Dear Ahmed,

Based on my personal experience using pocl3 will lead to the same result.

Yes you can use POCl3 for the chlorination of pyrimidine in the presence of base.

Please see the below link for further information

http://www.mdpi.com/1420-3049/17/4/4533/htm

Both the conditions are permissible but in typical conditions the reaction needs PCl5 to promote the reaction.

POCl3 will give the same result

Most of the time results will be similar, although in some situations addition of PCl5 could be beneficial. If a particular procedure requires POCl3/PCl5 mixture, I will try to read the paper carefully to understand why it is used instead of just POCl3. Perhaps sometimes POCl3 is of poor quality, then adding PCl5 will certainly help.

http://onlinelibrary.wiley.com/doi/10.1002/jhet.5570210447/pdf

Check this publication

The reaction of hydroxypyrimidines with phosphorous oxychloride (POCl3) is a simple procedure known for over 100 years and used widely in preparing chlorinated pyrimidine final products or intermediates for further transformations. Over the years, the experimental conditions used for such chlorination reactions have changed little, and generally involve heating a hydroxy-containing substrate in excess POCl3 to reflux in the presence of an organic base. While such a protocol may be adequate for small scale synthesis in a research laboratory, it becomes an environmental burden to deal with the excess POCl3 in large scale preparations. Furthermore, even the process of quenching excess POCl3 in large scale needs safety attention due to the potential for latent exothermic events.Therefore, improvements in reducing the amount of POCl3 used in large scale chlorination procedures would be welcomed for economic, environmental, and safety considerations.

We recently reported a protocol for large scale (milligram to kilogram batches) chlorination of hydroxypyrimidines using equimolar or less POCl3 with heating in a sealed reactor under solvent-free or low solvent conditions. Our procedure has simple work up steps involving filtration or distillation, and generally gives high yields and purity of final products. Except one, the examples used in our original report are essentially all pyrimidine derivatives (single or fused ring systems). In this report, we sought to expand the scope of our original study by applying our procedure to a wider range of starting materials to probe the potential for generalization of this solvent-free protocol.

Because our previous report only covered four examples of single-ring hydroxypyrimidines, we tested six more pyrimidines here with mono-chloro, bromo, methyl, or amino substitution at various positions. All the reactions were carried out at a scale of 0.3 moles (~30–60 g of pyrimidine starting materials) with equimolar POCl3 per OH group and one equivalent of pyridine as base. The reactions were performed in sealed reactors for 2 hours as before, but at 160 °C instead of the 180 °C used in our original procedure. Despite the slightly lower reaction temperature, all trials gave satisfactory results (>80% isolated yields).

In these trials, liquid final products were isolated by distillation after extraction (entries 1–3,5) and solid products (entries 4 and 6) were isolated by filtration after quenching the reaction with cold water. For comparison with literature reported results, we sought to compare our results with those with similar reaction scales and using POCl3 as reagent.

Given the safety concerns of quenching large scale POCl3 as studied in a recent report,we also investigated the event of quenching in our protocol. After the completion of reaction, due to the efficiency of our protocol and the fact that no excess of POCl3 was used, we expect that quenching of the reaction mixture will not involve hydrolysis of significant amount of POCl3 itself. Therefore, no significant exotherm was of concern upon initial quenching of the reaction. Instead, we believe that quenching of species such as phosphorodichloridic acid as a possible end product was the major event. This was supported by the low and delayed heat release during the first hour of quenching of a large scale reaction with cold water,by which time the desired product was already separated from the quenching solution.

1.4 mole of POCl3 was used in the reaction and the final reaction mixture was quenched with 500 mL of cold water. This quenching ratio was smaller than the quenching process detailed in a report by Amgen scientists, yet the temperature raise was also lower in our case. Therefore, any delayed heat release due to the hydrolysis of phosphorodichloridic acid and alike could be safely handled aside without significantly affecting the isolation of the desired products.

Next, our attention was turned to chlorination of pyridine derivatives. We used seven 2-hydroxypyridines and one quinolone. It was interesting to discover that the reactions could be efficiently carried out at an even lower temperature of 140 °C. Furthermore, no additional pyridine was needed for reactions involving 2-hydroxypyridines, as all the pyridine starting materials can effectively act as base. For the reaction with quinolone, 0.6 equivalents of pyridine were added.

All reactions for pyridines were performed at 0.5 moles scale, with 70–126 g of hydroxyl pyridine or quinoline starting materials. All trials for the pyridine substrates gave 90% or more isolated yields. Except for entry 4 where the product was isolated by distillation after extraction with ethyl acetate, all other products were solids and were isolated using filtration after quenching the reaction with cold water and adjusting pH to 8–9. For pyridine analogous, few reported examples used POCl3 for chlorination. For those that did, our method is comparable or better. Compared to reported synthesis using alternative protocols, our method is generally better in terms of isolated yields. an interesting case of good atom economy. There were two OH groups in the quinolone, and only 0.5 equivalent of POCl3 per OH was used. Yet, the isolated yield was very good at 88% for the dichloro product, indicating that each POCl3 provided more than one chlorine atom to form the final product. This result is consistent with findings in our original report that in some cases even substoichiometric amount of POCl3 was sufficient to produce respectable results using our solvent-free protocol.

The third class of starting materials we used were benzopyrazines (quinoxalines) or pyridopyrazine. Four different starting materials with either one or two hydroxyl groups were tested using our protocol at 0.3 moles scale. In those cases, high yield conversion required conditions similar to that of the pyrimidine cases, with one equivalent POCl3 per OH group, one equivalent of pyridine, and heating at 160 °C for 2 hours.

Given the excellent results of chlorination for the above three classes of aromatic starting materials, we thought about the possibility of using the same procedure of chlorination to convert a normal amide to an imidoylchloride, but imidoylchlorides are generally not stable enough for aqueous workup and purification. Therefore, we choose to test three examples where the imidoylchloride is either stable or can be further transformed during the reaction to another stable compound . The first example was the conversion of N-trifluoroacetylaniline to the corresponding imidoylchloride, which can be isolated. The conversion achieved 83% isolated yield after 4 hours of reaction. However, unlike previous cases of product isolation through either distillation of filtration, the imidoylchloride needs to be purified by silica gel chromatography. In literature reporting synthesis of the same compound, an alternative method was used and a 66% yield was achieved. Similarly, two 2,5-piperazinediones (dimeric condensation product from α-amino acids) were treated using the same protocol for 2 hours and were converted to the corresponding pyrazines instead of imidoylchlorides in 72–76% yields after purification by silica gel chromatography. Again, these results compare favourably with literature reported results of 25% and 41% for the two dichloropyrazines.