P Nitrobenzoyl chloride

Occasionally benzoyl chloride gives a product which does not crystallise well in such cases the difficulty may frequently be overcome by using p-nitrobenzoyl chloride, N02C,H4C0C1, or 3,5-dinitrobenzoyl chloride, (NOiljCjHjCOCl (p. 240), which usually give highly crystalline derivatives. 

A crystalline derivative of benzyl alcohol cannot be obtained by using benzoyl chloride, because the benzyl benzoate, C HiCOOCHiCaHj, so obtained has m.p. 18°, and is thus usually liquid the present preparation illustrates therefore the use of a substituted benzoyl chloride (p-nitrobenzoyl chloride, m.p. 75°) in order to obtain a crystalline derivative of suitably high m.p. 

The benzoyl compounds frequently occlude traces of unchanged benzoyl chloride, which thus escape hydrolysis by the caustic alkali it is therefore advisable, wherever possible, to recrystaUise the benzoyl derivatives from methyl, or ethyl alcohol or methylated spirit, since these solvents will esterify the unchanged chloride and so remove the latter from the recrystalKsed material. Sometimes the benzoyl compound does not crystallise well this difficulty may frequently be overcome by the use of p-nitrobenzoyl chloride or 3 5-dinitro-benzoyl chloride, which usually give highly crystalline derivatives of high melting point (see Section IV,114j. 

The esters formed with p-nitrobenzoyl chloride and 3 5-dinitrobenzoyl chloride (see Section 111,27,1 and 2 and Section IV,205) must be Includ under this heading. 

Either an oil bath (maintained at 210-215° for a pressure of 20 mm.) or an air bath must be used. If the flask is heated with a free flame, superheating will occur leading to decomposition (sometimes violent) of the p-nitrobenzoyl chloride. 

Thus, acylation of 3(W,iV-dibutylamino)propanol (39) with p-nitrobenzoyl chloride affords the intermediate, 40. Reduction of the nitro group gives butacaine (41), an agent equipotent as cocaine as a topical anesthetic. 

Replacement of chlorine on the pendant benzoyl group by azide is apparently consistent with antiinflammatory activity. Acylation of indomethacin intermediate with p-nitrobenzoyl chloride leads to the corresponding amide (7). Saponification ( ) followed by reduction of the nitro group gives the amine 9. The diazonium salt (10) obtained on treatment with nitrous acid is then reacted with sodium azide there is thus obtained zidomethacin (11). 

Diethyl sodium phthalidomalonate p-Nitrobenzoyl chloride Cinchonidine Hydrogen... 

Deoxy-l, 3,4,6-tetra-O-p-nitrobenzoyl-D-lyxo-hexose. To a stirred suspension of 4.64 grams (25 mmoles) of p-nitrobenzoyl chloride in 50 ml. of anhydrous pyridine at 0°C. is added, in small portions over a period of 15 minutes, 0.82 grams (5 mmoles) of 2-deoxy-D-Zt/xo-hexose purchased from Aldrich Chemical Co., Inc., Milwaukee, Wis. Stirring is maintained at 0°C. for 2 hours and the mixture is kept in a refrigerator... 

Para-Nitrobenzoate. A solid, mp 106-8° prepd the same as above using p-nitrobenzoyl chloride, yield 60%. Urbanski states that this compd has great expl strength and low sens to shock (Ref 4)... 

Derivatives of higher melting point may be obtained with p-nitrobenzoyl chloride the experimental details are similar to those given above for benzoyl chloride. 3 5-Dinitrobenzoyl chloride (Section 111,27,2) may also be used glycerol gives unsatisfactory results with this reagent. 

Thionyl chloride method. Mix 100 g. of pure p-nitrobenzoic acid and 126 g. (77 ml.) (1) of redistilled thionyl chloride in a 500 ml. round-bottomed flask. Fit the flask with a double surface reflux condenser carrying a calcium chloride (or cottou wool) guard tube and connect the latter to an absorption device e.g., Fig. II, 8, 1. c). Heat the flask on a water bath with occasional shaking for 1 hour or until the evolution of hydrogen chloride and sulphur dioxide ahnost ceases. Allow the reaction mixture to cool, transfer it cautiously to a Claisen flask connected with a water-cooled condenser and a receiver (compare Fig. II, 13, 1). Distil off the excess of thionyl chloride (b.p. 77°) slowly and continue the distillation until the temperature rises rapidly to about 120° this will ensure that all the thionyl chloride is remov. Allow to cool, and distil the residual p-nitrobenzoyl chloride under diminished pressure as detailed in the Phosphorus Pentachloride Method. The resulting p-nitrobenzoyl chloride (a yellow crystalline solid) weighs 107 g. and melts at 72-73°. 

A 600-cc. beaker containing 100 cc. of water and equipped with an efficient stirrer, a thermometer, and a 200-cc. separatory funnel is immersed in an ice-water bath. When the temperature of the water has fallen to 0-5°, 10 g. (0.13 mole) of sodium peroxide (Note 1) is added. Then, with vigorous stirring, a solution of 37 g. (0.2 mole) of p-nitrobenzoyl chloride in 100 cc. of dry toluene is added dropwise over a period of about thirty minutes. After the mixture has been stirred for an additional one and one-half hours, the precipitate is filtered and washed with 200 cc. of cold water (Note 2). The yield of p-nitrobenzoyl peroxide is 28.5-29 g. (86-88 per cent of the theoretical amount). It melts at 155-156°. 

Finally, the action of acid chlorides on alcohols and phenols is also used to separate them from solutions or to characterise them. For this purpose benzoyl chloride is usually employed. Methyl alcohol, for example, gives with p-nitrobenzoyl chloride the beautifully crystalline methyl ester and small amounts of the alcohol can thus be separated from aqueous solution. 

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