Replacement oxychloride

Assemble in a fume-cupboard the apparatus shown in Fig. 67(A). Place 15 g. of 3,5-dinitrobenzoic acid and 17 g. of phosphorus pentachloride in the flask C, and heat the mixture in an oil-bath for hours. Then reverse the condenser as shown in Fig. 67(B), but replace the calcium chloride tube by a tube leading to a water-pump, the neck of the reaction-flask C being closed with a rubber stopper. Now distil off the phosphorus oxychloride under reduced pressure by heating the flask C in an oil-bath initially at 25-30, increasing this temperature ultimately to 110°. Then cool the flask, when the crude 3,5-dinitro-benzoyl chloride will solidify to a brown crystalline mass. Yield, 16 g., i.e,y almost theoretical. Recrystallise from caibon tetrachloride. The chloride is obtained as colourless crystals, m.p. 66-68°, Yield, 13 g Further recrystallisation of small quantities can be performed using petrol (b.p. 40-60°). The chloride is stable almost indefinitely if kept in a calcium chloride desiccator. 

Triaryl phosphates are produced by reaction of phosphoms oxychloride with phenoHc compounds at 100—200°C with magnesium or aluminum chloride catalyst. Past use of cresols and xylenols from coal tar or petroleum is replaced for lower toxicity and cost by synthetic phenoHcs, primarily isopropyl phenol, /-butyl phenol, and phenol itself A range of viscosities is achieved by selection and proportioning of the phenols and their isomers used for the starting material. 

The second most important nucleophilic substitution in pyridazine A-oxides is the replacement of a nitro group. Nitro groups at the 3-, 4-, 5- and 6-position are easily substituted thermally with a chlorine or bromine atom, using acetyl chloride or hydrobromic acid respectively. Phosphorus oxychloride and benzoyl chloride are used less frequently for this purpose. Nitro groups in nitropyridazine A-oxides are easily replaced by alkoxide. The... 

The vinylic fluorine of perfluoroisobutylene can be replaced with chlorine by using phosphorus oxychloride or henzoyl chloride however, somewhat different mixtures result from these two chlorinating agents [72] (equation 59). 

The phosphorus oxychloride / nitrobenzene conditions were sometimes replaced with polyphosphoric acid at 150°C. R groups used in the study were H, Ph, o-aza, o-Cl, m-aza, m-Cl, p-aza, p- , p-Cl, p-Br, p-l, p-OMe, p-OH, P-NO2, p-NHi, p-NHCOMe, p-NHSOiMe. The yield of the cyclization step was not specified. 

An intramolecular 8 Ar2 mechanism (19) is possible in the replacement of 0X0 substituents with chloro or mercapto groups by means of phosphorus oxychloride or pentasulfide, respectively, via the intermediates shown. In the former, an intermolecular mechanism (20) is perhaps more likely. Frequently a base is not added in such reactions. 

The replacement of a heterocyclic hydroxyl group (generally in the 0X0 form, Section II,E, 2,e) with thioxo or chloro groups by phosphorus pentasulfide or phosphorus oxychloride presumably proceeds through nucleophilic substitution (frequently acid-catalyzed, 21 and 86) of thiophosphoryloxy and dichlorophosphoryloxy intermediates. The 4-position in pyrimidine is more reactive than the 2-position and, at low temperature, this type of thionation of pyrimidine-2,4-diones is specific for the 4-position. In as-triazine... 

Triazanaphthalenes (446) substituted with a single leaving group have been little studied. 4-Aminopyrido[3,2-d]pyrimidine and its 6-methyl derivative have been hydrolyzed with 5N acid (100°, 30 min) and lOA alkali (95°, 3 hr, 10% yield).Attempted replacement of the 4-oxo group (via acyloxy intermediates) with phosphorus oxychloride or pentasulfide failed,in contrast to the successful replacement in the more activated 4-oxo-l,3,8-triaza analog discussed below. Similarly, the 2,4-dioxo derivative could not be thionated with the pentasulfide, and its reaction with the oxychloride was less facile than that of the 2,4-dioxo-l,3,8-triaza compound. 

The hydroxyl group is then replaced by chlorine by means of phosphorus oxychloride (70). Displacement of the reactive halogen at the 4 position by means of the aliphatic diamine, 71, yields the synthetic antimalarial agent chloroquine (72). ... 

Because of resonance stabilization of the anion, a tet-nazolyl moiety is often employed successfully as a bioisosteric replacement for a carboxy group. An example in this subclass is provided by azosemide (27). Benzonitrile analogue is prepared by phosphorus oxychloride dehydration of the corresponding benzamide. Next, a nucleophilic aromatic displacement reaction of the fluorine atom leads to The synthesis concludes with the 1,3-dipolar addition of azide to the nitrile liinction to produce the diuretic azosemi de (27). ... 

Though the great majority of antiinflammatory agents contain some form of acidic proton, occasional compounds devoid of such a function do show that activity. Thus the nonacidic pyrazolylpyrimidine epi razole (47) is described as a nonsteroid antiinflammatory agent. Reaction of pyrimidinone 42 with phosphorus oxychloride leads to the chloro derivative Replacement of halogen with hydrazine gives... 

A piridazine ring forms the nucleus for a rather unusual nontricyclic antidepre.ssant. Condensation of the keto ester 136 with hydrazine leads to the cyclic hydrazide 137. Oxidation, for example with bromine, gives the corresponding pyridazone 138. The oxygen is then replaced by chlorine by reaction with phosphorus oxychloride. Displacement of the halogen in 139 with N-ethylami-nomorpholine affords minaprine 140 [30]. 

In a 2-1 three-necked flask equipped with a stirrer, a reflux condenser, and a dropping funnel (Note 1) 832 g (4 0 moles) of phosphorus pentachloride is stirred with 250 ml. of phosphorus oxychloride (Note 2) To this is added with stirring 264 g (272 ml, 4 4 moles) of methyl formate (Note 3). During the addition the reaction vessel is cooled in an ice bath to maintain a reaction temperature of 10-20° The addition requires about 1.75 hours When the addition is complete, the solution is stirred at a temperature under 30° until all the phosphorus pentachloride has dissolved (about 1 hour) Then the stirrer is removed, the reflux condenser is replaced by a distilling head, and the reaction... 

Treatment of 8 with phosphorus oxychloride leads to replacement of the hydroxyl group by chlorine... 

The incorporation of an indole ring system often leads to an improvement in the light fastness. A suitable example is Cl Acid Blue 123 (6.177), which is derived from 4,4 -dichlorobenzophenone. Condensation with l-methyl-2-phenylindole in the presence of phosphorus oxychloride produces the triarylmethane ring system. Replacement of the chlorine atoms with p-phenetidine, followed by sulphonation, gives the dye. 

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