p-Nitrobenzoyl Chloride

[122-04-3]  · C7H4ClNO3  · p-Nitrobenzoyl Chloride  · (MW 185.57)

(characterization of amines and alcohols by formation of crystalline amide and ester derivatives; forms suitable directing group for glycosidation reactions)

Physical Data: mp 72-74 °C; bp 202-205 °C/105 mmHg.

Solubility: sol THF, CH2Cl2, CHCl3, pyridine; reacts with water and alcohols.

Form Supplied in: commercially available; yellow crystalline solid.

Purification: recrystallization from CCl4 or C6H6.

Handling, Storage, and Precautions: extremely irritating to skin and eyes. Can cause burns. Use in a fume hood. Reacts with water, liberating HCl.

Amide Formation.

p-Nitrobenzoyl chloride forms p-nitrobenzamides by reaction with amines and these have been used in the characterization of amphetamines.1 These derivatives are chemically stable, easily prepared (eq 1), and have enhanced UV detectability.

Ester Formation.

The crystalline p-nitrobenzoate (PNB) esters formed by reaction of alcohols and p-nitrobenzoyl chloride are widely used in simplifying the characterization,2 purification, and isolation3,4 of alcohols. In certain cases, they allow ready enhancement of enantiomeric excess by recrystallization.3 They can be prepared from the alkoxide (eq 2)5 (useful for acid sensitive alcohols) or, more commonly, from the free alcohol, p-nitrobenzoyl chloride, and amine base such as pyridine4 (often as solvent), lutidine,2 or triethylamine.3

p-Nitrobenzoyl chloride has been used for the in situ derivatization of low molecular weight, water-soluble epoxy alcohols (eq 3).3


p-Nitrobenzoyl chloride forms O-p-nitrobenzoyl esters which are used in carbohydrate chemistry as protecting groups that can also direct the steric course of glycosidation reactions. The 4-O-p-nitrobenzoyl group gives steric control (by anchimeric assistance) in the coupling reactions of certain sugars to give trans-C-1,C-4 products.6,7 The O-PNB esters can also act as precursors to the glycosyl halides required for the Koenigs-Knorr coupling reaction. The example in eq 4 illustrates both these features.7 The 4-O-PNB group gives somewhat better selectivities than the 4-O-trifluoroacetyl or the 4-O-acetyl group.8 p-Nitrobenzoyl chloride is also used in the synthesis of highly crystalline p-nitrobenzoylaminobenzoyl esters of sugars.9

1. Clark, C. R.; Teague, J. D.; Wells, M. M.; Ellis, J. H. Anal. Chem. 1977, 49, 912.
2. Tius, M. A.; Astrab, D. P.; Gu, X. JOC 1987, 52, 2625.
3. Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. JACS 1987, 109, 5765.
4. Finch, N.; Fitt, J. J.; Hsu, I. H. S. JOC 1975, 40, 206.
5. (a) Kaiser, E. M.; Woodruff, R. A. JOC 1970, 35, 1198. (b) Bunnelle, W. H.; Rafferty, M. A.; Hodges S. L. JOC 1987, 52, 1603.
6. Dejter-Juszynski, M.; Flowers, H. M. Carbohydr. Res. 1972, 23, 41.
7. Smith, T. H.; Fujiwara, A. N.; Lee, W. W.; Wu, H. Y.; Henry, D. W. JOC 1977, 42, 3653.
8. Dejter-Juszynski, M.; Flowers, H. M. Carbohydr. Res. 1973, 28, 61.
9. Kiss, J. CI(L) 1964, 32.

Paul Brough

University of Bristol, UK

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