Anthranils applications

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

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 process was also applicable to microwave-assisted reactions. Thus, 140a, 140b, and 140 (R1 = z-Pr, R4 = indol-3-ylmethyl) were prepared in a two-step, one-pot synthesis in yields of 55%, 39%, 20%, and with 70%, 73%, 50% ee, respectively. In the first step anthranilic acid was reacted with the appropriate A-BOC-protected amino acid (glycine, L-alanine, and L-valine, respectively) in the presence of P(OPh)3 and dry pyridine under irradiation at 150 °C for 140a or conventional heating at 55 °C for 140b and 140 (R1 = z-Pr, R4 = indol-3-ylmethyl). In the second step the resulting... 

Anthranilic acid derivatives of genus D that possess carbamate and urea linkers (W contains an oxygen or nitrogen atom directly linked to the carbonyl carbon, e.g., compounds 18 and 19 respectively) were claimed as GPR109A agonists in a patent application [65]. 

Replacement of the phenyl group of anthranilic acid by a cycloalkene represents another strategy to obtain intellectual property. This endeavor resulted in three consecutive patent applications [73-75] and a publication [76]. The advantages of tetrahydro anthranilic acid as a surrogate for anthranilic acid include reduced CYP2C8 and 2C9 inhibition and improved oral exposure in mice (analogs 25 vs. 12). Ultimately, a pre-clinical candidate, MK-6892 (26), was selected from this series due to its... 

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. 

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... 

Our approach was based on the observation that it is possible to perform SwAr reactions on solid support with amino acids using a solvent system comprised, in equal parts, of acetone and an aqueous 0.5 M NaHC03 solution at temperatures around 70-75°C. Application of this solvent system to the synthesis of quinoxalin-2-ones 6 from la and a-amino acids is described in Section 3.3.2. With respect to the synthesis of 1,5-ben-zodiazepin-2-ones 4, more than 40 examples of aliphatic and aromatic P-amino acids 35 were found to furnish the desired o-nitro anilines 36, about 80% of which were successfully carried on to eventually afford the ben-zodiazepinone products 4 (Scheme 6). In general, the anthranilic acids required slightly harsher conditions to drive the fluorine displacement to completion (75-80°C, 72 h vs. 70-75°C, 24 h for aliphatic P-amino acids). 

The most frequently reported oxidation reaction of isatins is the oxidation with alkaline hydrogen peroxide to give anthranilic acids. This procedure has been both as a proof of structure of isatins and as a method of synthesis of anthranilic acids. The oxidation has been applied to alkyl 8"10 11 23 33>38-40>46 49>50>118halo n.18.35.36-38-40.47.10 .11 . 119,136,240 alkoxy,26,a8 39,47,75.io7,ii8,i36 trifluoromethyl,33,38,137 and nitro8,120,217 isatins. Use of N-substituted isatins led to N-substituted anthranilic acids.66,71,125,158,169,243 In the oxidation of 5-bromo-l-(y-carbethoxypropyl)-7-ethylisatin, 60 was isolated after treatment with ethanol and acid.11 Oxidation of isatin derivatives 61 led, after treatment with diazomethane, to the acridine derivatives 62.67 Application of this oxidation method to 7-hydroxyisatins gave rise to benzoxazo-lones (63).2,41... 

Anthranilic acid (2-aminobenzoic acid) is an N—O bidentate which commonly forms 2 1 complexes with a variety of bivalent metal ions. d Avignon and Brown16 provided details of some of the structures and applications of these chelates. The synthesis of ternary complexes of 2-aminobenzoic acid and l-nitroso-2-naphthol with a variety of transition metal ions has been reported.17 An X-ray structure shows an unusual N monodentate coordination mode to rhodium for the ligand.18... 

The UDC concept can be further extended by application of ethyl glyoxylate (a convertible aldehyde ). Simple reaction of 48 in the Ugi MCR with /V-Boc anthranilic acids, /V-Boc-rt-amino acids, mono-A-Boc diamines, and niono-A-Boc phenylenediamines, followed by acid treatment and in some cases proton scavenging, affords 1,4-benzodiazepines 49, diketopiperazines 50, ketopiperazines 51, and dihydroquinoxalinones 52, respectively.25 Note that products differ from those obtained from convertible isocyanides in that they contain an additional exocyclic amide... 

Ioannou et al. [41] reported the use of terbium sensitized fluorescence to develop a sensitive and simple fluorimetric method for the determination of the anthranilic acid derivative, mefenamic acid. The method makes use of radiative energy transfer from anthranilate to Tb(III) in alkaline methanolic solutions. Optimum conditions for the formation of the anthranilate-Tb(III) complex were investigated. Under optimized conditions, the detection limit was 1.4 x 10-8 mol/L, and the range of application was 2.5 x 10 8 to 5.0 x 10 5 mol/L. The method was successfully applied to the determination of mefenamic acid in serum after extraction of the sample with ethyl acetate, evaporation of the organic layer under a stream of nitrogen at 40°C, and reconstitution of the residue with alkaline methanolic terbium solution prior to instrumental measurement. The mean recovery from serum samples spiked with mefenamic acid (3.0 x 10-6, 9.0 x 10-6, 3.0 x 10-5 mol/L) was 101 5%. The within-run precision (RSD) for the method for the two serum samples varied from 2 to 8%, and the day-to-day precision for two concentration levels varied from 2 to 13%. 

A convenient synthesis of quinazolines has been reported, and has been applied to the synthesis of representative alkaloids of the quinazoline group (Scheme 5).27 The procedure depends on the formation of sulphinamide anhydrides (23) from the reaction of anthranilic acids with thionyl chloride and the generation in situ of the iminoketens (24). Addition of the latter to the imine (25) or to 2-piperidone, for example, afforded alkaloid (27). Arborine (26) was prepared similarly from N-methylanthranilic acid application of the method to the synthesis of rutecarpine is described in Chapter 11. 

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. 

L-Tryptophan (L-Trp) was produced, mainly by Japanese companies, on a scale of 500-6001 a-1 in 1997 [70]. It is an essential amino acid that is used as a food and feed additive and in medical applications. L-Trp is, at US 50 kg-1 (feed quality), the most expensive aromatic amino acid and it is thought that the market for L-Trp could expand drastically if the production costs could be brought down. There is no chemical process for L-TrP and enzymatic procedures starting from indole, which were very efficient, could not compete with fermentation [95]. L-Trp has been produced by precursor fermentation of anthranilic acid (ANT, see Fig. 8.16), but the serious effects of minor by-products caused the process to be closed down. Since the mid-1990s all L-Trp is produced by de novo fermentation. 

---