Polyphosphoric acid, ethyl ester—

DMAP 4-dimethylaminopyridine PPE polyphosphoric acid ethyl ester... 

Ethyl 4-oxo-7,8,9,10-tetrahydro-4//-pyrimido[l,2-b]isoquinoline-3-carboxy-lates (196) were prepared by the cyclization of diethyl [(5,6,7,8-tetrahydro-3-isoquinolinyl)amino]methylenemalonate (195) in boiling diphenyl ether (83KGS1279 84KFZ931) and by heating in polyphosphoric acid ethyl ester (88MI5). 

Aminopyridines were treated with cyclic fi-oxo esters to give the tricyclic compounds 244. Cyclocondensation was carried out in diethylbenzene, ethylene glycol monomethyl ether,acetic polyphosphoric acid, - " ethyl polyphosphate, a mixture of phos-phoryl chloride and polyphosphoric or in the presence of... 

The base-catalyzed reaction of dihydrocoumarin with ethyl formate leads to the 3-formyl derivative (183), which rearranges in the presence of methanolic hydrogen chloride to the chroman ester. Upon heating with polyphosphoric acid, the chrom-2-ene is produced (Scheme 32) (60CB1025). 

The amino benzopyran of step 5 (2.0 g) and dimethyl acetylene dicarboxylate (1.24 g 1.01 ml) were refluxed in ethanol (30 ml) for 26 hours. The reaction mixture was cooled to 0°C and the insoluble yellow-brown solid was collected by filtration and washed with a little ethanol and dried to give 2.0 g of a product which was a mixture of maleic and fumaric esters obtained by Michael addition of the amine to the acetylene. This mixture of esters (2.0 g) was treated with polyphosphoric acid (30 ml) and heated on the steam bath with stirring for 20 minutes. The reaction mixture was then poured onto ice and stirred with ethyl acetate. The organic layer was separated, washed with water and dried. The solvent was evaporated to leave 1.6 g of a yellow orange solid. Recrystallisation of this solid from ethyl acetate gave the required product as fluffy orange needles, mp 187°-188°C. 

Is it still necessary to portray the proposed mechanism in full Yes, perhaps for the sake of didactics we should (see Scheme 4). Little additional comment will be required though. The fragmentation of the 1,3-cyclohexadione ring mentioned would occur under the auspices of polyphosphoric acid as shown in XXVIII. The new carbon-carbon bond shared by C and the ethyl ester group would be constructed between the kinetic enol form of XXX and the carbonyl carbon five atoms away. The other two cyclization steps that follow from this have already been uncovered by our previous fragmentation analysis. 

A further solution to the problem of isomer formation in the synthesis of oxoacridine carboaylic acids is to mask one of the two carboxyl groups. The requisite 2-(2-metho carbonylphet lamino)benzoic acids are available from methyl anthranilates reaction with diphenyliodonium carboxylates. The esters which result after cyclisation with polyphosphoric ethyl ester undergo ready alkaline l drolysis to the acid (G.W. Rewcastle and W.A. Denny. Synthesis. 1985. 220). 

Nitrophenyl hydrazones of ketones reacted similarly. On heating aryUiydrazones of pyruvic ester 192 with polyphosphoric acid (PPA), mixtures of ethyl 4- and 6-nitroindole-2-carboxylates were formed [145, 146] (Scheme 95). 

Equimolar amounts of N-phthaloyl-j -alanine and p-nitrophenol refluxed 0.5 hr. or stored 24 hrs. at room temp, with polyphosphoric acid ester prepared from P2O5 and ethyl ether in chloroform N-phthaloyl-j -alanine p-nitrophenyl ester. Y 87%. F. e. s. Y. Kanaoka et al., Ghem. Ind. 196A, 2102. 

Isatins are indole derivatives with broad use in synthetic dye production and are intermediates in the synthesis of other heterocyclic molecules/ They also possess a variety of biological activities/ Aksenov et al. reported a one-pot synthesis of isatins using ethyl nitroacetate with substituted benzenes such as anisole (159) in polyphosphoric acid fScheme 5.38)/ The process for isatin formation likely includes a hybrid between the Nef and Vilsmeier reactions of anisole 159 and nitro ester 160 to form the oxime intermediate 161, which then undergoes a Beckmann rearrangement to give the anilide 162. Subsequent intramolecular acylation yields isatin 163. 

Hydrolysis methods for mono[ C]nitriles and the spectrum of chemical transformations of the resulting [l- C]carboxylic acids differ little from those for their unlabeled counterparts, so that the synthesis of [l- C]tetralones 42 and [l- " C]indanones 46 from w-arylalkyl [ C]nitriles will suffice as examples (Figure 7.11). Acid-catalyzed hydrolysis of 4-phenylbutyro[ C]nitrile followed by polyphosphoric acid-mediated cyclization of the resulting phenyl[l- C]butanoic acid converted it into 42 in 89% radiochemical yield. Sequential bromination and oxime formation provided the a-bromooxime 43, which upon treatment with polyphosphoric acid underwent a Beckman rearrangement to provide the ring-expanded tetrahydro-2H-l-[2- C]benzazepine-2-one derivative 44- This was a key intermediate for the preparation of a series of labeled ACE inhibitors" . The acid-catalyzed cyclization of a mixture of 3-(2-hydroxyphenyl[l- " C]propionic acid and its ethyl ester, prepared by treatment of the propio[ " C]nitrile with ethanolic HCI proved to be a two-step sequence. In the first step, 2- [2- " C ]chromanone I4SI was formed and had to be submitted to... 

The cyanoacrylate adhesives were introduced in the late 1950s. Unlike the epoxy or silicone adhesives, these materials contain a monomer that undergoes rapid polymerization at room temperatnre. The monomer ethyl cyanoacrylate is stable with trace amounts of an acid inhibitor snch as polyphosphoric acid. The commercial formulations may contain methyl and higher cyanoacrylate esters, thickeners such as organic polymers, and plasticizers for increased final film tonghness. A slightly basic surface is needed for ionic polymerization to occur. Even the snrface moisture of an ostensibly dry metal or ceramic surface is sufficiently basic. 

---