Amines, acetylation benzoylation

In addition to those described, there are many other methods for purifying organic compounds. Examples which might be irientioned are sublimation, chromatography, and conversion into more crystal-lizable derivatives, such as amines into their acetyl, benzoyl, or other acyl derivatives, or acids into their chlorides, amides, esters, etc. These are the methods which are generally used in research laboratories. Although they are used also in industrial laboratories, and the technical chemist should be familiar with them, it is beyond the scope of this book to treat them in detail. 

The acetyl, benzoyl and toluene-4-sulfonyl derivatives of amines are often crystalline, and have been used to characterize the amine. The addition of an amine to an isocyanate may lead to a substituted urea and these have also been used to characterize the amines. 

MONOHYDROXYMETHANE (67-56-1) Forms explosive mixture with air (flash point 50°F/10°C). Violent reaction with strong oxidizers, acetyl bromide, alkyl aluminum salts, beryllium dihydride, bromine, chromic acid, l-chloro-3,3-difIuoro-2-methoxycyclopropene, cyanuric chloride, diethylzinc, isophthaloyl chloride, nitric acid, perchloric acid, potassium-tert-butoxide, potassium sulfur diimide, Raneynickel catalysts, 2,4,6-trichlorotriazine, triethy-laluminum, l,3,3-trifluoro-2-methoxycyclopropene. Incompatible with strong acids, strong caustics, alkalineearth and alkali metals, aliphatic amines, acetaldehyde, benzoyl peroxide,... 

A -methoxymethyl-amines or-amides A -acetyloxymethyl-amines or -amides or A/, iV-dimethylfonnamide acetals, all react with phosphorus(III) esters in non-classical Michaelis-Arbuzov fashion. From these and similar reactions, quaternary salts of the type 186 have been isolated. The A-methylated dervative may be preformed or produced in situ in mixtures containing amide, formaldehyde and phosphite ester. The products of the reactions are A-acylated (acetyl, benzoyl, phthaloyl, pyridinecarbonyl or benzyloxycarbonyl) when derived from amides, or A,A-dialkyl derivatives from hydroxy (or methoxy)methylamines the use of Me2NCH(OMe)2 leads to dimethylaminomethyl-enebisphosphonic esters. Ivanov and coworkers have made a detailed study of the reactions which occur between phosphorus(III) amides Et2NPYZ and the substrates, RCONHOAc (Scheme 16). The reagent can attack the substrate by virtue of the nucle-... 

The 1,2-glycoseens 123) (2-hydroxyglycals) are prepared 124) by warming the acetylated, benzoylated, or methylated 125) glycosyl halides in an inert solvent with a secondary amine, usually diethylamine, or other bases. The elements of hydrogen bromide, thus, are eliminated between carbons 1 and 2 with the formation of the substituted 1,2-glycoseen. The CHaOAc CHaOAc... 

Conversion of an amine into a substituted amide is a convenient and widely used method for the protection of amino groups. Monoacylation of a primary amine often affords sufficient protection, i.e., against oxidation, alkylation, etc., and more complete protection is obtained by forming cyclic diacyl derivatives. Acyclic diacylamines easily revert to mono-acylamines and have only been used under very mild conditions [20]. Of the simple acylamines in common use the stability increases in the order formyl < acetyl < benzoyl and many more complex acyl groups have been evaluated in order to adjust the stability of the derivatives for various purposes. 

Aminopyrroles can usually be acetylated e and benzoylated a, 199, 200 (Schotten-Baumann conditions have been used), and have given benzal derivatives 200, 201 and ureas . In some cases these reactions fail the amines (81, = Me or C02Et) could not be acetylated, benzoylated,... 

Reference should be made to Tables 4, 5, 29, for amides, anilides and p-toluidides of carboxylic and sulphonic acids Tables 14, 15, 16, for formyl, acetyl, benzoyl and p-toluenesulphonyl derivatives of primary and secondary amines Table 18 for acyl derivatives of amino-acids Table 7 for acyl derivatives of aminophenols. 

For the identification of amines acylation methods (acetylation, benzoylation, 3,5-dinitrobezoylation), reaction with p-toluenesulfonyl chloride, preparation of substituted thioureas, diazotization and coupling (for aromatic primary amines), and the preparation of salts (picrates, tetraphenylboron salts) are most commonly used. 

The presence of free radicals in the reaction of tertiary amines and benzoyl peroxide has been observed by electron spin resonance (ESR) spectroscopy [67-69]. The reaction of amines with acyl peroxide is much more rapid than the thermal decomposition of the peroxide alone [70]. For example, benzoyl peroxide [53] with dimethylaniline at 0 C in styrene or chloroform exhibits an apparent second-order rate constant of 2,3 X 10 sec However, acetyl [41] and lauroyl peroxide [71,72] react somewhat slower. 

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)-... 

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 ... 

This acid chloride is much less reactive than acetyl chloride and indeed it may be employed to benzoylate a primary or secondary amine in the presence of a dilute... 

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 activated 4-0-trimethylsilylated-2, 3, 5 -0-acyluridines such as 3 are also obtained as reactive intermediates in the Friedel-Crafts-catalyzed silyl-Hilbert-Johnson reaction [59, 59 a] of persilylated uracils or 6-azauracils such as 227 with sugars such as l-0-acetyl-2,3,5-tri-0-benzoyl-/9-D-ribofuranose 228 in the presence of SnCl4, treatment of the reactive intermediate 229 with a large excess of pyrrolidine neutralizes the SnCLi. used and aminates 229 to afford the protected 6-aza-cytidine 230, although in 57% yield only [49, 59] (Scheme 4.20). 

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