Triphenylphosphine Dichloride1


[2526-64-9]  · C18H15Cl2P  · Triphenylphosphine Dichloride  · (MW 333.20)

(conversion of alcohols,6-10 phenols,13 and enols15 into alkyl chlorides; synthesis of vic-dichlorides16 or chlorohydrins17 from epoxides; conversion of carboxylic acids11 and derivatives20 into acyl chlorides; chlorination23,24 or dehydration11 of the CONH group; production of iminophosphoranes from amines and related compounds27-29)

Alternate Names: dichlorotriphenylphosphorane; triphenyldichlorophosphorane; chlorotriphenylphosphonium chloride.

Physical Data: adduct:2 white crystalline solid; mp 85-100 °C;4 fp 20 °C. Ph3P: mp 80.5 °C; bp 377 °C (in inert gas); d254 1.194 g mL-3; n80D 1.6358. Cl2: mp -101 °C; bp -34.6 °C; d0 3.214 g L-1.

Solubility: adduct: slightly sol ether, THF, PhMe; sol CCl4, CH2Cl2, DMF, MeCN, pyridine; insol petroleum ether. Ph3P: sol ether, PhH, CHCl3, AcOH; less sol alcohol; pract insol H2O. Cl2: sol CCl4, alcohol.

Form Supplied in: very hygroscopic solid; commercially available; purity ~80%; the remainder is 1,2-dichloroethane. The precursors Ph3P and Cl2 are both widely available. Ph3P: odorless platelets or prisms; purity ~99%; typical impurity is Ph3PO ~1%. Cl2: greenish-yellow gas, with suffocating odor; purity &egt;99.3%; typical impurities are Br2, C2Cl6, C6Cl6, and H2O.

Analysis of Reagent Purity: adduct:2,3 31P NMR (various solvents and solid state) +47 to +66 (ionic form), -6.5 to +8 (covalent form); Raman (solid state) n(P-Cl) 593 cm-1 (ionic form), 274 cm-1 (covalent form). Typical impurities, Ph3P and Ph3PO: 31P NMR (various solvents) -5 to -9 and +25 to +42, respectively.

Preparative Methods: various preparations have been described;5 the adduct is usually prepared just before use by addition of a stoichiometric amount of Chlorine to Triphenylphosphine in a dry solvent.2

Handling, Storage, and Precautions: adduct: exceedingly sensitive to moisture; incompatible with strong oxidizing agents and strong bases; may decompose on exposure to moist air or water; do not get in eyes, on skin, or on clothing; keep containers closed and store in a cool dry place; these reagents should be handled in a fume hood.

Alkyl Chlorides from Alcohols and Ethers.

The reaction of Ph3PCl2 with alcohols provides an excellent synthetic method for the preparation of alkyl chlorides.6 Mechanistic studies6c suggest the rapid initial formation of an alkyloxyphosphonium intermediate which then undergoes slow conversion into Ph3PO and alkyl chloride (eq 1).6b,c It is assumed that chlorination takes place by an SN2 reaction in most cases; thus, inversion of configuration is observed in the transformation of (-)-menthol to (+)-neomenthyl chloride (eq 2).6a As illustrated in eq 1, primary,6b,7 secondary,6 and even tertiary6b alcohols are chlorinated with Ph3PCl2, although reactions of tertiary alcohols are often accompanied by elimination (10%).

Ph3PCl2, generated in situ from Ph3P and Hexachloroacetone (HCA) has proven to be a very efficient reagent for the regio- and stereoselective chlorination of allylic alcohols (eq 3),8 and for the regioselective conversion of sterically hindered cyclopropylcarbinyl alcohols into cyclopropylcarbinyl chlorides (eq 4).9 Chlorination of allylic alcohols occurs in less than 20 min, with total preservation of the double bond geometry and with >99% inversion of configuration for optically active alcohols. Primary and secondary alcohols give predominantly the unrearranged chlorides, while tertiary alcohols provide mostly rearranged products, with elimination to dienes becoming an important side reaction with more highly substituted systems. Similarly, cyclopropylcarbinyl alcohols yield the corresponding chlorides with no trace of homoallylic chlorides or cyclobutane derivatives.

In the carbohydrate field, primary and secondary alcohols are chlorinated in excellent yield (80-95%) with the Ph3PCl2/ImH (Imidazole) reagent system in PhMe, MeCN, or a MeCN/pyridine mixture at rt to reflux temperature.10 Polymer-supported Ph3PCl2,11 prepared by the Ph3PO/COCl2 (Phosgene) procedure,5b has been used to transform PhCH2OH to PhCH2Cl (88%) in MeCN as a solvent; the simple workup consists of filtration of polymeric phosphine oxide and solvent removal. Several examples have been reported of the direct conversion of ethers into chlorides, as in eq 5.7 Enol ethers such as acetophenone trimethylsilyl ether give a-chlorostyrene (30%) by Ph3PCl2 treatment at CCl4 reflux.12

Aryl Chlorides from Phenols and Arenes.

Heating phenols with Ph3PCl2 at 120-140 °C leads to the corresponding aryl chlorides in good yield (eq 6).13 A related chlorination reaction employs the Ph3PCl2/BSPO (Bis(trimethylsilyl) Peroxide) reagent system as the electrophilic chlorine source. With this reagent, in MeCN at rt, aromatic hydrocarbons bearing electron-donating substituents, such as 2,4,6-tri-t-butylbenzene and mesitylene, afford 1-monochloroarenes, while anisole gives a mixture of 2- and 4-chloro derivatives, in moderate to good yields (44-86%).14a Similar aromatic para chlorination has also been observed by heating anisole with Ph3+PCl PCl5-, albeit in low yield (33%).14b

Vinyl Chlorides, Alkynyl Ketones, and b-Chloro-a-vinyl Ketones from Ketones and b-Diketones.

1-Chlorocyclohexene (45%) and a,a-dichlorotoluene (59%) are produced by the reaction of cyclohexanone and benzaldehyde with Ph3PCl2/Triethylamine and Ph3PCl2 alone, respectively, in refluxing PhH.6a In MeCN as solvent, polymer-supported Ph3PCl2 converts acetophenone into a-chlorostyrene (75%).11 In a similar fashion, unsymmetrical fluorinated b-diketones give 3:1 mixtures of a,b-ynones (eq 7) in good overall yields (slightly lower than those obtained with Triphenylphosphine Dibromide).15a b-Chloro-a,b-unsaturated ketones are prepared in high yield from cyclic b-diketones (eq 8).15b,c

Epoxide Cleavage to Vicinal Dichlorides and Chlorohydrins.

Early reports of work in this area described the ring opening of ethylene oxide with Ph3PCl2 in CCl4 at rt, leading to 1,2-dichloroethane.16a Subsequently,16b,c excellent yields were reported in the reaction of Ph3PCl2 with aliphatic epoxides to produce the corresponding vicinal dichlorides. The ring opening takes place stereospecifically with both cis and trans epoxides in PhH or CH2Cl2 at reflux, in each case providing the dichloride derived from SN2 displacement on each C-O bond (eq 9).16c Alkoxyphosphonium chloride intermediates have even been isolated and characterized in a study involving ethylene oxide derivatives.16d

The reaction of epoxides with Ph3PCl2 in anhydrous CH2Cl2 at rt17a results in chlorohydrins in generally high yields (90-96%). With conformationally rigid epoxides the oxirane ring cleavage appears to be quite stereoselective, leading only to the products resulting from the usual anti opening of the ring. Less hindered and rigid cyclic substrates provide regioisomeric mixtures of cyclic trans-chlorohydrins. The reaction of the polymer-supported Ph3PCl2 reagent proceeds in a similar fashion with even higher yields and easier workup; simple filtration and evaporation provides the product (eq 10).17b

Acid Chlorides from Acids and Esters.

Mono- and dicarboxylic acids give acyl chlorides on reaction with Ph3PCl26a or polymer-supported Ph3PCl211 in PhH, CH2Cl2, or MeCN (eq 11).11 On similar Ph3PCl2 treatment in PhH at -10 °C to rt, sulfamic acid (H2NSO3H) is transformed into Ph3P=NSO2Cl in 95% yield.18 Analogously, Ph3PCl2, generated in situ from Ph3P and (EtO)2P(=O)SCl, reacts with Et3N and (EtO)2P(O)SH at -78 °C to provide the corresponding acid chloride (EtO)2P(S)Cl.19

Direct cleavage of esters or lactones20 to both acid and alkyl chlorides is achieved with Ph3PCl2; halogenated esters (RCO2Me; R = CF3, CCl3, CH2Cl) are readily cleaved in refluxing MeCN, while esters of nonhalogenated acids and lactones (eq 12) require higher temperatures or/and the use of additives such as Boron Trifluoride. Cleavage is considerably retarded by steric hindrance in the alkoxy fragment. A mechanism involving initial nucleophilic cleavage of the O-alkyl bond with Cl- is proposed for halogenated esters, whereas an initial electrophilic attack by Ph3+PCl on the carbonyl oxygen is assumed for the cleavage of nonhalogenated esters.

Similar transformations of esters to acid chlorides have also been achieved in the phosphonate diester field21 and in the conversion of trialkyl phosphites into dialkyl chlorophosphites.22 Ph3PCl2 acts as a mild reagent for the replacement of a single ester linkage by a chloride in phosphonate diesters (eq 13).

Chlorination and Dehydration of Substituted Carboxamide Groups.

Secondary amides and N,N,N-trisubstituted ureas possessing an N-H bond are converted to imidoyl chlorides11,23 and chloroformamidines,5a,24 respectively, by reaction with Ph3PCl2 (eqs 14 and 15). Unsupported or polymer-supported reagent has been used, with or without Et3N, in a variety of solvents. Under very similar conditions, with Ph3PCl2 in CH2Cl2 at reflux, the primary amide PhCONH2 is dehydrated to the nitrile PhCN (78%),11 while aryl-substituted arylhydroxamic acids are dehydrated to the corresponding aryl isocyanates.25 In the latter case, dehydration occurs via Lossen-type rearrangement of a phosphorane intermediate. In a related reaction, chlorination-dehydrochlorination of N-acylated hydrazines with the Ph3PCl2/Et3N system is a smooth one-pot procedure to generate nitrilimines.26 Thus, by such treatment, PhCONHNHPh affords [PhC&tbond;+N--N-Ph] in situ; this reacts with alkenic or alkynic dipolarophiles to give pyrazolines and pyrazoles.

Iminophosphoranes from Amines, Hydrazines, and Related Derivatives.

Iminophosphoranes (or phosphinimines) are commonly used as intermediates, especially in heterocyclic synthesis. Phosphinimines can be obtained via phosphorylation of primary amines with Ph3PCl2 alone,27 or in the presence of Et3N,28 if necessary, to ensure the last dehydrochlorination step. In the heterocyclic b-enamino ester field, iminophosphoranes are submitted to vinylogous alkylation28a or cycloaddition (eq 16)28a,b with ring enlargement. The =PPh3 moiety, which serves as a temporary amino protecting group, is then cleaved hydrolytically. Reaction of phosphinimines with aryl isocyanates affords carbodiimides,28c whereas iminophosphoranes of acyl hydrazines undergo dimerization to tetrazines.28d Other phosphinimines and phosphonium salts have been prepared from phosphorylation of amino derivatives, such as hydrazines,29a urethanes,29b and N-silylated imines,29c with Ph3PCl2.

Other Applications.

Ph3PCl2 is a good condensation reagent for the synthesis of ketones (48-90%) from carboxylic acids and Grignard reagents. The versatility of the method is illustrated by the chemoselective reaction of carboxylic acids possessing such functional groups as halogen, cyano, and carbonyl (eq 17).30

Beckmann rearrangement of benzophenone oxime to PhC(Cl)=NPh (82%) is promoted by Ph3PCl2/Et3N in CH2Cl2 at rt.31a Cyclopentanone and cyclohexanone oxime are converted to d-valero- and ε-caprolactam (76 and 86%) with Ph3PCl2 in PhH at 50-60 °C.31b The action of heat (120-130 °C) on a mixture of Ph3PCl2 with the highly fluorinated propanol (CF3)2C(OH)CH2SO2CF3 leads to elimination of the CF3SO2 group and formation of the vinylic chloride (CF3)2C=CHCl.32 Ph3PCl2 reacts with Pb(SCN)2 to form Ph3+P-N=C=S SCN-, another reagent of the pseudohalophosphonium type, which is used for converting hydroxy groups into thiocyanate and isothiocyanate functions.33 Ylides such as triphenylphosphonio(vinylsulfonylphenylsulfonylmethanide), CH2=CHSO2-C--(+PPh3)SO2Ph, can be prepared by reaction of Ph3PCl2 with the very activated methylene derivative CH2=CHSO2CH2SO2Ph.34 Heating Ph3PCl2 with (Me3Si)2S at 60-70 °C leads to the formation of Ph3PS (85%) after distillation of the Me3SiCl byproduct.35 Ph3PCl2 is reduced to Ph3P with formation of alkyl or aryl chlorides by reaction with organometallic reagents (Mg, Li).36

1. Castro, B. R. OR 1983, 29, 1.
2. The Ph3PCl2 adduct can be prepared by different routes; the most common involves the reaction of Ph3P and Cl2, both being generally used in solution, in order to ensure a correct 1/1 stoichiometry. As illustrated by physical studies,3 the resultant product is often a mixture of several compounds depending on starting materials (Ph3P, Ph3PO, Cl2, COCl2, CCl3CCl3, CCl3COCCl3), on their stoichiometries, and on the polarity of the solvent used for the preparation. 31P NMR studies under various conditions, and solid state Raman measurements, lead to different values for ionic PIV and molecular PV species or to average values corresponding to equilibrated mixtures of the both structures according to the polarity of the solvent.
3. (a) Al-Juboori, M. A. H. A.; Gates, P. N.; Muir, A. S. CC 1991, 1270. (b) Dillon, K. B.; Lynch, R. J.; Reeve, R. N.; Waddington, T. C. JCS(D) 1976, 1243, and literature cited therein.
4. Another preparation from Ph3P and CCl3CCl3 in MeCN provides material of higher mp: 207-210 °C (from MeCN-petroleum ether); see Appel, R.; Schöler, H. CB 1977, 110, 2382.
5. Apart from the classical Ph3P + Cl2 method, the following routes have been reported: (a) Ph3P + COCl2: Appel, R.; Ziehn, K. D.; Warning, K. CB 1973, 106, 2093, and literature cited therein. (b) Ph3PO + COCl2: Masaki, M.; Kakeya, N. AG(E) 1977, 16, 552, and literature cited therein. (c) Ph3P + CCl4 in the presence of RNHCOCl: Appel, R.; Warning, K.; Ziehn, K. D.; Gilak, A. CB 1974, 107, 2671. (d) With Ph3P + CCl4 alone, a mixture of equal amounts of Ph3PCl2 and Ph3P=CCl2 is obtained: Rabinowitz, R.; Marcus, R. JACS 1962, 84, 1312; Appel, R.; Knoll, F.; Michel, W.; Morbach, W.; Wihler, H.-D.; Veltmann, H. CB 1976, 109, 58. (e) Ph3P + CCl3CCl3, e.g. Ref. 4 and: Appel, R.; Halstenberg, M. In Organophosphorus Reagent in Organic Synthesis, Cadogan, J. I. G., Ed.; Academic: New York, 1979; Chapter 9 and literature cited therein. (f) Ph3P + CCl3COCCl3 for in situ preparation of Ph3PCl2: see Ref. 8 and 9. (g) Ph3PO or Ph3P + PCl5: Dillon, K. B.; Reeve, R. N.; Waddington, T. C. J. Inorg. Nucl. Chem. 1976, 38, 1439, and literature cited therein.
6. (a) Horner, L.; Oediger, H.; Hoffmann, H. LA 1959, 626, 26. (b) Wiley, G. A.; Hershkowitz, R. L.; Rein, B. M.; Chung, B. C. JACS 1964, 86, 964. (c) Wiley, G. A.; Rein, B. M.; Hershkowitz, R. L. TL 1964, 2509.
7. Skvarchenko, V. R.; Lapteva, V. L.; Gorbunova, M. A. JOU 1990, 26, 2244.
8. (a) Magid, R. M.; Fruchey, O. S.; Johnson, W. L. TL 1977, 2999. (b) Magid, R. M.; Fruchey, O. S.; Johnson, W. L.; Allen, T. G. JOC 1979, 44, 359.
9. (a) Hrubiec, R. T.; Smith, M. B. SC 1983, 13, 593. (b) Hrubiec, R. T.; Smith, M. B. JOC 1984, 49, 431.
10. (a) Garegg, P. J.; Johansson, R.; Samuelsson, B. S 1984, 168. (b) Garegg, P. J. PAC 1984, 56, 845.
11. Relles, H. M.; Schluenz, R. W. JACS 1974, 96, 6469.
12. Lazukina, L. A.; Kolodyazhnyi, O. I.; Pesotskaya, G. V.; Kukhar', V. P. JGU 1976, 46, 1931.
13. Hoffmann, H.; Horner, L.; Wippel, H. G.; Michael, D. CB 1962, 95, 523.
14. (a) Shibata, K.; Itoh, Y.; Tokitoh, N.; Okazaki, R.; Inamoto, N. BCJ 1991, 64, 3749. (b) Timokhin, B. V.; Dudnikova, V. N.; Kron, V. A.; Glukhikh, V. I. JOU 1979, 15, 337.
15. (a) Chechulin, P. I.; Filyakova, V. I.; Pashkevich, K. I. BAU 1989, 38, 189. (b) Piers, E.; Nagakura, I. SC 1975, 5, 193. (c) Piers, E.; Grierson, J. R.; Lau, C. K.; Nagakura, I. CJC 1982, 60, 210.
16. (a) Gloede, J.; Keitel, I.; Gross, H. JPR 1976, 318, 607. (b) Sonnet, P. E.; Oliver, J. E. JOC 1976, 41, 3279. (c) Oliver, J. E.; Sonnet, P. E. OS 1978, 58, 64. (d) Appel, R.; Gläsel, V. I. ZN(B) 1981, 36, 447.
17. (a) Palumbo, G.; Ferreri, C.; Caputo, R. TL 1983, 24, 1307. (b) Caputo, R.; Ferreri, C.; Noviello, S.; Palumbo, G. S 1986, 499.
18. Arrington, D. E.; Norman, A. D. Inorg. Synth. 1992, 29, 27.
19. Krawczyk, E.; Mikolajczak, J.; Skowronska, A.; Michalski, J. JOC 1992, 57, 4963.
20. (a) Burton, D. J.; Koppes, W. M. CC 1973, 425. (b) Burton, D. J.; Koppes, W. M. JOC 1975, 40, 3026.
21. Ylagan, L.; Benjamin, A.; Gupta, A.; Engel, R. SC 1988, 18, 285.
22. Gazizov, M. B.; Zakharov, V. M.; Khairullin, R. A.; Moskva, V. V. JGU 1986, 56, 1471.
23. Appel, R.; Warning, K.; Ziehn, K.-D. CB 1973, 106, 3450.
24. Appel, R.; Warning, K.; Ziehn, K.-D. CB 1974, 107, 698.
25. von Hinrichs, E.; Ugi, I. JCR(S) 1978, 338; JCR(M) 1978, 3973.
26. Wamhoff, H.; Zahran, M. S 1987, 876.
27. (a) Roesky, H. W.; Giere, H. H. CB 1969, 102, 2330. (b) Gotsmann, G.; Schwarzmann, M. LA 1969, 729, 106.
28. (a) Wamhoff, H.; Haffmanns, G.; Schmidt, H. CB 1983, 116, 1691. (b) Wamhoff, H.; Hendrikx, G. CB 1985, 118, 863. (c) Wamhoff, H.; Haffmanns, G. CB 1984, 117, 585. (d) Farkas, L.; Keuler, J.; Wamhoff, H. CB 1980, 113, 2566.
29. (a) Zhmurova, I. N.; Yurchenko, V. G.; Pinchuk, A. M. JGU 1983, 53, 1360. (b) Shevchenko, V. I.; Shtepanek, A. S.; Kirsanov, A. V. JGU 1962, 32, 2557. (c) Lazukina, L. A.; Kristhal', V. S.; Sinitsa, A. D.; Kukhar', V. P. JGU 1980, 50, 1761.
30. Fujisawa, T.; Iida, S.; Uehara, H.; Sato, T. CL 1983, 1267.
31. (a) Appel, R.; Warning, K. CB 1975, 108, 1437. (b) Sakai, I.; Kawabe, N.; Ohno, M. BCJ 1979, 52, 3381.
32. Samusenko, Y. V.; Aleksandrov, A. M.; Yagupol'skii, L. M. JOU 1975, 11, 622.
33. Burski, J.; Kieszkowski, J.; Michalski, J.; Pakulski, M.; Skowronska, A. CC 1978, 940.
34. Diefenbach, H.; Ringsdorf, H.; Wilhelms, R. E. CB 1970, 103, 183.
35. Markovskii, L. N.; Dubinina, T. N.; Levchenko, E. S.; Kukhar', V. P.; Kirsanov, A. V. JOU 1972, 8, 1869.
36. (a) Denney, D. B.; Gross, F. J. JOC 1967, 32, 3710. (b) Dmitriev, V. I.; Timokhin, B. V.; Kalabina, A. V. JGU 1979, 49, 1936.

Jean-Robert Dormoy & Bertrand Castro

SANOFI Chimie, Gentilly, France

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