Replacement of OH by halogen in phenols or heterocycles

PX5 and POX3 (X = Cl or Br) is occasionally used for replacement of phenolic OH by halogen, and more often for OH in heterocycles. 

The equilibrium PBr5 PBr3 + Br2 is shifted so far to the right at temperatures above 100° that when PBr5 is used substitution by bromine and sometimes dehydrogenation are to be expected as side reactions. 

The reaction has special preparative importance for chlorine-substituted heterocycles. The hydrochloride of the corresponding hydroxy-N-hetero-cycle is usually heated under reflux for several hours with an excess of POCl3, then the excess of POCl3 is distilled off, the residue is decomposed with ice and made alkaline, and the chloro heterocycle is extracted in ether. In this way, 2-chloro-,1060 2-chloro-4-methyl-,1061 2-chloro-4,6-dimethyl-,1062 and 4,6-dichloro-2-methyl-pyrimidine,1063 and 2-chloro-4-methylquinoline,1064 inter alia, have been prepared. 

The reaction may also be carried out in the presence of a tertiary amine. 2,6,8-Trichloropurine is obtained from 2,6-dichloro-8-hydroxypurine by means of POCl3 and dimethylaniline,1065 and the preparation of 3-chloroindazole from 0.2 mole of dry indazolone, 0.2 mole of dry pyridine, and 0.3 mole of POCI3 is detailed in Organic Syntheses.1066 

The POCI3 may be replaced by PC15 or a mixture of the two.1062,1067 For instance, 1,4-dichlorophthalazine is formed when phthalodihydrazide (32 g) is heated with PC15 (100 g) for 4 hours at 150°.1068 

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