Isatoic anhydride synthesis

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

These formulae explain the scission products of the two alkaloids and the conversion of evodiamine into rutaecarpine, and were accepted by Asahina. A partial synthesis of rutaecarpine was effected by Asahina, Irie and Ohta, who prepared the o-nitrobenzoyl derivative of 3-)3-amino-ethylindole-2-carboxylic acid, and reduced this to the corresponding amine (partial formula I), which on warming with phosphorus oxychloride in carbon tetrachloride solution furnished rutaecarpine. This synthesis was completed in 1928 by the same authors by the preparation of 3-)S-amino-ethylindole-2-carboxylic acid by the action of alcoholic potassium hydroxide on 2-keto-2 3 4 5-tetrahydro-3-carboline. An equally simple synthesis was effected almost simultaneously by Asahina, Manske and Robinson, who condensed methyl anthranilate with 2-keto-2 3 4 5-tetrahydro-3-carboline (for notation, see p. 492) by the use of phosphorus trichloride (see partial formulae II). Ohta has also synthesised rutaecarpine by heating a mixture of 2-keto-2 3 4 5-tetrahydrocarboline with isatoic anhydride at 195° for 20 minutes. 

The substance represented by formula (IV), viz., 4-hydroxy-3-allyl-3 4-dihydroqviinazoline, m.p. 130°, was synthesised by Reynolds and Robinson, and proved to be different from vasicine. Spath and Kuffner established the identity of the degradation product (V), upon which formula (IV) for vasicine was chiefly based by synthesis from isatoic anhydride, which, on treatment with glycine ester hydrochloride and sodium meth-oxide, gave the substituted Wppuric acid (VI), and this, on heating with... 

The benzodiazepine nucleus is extremely important, as it is the base of several drugs and other biologically active compounds with different properties. A facile synthesis of 2-methyl-l,4-benzodiazepin-5-ones has been described by Santagada and co-workers [162]. Isatoic anhydride 254 was reacted with M-substituted allylamines under microwave irradiation to give compound 255... 

Although the 3,l-perhydrobenzoxazine-2,4-diones are the saturated analogs of the versatile synthon isatoic anhydride, few articles deal with the synthesis of these derivatives. 

The synthesis of quinazoline derivatives by ring-opening and ring-closure reactions involving isatoic anhydrides and 3,l-benzoxazin-4-ones is covered in Section 8.02.9.2. 

Isatoic Anhydrides and Their Uses in Heterocyclic Synthesis T. Kappe and W. Stadlbauer, Adv. Heterocycl. Chem., 1981, 28, 127-182. 

A similar rapid microwave one-pot synthesis of substituted quinazolin-4-ones was also reported, which involved cyclocondensation af anthranilic acid, formic acid (or an orthoester) and an amine under solvent-free conditions (Scheme 3.37)61. A complimentary approach was adopted to synthesise 4-aminoquinazolines in very good yields, involving the reaction of aromatic nitrile compounds with 2-aminobenzonitrile in the presence of a catalytic amount ofbase (Scheme 3.38)62. The reactions were performed in a domestic microwave oven and required only a very short heating time. A microwave-assisted synthesis of a variety of new 3-substituted-2-alkyl-4-(3H)-quinazolinones using isatoic anhydride, 2-aminobenzimidazole and orthoesters has also been described (Scheme 3.38)63. 

Isatoic anhydride can be used as a versatile synthon for the synthesis of a diverse set of molecules. The isatoic anhydride can be reacted with amines, amides, hydrazides, isothiocyanates, diketo substrates, aminoacids, amino-, thio or hydroxy anilines, as well as in a three-component reaction with aldehydes and amines to form a large set of diverse pharmacophores. 

Indolizine chemistry, advances in, 23, 103 Indolones, isalogens and. 22, 123 lndoxazenes. 8, 277 29, 1 Isatin, chemistry of, 18, I Isalogens and indolones, 22, 123 Isatoic anhydrides, uses in heterocyclic synthesis, 28, 127... 

Reaction of carboxamides with isatoic anhydrides 7 in place of anthranilic acid as a source of the anthraniloyl group is an attractive extension of the Niementowski synthesis (cf. p 30). The reaction of isatoic anhydrides 7 with formamide or 2-hydroxybenzamides at elevated temperatures in a melt or in tbe presence of suitable solvents gives high yields of tbe respective quinazolin-4(3//)-oncs 8/ whereas with alkyl-, aralkyl-, or arylcarboxamides the yields of the corresponding 2-substituted quinazolin-4(3//)-oncs arc low Guanidine and ami-... 

Isatoic anhydrides 11 are transformed with ammonia into quinazoline-2,4(li/,3i/)-diones 12 with concomitant formation of the corresponding anthranilic acids -or anthranil-amides. The reaction lacks generality and has seldom been used for the synthesis of quin-azoline-2.4(177,37f)-diones. 

In a one-pot synthesis, treatment of isatoic anhydrides 13 with ammonia, phosphoryl chloride, and a primary amine in dimethylformamide gives high yields of quinazolin-4-amines 16. The intermediates 14 and 15 can be isolated if desired. This method appears to be a general, one-pot method for the synthesis of quinazolin-4-amines in good yields. ... 

H-3,1-Benzoxazine-2,4(1 H)-dione known as isatoic anhydride (VI) is the most popular six membered cyclic O-acyl carbamate. The synthesis of isatoic anhydride by ring closure of anthranilic acid with phosgene is well described (Ref. 250). However, we have developed an... 

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