Anthranilic acids, decarboxylation

N-(m-methylmercapto-phenyl)-aniline (MP 59° to 61°C) is prepared by condensing m-methyl-mercapto-aniline (BP 163° to 165°C/16 mm Hg) with the potassium salt of o-chloro-benzoic acid and decarboxylating the resultant N-(m-methylmercapto-phenyl)-anthranilic acid (MP 139° to 141°C) by heating, and then distilling. 

The kinetics of the decarboxylation of anthranilic acid have recently been examined. Earlier, an investigation of the decarboxylation of anthranilic acid in aqueous or acidic solution at 100 °C gave a C12 C13 value of 108.02 after 72 % reaction in 1.0 M sulphuric acid compared with 108.5 from complete decarboxylation, so that there is virtually no kinetic isotope effect for this compound646. First-order rate coefficients are given in Table 218 and from the variation of rate... 

Heuma nn II Process. In the Heumann II process, starting from anthranilic acid,, V-phcnylglycine-o-carboxylic acid, prepared from anthranilic acid and chloroace-tic acid, is added in the form of the alkali metal salt 13 to a KOH/NaOH melt at 200 °C to produce indoxylcarboxylic acid salt 14. After hydrolysis and decarboxylation, the product is oxidized in air to yield indigo [19],... 

Weak general catalysis by acetic acid (just above the limits of experimental error) has been found in the decarboxylation of 4-aminobenzoic acid in the pH region near 5 [78]. Under similar conditions, general catalysis cannot be detected in the decarboxylation of anthranilic acid [77]. The solvent isotope effects are (feH S)H 0/(feD2s)D2o = 4.9 for 4-aminobenzoic acid at 85 °C [78] and rh Q/kno = 4.7 for anthranilic acid in 0.1 M aqueous hydrochloric acid at 5 °C [251]. The latter result (ratio... 

Rate coefficients [254] and carbon isotope effects [257] in the decarboxylation of 4-methoxy-anthranilic acid at 60 °C (/Li = 0.50)... 

The first quinazoline derivative, 4-oxo-3,4-dihydroquinazoline-2-carbonitrile, was prepared by Griess in 1869 by the reaction of anthranilic acid with cyanogen 26 years later Bischler and Lang" obtained the parent quinazoline by decarboxylation of quinazoline-2-carboxylic acid. Since then, a large number of quinazolines were synthesized and a monograph covering... 

In an I.G. Farben patent [180] the use of disulfur dichloride is described in place of sulfur (method BJ. Possibly the intermediates here are 1,3,2-benzothiazathiolium chlorides (CV) which react with carbon disulfide to give benzothiazoline-2-thiones (CIII). In some instances, the cycUzations are carried out in the presence of sodium hydrosulfite or sodium sulfide. A peculiarity of this reaction is that, simultaneously with the cyclization, chlorination of the arylene ring occurs. Thi.s is not a general rule though. It happens with aniline, o-toluidine, o-anisidine and oc-naphthylamine but not with /)-phenetidine, )S-naphthylamine or benzidine. It seems quite clear therefore that the para position of the aniline must be free if chlorination is to take place, since it is in this position that the chlorine atom is brought in. With anthranilic acid there is formed 4-carbox -6-phenylaminobenzothiazoline-2-thione which shows that the chlorine atom, which is substituted during the reaction, is replaced by a second molecule of anthranilic acid and that decarboxylation occurs at the same time. 

With hydroxylamine, IA reacts to give the O-acylated product,10 95 while O-substituted hydroxylamines yield the anthranilic acid hydroxylamides96 [cf. Eq. (14)]. Reaction of amides with IA results in the formation of quinazo-line derivatives (see Section III,A), and the first reaction step has been proposed as acylation of the amide followed by decarboxylation and ring closure.92,97 A similar reaction mechanism98 can be proposed for the reaction between IA and C=N double bond systems (Eq. 8) (see Section IV). 

The decarboxylation of diazotized anthranilic acid carried out by Stiles and Miller49 is also a fragmentation reaction it affords dehydrobenzene (benzyne), which reacts at once as a dienophile with, e.g., furan, giving 1-naphthol by way of an epoxide. 

The addition products of IV-Boc anthranilic acid and IV-carboxy-a-amino add anhydrides (138) undergo ring expansion and decarboxylation on treatment in situ with HCl to give 1,4-benzo-diazepine-2,5-diones (139) (Scheme 23) <9479051 >. This reaction is interesting because no race-mization was observed. However, there was considerable racemization during the cyclisation of the isolated coupling product of iV-Boc anthranilic acid with an amino acid <93SC2265,9479051). 

The action of a solution of potash in amyl alcohol on rutaecarpine produces anthranilic acid and a second acid which, when boiled with hydrochloric acid, is readily decarboxylated to tryptamine (6, 25, 94, 134, 135, 169). A close relationship between rutaecarpine and evodiamine was demonstrated by fusion of isoevodiamine hydrochloride. Rutaecarpine was formed with liberation of chloromethane. A number of syntheses of (63) have been reported 101, 135, 161), including some under so-called physiological conditions. Some of the more recent examples will be mentioned. Kametani et al. 102,108) obtained (63) in 80% yield through a regiospecificH s+n s cycloaddition of a keteneimine (generated in situ by extrusion of sulfur dioxide from the sulfmamide anhydride of anthranilic acid) with 3,4-dihydro-p-carboline or with 1,2,3,4-tetrahydro-l-keto-P-carboline 109) (also called 1,2,3,4-tetrahydronorharman-l-one or, as in Chemical Abstracts, 2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-l-one) ac-... 

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