Schotten-Baumann benzoylation reaction

When these benzoyl compounds separate in the course of the Schotten-Baumann reaction, they frequently occlude traces of unchanged benzoyl chloride, which thus escapes hydrolysis by the alkali it is advantageous there fore to recrystallise the benzoyl compounds whenever possible from ethanol or methylated spirit, since these solvents will esterify the unchanged chloride and so remove the latter from the recrystallised material. 

The Schotten-Baumann reaction may also be carried out, using, for example, benzene sulphonyl chloride, CeH,SO,Cl (. e., the acid chloride of benzene sulphonic acid, C H5SOjOH) in place of benzoyl chloride, and similar deri a-tives are obtained. Thus when phenol is dissolved in an excess of 10% sodium hydroxide solution, and then shaken with a small excess of benzene sulphonyl... 

Give benzoyl and toluene-/>-sulphonyl derivatives (Schotten-Baumann reaction) (p. 243) also benzene-sulphonyl derivatives. 

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 )... 

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). 

Bemoyl chloride may replace acetyl chloride as a class reagent it possesses the advantage that it is only very slowly decomposed by cold water and consequently may be employed for detecting alcohols even in aqueous solution. The reaction is usually carried out in aqueous solution containing sufficient caustic alkali to decompose any excess of benzoyl chloride into the water-soluble alkali benzoate (Schotten - Baumann reaction compare Section IV,52). The benzoyl esters formed are insoluble in water ... 

In other reactions also the OH-group of the phenols shows itself to be more reactive than that of the aliphatic alcohols. Phenols, but not alcohols, react easily with diazomethane. With other alkylating agents also, such as alkyl halides, and dialkyl sulphates, the phenols react even in aqueous alkaline solution whilst the alcohols do not react under such conditions. Benzoyl derivatives, most of which crystallise readily, are excellently adapted for the characterisation of phenols (Schotten-Baumann reaction). 

Benzoyl chloride is an important benzoylating agent. In this use the benzoyl radical is introduced into alcohols, phenols, amines, and other compounds through the Friedel-Craffs reaction and the Schotten-Baumann reaction. Other significant uses are in the production of benzoyl peroxide [94-36-0], benzophenone [119-61-9], and in derivatives employed in the fields of dyes, resins, perfumes, pharmaceuticals, and as polymerization catalysts. 

The Schotten-Baumann reaction can also be applied to primary and secondary aromatic amines (see p. 303) it is much used in the identification of compounds to which it can be applied, by the preparation of their benzoyl, phenylacetyl, or benzene sulphonyl derivatives. 

When benzoyl chloride is used it is necessary to have present, or to add subsequently, an excess of caustic soda or some other basic substance (Schotten-Baumann Reaction). 

In the above process only one-half of the amine is transformed into its benzoyl derivative. By working in presence of dilute caustic soda or other alkali (Schotten-Baumann Reaction, see benzoyl-p-toluidine), the amine is completely converted into its benzoyl derivative. 

This methodology also enables stereospecific synthesis of the side-chain of taxol [56]. The A-benzoyl-3-phenylisoserine side chain at C-13 of the taxol molecule is essential for its antitumor activity. The stereoselectivity in this reaction depends on the geometry of the silyl ketene acetal (Eq. 77). The reaction of the (E)-ketene acetal with (i )-27 produces the anti adduct with high stereoselectivity anttsyn = 98 2, 92 % de anti). In contrast, the reaction of the (Z)-silyl ketene acetal with S)-27 produces the enantiomerically pure syn adduct (symanti = > 99 1, > 99 % de syn). Aus, our methodology provides the first practical and efficient route for the preparation of both diastereomers of an a-hydroxy /3-amino ester. The syn adduct 52 is transformed to the desired A-benzoyl-(27 ,35)-phenylisoserine methyl ester by hydrogenolysis over a palladium catalyst then the Schotten-Baumann reaction. 

Hippuric Acid.—When the benzoyl group is introduced into an amino acid in place of an amino hydrogen, by means of the Schotten-Baumann reaction, a benzoyl amino acid is obtained. With amino acetic acid or glycine (p. 388) the product is benzoyl amino acetic acid or benzoyl glycine, also known as hippuric acid. 

For the introduction of the benzoyl group (benzoylation) the procedure generally adopted is to use benzoyl chloride in dilute (10 per cent) alkaline solutions. Since benzoyl chloride reacts slowly with water at room temperature, the amino compound reacts fairly rapidly when shaken with it. The hydrogen chloride produced in the acylation is removed by the alkali. This method is known as the Schotten-Baumann reaction. The benzoyl derivatives nearly always crystallize well. The product is recrystallized to remove adsorbed and occluded impurities. If the derivative does not crystallize well, then a substituted benzoyl chloride is used, for example, p-nitrobenzoyl chloride. It will be recalled that for the characterization of the alcohols use was made of 3, 5-dinitrobenzoyl chloride. 

Another procedure for converting carbonyl chlorides into aldehydes proceeds by way of Reissert compounds.3448 Reissert found that 1-benzoyl-1,2-dihydro-2-quinolinecarbonitrile is formed in very good yield when benzoyl chloride reacts with quinoline in the presence of aqueous potassium cyanide, the technique being that of a Schotten-Baumann reaction the nitrile can then be hydrolysed to benzaldehyde and quinaldic acid by acid. 

Schotten-Baumann Reaction. In the Schotten-Baumann method of benzoylation, the hydroxyl or amino compound (or a salt of the latter) is either suspended or dissolved in an excess of freshly prepared 10% (w/v) aqueous sodium hydroxide solution, together with a small excess of benzoyl chloride ii.e., nearly 10% more than the theoretical quantity), and the resulting mixture is shaken vigorously in ambient conditions. It has been observed that under these experimental parameters benzoylation proceeds smoothly. Thus, the solid benzoylated product, which being insoluble in the aqueous medium, gets separated briskly. Simultaneously, the NaOH solution hydrolyses the excess of benzoyl chloride present in reaction mixture, thereby resulting into the formation of sodium chloride and sodium benzoate, which being water-soluble remain in solution. 

It has been observed that the benzoylated products when get separated during the course of Schotten-Baumann reaction, they invariably occlude tracess of imreacted benzoyl chloride fi"om the reaction mixture, which eventually escapes hydrolysis by the alkali (NaOH) in the reaction medium. Therefore, it is not only an absolute necessity but also advantageous to recrystallize the benzoylated products either fi"om ethanol or methylated spirit so as to enable these solvents to esterify the unchanged benzoyl chloride and allow them subsequently to be removed from the final recrystallized benzoylated material, and... 

Another important aspect of Schotten-Baumann reaction is sulphonylation whereby benzene sulphonyl chloride, CgH SOgCl (i.e., the corresponding acid chloride of benzene sulphonic acid, CgH SOgOH) is employed instead of benzoyl chloride, and almost similar structural analogues may be obtained. 

Schotten-Baumann reaction /shot-en bow-mahn/ A method for the preparation of N-phenylbenzamide (benzanilide) in which a mixture of phenylamine (aniline) and sodium hydroxide is stirred while benzoyl chloride is added slowly. The N-phenylbenzamide precipitates and can be recrystallized from hot ethanol ... 

This reaction was first reported by Schotten in 1884 and subsequently extended by Baumann in 1886. It is the acylation of alcohols and amines from acyl halide or anhydride in an aqueous alkaline solution (e.g., 1 M NaOH), and is generally known as the Schotten-Baumann reaction or Schotten-Baumann acylation. Occasionally, it is also referred to as the Schotten-Baumann method,or Schotten-Baumann esterification. Likewise, the formation of benzoyl ester under these conditions is called the Schotten-Baumann benzoylation." It is assumed that the reaction would perform well if carried out in a biphasic system of water and an immiscible organic solvent (e.g., CH2CI2), which has an important application in the acylation of amino acids.For example, p-nitrohippuric acid and dibenzoylornithine (ornithuric acid) all can be prepared under these conditions. 

The preparation of amides by reaction of an amine, an acyl chloride, or an acid anhydride in the presence of aqueous alkali is the well-known Schotten-Baumann reaction. Since the rate of reaction of the acyl chloride with amines is greater than the rate of hydrolysis of the acyl chloride, amide formation is favored. In some cases, the stability of acyl chlorides to aqueous caustic solution is surprising. For example, benzoyl chloride may be kept in contact with sodium hydroxide solutions for long periods of time. We presume that a thin layer of sodium benzoate forms rapidly and that this acts as a protective coating unless the benzoyl chloride is stirred or shaken to disturb the protective layer. As a matter of fact, the Schotten-Baumann reaction (and the analogous Hinsberg reaction with aromatic sulfonyl chlorides) appears to be most satisfactory when acyl chlorides are used which are relatively insoluble in water. Many years ago, we noted that the addition of a small percentage of a surfactant (e.g., sodium lauryl sulfate as well as cationic surfactants) assisted in the dispersion of the acyl chloride with an increase in reaction rate. These may have been early examples of phase-transfer reactions. 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

The transformation 401 - 406 by Schotten-Baumann benzoylation is a mysterious reaction, the mechanism of which is not obvious. Clearly a change in oxidation level has occurred, but related changes are known, and this is an incompletely understood aspect of the chemistry of for-mazans (393) and the corresponding tetrazolium cations. In contrast, the reaction of the salt with p-toluenesulphonyl chloride yields the meso-ionic l,2,3,4-tetrazol-5-imine (411) directly. 

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