Arsanilic acid

Chemistry

Synthesis was first reported in 1863 by Antoine Béchamp and became the basis of the Bechamp reaction. The process involves the reaction of aniline and arsenic acid via an electrophilic aromatic substitution reaction.

:C6H5NH2 + H3AsO4 → H2O3AsC6H4NH2 + H2O

Arsanilic acid occurs as a zwitterion, H3N+C6H4AsO3H−, yet is typically represented with the non-zwitterionic formula H2NC6H4AsO3H2.

History

Roots and synthesis

Since at least 2000 BC, arsenic and inorganic arsenical compounds were both medicine and poison. In the 19th century, inorganic arsenicals became the preeminent medicines, for instance Fowler's solution, against diverse diseases.

In 1859, in France, while developing aniline dyes, Antoine Béchamp synthesized a chemical that he identified, if incorrectly, as arsenic acid anilide. the first organic arsenical drug.

Medical influence

In 1905, in Britain, H W Thomas and A Breinl reported successful treatment of trypanosomiasis in animals by Atoxyl, and recommended high doses, given continuously, for human trypanosomiasis (sleeping sickness). By 1907, more successful and less toxic than inorganic arsenicals, Atoxyl was expected to greatly aid expansion of British colonization of Africa and stem loss of cattle in Africa and India. (So socioeconomically valuable was colonial medicine

• Nadav Davidovitch & Zalman Greenberg, "Public health, culture, and colonial medicine: Smallpox and variolation in Palestine during the British Mandate", Public Health Reports (Washington DC 1974), 2007 May–Jun;122(3):398–406, § "Colonial medicine in context".
• Anna Crozier, Practising Colonial Medicine: The Colonial Medical Service in British East Africa (New York: I.B. Tauris & Co Ltd, 2007).
• Deborah Neill, Networks in Tropical Medicine: Internationalism, Colonialism, and the Rise of a Medical Specialty, 1890–1930 (Stanford CA: Stanford University Press, 2012). that in 1922, German company Bayer offered to reveal the formula of Bayer 205—developed in 1917 and showing success on sleeping sickness in British and Belgian Africa—to the British government for return of German colonies lost via World War I.)

Soon, however, Robert Koch found through an Atoxyl trial in German East Africa that some 2% of patients were blinded via atrophy of the optic nerve. or aminophenyl arsonic acid—which suggested possible derivatives. Ehrlich asked Bertheim to synthesize two types of Atoxyl derivatives: arsenoxides and arsenobenzenes.

Ehrlich and Bertheim's 606th arsenobenzene, synthesized in 1907, was arsphenamine, found ineffective against trypanosomes, but found in 1909 by Ehrlich and bacteriologist Sahachiro Hata effective against the microorganism involved in syphilis, a disease roughly equivalent then to today's AIDS. In the late 1940s, Salvarsan was replaced in most regions by penicillin, yet organic arsenicals remained in use for trypanosomiasis.

Contemporary usage

Arsanilic acid gained use as a feed additive for poultry and swine to promote growth and prevent or treat dysentery. In 2013, the FDA denied petitions by the Center for Food Safety and by the Institute for Agriculture and Trade Policy seeking revocation of approvals of the arsenical animal drugs, but the drugs' sponsors voluntarily requested the FDA to withdraw approvals of three, including arsanilic acid, leaving only nitarsone approved. In 2015, the FDA withdrew nitarsone's approval.

Arsanilic acid is still used in the laboratory, for instance in recent modification of nanoparticles.

It is a reagent for the detection of nitrite in urinalysis dipsticks.

Citations

References

1. Burke ET. (1925). "The arseno-therapy of syphilis; stovarsol, and tryparsamide". British Journal of Venereal Diseases.
2. (1977). "Arsenic: Medical and Biological Effects of Environmental Pollutants". National Academies Press.
3. (July 2017). "The use of arsanilic acid in the production of market pigs". [[Journal of Animal Science]].
4. (Sep 2006). "Arsanilic acid—MIB #4". Canadian Food Inspection Agency.
5. Still sometimes used in laboratories, arsanilic acid's legacy is principally through its influence on [[Paul Ehrlich]] in launching the [[antimicrobial chemotherapy]] approach to treating infectious diseases of humans.Patrick J Collard, ''The Development of Microbiology'' (Cambridge, London, New York, Melbourne: [[Cambridge University Press]], 1976), [https://books.google.com/books?id=LPI8AAAAIAAJ&pg=PA53&dq=Bechamp pp 53–4].
6. M. A. Bechamp. (1863). "de l'action de la chaleur sur l'arseniate d'analine et de la formation d'un anilide de l'acide arsenique". [[Compt. Rend.]].
7. C. S. Hamilton and J. F. Morgan. [[Organic Reactions]]. (1944)
8. (1996). "P-arsanilic acid, a redetermination". Acta Crystallographica Section C.
9. Jolliffe DM. (1993). "A history of the use of arsenicals in man". [[Journal of the Royal Society of Medicine]].
10. (2010). "Medicinal Organometallic Chemistry".
11. Boyce R. (1907). "The treatment of sleeping sickness and other trypanosomiases by the Atoxyl and mercury method". BMJ.
12. Steverding D. (2010). "The development of drugs for treatment of sleeping sickness: A historical review". Parasites & Vectors.
13. "Paul Ehrlich, the Rockefeller Institute, and the first targeted chemotherapy". Rockefeller University.
14. U.S. Food and Drug Administration. (8 Jun 2011). "Questions and answers regarding 3-nitro (roxarsone)".
15. U.S. Food and Drug Administration. (1 Oct 2013). "FDA response to citizen petition on arsenic-based animal drugs".
16. U.S. Food and Drug Administration. (April 1, 2015). "FDA announces pending withdrawal of approval of nitarsone".
17. (2013). "Arsonic acid as a robust anchor group for the surface modification of Fe3O4". Langmuir.