 1.3 p.p.m.).Reaction of Tetra-0-neopentyl sym-Selenopyrophosphate (1 Id) with Methanol.-A solution of the selenopyrophosphate (10 mmol) in methanol (10 ml) was stirred overnight at room temperature. The mixture was shown (31P n.m.r.) to consist only of di-0-neopentyl hydrogen phosphoroselenoate and methyl dineopentyl phosphate (6, -0.2 p.p.m.). Acknowledgements This work was supported by the Polish Academy of Sciences, Research Project CPBP 01.13. J. CHEM. SOC. PERKIN TRANS. I 1988 References 1 R. Dembinski, R. Kaminski, J. Michalski, and A. Skowronska, J. Chem. Soc., Chem. Commun., 1986, 1770. 2 J. Michalski, M. Mikolajczyk, B. Mlotkowska, and J.Omelanczuk, Tetrahedron, 1969, 25, 1743 and references therein. 3 J. A. Gerlt, J. A. Coderre, and S. Mehdi, Adv. Enzymol., 1983,55,291; F. Eckstein, Annu. Rev. Biochem., 1985, 54, 367. 4 J. Michalski, W. Reimschiissel, and R. Kaminski, Usp. Khim., 1978, 47, 1528; Russ. Chem. Rev., 1978, 47, 814 and references therein. 5 (a)J. Michalski, M. Mikoiajczyk, B. Miotkowska, and A. Zwierzak, Angew. Cheni., 1967,79, 1069; (b)J. Michalski, B. Miotkowska, and A. Skowronska, J. Chem. SOC.,Perkin Trans. I, 1974, 319. 6 J. Michalski, and A. Skowronska, J. Chem. SOC.C, 1970, 703; A. Skowronska, E. Krawczyk, and J. Burski, Phosphorus Sulfur, 1983, 18, 233. 7 D. S. Rycroft and R. F. N. White, J. Chem. Soc., Chem. Commun., 1974,444. 2201 8 W. J. Stec and B. Uznanski, Synth. Commun., 1978, 8, 473. 9 A. Skowronska and J. Gwara, unpublished results. 10 (a) J. Michalski, J. Mikolajczak, and A. Skowronska, J. Am. Chem. Soc., 1978, 100, 5386; (b) J. Michalski, M. Pakulski, and A, Skowronska, J. Chem. Soc., Perkin Trans. I, 1980, 883. 11 W. J. Stec, A. Okruszek, B. Uznanski, and J. Michalski, Phosphorus Sulfur, 1972, 2, 97. 12 J. Michalski and J. Wieczorkowski, Rocz. Chem., 1954, 29,233. 13 E. F. Bugerenko, E. A. Chernyshev, and E. M. Popov, Bull. Acad. Sci. USSR, 1966,1334;L. V. Nesterov, N. E. Krepysheva, R. A. Sabirova, and G. N. Romanova, J. Gen. Chem. USSR (Engl. Transl.), 1971,41, 2449. 14 A. Zwierzak, Tetrahedron, 1969, 25, 5186. Received 20th July 1987; Paper 7/1305