Anthranilic ester

It was found inadvisable to use more than four molecules of form-amide [ (47) when R = H] per molecule of anthranilic acid and the condensation produces best results when the mixture is heated at 120 -130°C for 2 hr followed by further heating at 170°-180 C for 2 hr. Other variants of this reaction involve the use of ammonium o-acylaminobenzoates, anthranilic acid in the presence of nitriles and acetic anhydride, o-acetamidonitrile with acetic anhydride or hydrogen peroxide, anthranilic esters and aliphatic or aromatic amides or amidines, isatoic anhydride with amides or amidines, and anthranilic esters with aryl iminochlorides in acetoned The mechanism proposed by Bogert and Gotthelf has had experimental supporR and is represented in Scheme 12. 

To reduce conjugative first-pass metabolism and increase the oral bioavailability of P-estradiol, estradiol-3-salicylate, and P-estradiol-3-anthranilate, ester prodrugs were synthesized and their oral bioavailabilities in dogs were evaluated... 

Nitroketene dithioacetal reacts with anthranilic esters to afford quinolone derivatives, which are converted into diazepinones by reductive cyclization. The review by Kolb covers synthetic application of nitroketene dithioacetal for heterocyclic compounds (see Scheme 10.26).145... 

The pyrimidine ring is formed from [4+2] atom fragments in the synthesis of 114 from 3-chloro-6-arylpyridazine 113 and anthranilic ester <2000HC0147> or acid <2001RRC649, 2003MOL322> (Equation 13). 

B. J. Aungst, M. J. Myers, E. Shefter, E. G. Shami, Prodrugs for Improved Oral Nalbuphine Bioavailabihty Inter-Species Differences in the Disposition of Nalbuphine and Its Acetylsalicylate and Anthranilate Esters , Int. J. Pharm. 1987, 38, 199 - 209. 

Feeding repellents for pest birds are the most important application of chemical stimuli to manipulate bird behavior. Methyl anthranilate (Fig. 13.1) and dimethyl anthranilate, esters of benzoic acid, are found in concord grapes and are used as artificial flavorings. Starlings, Sturnus vulgaris, have an aversion to methyl anthranilate, which irritates the trigeminal nerve, and they feed less on food flavored with a variety of anthranilates. They avoid the more volatile anthranilates most. The odor is partly responsible for the effect contact is not necessary. In one particular experiment, only volatile compounds were aversive (Mason and Clark, 1987). If only anthranilate-treated food is offered, the birds will accept more of the flavored food than they do if they offered a choice between... 

A quinazolone moiety also provides the nucleus for a highly simplified leukotriene antagonist (compare this compound with verlukast (29-6), discussed earlier in this chapter). Condensation of the anthranilate ester (85-1) with formamide leads to the formation of the quinazolone (85-2). Reaction of the salt from the reaction of this product with a strong base with ethyl 3-bromoacrylate leads to vinylation on nitrogen by what is probably an addition-elimination sequence the product is largely the E isomer (85-3). Saponification then affords tiacrilast (85-4) [95]. 

Alkaloids of Delphinium dictyocarpum N- Acetyldelectine and Demethylenedelt-amine.—Further investigations of the aerial parts of D. dictyocarpum DC. have yielded a new base (34), C26H41N08, m.pt. 116—118 °C.27 Spectral analyses (i.r., n.m.r., and mass) indicate the presence of an N-ethyl and three methoxy-groups, and an N-acetyl anthranilate ester, on a lycoctonine-type skeleton. Saponification of (34) gave anthranilic acid and a base identical with that obtained from delectine (35). Therefore, this new alkaloid was assigned the structure of N-acetyldelectine (34). 

Delectine.—A new diterpenoid alkaloid, delectine, has been isolated from Delphinium dictyocarpum7 This base, C31H44N2O8, m.p. 107—109 C, was shown to be the anthranilate ester (6) by chemical and spectral studies and by conversion into 00 -dimethyl-lycotonine (7). Acetylation of delectine gave an NO-diacetyl derivative (8). On alkaline hydrolysis of delectine, anthranilic acid and the alkamine (9) were obtained. Methylation of (9) with methyl iodide-sodium hydride gave (7), which was... 

The use of dimethyl penta-2,3-dienedioate (dimethyl allenedicarboxylate) in cyclizing salicylic acid (p. 139) has been extended to that of anthranilic esters... 

Benzoylcyanamide in DMF reacts with anthranilic acid, its allyl ester or amide to form 4-quinazolinone in moderate-to-good yield, but an electron-withdrawing substituent in the amino acid prevented cyclization [2625]. Cyciization of anthranilic esters with an imino ether proceeds without external heating and can give high yields [2574]. An almost theoretical yield of a 2-amino-4-quinazolinone is reported in a reaction between an anthranilic ester and chloroformamidine hydrochloride [3772]. 

Similarly, 3-amino-4(3//)-quinazolinones (600) are formed in high yields when methyl or ethyl o-acylaminobenzoates are heated with hydrazine in an alcohol. Alternatively, acylation and cyclization of an o-aminobenzoylhydrazine is effected by heating with anhydrous formic acid, ethyl orthoformate, or acetic anhydride. Related is the action of heat on a mixture of anthranilic esters and semicarbazides to yield A3-aminated 2,4(1//,3//)-quinazolinediones (601). Reactions which involve... 

In another route, the B and C rings were formed in one reaction by treatment of anthranil hydrazide with succinic or maleic anhydrides <74Mi 825-02, 78EJM296, 92KFZ32>. In a multistep approach, A-succinoyl anthranilic ester was converted into the tricyclic system <88IJC(B)906>. The pyridazino[l,6-a]quinazoline system has been obtained in two ways. The 7V-aminoquinazolinium salt (92) cyclized easily on treatment with alkali at room temperature to give (93) (Equation 24) <83ACH43>. 

The developed solid-phase approach started with the preparation of immobilised ureas 114 obtained via acylation of amino acids linked to acid-labile Sasrin resin 104 with ortho-methoxycarbonyl aryl isocyanates or activated para-nitrophenyl carbamates 113. Alternatively, ureas of type 114 could also be generated by reaction of anthranilic esters 115 with immobilised amino acid-derived isocyanates (easily generated from tethered amino acids with triphosgene or phosgene in toluene in excess of a base such as 2,6-lutidine) or activated carbamates 116 (Scheme 4.1.23). 

In the presence of sodium hydride in boiling pyridine the anhydride (1) reacts with the alcohols 302 with the formation of anthranilic esters 303 with yields of 41-56%. After diazotization and reaction with a-chloroacetoacetic esters the products are converted into the hydrazonyl chlorides 304 (yields 75-78%). Treatment of the latter with silver carbonate in acetonitrile leads to the tricyclic compounds 305 (yields 14-61%) [189],... 

Many wines with a strong labrusca character have been found to have a methyl anthranilate content well below the apparent odor threshold (JXL). Furthermore the addition of this compound to vinifera wines at very high concentrations does not produce a labrusca aroma nor does it produce a wine with any foxiness. There are small amounts of other anthranilate esters ethyl propyl ..-butyl and the analogous compound Q.-aminoacetophenone in labrusca grapes but there are no data explaining their precise contribution if any to the methyl anthranilate-like aroma. 

Analogously, anthranilonilrile 79 was also used as starling material for the preparation of quinazolinones. Chowdhury and co-workers reported the synthesis of ting fused thioquinazolinone 82 by condensing anthranilonilrile 79 with JV-melhylsulfanylthiocarbonyl-glycine ester 81 <01H1747>. In comparison, reaction of 81 with anthranilate ester 80 led to 83. 

Anthranilonilrile derived isothiocyanale 84 was also used to construct quinazolinones. Nanni and co-workers reported a dimerization of 84 in the presence of Mn(OAc)j in HOAc to give fused quinazolinc 86 in excellent yield <01T7221>. In contrast, dimerization of the anthranilate ester 85 gave quinazoline 87 as the major product, though in only 30% yield. It was assumed that a thiourea intermediate was initially formed which then cyclized through an ionic and/or radical mechanism. However, when thiourea 88 was treated under the same conditions, 89 was the major product along with minor products 90, 91,92 and 93. 

Langer and co-workers generated 2,2 -bis-quinazolin-4-ones by condensing substituted anthranilic esters with substituted bis(imidoyl)-chlorides. These compounds, which are structurally similar to the quinazoline alkaloid febrifUgine, have the potential to serve as anti-malarials. Treatment of methyl-2-amino-4,5-dimethoxybenzoate with bis(p-methoxyl-phenylimidoyl)chloride in the presence of two equivalents of TEA in refluxing toluene gave the desired product in 60% yield. 

A soln. of o-nitrotoluene in methanol pyrolyzed at 600° with a contact time of 11 sec. methyl anthranilate. Y 48%. - A wide variety of subst. anthranilic esters difficult to prepare otherwise can be obtained by this method. F. e. s. E. K. Fields and S. Meyerson, Tetrah. Let. 1968, 1201. 

This reaction has been extended to occur between an anthranilic acid and a thiobenzamide. In addition, different anthranilic acid derivatives—including o-acylaminobenzamides, ammonium 6>-acylaminobenzoates, o-acetaminobenzonitrile, acetanthranil and anthranilic ester —have been used successfully in this reaction. Moreover, efficient reaction conditions have been established under microwave... 

An advantage of this method is that the starting triphenylphosphoranylidene ketones 1 are prepared from the more commonly available anthranilate esters 4. 

It should be noted that the somewhat related Baumgarten method has not been successfully employed to produce 3-nitro-4-cinnolones. In this method, an ortho-ammo acetophenone (or benzaldehyde, Ri = H) is diazotized, and the resulting diazonium salt is intercepted with the sodium salt of nitromethane to afford a nitroformaldehyde phenylhydrazone (5), which may be isolated. Cyclization of 5 may be viewed as occurring by a Knoevenagel condensation between the methylene group and the ketone carbonyl. However, attempts to extend this chemistry to anthranilate esters were not successful. 

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