Succinic anhydride acylation with

In addition to acylating a- and e-amino groups, succinic anhydride reacts with tyrosyl, histidyl, cysteinyl, seryl and threonyl side-chains. The tyrosyl derivative hydrolyzes spontaneously at alkaline pH, and is rapidly decomposed by hydroxylamine at neutral pH. The histidyl derivative is presumably very labile. The lability of all of the ester derivatives to hydroxylamine at pH 10 permits preparation of a protein modified solely on the a- and e-amino groups (e.g. Gounaris and Perlmann 1967). 

It is now evident that acylation with anhydrides (such as acetic and succinic anhydrides) and with lactones (such as -propiolactone) is being proposed (< ) for improving the solubility of soy protein isolates at acidic pH, particularly for the preparation of coffee whiteners. Moreover, this chemical modification has been evaluated for altering the food-use properties of several milk proteins (40), egg protein (41), wheat protein (42), fish protein (43), and single-cell protein (44). 

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

Friedel-Crafts acylation of 3,3-dimethyl-2-indolinone by succinic anhydride gives 3,3-dimethyl-5-(3-catboxyptopionyl)-2-indoline, which is used as an intermediate in the preparation of inotropic agents for treatment of heart failure (94). Antibacterial phlotophenone derivatives have been prepared by Friedel-Crafts acylation with ptopanoyl chlotide (95). 

Condensation with Aldehydes and Ketones. Succinic anhydride and succinic esters in the presence of different catalysts react in the gas phase with formaldehyde to give citraconic acid or anhydride and itaconic acid (94—96). Dialkyl acyl succinates are obtained by reaction of dialkyl succinates with C 4 aldehydes over peroxide catalysts (97). 

Friedel-Crafts acylation of unsaturated fatty acids can be carried out with succinic anhydride ia the presence of alkyl aluminium haUde (104). 

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). 

An interesting application of this reaction was the use of macro-molecular anhydrides, namely, styrene-maleic anhydride or vinyl acetate-maleic anhydride copolymers in the presence of perchloric acid as catalyst, these copolymers acylate mesityl oxide or d rpnone to macromolecular pyrylium salts which, with aryl substituents, are fluorescent.No crystalline products could be obtained from succinic anhydride because of the solubility and ease of decarboxylation. 

The second route employs acylation of tryptamine (259) as the first step by reacting it with succinic anhydride. After methylation with CH2N2, the resultant iVb-methoxysuccinyltryptamine (266) is transformed to the corresponding... 

An amine-terminated polyoxyalkylene having an average molecular weight from about 600 to about 10,000 can be acylated with a succinic acylating agent (e.g., hexadecenyl succinic anhydride or a Diels-Alder diacid) obtained from an unsaturated fatty acid [628,629] similarly, alkyl-aryl sulfonate salts [1319] can be used in lubrication. 

Almost every major structural class discussed to date has featured at least one nonsteroidal antiinflammatory carboxylic acid. It is thus perhaps not surprising to find a dibenzoheterocycle serving as the nucleus for one of these agents, furobufen (34). Straightforward Friedel-Crafts acylation of dibenzo-furan (33) with succinic anhydride affords a mixture of 2- and 3-acylated products, with the latter predominating. The mixture is esterified with methanol, and the methyl ester of the 3-isomer is separated by fractional crystallization. Hydrolysis back to the... 

Modification of amines with maleic anhydride is done essentially the same as that described for succinic anhydride (this section, Part A), except the pH of the reaction should be kept alkaline (pH 8-9) at all times to prevent unwanted de-acylation. Deblocking of maleylated amines can be accomplished according to the following procedure of Butler et al. (1967). 

By screening a variety of lipases in organic solvent for their ability to acylate the racemic hydroxynitrile with succinic anhydride, Novozym 435 was found to yield the best results, affording product in 94-95 % ee at conversions of 47 9 % (Scheme 1.34). After optimization, the reaction was successfully run at 22 kg scale. The immobilized catalyst could be easily isolated by filtration and reused. 

Block (cap) residual lysine residues with a carboxylic acid by acylation using succinic anhydride prepared in l-methyl-2-pyrrolidinone,... 

Octahydrodibenzothiophene (73) has been prepared by the following sequence. Friedel-Crafts acylation of 4,5,6,7-tetra-hydrobenzo[6]thiophene with succinic anhydride (87%) or with the ester chloride of succinic acid followed by hydrolysis (80%), yields the keto acid (74). Huang-Minlon reduction of 74 followed by cyclization of the derived acid chloride with stannic chloride yields l-keto-1,2,3,4,6,7,-8,9-octahydrodibenzothiophene (53) (Section V,A). Reduction of 53 gives 73 as a solid (overall yield 32%). 

Friedel-Crafts acylation of dibenzothiophene with succinic anhydride is known to occur in the 2-position, yielding y-oxo-2-dibenzothiophene-but3Tic acid (135a). Subsequent Wolff-Kishner reduction and internal cyclization yields 7-keto-7,8,9,10-tetrahydrobenzo[6]naphtho[2,3-d]thio-phene (136a). - This reaction has been extended to 4-methyldibenzo-... 

The diacylation of isopropenyl acetate with anhydrides of dicarboxylic acids is applicable for the synthesis of several other cyclic jS-triketones in moderate yield. - It has been used for the synthesis of 2-acetylcyclohexane-l,3-dione (40% yield), 2-acetyl-4-methylcyclopentane-l,3-dione (10% yield), 2-acetyl-4,4-dimethylcyclopentane-l,3-dione (10% yield), 2-acetyl-5,5-dimethylcyclohexane-l,3-dione (10% yield), 2-acetylcyclo-heptane-l,3-dione (12% yield) and 2-acetylindane-l,3-dione (26% yield). Maleic anhydrides under more drastic conditions give acetylcyclopent-4-ene-l,3-diones in yields from 5% to 12%. The corresponding acylation of the enol acetate of 2-butanone with succinic anhydride has been used to prepare 2-methylcyclopentane-l,3-dione, an important intermediate in steroid synthesis. - ... 

The main group of methods for the preparation of a 1,2,4-oxadiazole ring is based on cyclization of amidoxime derivatives in the presence of acylating agents °. A surprisingly easy cyclization of O-benzoyl-/ -piperidinopropioamidoxime 247 to oxadiazole 248 in DMSO at room temperature was described (equation 107) . 3-(3-Aryl-1,2,4-oxadiazol-5-yl)propionic acids 250 were obtained by the reaction of amidoximes 249 with succinic anhydride under microwave irradiation or conventional heating (equation 108) °°. 

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