Phosphorylation, with phosphoryl chloride

Reaction of (EtOfsPOCl with the sodium salt of A-4-thiazoline-2-one (93) in dry acetone provides the corresponding diethyl thiazolyl-2-phosphate (94) (Scheme 46) (220-223). (EtO) PSCl reacts in the same way with various A-4-thiazoline-2-ones (224-227). When phosphoryl chloride is used the reaction goes further, and 2-chlorothiazole is obtained (7, 193, 194, 217, 228-2.30). 

Thiazole carboxamides are readily dehydrated to nitriles in good yields by heating with phosphorus oxychloride (91), phosphorus pentoxide (87, 71), or phosphoryl chloride (16) (Scheme 19). 

A simpler nonphosgene process for the manufacture of isocyanates consists of the reaction of amines with carbon dioxide in the presence of an aprotic organic solvent and a nitrogeneous base. The corresponding ammonium carbamate is treated with a dehydrating agent. This concept has been apphed to the synthesis of aromatic and aUphatic isocyanates. The process rehes on the facile formation of amine—carbon dioxide salts using acid haUdes such as phosphoryl chloride [10025-87-3] and thionyl chloride [7719-09-7] (30). 

Monsanto has disclosed the use of carbon dioxide—amine complexes which are dehydrated, at low temperatures, with phosphoryl chloride [10025-87-3] or thionyl chloride [7719-09-7] as a viable route to a variety of aUphatic isocyanates. The process rehes on the facile formation of the intermediate salt (30).REPLACEVariations of this process, in which phosgene is used as a dehydrating agent, have been reported earlier (84). Table 2 Hsts commercially available aUphatic isocyanates. 

Finally, the importance of quinolinium salts to dye chemistry accounts for the long, productive history of their synthesis. The reaction of A/-methylformanihde with ketones, aldehydes, ketone enamines, or enol acetates in phosphoryl chloride leads to high yields of /V-methylquinolinium salts (60). 

Several modified forms of this synthesis are available. For example, treatment of either isocyanate (28) or urethane (29) derivatives with phosphoryl chloride followed by stannic chloride has been reported to give the substituted isoquinoline [80388-01-8] (158). 

Direct chlorination of 3,6-dichloropyridazine with phosphorus pentachloride affords 3,4,5,6-tetrachloropyridazine. The halogen is usually introduced next to the activating oxo group. Thus, 1,3-disubstituted pyridazin-6(l//)-ones give the corresponding 5-chloro derivatives, frequently accompanied by 4,5-dichloro compounds as by-products on treatment with chlorine, phosphorus pentachloride or phosphoryl chloride-phosphorus pentachloride. 

Orotic acid undergoes 5-nitration, 5-bromination in hydrobromic acid with peroxide, 5,5-dibromination following decarboxylation in bromine water, esterification, methylation (rather complicated), conversion into its acid chloride (containing some anhydride) by treatment with thionyl chloride, and conversion into 2,6-dichloropyrimidine-4-carboxylic acid by phosphoryl chloride (62HC(16)422). 

The cyclization of 5-(2-carboxyanilino)pyrimidine (170) with sulfuric acid/phosphoric acid leads to the 7-chloropyrimido[5,4-A]quinolinetriones (171) (57JCS4997, 74KGS131), the 2,4,10-trichloro compounds being obtained with phosphoryl chloride (72JHC91), whilst a formally similar cyclization of 4(6)-arylamino-5-ethoxycarbonylpyrimidines gives... 

The most useful general method for the C-acylation of pyrroles is the Vilsmeier-Haack procedure in which pyrrole is treated with the phosphoryl chloride complex (55a, b) of an AiA-dialkylamide (54). The intermediate imine salt (56) is hydrolyzed subsequently under mildly alkaline conditions to give the acylated pyrrole (57). On treatment of the imminium salt (56 R =H) with hydroxylamine hydrochloride and one equivalent of pyridine and heating in DMF, 2-cyanopyrrole (58) is formed (80CJC409). 

Thiophene-2-sulfonic acid is a strong acid, similar to benzenesulfonic acid. It forms a sulfonyl chloride with phosphoryl chloride which on reduction with zinc yields thiophene-2-sulfinic acid. 

An alternative method involves reaction of an a-acylaminoketone (12) with a primary amine and subsequent ring closure of the resultant Schiff s base (13) with phosphoryl chloride. This enables the introduction of a 1-substituent as in (14) to be carried out efficiently, and if the amine were replaced with a monosubstituted hydrazine, the imidazole derivative (IS) resulted (78LA1916). 

The reaction of 2,2 -bipyrrole with orthoformic acid triethyl ester in the presence of phosphoryl chloride (POCI3) produced a compound which gave the H NMR spectrum 5. Which compound has been prepared ... 

In an effort to prepare 1 2-dihydropapaverine, Buck dehydrated with phosphoryl chloride, and subjected the product (V) to catalytic reduction, followed by the action of phosphorus pentachloride in the cold. The final product was assumed to be 1 2-dihydropapaverine but Young and Robinson interpret this synthesis differently, and their formulae (V) and (VI) are given above, the final product being 3 4-dihydropapaverine (VII), which Buck thus prepared for the first time in a crystalline condition, m.p. 97-8° picrate, m.p. 151° perchlorate, m.p. 238° dec.). 

Phosphoryl chloride converts protopine into the quaternary salt isoprotopine chloride, C20H18O4NCI, m.p. 215° (dec.), which on treatment with potassium hydroxide in methyl alcohol yields anhydroprotopine, C2qH4,04N, m.p. 114-5°,1 just as crj ptopine is convertible into iso-cryptopine chloride and this into anliydrocryptopine. Similarly, protopine forms protopine methosulphate, CjoHigOjN. Me2S04, m.p. 252°, which is converted by potassium hydroxide in methyl alcohol, into two methyl-protopines, a-, m.p. 145°, and y-, m.p. 112°, corresponding with the two methyleryptopines, a-, m.p. 153°, and y-, m.p. 110°, respectively. 

The proeess used is analogous with that adopted for the sjmthesis of eryptopine (p. 298). The methyl ester of JV- -piperonylethyl-3 4-methy-lenedioxyAomophthalamie acid (I), was treated with phosphoryl ehloride and so eonverted into 2 3 9 10-6wmethylenedioxyoxyprotoberberine (II), which was reduced electrolytically to 2 3 9 10-6ismethylene-dioxytetrahydroprotoberberine (III), of which the methochloride (IV) is identical with wodihydroprotopine chloride, which can be prepared from protopine as already stated above. 

The American authors suggested (X) or (XI), already considered by Spath and Nikawitz for vasicine, and support for a formula of type (XI) was provided by Spath, Kuffner and Platzer, who, by condensing o-nitrobenzyl chloride with methyl y-aminobutyrate to o-nitrobenzyl-pyrrolidone (XII), reduction of this to the amino-compound (XII NOa —> NHj) and ring-closure in presence of phosphoryl chloride obtained the base d -pegene (XIII), m.p. 99-100°, identical with the product formed by the reduction of deoxychloropeganine. The same substance... 

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