Cyclodehydration polyphosphoric acid

Dibenz[(j,/][1,4]oxazepines 2 are readily obtained by the cyclodehydration of 2-(acylamino)-phenyl phenyl ethers 1 in polyphosphoric acid.38... 

A mixture of acetic anhydride/polyphosphoric acid/sodium acetate was used to carry out cyclodehydrations. The water treatment at the end of the reaction caused an extremely violent hydrolysis. 

Aryloxy-l,2-diarylethanones can be cyclodehydrated to diarylbenzofurans by heating with sodium acetate and acetic anhydride in polyphosphoric acid. Quenching the hot reaction mixture with water leads to initially violent acid-catalysed hydrolysis of the excess anhydride. 

The first synthesis of the benzo[6]quinolizinium ion (Scheme 98, Table 9, example 1) was by hydrobromic acid-catalyzed cyclization of the quaternary salt formed between 2-pyridinecarbaldehyde and benzyl bromide. Aromatic cyclodehydration has continued to the present as almost the only method used for the preparation of the acridizinium ion, its derivatives and benzo analogs. Because of its instability, 2-pyridinecarboxaldehyde has been replaced by more efficient derivatives. The first of these was the oxime (example 2) which not only gave a better overall yield, but also made possible the isolation of a crystalline intermediate (181 Z = NOH). The disadvantages are that it is not suitable for high temperature cyclizations involving polyphosphoric acid, and some products (182) (e.g. example 10, Table 10) may tend to form double salts with hydroxylamine hydrobromide. 

A synthesis of the [l]benzothieno[3,2- ][l]benzofuran 63 based on the formation of the furan ring in the key step was elaborated. Alkylation of methyl 2-sulfanylbenzoate 349 with 2-hydroxybenzylalcohol 348 was effected with freshly prepared Znl2 in CH2CI2 and 350 was obtained. Cyclization with lithium diisopropylamide (LDA) in THF afforded 351, which on subsequent cyclodehydration with polyphosphoric acid (PPA) gave 63 in moderate yield (Scheme 36) <2000CCC1939>. 

The sequence for the synthesis of l,3,6-triazacycl[3,3,3]azines (58) is based on the reaction of 2,6-diaminopyridine with ethoxymethylene-malononitrile or ethyl ethoxymethylenecyanoacetate, leading to compounds 56. These on acylation gave 57, which after cyclodehydration yielded the desired cyclazines (58). Small amounts of the unsubstituted parent triazacyclazine (58a) were observed when the cyclization of 57 was carried out in a refluxing mixture of biphenyl and diphenyl ether. Decyanation of 4-cyano-2-methyl-l,3,6-triazacycl[3,3,3]azine (58f) with polyphosphoric acid at 200° yields 2-methyl-l,3,6-triazacycl-[3,3,3]azine (58b).18-80 The synthesis of 58d was carried out by a closely related route.74... 

AHC(18)337>. The 3-alkylbenzo[6 ]furans result from cyclodehydration of aryloxyacetones the most common dehydrating agents are sulfuric acid, phosphorus oxychloride and poly-phosphoric acid. The allyl ethers of phenols can be converted to 2-alkyl-2,3-dihydro-benzo[6]furan by heating with polyphosphoric acid, pyridine hydrochloride or magnesium chloride at 180 °C the intermediate o-allylphenol is not isolated. 

This synthesis of benzo[6]thiophenes is probably the most widely exploited single method for such syntheses since its introduction about 1950 by a variety of workers. It is applicable to a great number of highly substituted benzo[6]thiophenes, and intermediates are generally readily available. In 1949 Werner (49RTC509) reported the synthesis of several 3-alkyl- and 2,3-dialkyl-benzo[( ]thiophenes by cyclodehydration of arylthioacetones (99) with phosphorus pentoxide or anhydrous zinc chloride. Arylthioacetaldehydes (99 R = H, R1=H, R2 = Me, Et or Ph) have been cyclized in 65-80% yields with phosphorus pentoxide. In 1950 Tilak (50PIA(A)(32)390) introduced the polyphosphoric acid-promoted cyclization of... 

Cyclodehydration. Neat, anhydrous CH3S020H is at least as useful as polyphosphoric acid for cyclization of 3-arylpropanoic acids and 4-arylbutanoic acids to indanones and tetralones.1 However, it does not appear to be useful for intermolecular Friedel-Crafts condensation. Examples ... 

Cyclodehydration. The commercial preparation of an antihistamine (Lorata-dine, 3) requires cyclodehydration of the ketone 1. Use of the usual reagent for this reaction, polyphosphoric acid at 190°, leads to a mixture of two products in about 45% yield. The most useful and reasonably priced reagent is HF and BF3 at -30°, which gives 2 in >90% yield. 

To obtain the [l,2,4]triazolo[4,3- ]isoquinoline series it was not possible to displace the halogen atom of 3-chloroisoquinoline with hydrazine. However, 3-hydrazinoisoquinoline 2-oxide could be prepared from the corresponding 3-chloro 2-oxide, and it could be selectively reduced by titanium trichloride to 3-hydrazinoisoquinoline, a relatively unstable compound (78JHC463). This hydrazino derivative was unresponsive to the usual carboxylic acid type ring closures generally used to make fused [4,3-x] systems. The desired products (299) could be obtained by cyclodehydration of the monoacylhydrazino compounds (300) with polyphosphoric acid. These derivatives (299) were, however, unstable and had to be characterized as their perchlorate salts (301 Scheme 32) (78JHC463) to eliminate the o-quinoid structure. 

The two most useful routes to (32) and some of its derivatives are (i) the ring closure of the Af-aminodiazinium salt (342) with carboxylic acids, anhydrides or acid chlorides as previously mentioned for the pyridazines and pyrimidines (75JHC107) and (ii) the cyclodehydration of the hydroxyiminomethyleneamino compound (343) with polyphosphoric acid as reported herein for the pyridine, pyridazine and pyrimidine analogs (74JOC2143). These two methods are shown in Scheme 59. 

In the laboratory of S. Gupta, the synthesis of novel heterocyclic ring systems was accomplished utilizing the Combes reaction The condensation of 1-naphthylamine with 2-acylindan-1,3-diones produced the corresponding anils in good yield. The anils were cyclodehydrated to benz[/ ]indeno[2,1-c]quinoline-7-ones in the presence of polyphosphoric acid. Subsequent Wolff-Kishner reduction gave rise to the novel 7H-benzo[/ ]indeno[2,1-c]quinolines. 

Similarly, diethyl 3-aryloxy-2-oxopropylphosphonates, prepared from diethyl 3-bromo-2-dielh-ylaminopropenylphosphonate and substituted sodium phenoxides, undergo cyclodehydration in refluxing toluene in the presence of polyphosphoric acid to produce 3 -benzofuryImethyIphosphonates. 

Cyclodehydration 1,5-Diazabicyclo[4.3.0]nonene-5. 2,3-Dichloro-5,6-dicyano-l, 4-benzo-quinone. l,l-Dichloro-2,2-difluororoethyIene. Dichloroketene. Hydrobromic acid. Phos-phoryl chloride-Phosphoric acid-Phosphorus pentoxide. Polyphosphoric acid. Thionyl chloride. 

Benzyl-1-indanol 32, readily available in a few steps from 1-indanone, has been converted into 2-benzylindene 33 in various ways [66 - 68]. Treatment of 32 with orthophosphoric acid in chlorobenzene, for example, gives 33 as the sole product. However, use of polyphosphoric acid in the same solvent effects clean cyclodehydration of both 32 and 33 giving the mono-/uso-diindane 34 in high yield [65]. Several cenfro -alkylated derivatives of 34, including the methyl... 

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