Coop, Leslie B.

Setliff, Frank L.

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Journal of the Arkansas Academy of ScienceVolume 51 Article 371997Reductive Dechlorinatin of a 2-ChloronicotinicAcid Under Finkelstein ConditionsFrank L. SetliffUniversity of Arkansas at Little RockLeslie B. CoopUniversity of Arkansas at Little RockFollow this and additional works at: http://scholarworks.uark.edu/jaasPart of the Organic Chemistry CommonsThis article is available for use under the Creative Commons license: Attribution-NoDerivatives 4.0 International (CC BY-ND 4.0). Users are able toread, download, copy, print, distribute, search, link to the full texts of these articles, or use them for any other lawful purpose, without asking priorpermission from the publisher or the author.This General Note is brought to you for free and open access by ScholarWorks@UARK. It has been accepted for inclusion in Journal of the ArkansasAcademy of Science by an authorized editor of ScholarWorks@UARK. For more information, please contact scholar@uark.edu.Recommended CitationSetliff, Frank L. and Coop, Leslie B. (1997) "Reductive Dechlorinatin of a 2-Chloronicotinic Acid Under Finkelstein Conditions,"Journal of the Arkansas Academy of Science: Vol. 51 , Article 37.Available at: http://scholarworks.uark.edu/jaas/vol51/iss1/37212Reductive Dechlorination of a 2-Chloronicotinic Acid UnderFinkelstein ConditionsFrank L.Setliff and Leslie B. CoopDepartment of ChemistryUniversity of Arkansas at Little RockLittle Rock, AR 72204We reported previously the preparation of 5-fluoro-6-iodonicotinic acid and 5-bromo-6-iodonicotinic acid (Setliff,IJ. Chem. Eng. Data 18: 449-450, 1973) as well as 5-oro-6-iodonicotinic acid (Setliff, E,J. Chem. Eng. Data246-247, 1976) by the Finkelstein Reaction (Klingsberg,E.,J. Am. Chem. Soc. 72:1031, 1950). The process involves|:leophilic displacement of chloride by iodide (as sodiumpotassium iodide) in refluxing acetone or methyl ethylone (MEK),and the reaction is driven by the insolubili-of the resultant sodium or potassium chloride in theone solvent. The aforementioned 5-halo-6-iodonicotinicds were thus generated from their respective 6-chloroivatives in acceptable yields. Although these reactionspresumably catalyzed by autoprotonation of the ringogen, itwas found that our conversions proceeded moreciently when a small amount of hydroiodic acid wasled. The electron withdrawing carboxyl group para to6-chloro, together with the halogen in the five position,and the protonated ring nitrogen all serve to activate the 6-chloro for nucleophilic displacement by iodide.IReasoning that an ortho carboxyl group and a paramo should also promote chloride displacement, weimpted the preparation of 5-bromo-2-iodonicotinic acidn 5-bromo-2-chloronicotinic acid by the Finkelsteininique, but the expected bromoiodoacid was not formed,prisingly, 5-bromonicotinic acid was the only productated, and the reaction was accompanied by the forma-lof copious amounts of molecular iodine. Evidently,uctive dechlorination occurred at the expense of dis-cement, possibly due to steric interference by the orthoboxyl group. The overall reaction is shown inFig. 1.BrvT«#^NvrCOOH Br^^v^cOOH+ Nal + HI MEOK » + NaCI + l2B. 1. Reductive dechlorination of 5-bromo-2-chloronico-c acid.Although iodide-induced reductive dechlorinations ofseveral 4-chloro-2-pyridinecarboxylic acids (4-chloropicol-inic acids) have been reported (Graf, H., J. Prakt. Chem.148:13-19, 1937), high concentrations of hydroiodic acidtogether with red phosphorus and extremely elevatedtemperatures were required. To our knowledge, this noterepresents the first example of a reductive dechlorination ofa 3-pyridinecarboxylic acid (nicotinic acid) and more signif-icantly, under such mild conditions.No exact mechanism for reactions of this type isdescribed in the literature, but the process could involve ini-tial iodide attack on chlorine of the N-protonated substrateyielding iodine monochloride and a 2-pyridyl anion, whichcould subsequently undergo protonation to afford the reduc-tion product. Further reaction of iodine monochloride withiodide ion could then produce molecular iodine, which weobserved.The experiment was conducted as follows. A mixture of5-bromo-2-chloronicotinic acid (Setliff, E, J. Chem. Eng.Data 590-591, 1970), (0.9 g, 0.0038 mole), sodium iodide(2.0 g, 0.013 mole), 57% hydroiodic acid (2 ml), water (1mL), and methyl ethyl ketone (25 mL) was stirred underreflux for 48 hr. The reaction mixture was cooled to roomtemperature, and the sodium chloride which had precipitat-ed (0.16 g, 72% of the theoretical) was removed by suctionfiltration. The reddish-brown filtrate was evaporated leavinga dark brown solid, which was washed with 10 mL of 10%sodium bisulfite to remove the iodine. The resulting lightyellow powder was recrystallized from water, yielding lighttan leaflets of 5-bromonicotinic acid (0.25 g,32%), mp 180-182° C. The infrared spectrum was superimposable on thatof an authentic sample obtained from Aldrich ChemicalCo., Milwaukee, WI. A mixture melting point with anauthentic sample showed no depression. The 200 MHzpro-ton NMR spectrum in DMSO-d*. with tetramethylsilane asthe internal standard showed three aromatic protons: 8 9.04(H-2), 8.96 (H-6), and 8.42 (H-4) ppm, all singlets in the arearatio of 1:1:1. The carboxyl proton appeared in the watersignal at 3.42 ppm as a result of exchange with the waterpresent in the DMSO.Acknowledgments. —We thank the UALR FacultyResearch Fund for partial support of this work. The NSF ILIprogram from which funds were obtained for the purchaseof the NMR spectrometer is also gratefully acknowledged.Journal of the Arkansas Academy of Science, Vol. 51, 1997212Journal of the Arkansas Academy of Science, Vol. 51 [1997], Art. 37Published by Arkansas Academy of Science, 1997

Reductive Dechlorinatin of a 2-Chloronicotinic Acid Under Finkelstein Conditions

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Reductive Dechlorinatin of a 2-Chloronicotinic Acid Under Finkelstein Conditions

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