Benzoyl derivatives

The sensitized photolysis of the 3-acetyl and 3-benzoyl derivatives (355a, b) afforded 7-acetyl-3-methyloxepin-2(3//)-one (356 35%) and its cyclization product (357 19%) (Scheme 96) (81CC1163). 

The structural problem was finally cleared up by physical methods, including molar refraction,255-252 and ultraviolet263 and Raman254 spectroscopy. The 3-benzoyl derivative has also been submitted to X-ray analysis.233-235 All the evidence supports a planar fused system of six- and five-membered rings, although some of the earlier work was interpreted in terms of other structures. The proton NMR spectrum of anthranil has been analyzed 265 the parameters are listed in Table A. 

Acyldihydrocodeinones (146) were made in a similar manner. The 8/3-(trans-1 -oxo-2-butenyl)- and 8/3-benzoyl derivatives were prepared from protected acyl lithium cuprates, and the 8/3-methylcarbonyl- (146) from the lithium bis(a-ethoxyvinyl) cuprate with codeinone, followed by mild hydrolysis of the intermediate, 147. Preparation of 8/3-t-alcohols may be achieved from 147 after reduction of the ring carbonyl, treatment with an appropriate alkyl lithium to 148, and oxidation back to a ketone, 149. 

Selective alkylation of uracil at N-1 can be achieved via alkylation of the 3-benzoyl-derivative, itself obtained by selective hydrolysis of the dibenzoyl compound. ... 

Ketones are formed from pyridylzinc halides on acylation with acid chlorides or anhydrides in reactions with benzoyl chloride or benzoic anhydride, pyridyl ketones (307) are formed in moderate yields. Reactions with 3-iodoquinoline gave the 3-benzoyl derivative 308. Organostannanes may be a better choice for ketone formation (see above). 

Add I ml. (1 04 g.) of aniline to 15 ml. of 10% aqueous sodium hydroxide solution contained in a wide-necked bottle as before, and then add 1-5 ml. (1-7 g.) of benzoyl chloride, and shake vigorously for 15-20 minutes. The mixture becomes warm, and the crude benzoyl derivative separates as a white... 

B) Benzoyl derivatives. Most amino-acids can be benzoyl-ated when their solutions in 10% aqueous sodium hydroxide are shaken with a small excess of benzoyl chloride until a clear solution is obtained (Schotten-Baumann reaction, p. 243). Acidification of the solution then precipitates the benzoyl derivative and the excess of benzoic acid, and the mixture must be filtered off, washed with water, and recrystallised (usually from ethanol) to obtain the pure derivative. (M.ps., p. 555 )... 

A) Benzoyl Derivative. Since acetylation and benzoylation do not always proceed smoothly with nitrophenols, it is best to reduce them to the aminophenol as in (3) above. Add an excess of 20% aqueous sodium hydroxide to the reaction mixture after reduction, cool and then add a small excess of benzoyl chloride, and shake in the usual way. The dibenzoyl derivative wiU separate. Filter, wash with water and recrystalUse. (M.ps., p. 551.)... 

Z>) Benzoylation. Proceed exactly as for benzoylation of amines (Test 3 (a), p.374), but use a suspension of the finely ground nitroaniline in the 10% NaOH solution. This preparation of the benzoyl derivatives is rarely necessary, however, as the above acetylation proceeds very satisfactorily. (M.ps., p. 550.)... 

Primary and Secondary Amines. Picrates (pp. 374, 376), Acetyl derivatives (pp. 373, 376), Benzoyl derivatives (pp. 374, 376), Toluene-p-sulphonyl and benzene-sulphonyl derivatives (pp. 374, 376), Phenylurea derivatives (pp. 374, 377)-... 

Amino Aliphatic Carboxylic Acids. 3,5-Dinitrobenzoyl derivatives (p. 381), Benzoyl derivatives (p. 382), Sulphonyl derivatives (p. 382). 

Nitroamlines. Acetyl derivatives (p. 388), Benzoyl derivatives (p. 388). Diamines. Diacet> l derivatives (p. 388), Dibenzoyl derivatives (p. 388). Halogeno-hydrocarbons, a-Naphthyl ethers (from reactive halogen compounds, p. 391, and their Picratcs, p. 394), Nitro-derivatives (p.39i). Carboxylic acid (if oxidisable side chain) (p. 393). 

M.p. B.p. Picrate M.p. Acetyl deiiv. M.p. Benzoyl deriv. H.p. Benzene sulph. Onyl deriv. M.p. Toluene p-sulph> onyl deny. M.p. Phenyl urea deriv, M.p. 

Formula M.p. Methyl ester M.p. Ethyl ester M.p. Acetyl deriv M.p. Benzoyl deriv M.p 3.5 Dinitro. benzoyl deriv. M.p. Naphthal- ene sulphonyl deriv. M.p. 

Benzoates. Dissolve 0-5 g. of the amino acid in 10 ml. of 10 per cent, sodium bicarbonate solution and add 1 g. of benzoyl chloride. Shake the mixture vigorously in a stoppered test-tube remove the stopper from time to time since carbon dioxide is evolved. When the odour of benzoyl chloride has disappeared, acidify with dilute hydrochloric acid to Congo red and filter. Extract the solid with a little cold ether to remove any benzoic acid which may be present. RecrystaUise the benzoyl derivative which remains from hot water or from dilute alcohol. 

In general, benzoylation of aromatic amines finds less application than acetylation in preparative work, but the process is often employed for the identification and characterisation of aromatic amines (and also of hydroxy compounds). Benzoyl chloride (Section IV, 185) is the reagent commonly used. This reagent is so slowly hydrolysed by water that benzoylation can be carried out in an aqueous medium. In the Schotten-Baumann method of benzoylation the amino compound or its salt is dissolved or suspended in a slight excess of 8-15 per cent, sodium hydroxide solution, a small excess (about 10-15 per cent, more than the theoretical quantity) of benzoyl chloride is then added and the mixture vigorously shaken in a stoppered vessel (or else the mixture is stirred mechanically). Benzoylation proceeds smoothly and the sparingly soluble benzoyl derivative usually separates as a solid. The sodium hydroxide hydrolyses the excess of benzoyl chloride, yielding sodium benzoate and sodium chloride, which remain in solution ... 

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. 

Benzoyl derivatives. Both primary and secondary amines form benzoyl derivatives under the conditions of the Schotten-Baumann reaction (see Section IV,52 and preceding discussion). 

Suspend 1 g. (or 1 ml.) of the substance in 20 ml. of 5 per cent, sodium hydroxide solution in a well-corked boiling tube or small conical flask, and add 2 ml. of redistilled benzoyl chloride, ca. 0-5 ml. at a time, with constant shaking, and cooling in water (if necessary). Shake vigorously for 5-10 minutes until the odour of the benzoyl chloride has disappeared. Make sure that the mixture has an alkaline reaction. Filter oflF the solid benzoyl derivative, wash it with a little cold water, and recrystalHse it from alcohol or dilute alcohol. 

If the benzoyl derivative is soluble in alkali, precipitate it together with the benzoic acid derived from the reagent by the addition of hydrochloric acid filter and extract the product with cold ether or light petroleum (b.p. 40-60°) to remove the benzoic acid. 

Potassium hydroxide solution gives a slightly better yield of the benzoyl derivative. 

Benzoates. The benzoates of a few phenols (e.g. o-crcsol) are hquids. Many phenols do, however, yield crystaUine benzoyl derivatives these are useful for purposes of characterisation. 

N-benzoyl derivatives of o -aminoacids give 2-phenyl-5-alkoxythiazoles (64). A list of the thiazoles prepared by this method is given in Table 11-32 (711). 

Friedel-Crafts Acylation. The Friedel-Crafts acylation procedure is the most important method for preparing aromatic ketones and thein derivatives. Acetyl chloride (acetic anhydride) reacts with benzene ia the presence of aluminum chloride or acid catalysts to produce acetophenone [98-86-2], CgHgO (1-phenylethanone). Benzene can also be condensed with dicarboxyHc acid anhydrides to yield benzoyl derivatives of carboxyHc acids. These benzoyl derivatives are often used for constmcting polycycHc molecules (Haworth reaction). For example, benzene reacts with succinic anhydride ia the presence of aluminum chloride to produce P-benzoylpropionic acid [2051-95-8] which is converted iato a-tetralone [529-34-0] (30). 

Methyl groups in pyridopyrazines (64IMC240) and pyridopyrazinones (71TH21500) are oxidized to carboxylic acids with potassium permanganate. Aryl carbinol substituents are also very readily oxidized to benzoyl derivatives in alkaline conditions (76CPB238). Bromina-tion of 2,3-dimethylpyrido[3,4-f ]pyridazine gives the 2,3-bisbromomethyl derivative, whilst... 

Thiophene is also readily acylated under both Friedel-Crafts and Vilsmeier-Haack conditions and similarly to pyrrole and furan gives 2-acylated products. An almost quantitative conversion of thiophene into its 2-benzoyl derivative is obtained by reaction with 2-benzoyloxypyridine and trifluoroacetic acid. The attempted preparation of 2-benzoylthiophene under standard Friedel-Crafts conditions, however, failed (80S139). 

Two disadvantages are associated with the use of S-acetyl or 5-benzoyl derivatives in peptide syntheses (a) base-catalyzed hydrolysis of 5-acetyl- and 5-benzoylcys-teine occurs with /S-elimination to give olefinic side products, CH2=C-(NHPG)CO—(b) the yields of peptides formed by coupling an unprotected amino group in an 5-acylcysteine are low because of prior S-N acyl migration. ... 

The phenol (Imol) in 5% aqueous NaOH is treated (while cooling) with benzoyl chloride (Imol) and the mixture is stirred in an ice bath until separation of the solid benzoyl derivative is complete. The derivative is filtered off, washed with alkali, then water, and dried (in a vacuum desiccator over NaOH). It is recrystalUsed from ethanol or dilute aqueous ethanol. The benzoylation can also be carried out in dry pyridine at low temperature ca 0°) instead of in NaOH solution, finally pouring the mixture into water and collecting the solid as above. The ester is hydrolysed by refluxing in an alcohol (for example, ethanol, n-butanol) containing two or three equivalents of the alkoxide of the corresponding alcohol (for example sodium ethoxide or sodium n-butoxide) and a few ca 5-10) millilitres of water, for half an hour to three hours. When hydrolysis is complete, an aliquot will remain clear on dilution with four to five times its volume of water. Most of the solvent is distilled off. The residue is diluted with cold water and acidified, and the phenol is steam distilled. The latter is collected from the distillate, dried and either fractionally distilled or recrystalUsed. 

Liquid amines can be further purified via their acetyl or benzoyl derivatives (vide supra). Solid amines can be recrystallised from water, alcohol, toluene or toluene-petroleum ether. Care should be taken in handling large quantities of amines because their vapours are harmful (possibly carcinogenic) and they are readily absorbed through the skin. 

Because phenols are weak acids, they can be freed from neutral impurities by dissolution in aqueous N sodium hydroxide and extraction with a solvent such as diethyl ether, or by steam distillation to remove the non-acidic material. The phenol is recovered by acidification of the aqueous phase with 2N sulfuric acid, and either extracted with ether or steam distilled. In the second case the phenol is extracted from the steam distillate after saturating it with sodium chloride (salting out). A solvent is necessary when large quantities of liquid phenols are purified. The phenol is fractionated by distillation under reduced pressure, preferably in an atmosphere of nitrogen to minimise oxidation. Solid phenols can be crystallised from toluene, petroleum ether or a mixture of these solvents, and can be sublimed under vacuum. Purification can also be effected by fractional crystallisation or zone refining. For further purification of phenols via their acetyl or benzoyl derivatives (vide supra). 

A-Hydroxy-5-norbornene-2,3-dicarboxylic acid imide [21715-90-2] M 179.2, m 165-166", 166-169", pKesi-6 Dissolve in CHCI3, filter, evaporate and recrystallise from EtOAc. IR (nujol) 1695, 1710 and 1770 (C=0), and 3100 (OH) cm. 0-Acetyl derivative has m 113-114° (from EtOH) with IR bands at 1730, 1770 and 1815 cm only, and the 0-benzoyl derivative has m 143-144° (from propan-2-ol or C6H6). [Bauer and Miarka J Org Chem 24 1293 1959 Fujino et al. Chem Pharm Bull Jpn 22 1857 1974],... 

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