PPA reaction

In a kinetic study of the Beckmann rearrangement of acetophenone oximes, Pearson and Stone found that rearrangement is 12-35 times as fast in PPA as it is in sulfuric acid and that the rates of rearrangement of substituted acetophenone oximes in PPA are nearly all the same. They conclude that the PPA reaction follows a mechanism different from that of the H2SO4 reaction. 

Analytical studies of the PPA reaction processes by real-time infrared spectroscopy [19A] demonstrate that cycUzation to the corresponding quinacridones is very rapid at the typical reaction temperatures and although not confirmed directly, probably proceeds by a two-stage sequential mechanism. Analogous to the thermal process high dilution conditions favor monomolecular reactions and subsequently the quaUty of the ultimate products. The by-products of bimolecular reactions occasionally have been detected in some quinacridone pigments... 

Thus, the PPA reactions have been extensively investigated using a variety of nucleophiles such as alcohols, water, cyanide ion, and carboxylic acid. Among these PPA reactions, the present review deals with the PPA reaction with ammonia and the amines. 

As described above, the photoaddition of MeOH to 1,1-diphenylethene in the presence of methyl p-cyanobenzoate gave 2,2-diphenylethyl methyl ether, the Type I product [13]. Hixson reported the photoinduced intramolecular charge-transfer of 3-(p-cyanophenyl)-l-phenylpropene followed by the MeOH-addition [29]. On the other hand, McCullough et al. reported that the photoreaction of 2-naphthonitrile with 2,3-dimethyl-2-butene in the presence of MeOH gave the Type //products [30]. In 1978, Mazzocchi et al. [31] and Kubo and Maruyama [32] published the first reports on the PPA reaction using phthalimides which formed the Type II products. Mariano et al. reported the PPA reaction using pyrrolinium salts as A, leading to Type //product [33]. Type///product, for example, was found in the CNN-photosensitized reaction of indene with H O [34]. 

Phenethyl carbamate derivatives 30 have also been employed in Bischler-Napieralski reactions cyclization of these substrates affords 3,4-dihydroisoquinolones 31. These reactions have been conducted using a variety of different promoters including PPA, POCl3, and Tf20. Mixtures of P2O5 and POCI3 appear to afford the best results in some cases. 

Imine formation by reaction of aniline 58 and dione 49 under thermal conditions gave a mixture of imines. Cyclodehydration using PPA gave nearly a 1 1 mixture of isomers 59 and 60. These authors attempted thermal cyclization conditions (similar to Gould-Jacobs type conditions) to affect cyclization of this mixture and failed. Also, these authors reported difficulty in the clean formation of the imine. They observed large amounts of the A -acetyl compound presumably coming from fragmentation of the imine at the reported temperature... 

The cyclization step has been reported to work well in triglyme, mineral oil, paraffin, Dowtherm A , Ph20 or polyphosphoic acid (PPA). PPA has been used to promote the entire reaction in a single process (vide infra). 

More importantly, Peet and coworkers reported the reaction of o-nitroaniline 35 with acetylene dicarboxylate 32 to provide fumarate 36. Subsequent cyclization proved difficult under thermal conditions and only a 35% yield of quinolone 37 was isolated. Use of PPA for the cyclization improved the yield of 37 significantly. Using this modification allowed enamino-ester formation with a nitro-group attached to the arylamine. 

Reaction of 2-aininopyridine 59 with 3-keto-ester 60 in PPA provided pyrido-pyrimidine 61 in poor yield. Interestingly, upon heating isolated 61, rearrangement occurred to provide napthyridone 62 in good yield. 

Although phenols have not participated in the Conrad-Limpach reaction under certain conditions thiophenols were not as innocent. Lee and coworkers reported mixtures of thiochromenones and quinolones from reactions of amino-thiophenols with ethyl benzoyl acetate. Amino-thiophenol 67 reacted with ethyl benzoylacetate 68 in PPA to give a mixture of thiochromenone 70 and quinolone 69 in which the quinolone predominated. 

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. 

To date, only the parent benzoisotellurazole 9 has been obtained. For its synthesis, methods similar to those used for the preparation of benzoisothiazole andben-zoisoselenazole were employed. The reaction of 2-bromotellurenylbenzaldehyde with ammonia affords 9 in 74% yield, whereas cyclization of the oxime of o-butyltellurobenzaldehyde catalyzed by PPA gives 9 in 40% yield (78JHC865). In contrast to the reaction of 2-bromoselenenylacetophenone with ammonia, which leads to 3-methylbenzoisoselenazole (73JHC267), 2-bromotellurenylacetophe-none reacts with ammonia to give telluroindoxyl (78JHC865). 

Pyrolyses of Nl- or N3-substituted derivatives of compounds 4 and 5 have continued to find use as routes to azacarbazoles, although the yields are often indifferent and there are no recent examples. The photochemical reactions are dealt with in Section IV.G. Pyrolysis media are paraffin (P) or PPA, and examples of products are compounds 247 (P, cytostatic) (83MI2), 248 (P) (84MI1), and 249 (from a 1-substituted derivative) (86MI2). Indications of diradical intermediates are provided by the thermolysis of compound 250 (P) (83MI2) where one product is a dimer. 

Cyclocondensation of 2-amino-6-bromopyridine and 4-chloroacetoace-tate in PPA at 100 °C for 4h afforded a mixture of 2-chloromethyl-, 2-bromomethyl-6-bromo-, and 2-chloromethyl-, 2-bromomethyl-6-chloro-4//-pyrido[l,2-n]pyrimidin-4-ones in 84% yield (99JHC1065). The pyrido-[l, 2-a]pyrimidin-4-ones were separated by preparative reversed phase HPFC. The pure 2-bromomethyl-6-bromo-4//-pyrido[l,2-n]pyrimi-din-4-one was prepared from 2-amino-6-bromopyridine with ethyl 4-bromoacetoacetate in 63% yield. Reaction of 2-aminomethylpyridines and ethyl 4-chloroacetoacetate in PPA at 110°C gave 2-chloromethyl-4//-pyrido[l,2-n]pyrimidin-4-ones (95FFS69, 01H(55)535). 

Reaction of aniline derivatives with 4-chlorobutyroyl chloride followed by cyclization with sodium ethoxide and subsequent thionation promoted by sonication gave the corresponding A -arylpyrrolidine-2-thiones 126. Zinc-mediated condensation of diethyl bromomalonate with 126 using iodine as activator gave the vinylogous urethanes 127 whose cyclization with PPA gave the tricyclic compound 128 which upon hydrolysis afforded the acid 129 (96TL9403). 

Cyclization of the thiazolidine methylidinemalonate 684 with PPA gave thiazoloquinoline 3-carboxylate which upon hydrolysis afforded 685 and reaction with A-methylpiperazine or a pyrrolidine derivative gave 686 as antibacterial agent (82EP58392, 85USP4550104) (Scheme 116). 

We have also used poly(propynoic acid) in our studies of the photochemical interaction of PCSs with dienophiles, such as maleic anhydride, tetracyanoethylene, and styrene. This photochemical reaction of Diels-Alder type is accompanied by the breakdown of the conjugation system and the formation of slightly colored adducts266. Together with the cycloaddition reaction, photodegradation of PPA and its adducts takes place. A cycloaddition reaction is always preceded by the formation of a donor-acceptor complex of a PCS with a dienophile. 

The comparison of rates of cycloaddition of maleic anhydride, tetracyanoethylene, and styrene to PPA shows that the latter, irrespective of the presence of electronegative groups, behaves in these reactions not as an electron-poor diene system. This fact, together with the composition of side products (giving evidence of PPA decarboxylation), allows the assumption to be made that the cycloaddition of dienophiles involves mainly decarboxylated polyene sections of cis-transoid structure213, 266. This is in agreement with the fact that PPA with predominant trans-transoid configuration interacts with these dienophiles at a substantially lower rate. The ultimate amounts of the dienophile combined with PPA of this structure is also considerably smaller. 

While additive analysis of polyamides is usually carried out by dissolution in HFIP and hydrolysis in 6N HC1, polyphthalamides (PPAs) are quite insoluble in many solvents and very resistant to hydrolysis. The highly thermally stable PPAs can be adequately hydrolysed by means of high pressure microwave acid digestion (at 140-180 °C) in 10 mL Teflon vessels. This procedure allows simultaneous analysis of polymer composition and additives [643]. Also the polymer, oligomer and additive composition of polycarbonates can be examined after hydrolysis. However, it is necessary to optimise the reaction conditions in order to avoid degradation of bisphenol A. In the procedures for the analysis of dialkyltin stabilisers in PVC, described by Udris [644], in some instances the methods can be put on a quantitative basis, e.g. the GC determination of alcohols produced by hydrolysis of ester groups. 

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>. 

As noted in Section 12.16.4.3.2(i)(c), Equation 36 (Chapter 12.16), reaction of compound 402 with different catalysts and bases gives different ratios of the endo- (thienoquinolizinone) and -(thienoindolizine) products (Equation 147) <1997TL1057>. Structurally similar benzothienoquinolizinones such as 404 can be prepared by treatment of the amino acid precursor 403 with PPA (Equation 148) <1996JHC873>. 

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