Reduction anthranils preparation

Reduction of aromatic carboxylic acids to alcohols can be achieved by hydrides and complex hydrides, e.g. lithium aluminum hydride 968], sodium aluminum hydride [55] and sodium bis 2-methoxyethoxy)aluminum hydride [544, 969, 970], and with borane (diborane) [976] prepared from sodium borohydride and boron trifluoride etherate [971, 977] or aluminum chloride [755, 975] in diglyme. Sodium borohydride alone does not reduce free carboxylic acids. Anthranilic acid was reduced to the corresponding alcohol by electroreduction in sulfuric acid at 20-30° in 69-78% yield [979],... 

The above procedure is essentially that of Ullmann and Bleier.2 2-Aminobenzophenone has also been prepared by reduction of 2-nitrobenzophenone,3 by the Hofmann reaction of the amide of o-benzoylbenzoic acid with sodium hypobromite,4 by the action of an excess of benzoyl chloride on aniline at 220°,6 and by hydrolysis of the acetyl derivative which is obtained by the action of phenylmagnesium bromide on 2-methyl-3,l,4-benzoxaz-4-one (from anthranilic acid and acetic anhydride).6 Various methods for the preparation of 2-aminobenzophenones have been summarized critically by Simpson, Atkinson, Schofield, and Stephenson.7... 

Condensations of anthranilic acid 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,/][l,5]diazocine (280) (67CC1077). The NMR value (5 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 has been prepared by the reduction of diazotized anthranilic acid with cuprous ion,5 Ullman coupling of potassium... 

An alternative but equally cumbersome synthesis utilizes the more accessible bis(2-carboxyphenyl)disulfide, easily prepared from anthranilic acid. Byconversion to the corresponding anilide, then by successive reduction with zinc dust and acetic acid (yielding 2-mercaptobenzoyl anilide) and lithium aluminum hydride, the aldehyde (6) is obtained in fair overall yield.Although... 

Examples of this ring system (263) were prepared by cyclocondensation of anthranilic acid with the 1,3-thiazole derivatives 262 (82MI1 83AP394). Reductive cyclization of the 4-ethylamino-3-(2-nitrobenzyl)thiazolidines (264) was affected by heating with iron filings and acetic acid to give 4//-3,3a-dihydrothiazolo[4,3- >]quinazoline (265) (87JHC107). 

It was previously mentioned1 that cinnoline and 3-substituted cinnolines (94) could be prepared from the condensation products (95) between an o-nitrobenzaldehyde and a nitroalkane by electrochemical reduction. The reaction has been further studied,138 and it was noticed that when the reduction was carried out stepwise, anthranils (96) were formed, especially at elevated temperatures. The final ring closure was catalyzed by traces of oxygen, whereas too much oxygen produced the cinnoline JV-oxide (97) the ring closure was believed to be a radical chain reaction where the formation of the aromatic cinnoline was part of the driving force [Eq. (76)]. 

Of the several methods described for the production of thiosalicylic acid, only the following are of preparative interest heating of o-halogenated benzoic acids with an alkaline hydrosulfide at i50-200° in the presence of copper or copper salts,1 5 or by substitution of sodium sulfide at 200° 2 by reduction of dithiosalicylic add with glucose,3 or metals 4,5 in alkaline solution. The dithiosalicylic add is prepared by treating diazo-tized anthranilic acid with sodium disulfide in alkaline solution.4... 

The anthranilic acid derivative 4, prepared from isatoic anhydride and L-proline, on Birch reduction and alkylation affords pure 5, which is hydrolyzed by acid to the aminolactone 6, with the absolute configuration opposite to that of 3. 

Diphenic acid has been prepared by the reduction of diazotized anthranilic acid with cuprous ion,6 Ullman coupling of potassium o-bromobenzoate,6 and oxidation of phenanthrene or phen-anthrenequinone with various oxidizing agents.7 The latter methods have been reviewed recently.7 The ozonolysis method has also been carried out in solvents 8 that do not react with the zwitterion intermediate. ... 

The material of the glower is mostly without any influence on the reaction. Platinum, platinum-iridium, nickel, iron and carbon gave qualitatively equal results only copper wires are not applicable for the preparation of anthranilic acid. They primarily cause a reduction to o-toluidine and then complete combustion is brought about by the copper oxide which is formed. 

Anthranils 208 are formed by spontaneous cyclization of 0-acylphenylhydroxylamines 207, which are prepared by reduction of the corresponding nitro compounds. Treatment of the -amino ketone 209 with lead tetraacetate gives the anthranil 210 (Scheme 123). For similar cyclizations leading to other 3,4-fused isoxazoles see the related chapter of CHEC-III . 

For the preparation of 4-(1.2.3.4-tetrahydroquinolino)-phenol 17 three different procedures were worked out [Eqs. (6)-(8)]. 17 was prepared by reacting N-p-methoxyphenyl-anthranilic acid with acetic anhydride and subsequent saponification to l-p-methoxyphenyl-4-hydroxy-2-quinolone, reaction withPOCl3 to form l-p-methoxyphenyl-4-chloro-2-quinolone, hydrogenation to l-(p-methoxy-phenyl)-3.4-dihydro-2-quinolone, splitting the ether with HBr to l-(p-hydroxy-phenyl)3.4-dihydro-2-quinolone, and reduction with LiAlH4 [Eq. (6)J. Another synthetic possibility was the reaction of p-anilinophenol with (3-propiolactone and subsequent cyclization to l-(p-acetoxyphenyl)2.3-dihydro-4-quinolone 18. The next step, the Wolff-Kishner reduction, led directly to the desired product [Eq. (7)]. The third way, the direct amination of p-iodoanisole with 1.2.3.4-tetrahydro-quinoline and the subsequent splitting of 4-(1.2.3.4-tetrahydro-quinolino)-anisol with HBr was the best one [Eq. (8)]. Saponification of l-(p-acetoxyphenyl>2.3-... 

Table 2 Selected anthranilic acid derivatives prepared by reductive alkylation of the Step 2 amine intermediate using 4-pyridinecarboxaldehyde and their corresponding melting points. 111-NMR data supplied by author...

The first anthranil ( azo-opianic acid ) was made by this method in 1881,113 but was not recognized as such. In 1882 Friedlander and Henriques109 prepared the parent compound, by reduction of o-nitrobenzaldehyde with tin and acetic acid. They thought it to be the anhydride of anthranilic acid, and hence arose the name anthranil. It has been shown, using O18, that the carbonyl oxygen is lost, and the cyclic oxygen atom is derived from the nitro group, in the reductive cyclization.141... 

Aminoisoxazoles were obtained from (Z)-3-alkyl-3-nitro-2-phenylpropenenitriles using baker s yeast <1996SL695>. Reductive cyclizations of 2-nitroacylarenes allowed the synthesis of anthranil derivatives. For example, a series of 5-substituted 2,1-benzisoxazoles where prepared by reduction with SnCl, and subsequent... 

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. ... 

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... 

Up to now, several groups have devoted their efforts to synthesize it. In 1957, Lesiak and Schittek synthesized anthranilic acid from o-nitroethylbenzene. Jan Bakke et al prepared it from o-nitrotoluene. With the help of the Ullrnan reaction. Cook also synthesized it. Srinivasan, in 1957, described the synthesis of anthranilic acid from Shikimic acid-5-phosphate and L-glutamine. " Jana et al. ° explored for the first time a facile approach for the catalytic reduction of o-nitrobenzoic acid (o-NB A) to anthranilic acid (o-aminobenzoic acid) over a resin-bound silver nanocomposite as catalyst in the presence of sodium borohydride. 

The Cadogan reaction refers to the deoxygenation of o-nitrostyrenes 1 or o-nitrostilbenes with trialkyl phosphite or trialkylphosphine and subsequent cyclization of the resulting intermediate nitrene 2 to form indoles 3. The reductive cyclization protocol has also been exploited to prepare a variety of A -containing heterocyclic compounds including carbazoles, indazoles, benzimidazole, benzotriazoles, anthranils, phenazines, phenothiazines, quinolines, and related compounds. 

Cadogan himself further extended the scope of the Cadogan reaction. As early as in 1965, he already prepared carbazoles, indoles, indazoles, thiazoles and related compounds. In 1966, he synthesized phenothiazine (21) and anthranil 23, respectively, employing the reductive cyclization of nitrocompounds by triethyl phosphite. ... 

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