Anthranilic add

In contrast to the 3-amino derivatives, 3-hydroxy-2,l-benzisoxazoles are relatively labile. With nitrous acid they undergo ring fission to anthranilic add. Its 3-acetoxy derivative (258) reacts with primary amines to form the quinazolone (259) (67AHC(8)277, p. 297). 

Diversely substituted anthranilic adds were condensed with per-O-benzylated D-urafriwo-alkylsulfanyloxazoline as a model the results showed that the presence of an electron-withdrawing group hampered the reaction to some extent. 

An important application of the Hofmann reaction occurs in the first technical synthesis of indigo and consists in the degradation of phthalimide to anthranilic add. See p. 372. 

The only practical methods of preparing o-chlorobenzoic acid consist in the oxidation of o-chlorotoluene and the replacement of the amino group in anthranilic add by a chlorine atom. Both of these methods have been fully discussed by Graebe,1 who recommends the former for the preparation of relatively large quantities. The oxidation of o-chlorotoluene by permanganate was originally described by Emmerling.2... 

The moist cake is mixed with 27 g. of zinc dust and 300 cc. of glacial acetic acid in a x-1. round-bottom flask, and the mixture is refluxed vigorously for about four hours (Note 4). When the reduction is complete, the mixture is cooled and filtered with suction. The filter cake is washed once with water and then transferred to a i-l. beaker. The cake is suspended in 200 cc. of water and the suspension is heated to boiling. The hot solution is made strongly alkaline by the addition of about 40 cc. of 33 per cent aqueous sodium hydroxide solution. The alkaline solution is boiled for about twenty minutes to insure complete extraction of the product from the filter cake, filtered from the insoluble material (Note 5) and the thiosalicylic acid is then precipitated by the addition of sufficient concentrated hydrochloric acid to make the solution acid to Congo red paper. The product is filtered with suction, washed once with water and dried in an oven at 100-110°. The yield of a product which melts at 162-163° is 110-130 g. (71-85 per cent of the theoretical amount based on the anthranilic add). 

Another related reaction that goes through a ketimine is the conversion of the amino acid kynurenine to alanine and anthranilic add.225 It presumably depends upon hydration of the carbonyl group prior to P cleavage (Eq. 14-35). An analogous thiolytic cleavage utilizes CoA to convert 2-amino-4-ketopentanoate to acetyl-CoA and alanine.226... 

Condensations of anthranilic add derivatives lead to the 6,12-diamino- and 6,12-dioxo-dibenzodiazocines, and the dichloro compound (279) is available from the latter (54JCS3429). Reduction of (279) via the dihydrazino compound was used to prepare the parent dibenzo[6,/][ 1,5]diazocine (280) (67CC1077). The NMR value (8 8.53 p.p.m.) of the 6(12) proton is indicative of the diazocine structure, presumably in a tub form, rather than the valence isomeric dibenzodiazapentalene (281). 

Diphenic acid was first prepared by oxidizing phenanthrene-quinone with chromic acid.1 Many later workers2 have modified this process in minor details. Vorlander and Meyer 3 were the first to prepare diphenic acid from diazotized anthranilic add and cuprous oxide, but their process is not well adapted to large scale preparation. Inasmuch as pure phenanthrene is now very difficult to obtain in quantity, the present process was devised for relatively large scale operation. 

Fig. 125. Cyclizalion reactions of phenolic Mannich basc.s of anthranilic add.

Anisole, chlorination with sulfuryl chloride, 47, 23, 49,16 Anisole, -< -dichloeo-, 49,16 Anthranilic add, diazotization with isoamyl nitrite and trichloroacetic acid, 48,13, IS... 

Aminonaphtholsulfonic acids, coupling to form azo dyes, 16, i6 Aminopbenol, 15, 39 Amiuopiperole, 16, 6 P-Amlnopropionic acid, 16, 1 4-Aminoveraxroie, 16, 4-Ammonium dichromate, 16, 74 Ammonium thiocyanate, 16, 74 Ammonium vanadate, 13, no -Amyl alcohol, 13,17 feft.-Amyl alcohol, 13, 68 -Amyl benzene, 10, i -Amyl borate, 13,17 -Amyl bromide, 16, 41 ijo-Amyl iodide, 13, 62 -Amyl iodide, 13, 62 -Amylmagnesium bromide, 16, 4r ire-Amyl nitrite, 16, 8 -Amyl phosphate, 16,10 sec.-Amyl sulfide, 16, 73 Aniline, 11, 62 IS, 96 14, 24 16, 59 Aniline hydrochloride, 13, 46 Aotline-o-SULEONIC acid, 16, 55 Anisalacetone, 10, IIS Anthracene, 16, 74 Anthranilic add, 12, 76 Anthraquinone, 14, 4 16, 74 Apparatus... 

The low nucleophilicity of the amino (imino) groups in iminodiacetic and anthranilic adds meant that the DS of the products of their interaction with cellulose tosylate did not exceed 0.7-0.8. Hence, the appearance of a product with a DS of about 2 through the interaction of anthranilic acid with cellulose nitrate was unexpected (32). The reaction rates for cellulose toxyiate and nitrate are shown in Fig. 3. 

Iodoanthranilic acid has been prepared by the reduction of 2-nitro-s-iodobenzoic acid, by treatment of anthranilic add with iodine in potassium hydroxide solution, by treatment of the anhydride of s-hydroxymercurianthranilic acid with iodine in aqueous potassium iodide solution, and by iodination of anthranilic acid in glacial acetic acid solution with iodine mono-chloride. ... 

Usually, N-substituted IA s are synthesized by the action of phosgene on the corresponding N-substituted anthranilic adds, for example, the tricyclic derivative (26) was recently prepared in high yield from tetrahydroquinoline-8-carboxylic add (25).19 An earlier preparation of 26 required a five-step synthesis via 2752 (Eq. 2). (For the analogous synthesis of IA itself via the corresponding chloronitroquinoline derivative see Ref. 53). 

An excess of thioacetic acid converts anthranilic add into the benzothiazinone in theoretical yield. 

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