Phosphoryl chloride and pyridine

Methylquinoxaline-2,3-dione (173) is oxidized with Co(OAc)2 Mn(OAc)2 in HBr/H20 to the 6-carboxylic acid (174),183 which on treatment with thionyl chloride is converted into 2,3-dichloro-quinoxaline-6-carbonyl chloride (175).184 The 6-sulfonyl chloride is obtained from quinoxaline-2,3-dione and chlorosulfonic acid and treatment of the resulting 6-chlorosulfonyl derivative with phosphoryl chloride and pyridine.185 Such derivatives are useful synthetic dye intermediates. 

Reduction of iodohydrins. In Cornforth s stereospecific synthesis of a cis or irons olefin, an intermediate is a chlorohydrin of predictable configuration which cannot be reduced directly to the olefin. The conversion is accomplished by three strictly stereospeciflc steps formation of the epoxide, cleavage with HI (Nal—AcOH—EtCOgH), and reduction of the resulting iodohydrin with stannous chloride, phosphoryl chloride, and pyridine. 

The most common substitution reaction on hydroxy-substituted pyridazino[4.5-c/]pyridazines is the substitution by chlorine atoms. This is achieved by reaction of the hydroxy compound with phosphoryl chloride, a mixture of phosphoryl chloride and phosphorus pentachloride, or a mixture of phosphoryl chloride and pyridine at elevated temperatures. In most cases, yields are only moderate. 

Chloroquinoxalines are usually prepared by chlorination of quinoxalin-2-ones. Reagents that have been employed for chlorination include phosphoryl chloride, mixtures of phosphoryl chloride and phosphorus pentachloride, and phosphoryl chloride and pyridine. The reaction is normally uncomplicated by side reactions, but the use of phosphorus pentachloride alone as the chlorinating reagent is best avoided... 

Chloro-l//-l-benzazepines 2 are obtained as unstable red oils in excellent yields by heating 1 //-l-benzazepin-2(3//)-ones 1 with phosphoryl chloride in pyridine.208 Reaction conditions are important since in the absence of pyridine, or in dichloromethane solution, only poor yields of dimers, e.g. 3, are produced. The chlorobcnzazepines are stable for only short periods (24 hours in anhydrous pyridine) and rapidly polymerize. Isolation of the pure chloro compounds is difficult since they undergo very rapid hydrolysis to the benzazepinones. 

The addition products of MesSiCN 18 to carbonyl groups eliminate trimethylsilanol 4, in the presence of phosphoryl chloride in pyridine or of AICI3 in benzene, to give unsaturated nitriles. Thus ketone 1635 adds 18 and is subsequently converted, in a one-pot procedure, in 82% overall yield, into the olefin 1636 [27], whereas the adduct 1637 gives a mixture of the unsaturated nitriles 1638 [28] and ketone 1639 adds MesSiCN 18 and eliminates MesSiOH 4 or HMDSO 7, in one step, to give the a,y9-unsaturated nitrile 1640 [29] (Scheme 10.12). 

The strategies used in the synthesis of polymethine dyes are illustrated for a series of indoline derivatives in Scheme 6.1. There is an even wider range of synthetic routes to polymethine dyes than is described here, but they are based for the most part on a similar set of principles. The starting material for the synthesis of this group of polymethine dyes is invariably 2-methylene-1,3,3-trimethylindolenine (121), known universally as Fischer s base. As illustrated in the scheme, compound 121 may be converted by formylation using phosphoryl chloride and dimethylformamide into compound 122, referred to as Fischer s aldehyde, which is also a useful starting material for this series of polymethine dyes. When compound 121 (2 mol) is heated with triethylorthoformate (1 mol) in the presence of a base such as pyridine, the symmetrical cyanine dye, C. I. Basic Red 12 109 is formed. The synthesis of some hemicyanines may be achieved by... 

Cyclization of diethyl N-[cyclohepta(6)pyrrrol-2-yl]aminomethylene-malonates (1676), by heating in xylene, t-butylbenzene, or tetralin at reflux temperature, gave cyclohepta[4,5]pyrrolo[l, 2-a]pyrimidine-3-carboxyl-ates (1677) in 46-90% yields (87BCJ1053). Cyclization were also carried out in a mixture of phosphoryl chloride and polyphosphoric acid. While compound 1676 (R = COOEt) gave 1677 (R = COOEt) in 95% yield, the unsubstituted 1676 (R = H) afforded a mixture of 1677 (R = H) and 4-hydroxycyclohepta[4,5]pyrrolo[2,3-b]pyridine-3-carboxylate (1678) in 7% and 48% yields, respectively. The nitrogen bridgehead compound (1677, R = H) could not be transformed into pyridine derivative (1678). 

A further step toward the synthesis of nucleotides was taken in 1914, when Fischer succeeded in phosphorylating IV-glucosyltheophylline with phosphoiyl chloride and pyridine. The ciystalline product obtained bore the phosphate group on the glucose portion. 

The reaction of 0,jV,-dimethyllythranidine (77) with phosphoryl chloride in pyridine followed by catalytic hydrogenation gave a crystalline chloro compound (83) as a major product and an amorphous dichloroderivative (84). Both products underwent hydrogenolysis of the chlorine atom with sodium in iso- and //-propyl alcohol, respectively, to yield bisdcoxy-CUV-dimethyllythranidine (85). 

Whereas the ethoxyl group of 2-ethoxycycloheptimidazole (71) is readily replaced by dialkylamino and by halogen,97 when the corresponding cycloheptimidazol-2(l/7)-one (72) is treated with phosphoryl chloride in pyridine, very little of the 2-chloro compound is formed. The major product is a pyridinium derivative (73) which breaks down with hydrochloric acid to 2-aminocycloheptimidazole (74).97... 

The 2-halo-substituted benzimidazoles, then, more or less readily react with ammonia, amines and hydrazines (80AHC 27)241,70AHC(12)103,74CRV279), It is likely that the formation of the 2-pyridinium compound (123) when cycloheptimidazolin-2(l//)-one reacts with phosphoryl chloride in pyridine occurs via the 2-chloro intermediate (Scheme 56). The sulfur function of benzimidazole-2-sulfonic acid can be displaced by amino or alkylamino groups. 

Crabbe and Guzman have effected the same elimination with phosphoryl chloride in pyridine at room temperature see Phosphoryl chloride, this volume). 

Elimination of iodohydrias. Treatment of the iodohydrin (1) with freshly distilled phosphoryl chloride in pyridine first at 0° and then at room temperature (30 min.) affords the bicyclic olefin (2) in high yield. The reaction is generally applicable for olefin synthesis,... 

Dichloropyrazines have also been prepared from the corresponding hydroxy compounds as follows 2,3-dihydroxypyrazine with phosphoryl chloride containing pyridine (481, 757) [see Schneller and May (828) re the use of phenylphosphonic dichloride at 150-170°] 2,3-dihydroxypyrazine and its methyl, dimethyl, phenyl, diphenyl, and 5-methy 1-6-phenyl derivatives with phosphoryl chloride (483, 829) [N.B. error in work of Minovici and Bente (830)] 2-chloro-5-hydroxypyrazine with phosphoryl chloride (831) 2-chloro-6-hydroxypyrazine with phosphoryl chloride at reflux for 6hours (832) and 2,5-dihydroxy-3-phenylpyrazine and3,5-dihydroxy-2-phenylpyrazine with phosphoryl chloride at 180-200° (829). 

Rao et al treated anthranilamides with y-oxocarboxylic acids in pyridine at 45-50°C in the presence of phosphoryl chloride and obtained the diamides (82), which cyclized to the pyrrolo[ 1,2-fl]quinazolines 83 in refluxing benzene or toluene. 

Treatment of the thioacetal (34) with phosphoryl chloride in pyridine gave the expected dehydration product and, with longer reaction times, the 2,3-dihydro-1,4-benzodithiin (35). Photolysis of the latter afforded ethylene and the compound (36), the stable dithiet tautomer of a dithio-o-quinone, whose structure was established by A -ray analysis. 

Forrest and Todd developed a procedure for treatment of riboflavin with phosphoryl chloride in pyridine containing a small amount of water to form the cyclic riboflavin-4, 5 -phosphate (2). which on acid hydrolysis yields ribaflavln-.5-phos-phate (3), identical with the natural coenzyme. 

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