4-Substituted Anilides of 2,6- and 5,6- Dichlorolicotinic Acid. Potential Agricultural Agents

Journal of the Arkansas Academy of Science Volume 46 Article 10 1992 4-Substituted Anilides of 2,6- and 5,6Dichlorolicotinic Acid. Potential Agricultural Agents Frank L. Setliff University of Arkansas at Little Rock Nikhil G. Soman University of Arkansas at Little Rock Follow this and additional works at: http://scholarworks.uark.edu/jaas Part of the Organic Chemistry Commons Recommended Citation Setliff, Frank L. and Soman, Nikhil G. (1992) "4-Substituted Anilides of 2,6- and 5,6- Dichlorolicotinic Acid. Potential Agricultural Agents," Journal of the Arkansas Academy of Science: Vol. 46 , Article 10. Available at: http://scholarworks.uark.edu/jaas/vol46/iss1/10 This article is available for use under the Creative Commons license: Attribution-NoDerivatives 4.0 International (CC BY-ND 4.0). Users are able to read, download, copy, print, distribute, search, link to the full texts of these articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This Article is brought to you for free and open access by ScholarWorks@UARK. It has been accepted for inclusion in Journal of the Arkansas Academy of Science by an authorized editor of ScholarWorks@UARK. For more information, please contact , . Journal of the Arkansas Academy of Science, Vol. 46 [1992], Art. 10 5,6 - DICHLORONICOTINIC ACID. POTENTIAL AGRICULTURALAGENTS. FRANK L SETLIFF and NIKHILG. SOMAN Department of Chemistry University of Arkansas at LittleRock LittleRock, AR 72204 ABSTRACT A series of 4-substituted anilides of 2,6- and 5,6 dichloronicotinic acid were prepared. The acids were first converted to their acid chlorides, which were in turn treated with the appropriate 4-substituted aniline in chloroform. A total of 16 anilides was thus prepared, and their structures confirmed. These compounds were prepared for testing as possible herbicidal, pesticidal or fungicidal agents. INTRODUCTION For over two decades, we have been engaged in the preparation of dihalogenated nicotinic acids and their derivatives, together with their subsequent evaluation as potential herbicidal, fungicidal and pesticidal agents (Setliff, 1970). Most recently we reported the preparation and characterization of a series of substituted anilides of S-bromo-2chloronicotinic acid and 5-bromo-6-chloronicotinic acid (Setliff and Caldwell, 1991), and were encouraged by the moderate activity demonstrated by several of these derivatives. The details of these evaluations, performed by the Research Division of a leading Agricultural Chemical Company, are confidential and cannot be reported here. Unfortunately, the activities of these compounds were organism-specific, and further screening was not performed. In view of the limited success of the bromochloro nicotinanilides, it was decided to prepare a series of anilides of the isomeric 2,6- and 5,6dichloronicotinic acids, in the hope that enriching the chlorine content might result in a more active and broader spectrum activity profile. We thus prepared the eight 4-substituted 2,6-dichloronicotinanilides (Ia-h) and the eight 4-substituted 5,6-dichloronicotinanilides (Ila-h), all of which are depicted in Figure 1 . MATERIALSANDMETHODS Melting points were determined on a Mel-Temp IIapparatus and are uncorrected. Infrared sp-xtra were taken on a Perkin Elmer 1430 ratio recording instrument equipped with a Model 7300 data station and with samples prepared as KBr disks. *H nmr spectra were determined in DMSO-d 6 containing 1% TMS and were obtained on a Bruker 200 MHz FTAC-F superconductivity spectrometer equipped with ASPECT 300 computer control. Carbon, hydrogen, and nitrogen elemental analyses were done by Desert Analytics Organic Microanalysis, Inc., Tucson, Arizona. Technical grade 2,6-dichloronicotinic acid (m.p. 141°-143°C) was obtained from Aldrich Chemical Company and was used without further purification. 5,6-Dichloronicotinic acid was prepared by oxidation of 5,6dichloro-3-picoline (Setliff and Lane, 1976), and after recrystallization from water melted at 162-163°C. The following general procedure was employed in the preparation of both the series Iand IIanilides. The dichloroacid (0.50 g; 0.0026 mol) and thionyl chloride (3 ml) were combined and magnetically stirred under gentle reflux for 30 minutes, whereupon the acid dissolved. The reaction mixture was allowed to cool to room temperature, and the excess thionyl chloride was removed under reduced pressure on a rotary evaporator. The residual acid chloride was taken up in dry chloroform (3 ml) and added to the appropriately substituted aniline (0.0058 mol) which had been dissolved in dry chloroform (10 ml). The resulting suspension was then stirred under reflux for 30 minutes. (Note: Incase of the 4-nitroanilides Ih Figure 1. Structures of the dichloronicotinanilides. and Ilh, dry benzene was used as solvent and the reflux lime was extended to 1 hour). The reaction mixture was cooled, and the solid collected by vacuum filtration. The chloroform filtrate was washed with 2 x 10 ml water, then 2 x 10 ml 10% HC1, followed again by 2 x 10 ml H20. Evaporation of the chloroform afforded the crude anilide. In some cases a considerable amount of anilide product occluded with the aniline hydrchloride that was filtered from the reaction mixture. In those instances, the solid from the reaction mixture was dried, stirred vigorously with 100 ml water for 30 minutes, and then filtered by vacuum. The water insoluble anilide, and the residue from the chloroform evaporation were combined and recrystallized from aqueous ethanol. A second recrystallization was performed to produce a sharp melting analytical sample for C,II,N and spectroscopic analysis. Proceedings Arkansas Academy of Science, Vol. 46, 1992 Published by Arkansas Academy of Science, 1992 69 69 Journal of the Arkansas Academy of Science, Vol. 46 [1992], Art. 10 • RESULTS ANDDISCUSSION Preliminary experiments showed that the Schotten Bauman method (reaction of the acid chloride with the aniline in the presence of 5% NaOH) was unacceptable for the preparation for these particular anilides, since products were isolated in only trace amounts and were attended by large quantities of intractable material. Therefore, it was decided to conduct the reactions using a 2.25:1 molar ratio ofamine to acid chloride, so that the excess amine rather than sodium hydroxide would catalyze the reaction. The transformations were thus accomplished smoothly and without complication. Yields and melting points of the anilides are reported in Tables 1 and 2. With the exception of compounds Ih and Ha, yields were extremely good. Repeated attempts to improve the yields of the aforementioned anilides proved unrewarding and the reason for these exceptions remains unexplained. The melting characteristics of the isomeric anilides followed the general pattern of a higher melting 5,6-dichloro isomer, with the notable exception being the 4-trifluoromethyla (...truncated)