Benzoyl Chloride1

[98-88-4]  · C7H5ClO  · Benzoyl Chloride  · (MW 140.57)

(useful acylating agent; preparation of ketones from organometallic compounds;2,3 preparation of 1,3-dicarbonyl compounds from enolates or enols;4,5 Friedel-Crafts acylation and related reactions6 with aromatic and heterocyclic compounds,7 alkenes,8 alkynes,9 enoxysilanes,10 and silicon compounds;11 acylation of enol ethers, ketene acetals,12 and enamines;13 protection of alcohols as benzoates;14 protection of amines as benzamides15)

Physical Data: bp 197.2 °C; mp -1 °C; d 1.21 g cm-3.

Solubility: slowly decomposed by water and alcohols; sol most organic solvents.

Form Supplied in: colorless liquid; penetrating odor; widely available.

Purification: the good commercial grade of benzoyl chloride can be purified by distillation. The technical material must be purified as follows: a 50% solution of PhCOCl in ether or cyclohexane is washed with cold 5% aqueous sodium bicarbonate; after drying over CaCl2 the solvent is eliminated under vacuo and the PhCOCl is distilled.16

Handling, Storage, and Precautions: use in a fume hood; lachrymatory, irritating to skin, eyes and mucous membranes; toxic by inhalation and ingestion.

Acylation of Organometallic Compounds.2,3

PhCOCl reacts with various organometallic reagents to give the corresponding phenyl ketones in variable yields. The first acylation reactions were performed with organocadmium and organozinc compounds (eqs 1 and 2).3a,b In THF, organozinc reagents give poor results; however, the yields are clearly improved in the presence of Tetrakis(triphenylphosphine)palladium(0) (eq 3).3c

With the very reactive organomagnesium compounds, the acylation takes place in the presence of Fe(acac)33d or MnCl23e (eqs 4 and 5). It is worthy of note that the 1,2-addition, which is rapid under these reaction conditions (10-20 °C), is completely avoided.

Organocopper (60% of PhCOMe from MeCu.PBu3)3f and cuprate reagents (eq 6),3g which are now widely used, give only moderate yields of phenyl ketones. Better yields are obtained at low temperature by using a large excess of organocuprate3h or heterocuprate (eq 7).3i

Organomanganese compounds afford excellent yields by the use of a stoichiometric amount of reagents under mild conditions (eq 8).3j

Acylation of Enolates, Enols, and Related Reactions.4,5

According to the reaction conditions, PhCOCl reacts with ketone enolates to lead to enol benzoates (O-acylation, kinetic product) or b-diketones (C-acylation, thermodynamic product) (eq 9).5a

PhCOCl very often gives a mixture of the O- and C-acylated products. To prepare the enol ester (kinetic conditions) a more reactive acylating agent such as Acetyl Chloride is generally used. Moreover, carboxylic acid anhydrides are generally preferred to acyl halides. Accordingly, PhCOCl is preferred to prepare 1,3-dicarbonyl compounds. Ketones (eq 10),5b esters (eq 11),5c and more commonly b-keto esters or related CH acidic compounds (eqs 12-15)5d-g can be C-acylated via the preformed enolate (eq 11) or directly under basic conditions (eq 13).5e

Friedel-Crafts Acylation and Related Reactions.6,7

Aromatic compounds (eqs 16 and 17)7a,b are acylated by PhCOCl in the presence of a Lewis acid such as AlCl3, TiCl4, BF3, SnCl4, ZnCl2, or FeCl3, or of a strong acid such as polyphosphoric acid or CF3SO3H.6 Metallic Al or Fe and iodine (in situ formation of a Lewis acid) can also act as a catalyst.6 Various solvents that have been used to perform this reaction are CS2, CH2Cl2, 1,2-dichloroethane, nitrobenzene, and nitromethane.6 PhCOCl is less reactive than aliphatic carboxylic acid chlorides (with benzene in nitromethane the relative reaction rates are PhCOCl:MeCOCl = 6:100).7a As for all electrophilic substitutions, the rate and the regioselectivity of the acylation closely depend on the nature and on the position of the substituents on the aromatic system6 (eqs 16 and 187c). The nature of the solvent can also exert a strong influence.6

The electrophilic acylation of alkenes or alkynes is another example of Friedel-Crafts reactions and is carried out under similar conditions.6,8,9 With PhCOCl, alkenes can lead to b-chloro alkyl ketones or, more frequently, to the corresponding a,b-ethylenic ketones (eq 19)8b according to the reaction conditions.6,8a PhCOCl also adds to triple bonds to give a b-chloro vinyl ketone9 (eq 20).9b

Under Friedel-Crafts conditions, PhCOCl reacts with various silicon compounds. Thus b-diketones are easily obtained from enoxysilanes10a,b (eq 21).10c Conversely, vinyl-, aryl-, and allylsilanes lead to the corresponding vinyl, aryl, and allyl ketones in good yields11a-c (eq 2211d and eq 2311e). Vinylsilanes can lead to a mixture of b-chloro alkyl ketones and conjugated enones; a basic treatment is then necessary to obtain only the enone (eq 23).

Acylation of Enol Ethers, Ketene Acetals,12 and Enamines.13

Enol ethers,12a ketene acetals (eq 24),12b and enamines (eq 25)13g react with PhCOCl to provide the corresponding b-acylated products (eq 24).12b The acylation of enamines has been extensively studied (eq 25);13a-f the resulting b-acyl enamine is generally hydrolyzed to give b-diketones (eq 25).

Protection of Alcohols as Benzoates14 and of Amines as Benzamides.15

PhCOCl easily reacts with alcohols to give the corresponding benzoates in excellent yields.14a The acylation is performed in the presence of an amine, very often pyridine or triethylamine. CH2Cl2 or a large excess of amine is generally used as solvent (eq 26).14d The reaction has also been performed by phase transfer catalysis (PhCOCl, benzene, Bu4NCl, 40% NaOH).14e Alternatively, the alcohol can be converted to lithium alcoholate (with BuLi), which readily reacts with PhCOCl to give quantitatively the corresponding benzoate (eq 27).14f Tributyltin ether prepared by treatment of the alcohol with Bis(tri-n-butyltin) Oxide has also been used as intermediate.14g Benzoates are very often prepared to protect alcohols14b,c because they are more stable than acetates and their tendency to migrate to adjacent hydroxyl groups is lower.14h,i In most cases the benzoylation of polyhydroxylated molecules is more selective than the acetylation.14h,i PhCOCl has also been used to monoprotect diols,14f and to acylate a primary alcohol in the presence of a secondary alcohol.14j Under similar conditions (pyridine), phenols are converted to aryl benzoates.14a,k

PhCOCl reacts also easily with primary or secondary amines in the presence of a base, aqueous alkali (Schotten-Bauman procedure), or tertiary amines (pyridine or Et3N), to afford the corresponding amides (eq 28).15b This reaction is used to protect amines.15c

Miscellaneous Reactions.

PhCOCN (see Acetyl Cyanide), which is used as acylating agent (for instance, to protect alcohols)17a can be prepared by reacting PhCOCl with Copper(I) Cyanide (60-65%).17b,c Diazoalkanes are readily acylated by PhCOCl to give diazo ketones.18a,b These compounds are interesting as intermediates18c-e to prepare a-halo ketones, a-hydroxy ketones or arylacetic acids (Arndt-Eistert reaction).18e PhCOCl has also been used to prepare volatile acyl chlorides (C2 to C6) from the corresponding carboxylic acids.19 On the other hand, it reacts with sulfoxides to lead generally to the corresponding a-chloro sulfides (Pummerer rearrangement).20

Related Reagents.

Acetyl Chloride; Acetyl Cyanide; Benzoic Anhydride.

1. The Chemistry of Acyl Halides; Patai, S., Ed. Wiley: London, 1972. (b) Sonntag, N. O. V. CRV 1953, 52, 237.
2. (a) March, J. Advanced Organic Chemistry, Reactions, Mechanisms and Structures. 4th ed.; Wiley: New York, 1992; pp 487-488. (b) Sheverdina, N. I.; Kocheskov, K. A. The Organic Compounds of Zinc and Cadmium; North Holland: Amsterdam, 1967. (c) Shirley, D. A. OR 1954, 8, 28. (d) Jorgenson, M. J. OR 1970, 18, 1. (e) Posner, G. H. OR 1975, 22, 253. (f) Wipf, P. S 1993, 537. (g) Larock, R. C. Comprehensive Organic Transformations; VCH: New York, 1989; pp 686-692. (h) See also n-Butylmanganese Chloride.
3. (a) Gilman, H.; Nelson, J. F. RTC 1936, 55, 518. (b) Blaise, E. E. BSF 1911, 9, I-XXVI. (c) Negishi, E.; Bagheri, V., Chatterjee, S.; Luo, F.; Miller, J. A.; Stoll, A. T. TL 1983, 24, 5181. (d) Fiandanese, V.; Marchese, G.; Martina, V.; Ronzini, L. TL 1984, 25, 4805. (e) Cahiez, G.; Laboue, B. TL 1992, 33, 4439. (f) Whitesides, G. M.; Casey, C. P.; San Filippo Jr, J.; Panek, E. J. Trans. N.Y. Acad. Sci. 1967, 29, 572. (g) Jallabert, C.; Luong-Thi, N. T.; Rivière, H. BSF 1970, 797. (h) Posner, G. H.; Whitten, C. E. TL 1970, 4647. (i) Posner, G. H.; Whitten, C. E. OSC 1988, 6, 248. See also also Ref. 2e. (j) Cahiez, G.; Laboue, B. TL 1989, 30, 7369.
4. (a) House, H. O. Modern Synthetic Reactions, 2nd ed; Benjamin: Menlo Park, CA, 1972, pp 734-786. (b) See Ref. 2a, p 490. (c) See Ref. 2g, pp 742 and 764-768. (d) Hauser, C. R.; Swamer, F. W.; Adams, J. T. OR 1954, 8, 59.
5. (a) Muir, W. M.; Ritchie, P. D.; Lyman, D. J. JOC 1966, 31, 3790. (b) Vavon, G.; Conia, J. M. CR 1951, 233, 876. (c) Logue, M. W. JOC 1974, 39, 3455. (d) Lawesson, S. O.; Busch, T. ACS 1959, 13, 1717. (e) Wright, P. E.; McEven, W. E. JACS, 1954, 76, 4540. (f) Korobitsyna, I. K.; Severina, T. A.; Yur'ev, Yu. K. ZOB 1959, 29, 1960 (CA 1960, 54, 8772). (g) Gough, S. T. D.; Trippett, S. JCS 1962, 2333.
6. (a) Olah, G. O. Friedel Crafts and Related Reactions; Wiley: New York, 1963-1965. Vol. 1-4. (b) See Ref. 4a, pp 786-816. (c) Gore, P. H. CRV 1955, 55, 229. (d) Gore, P. H. CI(L) 1974, 727. (e) Pearson, D. E.; Buehler, C. A. S 1972, 533. (f) See Ref. 2a, pp 539, 598 and 821. (g) See Ref. 2g, pp 703 and 708.
7. (a) Gore, P. H.; Hoskins, J. A.; Thornburn, S. JCS(B) 1970, 1343. (b) Minnis, W. OSC, 1943, 2, 520. (c) Orchin, M.; Reggel, L. JACS 1951, 73, 436.
8. (a) Groves, J. K. CSR 1972, 1, 73. (b) Matsumoto, T.; Hata, K. JACS 1957, 79, 5506.
9. (a) Pohland, A. E.; Benson, W. R. CRV 1966, 66, 161. (b) Kochetkov, N. K.; Khorlin, A. Ya.; Karpeiskii, M. Ya. ZOB 1956, 26, 595 (CA 1956, 50, 13 799).
10. (a) Weber, W. P. Silicon Reagents for Organic Synthesis; Springer: Berlin, 1983; pp 214. (b) See Ref. 2g, p 753. (c) Fleming, I.; Iqbal, J.; Krebs, E. P. T 1983, 39, 841.
11. (a) See Ref. 10a, pp 86, 120, and 175. See Ref. 2g, pp 687 and 688. (c) Fleming, I.; Dunoguès, J.; Smithers, R. OR 1989, 37, 57. (d) Fleming, I.; Pearce, A. JCS(P1) 1980, 2485. (e) Calas, R.; Dunoguès, J.; Pillot, J. P.; Biran, C.; Pisciotti, F.; Arreguy, B. JOM 1975, 85, 149.
12. (a) Andersson, C.; Hallberg, A. JOC 1988, 53, 4257. (b) McElvain, S. M.; McKay, Jr., G. R. JACS 1956, 78, 6086.
13. (a) See Ref. 4a, pp 766-772. (b) See Ref. 2a, pp 601-603 (c) Enamines: Synthesis, Structure and Reactions, 2nd ed; Cook, A. G., Ed.; Dekker: New York, 1988. (d) Hünig, S.; Hoch, H. Fortschr. Chem. Forsch. 1970, 14, 235. (e) Hickmott, P. W. CI(L) 1974, 731. (f) Hickmott, P. W. T 1984, 40, 2989; T 1982, 38, 1975 and 3363. (g) Campbell, R. D.; Harmer, W. L. JOC 1963, 28, 379.
14. (a) See Ref. 2a, p 392. (b) Greene, T. W. Protective Groups in Organic Synthesis; Wiley: New York, 1981; p 61. (c) Reese, C. B. Protective Groups in Organic Chemistry; McOmie, J. F. W., Ed.; Plenum: London, 1973; p 111. (d) Seymour, F. R. Carbohydr. Res. 1974, 34, 65. (e) Szeja, W. S 1979, 821. (f) Castellino, A. J.; Rapoport, H. JOC 1986, 51, 1006. (g) Hanessian, S.; Roy, R. CJC 1985, 63, 163. (h) Haines, A. H. Adv. Carbohydr. Chem. Biochem. 1976, 33, 11. (i) Kozikowski, A. P.; Xia, Y.; Rusnak, J. M. CC 1988, 1301. (j) Schlessinger, R. H.; Lopes, A. JOC 1981, 46, 5252. (k) See Ref. 14b, p 103 and Ref. 14c, pp 171-177.
15. (a) See Ref. 2a, pp 417-418. (b) White, E. OSC, 1973, 5, 336. (c) See Ref. 14b, pp 261-263 and Ref. 14c, pp 52-53.
16. See Ref. 17b, p 113, note 3.
17. (a) See Ref. 14b, p 61. (b) Oakwood, T. S.; Weisgerber, C. A. OSC 1955, 3, 112. (c) See Ref. 2a, p 495.
18. (a) Franzen, V. LA 1957, 602, 199. (b) Bestmann, H. J.; Kolm, H. CB 1963, 96, 1948. (c) Bridson, J. N.; Hooz, J. OSC, 1988, 6, 386. (d) Ried, W.; Mengler, H. Fortschr. Chem. Forsch. 1965, 5, 1. (e) Fridman, A. L.; Ismagilova, G. S.; Zalesov, V. S.; Novikov, S. S. RCR 1972, 41, 371. (f) See Ref 2a, pp 1083-1085. (g) Meier, H.; Zeller, K.-P. AG(E) 1975, 14, 32.
19. (a) Finan, P. A.; Fothergill, G. A. JCS 1963, 2723. (b) Brown, H. C. JACS 1938, 60, 1325.
20. (a) See Ref 2a, p 1236. (b) Mikolajczyk, M.; Zatorski, A.; Grzejszczak, S.; Costisella, B.; Midura, W. JOC 1978, 43, 2518. (c) De Lucchi, O.; Miotti, U.; Modena, G. OR 1991, 40, 157.

G. Cahiez

Université Pierre et Marie Curie, Paris, France

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