With polyphosphoric acid

CONHj, COjEt, were also prepared by ring closure of thioamides such as RiCONHCH(R2)C(=S)NH2 with polyphosphoric acid (2 hr at 120°C) (718). 

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). 

Other C—C fused systems are also available by utilization of 1,4-dicarbonyl-type systems. The substituted pyrimidinethione (59) on treatment with polyphosphoric acid readily formed the thiazolo[5,4-d]pyrimidine system (60) without any of the alternative ring closure product (65JOC1916). 

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). 

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. 

Proceeding from 5 -0-acetylazauridine (80), a mixture of 2 - and 3 -monophosphates (81, 82) was prepared by phosphorylation with polyphosphoric acid, and these were converted into the 2, 3 -cyclic phosphate (83). From the 2, 3 -0-isopropylidene derivative of 3-methyl-6-azauridine the 5 -phosphate was prepared by treatment with cyanoethylphosphate and the corresponding diphosphate from its morpholidate through the action of phosphoric acid. ° Furthermore, a diribonucleoside phosphate (85) with a natural 3 -5 internucleotide linkage was prepared from 6-azauridine, The starting material for the preparation of such derivatives was 5 -0-acetyl-2 -0 -tetrahydro-pyranyluridine-3 -phosphate (84) which was condensed with di-G-acetylazauridine (86) or with 2b3 -0-isopropylidene-6-azauridine (76) with the aid of dicyclohexylcarbodiimide. ... 

The hydroxamic acid function in most alicyclic and aromatic compounds is stable to hot dilute acid or alkali, and derivatives cannot undergo normal base-catalyzed Lessen rearrangement. Di Maio and Tardella," however, have shown that some alicyclic hydroxamic acids when treated with polyphosphoric acid (PPA) at 176°-195° undergo loss of CO, CO.2, or H2O, in a series of reactions which must involve earlj fission of the N—0 bond, presumably in a phosphoryl-ated intermediate. Thus, l-hydroxy-2- piperidone(108) gave carbon monoxide, 1-pyrroline (119), and the lactams (120 and 121). The saturated lactam is believed to be derived from disproportionation of the unsaturated lactam. 

R = OCHg, R = N(CHg)2] on treatment with polyphosphoric acid give the corresponding 2-aroyl-l-oxo-l,2,3,4-tetrahydro-j8-carboline (177). In the latter instance the use of acetic anhydride... 

Benzyl-l,3-dioxo-l,2,3,4-tetrahydro-j8-carboline (189) was prepared by heating the benzylamide 188 with polyphosphoric acid on a... 

Attempted dehydrocyclization of the 6-acylhydrazinopyrimidine 65 by heating with polyphosphoric acid led, instead, to pyrimidine ring rupture, yielding the l,l-diamino-2-nitro-2-(3-phenyl-l,2,4-triazol-5-yl)ethene 66. Cyclocondensation of the latter with triethyl orthoformate gave the fully aromatic triazolopyrimidine 67 (94JHC1171) (Scheme 23). 

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. 

This ring system may be prepared from 527 by condensation with ami-drazone or aminoguanidine derivatives to afford 528, which on reaction with polyphosphoric acid gave imidaz[5, -/][ ,2,4]triazin-4(2//)one 529... 

For a review of Beckmann rearrangements with polyphosphoric acid, see Beckwith, A.L.J. in Zabicky, Ref. 253, p. 131. 

Dehydration of the aminopyrimidin-6-yl-benzamide 288 with polyphosphoric acid gives rise to the purin-4-one angular tricyclic system 289 in moderate yield (Equation 78) <1995JHC1725>. 

An alternative approach to thienothienopyridines involves intramolecular electrophilic attack at C-3 of the thiophene ring. In this way, the thienothiophene 82 can be cyclized to the benzothieno[2,3-/]thieno[2,3-c]pyridine 83 upon treatment with polyphosphoric acid (PPA) at 150°C (Equation 3). Similarly, treatment of the amide 84 with POCI3 gives the corresponding 1-alkyl-3,4-dihydro-benzothieno[3,2-g]thieno[3,2-f]pyridine 85 <1999PS(153)401> (Equation 4). 

A route involving the closure of the other six-membered ring is exemplified by the reaction of the phenylhydrazone 359 with polyphosphoric acid (PPA) (Equation 127) <2004TL1299>. 

Compound 34 can be synthesized by a Bamford-Stevens procedure from compound 33. Loer explored the cyclization of 32 with polyphosphoric acid (PPA), followed by decomposition of the tosylhydrazone to form the desired 177-2,1-benzothiazine 2,2-dioxide 34 in good overall yield (Scheme 8) <66JOC3531>. 

In order to study heterocyclic steroid analogues, such as the 7,11-dithiaazasteroid analogues, Fravolini developed the synthesis of new heterocyclic ring systems tri- and tetracyclic 2,1-benzothiazines <82JHC1045>. Intermediate 137 was prepared from 1-methyl-4-oxo-lH-2, -bcnzothiazinc-4(3f/)-onc 2,2-dioxide 37 and thioglycolic acid and could be converted into 6-methyl-4-oxo-3,4-dihydro-2//,6//-thiopyrano[3,2-c][2,l]benzothiazine 5,5-dioxide 138 by cyclization with polyphosphoric acid. The reaction of 138 with dimethyl... 

The literature is replete with synthetic methods to prepare 5-bromofurans. One of the more practical syntheses [10, 11] commenced with etherification of 4-bromophenol with bromoacetaldehyde diethyl acetal using either NaH in DMF or KOH in DMSO. Treatment of the resulting aryloxyacetaldehyde acetal with polyphosphoric acid (PPA) afforded 5-bromofuran in good yield via intramolecular cyclocondensation. However, cyclization of m-aryloxyacetaldehyde acetal 1 resulted in a mixture of two regioisomers, 6-bromofuran (2) and 4-bromofiiran (3). Finally, 7-bromofuran 5 can be prepared similarly using the intramolecular cyclocondensation of aryloxyacetaldehyde acetal 4 generated from etherification of 2-bromophenol with bromoacetaldehyde diethyl acetal. 

Nagai et al. carried out various transformations with camphor-fused amino[l,2,4]triazine 191 <1998JHC293> (Scheme 39). Reaction of 191 with chlorocarbonylsulfenyl chloride yielded the fused thiadiazolone 192 in high yield (83%). The same starting compound also proved to be suitable for the synthesis of the fused triazole derivative 193. To this end, 191 was first subjected to two subsequent transformations first by dimethylformamide dimethylacetal followed by treatment with hydroxylamine hydrochloride to give an Ar-hydroxyamidine 193 in 90% overall yield, and then this compound was treated with polyphosphoric acid to yield the fused triazole product 194 in 92% yield. 

Isopropylidene 2-quinoxalinylaminomethylenemalonate was treated in methylene chloride with polyphosphoric acid at 60°C to give pyrimido[l, 2-a]quinoxaline-2-carboxylic acid (1201) in 97% yield (83EUP86723). 

D-Glucose 6-phosphate is converted enzymically into L-wyo-inositol 1-phosphate (20) in a process which requires NAD+. The base-catalysed cyclization of d-xylo-hexos-5-ulose 6-phosphate (21), followed by reduction with borohydride, leads to (20) and epi-inositol 3-phosphate (22) (Scheme 3).59 This has been put forward as a chemical model for the enzymic synthesis. The phosphorylation of inositols with polyphosphoric acid has been described80 and the p-KVs of inositol hexaphosphate have been determined by 31P n.m.r.61... 

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