War-time pharmaceutical chemistry (continued)

Yet another sulphadrug synthesised during the war was sulphamerazine; it was more complex because it was a heterocyclic compound. Malaria was perhaps the most serious threat to Austalia's striking power in the Pacific -Mellor[62] reports that '5816 Australians were killed or wounded while 21,600 were stricken with malaria during the Kokoda-Buna campaign'. Local manufacture of sulphamerazine was given highest priority. Professor A. K. MacBeth of Adelaide University developed an eight step synthesis from benzene, chlorine, ammonia, carbon bisulphide, alcohol (CSR) and pyridine (Timbrol). A team of chemists and engineers (led by J. A. R. Glenn, F. Lament, L. W. Weickhardt) built a pilot plant and almost simultaneously the full scale plant. Amongst the war-time shortages were suitable vessels. The development of the first glass-lined reactor in Australia (W. Bonython) was part of the task. It was Australia's first experience of progressively declining yields in an eight step process; 30 tonnes of raw materials and virtually the whole factory's resources were required to produce one tonne of the drug. Eventually a production rate of two tonnes per month was achieved.[63] By then medicine had overtaken events: It was demonstrated that sulphamerazine was effective against the malignant form of malaria only, almost ineffective against benign malaria and, in any case, no better than the established drug, atebrin. Yet, subsequently the compound became important as the starting point to yet another drug, paludrine.

An effective attack on malaria was by prevention. The Swiss (P. Mtiller, 1940) had discovered the insecticidal properties of D.D.T. and the Americans had established its efficacy in the control of the mosquitos carrying the malaria infection. Synthesis from benzene, chlorine and ethanol was well within the resources of ICI Australia. After experiments on the sulphamerazine pilot plant at Deer Park a full scale plant was erected at Yarraville in 1943 which supplied a substantial proportion of the antimalarial campaign in the South Pacific war arena.[64] Yet another preventive measure against malaria were the insect repellents evolved in the USA and produced in Australia by Stanco (Australia) Pty Ltd, a Vacuum Oil subsidiary. Dimethyl phthalate was found by Professor J. C. Earl of Sydney University to be the most effective repellent; the intermediate phthalic anhydride made from naphthalene at Newcastle Chemicals (later ICI Australia) was locally available and by 1943 a plant producing the dimethyl phthalate repellent was in operation. When R. N. McCulloch of the CSIRO established that phthalates were effective against scrub mites and that dibutyl phthalates were more persistent, CSR-Chemicals (then Robert Corbett Pty Ltd) adopted the Weizmann process for butyl alcohol to produce this ester. Dibutyl phthalate substantially reduced the incidence of scrub typhus.

Australian Academy of Technological Sciences and Engineering