Polyphosphoric acid cyclization

Reaction of p-fluorobenzyl chloride with the anion of diethylmethylmalonate ester followed by saponification and decarboxylation leads to acid 9. Polyphosphoric acid cyclization leads to indanone 10. A Reformatsky reaction with zinc amalgam and bromo-acetic ester leads to carbinol 11 which is then... 

Tetracyclic pyridodibenzothiazepine derivative 181 was prepared via polyphosphoric acid cyclization of glutar-imide 180 (Equation 12) <1996J(P1)545>. 

Another electrophilic cyclization strategy is reported in which polyphosphoric acid cyclization of thienyl 2-hydrazones (89) affords l-(p-nitrophenyl)thieno[3,2-c]pyrazoles (90) (Equation (23)) <67CJC697>. On initial analysis, the process appears limited to p-nitrophenylhydrazones but the p-nitrophenyl unit is easily removed in a tandem reduction-oxidation sequence to afford the 1H-thieno[3,2-c]pyrazoles (3). 

Dimethylaminoethyl-l-tetralone (59) may be generated from 4-phenyl-cyclohexanone by Beckmann rearrangement to 5-phenylcaprolactam (58), followed by hydrolysis, yV-methylarion, and polyphosphoric acid cyclization.(219) Conventional transformations afforded the desired 3-methylben-zomorphan (60), first synthesized from 4-phenylpyridine in 1968.(2(,)... 

Loev and co-workers152 prepared the unsubstituted lH-2,l-benzothia-zine 2,2-dioxide (239) by the route of Scheme 11. Methyl chlorosulfonyl-acetate was converted into the sulfonanilide (235) by reaction with aniline. Hydrolysis of the ester group in 235 gave 236 which, with polyphosphoric acid, cyclized to 1 H-2,l-benzothiazin-4-one (237). Spectral data indicated that 237 existed in the keto form. Ketone 237 was converted to the tosylhydra-zone 238 which, by a Bamford-Stevens reaction, afforded 239 in good overall yield. The iV-methyl analog of 239 was also prepared by the above reaction sequence using N-methylaniline. 

The predominant product of polyphosphoric acid cyclization of dehydro-linalool (cf. Vol. 1, p. 9) is dependent upon the amount of acid and upon the reaction temperature. ... 

Indeed, one of the main uses of j -phosphorylated ketones is the synthesis of C-phos-phorylated heterocyclic systems, and in this respect the reactions very often complement those of isomeric acylphosphonates. In the first of the examples chosen, the ketone 304 cannot be converted into 305 in a direct reaction with the appropriate amine instead, the carbonyl group must be protected as in 307, when a reaction with the amine then gives 308 hydrolysis of 308 with 3 M HCl yields 305. When treated with ZnCl2 under toluene, 305 yields the indolylphosphonic diester 310" In the same way, a direct reaction between 304 and ArONa fails to give 306, which must therefore be prepared via 307 and 309 with acid hydrolysis to 306 when the latter is treated with hot polyphosphoric acid, cyclization occurs to give the benzofuranylphosphonic diester In order to obtain the isomeric... 

This reaction corresponds to the Bischler-Napieralski synthesis of isoquinoline (see p 343) and proceeds as an intramolecular S Ar process by way of nitrilium ions as intermediates. By an anlogous reaction, biphenyl-2-isocyanates 29, derived from 2-aminobiphenyl, on treatment with polyphosphoric acid, cyclize to yield phenanthridones 30. 

Reports of 1,4-oxazepine derivatives have been more numerous than those concerning the 1,3-oxazepine system. Polyphosphoric acid cyclization of the amides (290) followed by reduction with Pt02 gives (291), condensation of l,2,3-trioxo-2,3-dihydrophenaline with aniline derivatives yields the pentacyclics (292), and the reaction of aminochloropyrazole... 

Pomeranz-Fntsch Synthesis, Isoquinolines aie available fiom the cycUzation of benzalamiaoacetals undei acidic conditions (165). The cyclization is preceded by the formation of the Schiff base (33). Although the yields ate modest, polyphosphoric acid produces product in all cases, and is especially useful for 8-substituted isoquinolines (166). 

An interesting case of ipso intramolecular alkylation has been observed in the case of the acid-promoted cyclization of the amino alcohols (61). With trifluoroacetic acid the major product was the rearranged thienopyridine (62), whereas with polyphosphoric acid the product formed exclusively was the non-rearranged thienopyridine (63) (82CC793). 

The Frasca method for obtaining 1-arylindazoles also involves a C(3)—C(3a) ring closure (67CJC697). It consists in the cyclization of p-nitrophenylhydrazones of ketones and aldehydes with polyphosphoric acid. The Barone computer-assisted synthetic design program has found several new methods for preparing indazoles (79MI40409). The selected method involves the transformation of jV, jV -diphenylhydrazides (596) into 1-phenylindazoles (597) by means of trifluoromethanesulfonic anhydride. The yields vary from 2% (R = H) to 50% (R = Ph). 

Although 1,2-benzisothiazoles can be prepared by the oxidation method, they are also available by cyclization of o-mercaptobenzaldoximes and ketoximes with polyphosphoric acid (72AHC 14)43, 73JCS(P1)356, 77JCS(P2)1114). This method has been improved by the use of S-t- butyl analogues, which do not suffer from the instability of the free thiols (79SST 5)345). 

In 1909, Robinson demonstrated the utility of acylamidoketones as intermediates to aryl-and benzyl-substituted 1,3-oxazoles through cyclization with sulfuric acid. Extension of sulfuric acid cyclization conditions to alkyl-substituted oxazoles can give low yields, for example 10-15% for 2,5-dimethyl-l,3-oxazole. Wiegand and Rathbum found that polyphosphoric acid can provide alkyl-substituted oxazoles 4 in yields equal to or greater than those obtained with sulfuric acid. Significantly better yields are seen in the preparation of aryl- and heteroaryl-substituted oxazoles. For example, reaction of ketoamides 5 with 98% phosphoric acid in acetic anhydride gives oxazoles 6 in 90-95% yield. ... 

The phosphorus oxychloride / nitrobenzene conditions were sometimes replaced with polyphosphoric acid at 150°C. R groups used in the study were H, Ph, o-aza, o-Cl, m-aza, m-Cl, p-aza, p- , p-Cl, p-Br, p-l, p-OMe, p-OH, P-NO2, p-NHi, p-NHCOMe, p-NHSOiMe. The yield of the cyclization step was not specified. 

A recent report describes the conversion of A-formyl- and N-acetyl-L-leucine into optically active azlactones with dicyclohexyl-carbodiimide (DCC) [Eq. (29)]. Other cyclization reagents, e.g. acetic anhydride, POCI3, SOCI2, and polyphosphoric acid, cause racemiza-tion. These azlactones react with optically active amino acid esters to give esters of dipeptides with retention of activity. 

On saponification l-(2-methoxycarbonylphenyl)pyrrole yields l-(2-carboxyphenyl)pyrrole, m.p. 106-107°, which on reaction with polyphosphoric acid at 70° is cyclized to 9-keto-9H-pyrrolo-(l,2-a)indole in 28-32% yield. Through the choice of the appropriate amine and acetal components, the substituted l-(2-meth-oxycarbonylphenyl)pyrroles become readily available intermediates in the preparation of a variety of derivatives of the pyrrolo( 1,2-a) indole ring system. 

Substituted 2-phenoxyphenylacetic acids readily cyclize under Friedel-Crafts conditions or acid catalysis to give dibenz[Z>,/]oxepin-10(l l//)-ones.71 85,104- 108 When this reaction is carried out in methanolic hydrochloric acid the 10-methoxy-substituted dibenz[6,/]oxepin system 9a can be isolated.109 5-(Nitro-2-phenoxyphenyl)-2-oxopropanoic acid undergoes cyclization in the presence of polyphosphoric acid yielding the carboxylated dibenzoxepin 9b.107... 

Polyphosphoric acid in cyclization of ethyl a-acetyl-/3-(2,3-dimethoxy-phenyl)propionate to 6,7-dimeth-oxy-3-methylindene-2-carboxyl-ate, 40, 43... 

---