Isatoic anhydride chloride

Treatment of isatoic anhydrides with thionyl chloride furnishes the isocyanates 22, which react with methylhydrazine to yield Ihe benzotriazepinediones 23.362... 

A more highly oxidized derivative of quinazoline forms the heterocyclic moiety of a compound with CNS activity. Condensation of the aminopropylpiperazine 141 with isatoic anhydride gives the anthranilamide 142. Reaction of that amide with phosgene gives directly the heterocyclic ring. (The reaction may proceed by initial formation of the carbamoyl chloride ... 

It is clear from Table 44 that the E2/SN2 ratios observed for reactions of crown ether-separated KOt-Bu ion pairs will greatly depend on the type of substrate and solvent. Di Biase and Gokel (1978) have recently reported many examples of the use of this reagent either as a nucleophile [for example, in its reaction with benzyl chloride and in the reaction with isatoic anhydride (34)] or as a strong base [for example, in the basic oxidation of fluorene to 2-carboxybiphenyl (35)]. 

The reaction of maleic anhydride with trimethylsilyl azide was reported to provide l,3-oxazine-2,6-dione in good yield. Control of the temperature proved essential in order to avoid a violent, exothermic reaction this could readily be accomplished by running the reaction in methylene chloride at 0°C <19950PP651>. Similar transformations of 3-substituted phthalic anhydrides 546 resulted in formation of 8- 547 or 5-substituted 548 isatoic anhydrides (Equation 66). The ratio of the regioisomeric products was strongly influenced by the substituent X while nitro and acetylamino derivatives 546 (X = NO2, NHAc) gave exclusively the 8-substituted isomers, only the 5-substituted product was formed from 3-aminophthalic anhydride 546 (X = NH2) <1998JOC6797>. 

The azathio isatoic anhydride 99 has been prepared by the reaction of 2-aminonicotinic acid 303 and thionyl chloride in ecu <2001JOC4413>, benzene, or cyclohexane as the solvent (Equation 40) <2004TL1377>. 

The use of activated anthranihc acid derivatives facUitates the preparation of the amides in those cases where the amines are either umeactive or difficult to obtain. Thus, reaction of (87-1) with phosgene gives the reactive the isatoic anhydride (89-1). Condensation of that with ortho-toluidine leads to the acylation product (89-2) formed with a simultaneous loss of carbon dioxide. This is then converted to the quinazolone (89-3) by heating with acetic anhydride. Reaction with sodium borohydride in the presence of aluminum chloride selectively reduces the double bond to yield the diuretic agent metolazone (89-4) [99]. 

Performing a Vilsmeier-Haack reaction on 3-benzoyloxy-2-methyl-quinazolin-4-one (184) afforded the isoxazolo[3,2- ]quinazolinone (185) [86IJC(B)709]. This ring system (187) was also synthesized by cyclocondensation of anthranilic acids or isatoic anhydrides with the isoxazolin-3-ones (186) (77AF766 83MIP1), or by condensation of methyl anthrani-late with 3-chloropropanoyl chloride followed by cyclization with hydroxylamine hydrochloride (77AF766). 

Isocyanatobenzoyl chloride reacted with isatoic anhydride (76JOC2728) or nitromethane in benzene [83IJC(B)485] to yield 5H,12H-quinazolino[3,2-a]3,1 -benzoxazine-5,12-dione (540) (76JOC2728). Cyclodehydration of 3-(2-carboxyphenyl)quinazoline-2,4(l//,3/f)-dione (575) (66ACH77 67MI1) also afforded the same compound (540). 

Cross and Bevan first succeeded in fixing dyes covalently onto cellulose fibers (in 1895) [1], but their multistep process was too complicated for practical application. Early work by Schroter with sulfonyl chloride-based dyes was unsuccessful [2], but Gunther later did succeed in fixing derivatives of isatoic anhydride onto cellulose fibers [3],... 

Isatoic anhydride (180.3 g) and 367 ml chlorosulfonic acid were mixed and stirred 21 hours at ambient temperature, then treated with 80.6 ml thionyl chloride over 2 hours. The mixture was stirred an additional 16 hours and then poured over ice (4.5 kg). The mixture was filtered, washed twice with 500 ml water, dried, and the product isolated. 

When substituted anthranilic acids 346 were reacted with thionyl chloride 347 was produced, the thio analogues of isatoic anhydride, which readily underwent reaction with differently substituted iV-alkylanthranilic acids 348 to... 

The so-called acylanthranils played an important role in the discussion on the structure of anthranils. Heller regarded the possibility of obtaining them by acylation of anthranils as evidence for structure 164, and for the lactam structure for anthranils in general. However, he was soon forced to reconsider this view. In particular, it was realized that the product from ethyl chloroformate and anthranil was not anthranil carboxylic ester,243 but rather the known compound isatoic anhydride (165).1I7,121,289, 291-293 jsatoic anhydride and benzoyl chloride formed benzoylanthranil, 291,294 and the structural connection between the two compounds was recognized. Nevertheless, structure 163, (R = Ph), first suggested by Angeli,295 and undoubtedly correct, has been too often overlooked, and some later authors, even up to the present day, have persisted with the lactam formula.296-301... 

The major use of phthalic anhydride is for ester derivatives used as plasticizers in the manufacture of flexible poly(vinyl chloride), e.g., wallpaper. The largest volume plasticizer is the di(2-ethylhexyl)phthalate. Other uses of phthalic anhydride are for unsaturated polyester and alkyd resins, for dye intermediates, and for isatoic anhydride (for the production of saccharin). 

Oxidation with chromium trioxide in acetic acid, chromium trioxide in acetic anhydride-acetic acid, 3-chloroperbenzoic acid in methylene chloride or benzeneor peracetic acid in acetic acid gave rise to isatoic anhydrides (64). 

In a one-pot synthesis, treatment of isatoic anhydrides 13 with ammonia, phosphoryl chloride, and a primary amine in dimethylformamide gives high yields of quinazolin-4-amines 16. The intermediates 14 and 15 can be isolated if desired. This method appears to be a general, one-pot method for the synthesis of quinazolin-4-amines in good yields. ... 

A study of all the stages in the synthesis of 4-aminoquinazolines from isatoic anhydride, via anthranilamide and o-aminobenzonitrile, made possible the preparation of these compounds by a one-pot synthesis. The anhydride was treated with ammonia in dimethylformamide, nitrogen was then bubbled through the solution to remove excess of ammonia, phosphoryl chloride was added and heated at 40°-60°C for conversion into the nitrile, and finally the respective amine was added to yield the 4-(substituted-amino)-quinazolines in 44-79% yields. ... 

Zhang and coworkers have developed the use of fluorous-tagged isocyanate as well as isatoic anhydride and acid chloride for the scavenging of amines for use in combinatorial as well as conventional chemistry (Figure 8.3) [30]. All reagents were readily prepared from commercially available sources, and the F-isatoic anhydride was prepared via a simple NaH-mediated alkylation of isatoic anhydride with per-fluoroalkyl halide. 

Figure 8.3 Fluorous-tagged isocyanate, isatoic anhydride and acid chloride for the scavenging of amines.

Some indirect applications of this reaction have been made. Isatoic anhydride (119) was converted to anthranilamide by ammonia in dimethyl-formamide addition of phosphoryl chloride converted this amide to 2-dimethylaminomethyleneaminobenzonitrile (analog of 118), which methyl-amine converted to 4-methylaminoquinazoline (see 1). It is remarkable that this was done in one vessel without isolation of intermediates and in good overall yield.158 Again, isatin-3-oxime (120) with phosphoryl chloride and dimethylformamide gave 2-dimethylaminomethyleneaminobenzonitrile, which was cyclized to 4-aminoquinazoline with ammonium acetate and to... 

This compound has been known since 1892 and was previously synthesized in 1915 by oxidation of isatin with neutral potassium permanganate 134). Bird 135) has synthesized 53 from 0-methylisatin and o-aminobenzaldehyde. The isatin-a-(2-formylanil) 54 (appears to exist predominantly as 55) was converted to 53 by oxidation with CrO. The reaction of 7 l-sodioi satin with o-nitrobenzoyl chloride gave l-(2 -nitrobenzoyl)isatin, and its reduction afforded 53 (756). Bergman et al. 126,153) have developed a simple method heating of isatin, isatoic anhydride, and diisopropyl carbodiimide in pyridine with A-meth-ylpiperidine as catalyst afforded 53 in high yield. For information on other... 

Figure 2 illustrates the synthesis of several anthranilic diamides prepared in our early discovery program. Our initial targets consisted of derivatives including those of formula D1-D3. These were prepared by coupling of anthranilamide 2 with substituted benzoyl chlorides 3 in the presence of base. The anthranilamide intermediates 2 could be prepared from isatoic anhydrides by treatment with isopropylamine. 

The phosgenation of isatoic anhydride and aminocarboxylic and amino-sulfonic acids, to afford isocyanatoarylcarbonyl chlorides and isocyanato-arlsylfonyl chlorides, is also catalyzed by iminium chlorides. 

Another interesting example of DMF catalysis involves the reaction of isatoic anhydride (XCVI) with phosgene to afford 2-isocyanatobenzoyl chloride (XCVII), which most likely occurs via o-isocyanatobenzoic acid (XCVIII) as the intermediate... 

The alkaloid rutaecarpine (111) was synthesized from l-oxo-1,2,3,4-tetrahydro-j8-carboline (183 R = H) by condensation with methyl anthranilate in the presence of phosphorous chloride or by heating with isatoic anhydride at 195°. The alkaloid was also obtained by boiling l-methoxy-3,4-dihydro-j8-oarboline (152 R = H, R = CHg) with anthranilic acid in methanol. In this connection might be... 

Some new facile syntheses for 2-methyl-3-(o-tolyl)quinazolin-4-one (methaqualone) " and 3-aryl-2-mercapto-quinazolin-4-ones have been announced. The former synthesis can be carried out in high yield in one pot by allowing isatoic anhydride to react sequentially with aniline in toluene and pentane-2,5-dione in ethanolic hydrogen chloride. The latter preparation consists of condensing aryl isothiocyanates with anthranilic acid in hot acetic acid-sodium acetate mixture. 

Oxidation of isatin. Two products are possible from Baeyer-Villiger oxidation of isatin (1). Oxidation with K2S208 in sulfuric acid gives only the 1,4-beiuoxazine 2, whereas oxidation with H202-H0Ac gives the anhydride (3) of isatoic acid.1 An earlier preparation of compounds of type 2 involves reaction of o-aminophenols and oxalyl chloride.2... 

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