Anthranils ring opening

Isoxazoles substituted in the 3-position, but unsubstituted in the 5-position, react under more vigorous conditions to give acids and nitriles (Scheme 24). Anthranils unsubstituted in the 3-position are similarly converted into anthranilic acids by bases (Scheme 25) (67AHC(8)277). Attempted acylation of anthranils gives benzoxazine derivatives via a similar ring opening (Scheme 26) (67AHC(8)277). 

Similar instability is found for 3-unsubstituted 2,1-benzisoxazole in the presence of base, ring opening to anthranilic acid derivatives occurring readily (see Section 4.16.3.1.6). 

The readiness with which the anthranil ring is opened is a particular feature of reactions in this series. The fission takes place with a wide variety of reagents and leads to many different products. 

Reisch et stated that 6-chloro-3-cyanopyridin-2(l//)-one and anthranilic acid in acetic acid or in dimethylformamide in the presence of potassium carbonate and copper powder gave the hydrate of pyrido[2,l-i ]quinazolinone (492). When compound 492 was treated with diazomethane, a ring-opened product (493) was obtained. 

Initial investigations of I A chemistry brought two types of reaction ring opening to anthranilic acid derivatives1-3,6,7,9,10 and substitution in the aromatic nucleus.2,9,11... 

The reaction with ammonia or primary amines in aqueous systems has been investigated repeatedly. Generally, two types of products are obtained during the reaction. The primary product is the ring-opened isatoic amide 42, which reacts with loss of C02, favored by a low ratio of amine, to the anthranilic acid amide (43),2 6 10,86 88 while a high ratio of amine or bulky amines leads to isatoic diamides (45), which undergo facile cyclization to the quinazoline diones 36 by heating.86,89 93 The kinetics of the reaction of IA with n-butylamine show that the rate law for formation of 43 is zero order... 

Reaction of IA with aziridine in the presence of hydrogen sulfide leads to the unstable intermediate 277, which produced the thiazoloquinazoline 278 with ethyl chloroformate (Eq. 24).293 Ring opening of IA to the anthranilate... 

Lactim ethers and thioethers (300) furnish condensed quinazolones 301 when interacted with IA.303 Ring opening of IA s to the corresponding anthranilic acids and reaction of its potassium salts with chloroacetone yields 2-indolyl ketones 302.304 Potassium cyanide with (V-substituted IA s produces iminoindolinones 303, which were readily hydrolyzed to the corresponding isatins.305 Reaction of 303 to the spiroindoloquinazoline... 

Oxidative cyclization of o-aminoacylbenzenes is a much less common process for the synthesis of anthranils than the reductive cyclizations discussed in the previous section, mainly because the o-aminoketones are in many instances best prepared by reductive ring opening of anthranils (see Section III,C,3). Nevertheless, a few examples have been recorded. Oxidation of o-aminobenzophenones to the nitroketones using peroxytrifluoro-acetic acid, permaleic acid, or persulfuric acid proceed via the 3-phenyl-anthranil which occasionally is isolable.168 Caro s acid is also a useful oxidant.169... 

Pyrylium)anthranils, e.g., 121 (X = 0+C104 H in place of N02) with carbanions yield 3-arylanthranils by a sequential ring-opening/ring-closure process.148 For example, with nitromethane anthranil 115 (R = 3,5-Ph2-4-02NC6H2) is obtained. 

The authors explain their results in terms of initial ring opening of the anthranil to a nitrenoketone (148) followed by singlet, electrophilic nitrene attack at the electron-rich l -carbon position to yield the resonance-stabilized dipolar spiro intermediate 149. Acridone formation then occurs either via the polar intermediate 150 or, more likely, by electrocyclization of its valence tautomer, the iminoketene 151. 

Benzotriazines are ring-opened by aqueous acid at room temperature yielding o-aminobenz-aldehydes, whereas 4-substituted derivatives require heating to form <9-aminoaryl ketones. 1,2,3-Benzotriazin-4(37/)-ones 1 suffer acid cleavage of the heterocycle producing the diazonium ion 2 derived from anthranilic acid amide. Subsequent reactions of these ions involving the A-amino system 3 lead to the anthranilic acid azide 4 by an internal redox disproportionation ... 

Quinoline was converted in good yield to nicotinic acid (Sturrock et al., 1960). With indoles, the pyrrole ring opens to give aniline derivatives, as in the formation of 2-aminobenzaldehyde and anthranilic acid from indole (Equation 5.44) (Jurs, 1966). 

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