Acylation glutaric anhydride

Alkylation of l-(2-pyrimidyl)piperazine (129) with 3-chloro-l-cyanopropane gives nitrile 130, which is reduced with LAH and then acylated with spiro-glutaric anhydride 131 to synthesize the tranquilizer buspirone (132).40... 

Benters et al. (2002) used two approaches to modify APTS surfaces. In one instance, the amine groups were acylated using glutaric anhydride to create carboxylate functionalities, which were then activated with NHS/DCC to form the NHS ester. This derivative could be... 

In 1976, Dolby reported the preparation of the hydrindan 15 (Scheme IX) (23). Dimethyl pyruvic acid 45 was prepared according to the procedure of Ramage and Simonsen (28). The condensation of hippuric acid (43) and acetone yields tFfe oxazolone 44, which affords 45 upon treatment with concentrated hydrochloric acid. The Friedel-Crafts acylation of ethylene with glutaric anhydride afforded 5-oxo-6-heptenoic acid 46 in low yield (14-45 ). Base-catalyzed condensation of 45 with 46 gave the crude dibasic acid 47 in 79 yield. Treatment of 47 with excess diazomethane provided the diester 48 in quantitative yield. The esterification also can be accomplished in 90 yield with DBU and iodomethane (L. 0. Dolby, University of Oregon, personal communication, 1979). Base-catalyzed cyclization of 48 afforded 15 in 98 yield. 

We have already considered the use of mixed anhydrides and so in this section we shall be concerned with homocarboxylic anhydrides. The use of anhydrides constitutes the most frequently reported method after the use of an acyl chloride and aluminum chloride. Anhydrides from monocarboxylic acids yield ketones, and cyclic anhydrides derived from dicarboxylic acids afford keto acids. Very nucleophilic aromatic compounds react with trifluoroacetic anhydride in the absence of a catalyst. The confirmation of aromatic character invariably involves establishing reactivity towards a range of electrophiles. Trifluoroacetic anhydride reacts with homoazulene in the presence of an excess of triethylamine to afford 1-tri-fluoroacetylhomoazulene in 91-95% yield. The preparations of 3-aroylpropanoic acids from succinic anhydride and 4-aroylbutanoic acids from glutaric anhydride have been known for many years. Maleic anhydride can be used in a similar way to prepare 3-aroylacrylic acids. We will now concentrate our attention on more recent examples. 

Other derivatives from carboxylic acids can be used as substrates in Friedel-Crafts acylation reactions, including anhydrides and esters. Toluene reacted with glutaric anhydride in the presence of aluminum chloride to give 197, which was used in the Vig et al. synthesis of curcumene ether.128 Lactones are also effective substrates in this cyclization, generating ketones. 129... 

Similar simple reactions can be carried out in solution. Terminal hydroxy groups can be esterified with trifluoroacetic anhydride or glutaric anhydride , although the reaction in the latter case is probably incomplete. Amino groups in the monolayer of cysteamine were reported to react with active esters, such as JV-hydroxysuccinimide (equation 8) . No characterization of the resultant monolayer was, however, given. Cysteamine mono-layers were also acylated with terephthaloyl chloride and an isocyanate derivative . ... 

Cyclic anhydrides are known to be useful acylating agents (2). On reaction of 10-un-decenol [2c] with glutaric anhydride, the co-hydroxy carboxylic acid [18] with an additional 3,y-unsaturated keto functionality could be synthesized (Scheme 8). After recrystallization, the product was obtained as pure ( )-isomer. 

SCHEME 8. Ethylaluminum dichloride-induced acylation of 10-undecenol [2c] with glutaric anhydride. 

Amino-l-cyclohexylmethylphosphonic acid diethyl ester was utilized for the preparation of hapten 1, recently employed to induce the first monoclonal catalytic antibodies capable of catalyzing peptide bond formation[97]. The key steps of the synthesis of 1 include (a) preparation of scalemic a-aminophosphonate, (b) generation of the p-nitrobenzyl ester, (c) installation of a suitable second phosphonate ester linkage, (d) M-acylation with glutaric anhydride. 

Benzene undergoes electrophilic aromatic substitution with anhydrides, compounds having the general structure (RC0)20, in a reaction that resembles Friedel-Crafts acylation. Draw a stepwise mechanism for the reaction of benzene with glutaric anhydride in the presence of AICI3. 

Reactions leading to a ring closure are always of interest. Two 5,6,7,8-tetrahydro-4//-cyclohepta[6]thiophen-4-ones were synthesised as intermediates for new cytotoxic agents [51] using two successive Friedel-Crafts reactions, the last intramolecular. Friedel-Crafts acylation of thiophene or 2-methylthiophene with glutaric anhydride in the presence of AICI3 gave 5-(thien-2-yl)-5-oxopentanoic acid 27a (R=H) and 5-(5-methylthien-2-yl)-5-oxopentanoic acid 27b (R=Me),... 

The synthesis of nonsymmetric cyclopentenes, containing both thien-3-yl and benzo[Z7]thien-3-yl units, was aimed at more sophisticated photochromic molecules (Scheme 54) [73]. By the application of glutaric anhydride with 2-chloro-5-methylthiophene and 5-bromo-2-methylbenzo[h]thiophene in the presence of AICI3, keto acids 52 and 53 were obtained. Conversion of the keto acids into acid anhydrides then Friedel-Crafts acylations produced the desired diketone albeit in only 31% yield (over 2 steps) in the first case and in 14% yield (over two steps) in the second case (Scheme 54) [73]. 

All the syntheses of tricyclic ketones in Scheme 8 described so far have been carried out from comparatively poorly accessible meta-substituted anisoles. Consequently, the possibility of using themore accessible para-substituted anisoles as starting materials offered considerable interest [219]. The acylation of anisole (82) with glutaric anhydride, esterification, the Stobbe reaction, and hydrolysis led to the triacid (87). 

The synthesis of estrone from anisole and glutaric anhydride was first described by Johnson and coworkers [225, 563, 564] in 1951 and was perfected by Kipriyanov and Kutsenko [565] in 1961 (yields and reagents in Scheme 46 are given in accordance with [565]). The Friedel—Crafts acylation of anisole (82) with glutaric anhydride and subsequent esterification led to the keto ester (474) which was converted by the Stobbe reaction into a mixture of tricarboxylic acids isomeric with respect to the position of the... 

Mixed acylation with fatty acid and succinic (or glutaric) acid anhydride... 

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