Preparation of a Series of N-Phenylamides of 5-Bromo-6-Chloronicontinic Acid and 5-Bromo-2-Chloronicontinic Acid

Journal of the Arkansas Academy of Science Volume 45 Article 28 1991 Preparation of a Series of N-Phenylamides of 5-Bromo-6-Chloronicontinic Acid and 5-Bromo-2-Chloronicontinic Acid Frank L. Setliff University of Arkansas at Little Rock Jody Z. Caldwell 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 Caldwell, Jody Z. (1991) "Preparation of a Series of N-Phenylamides of 5-Bromo-6-Chloronicontinic Acid and 5-Bromo-2-Chloronicontinic Acid," Journal of the Arkansas Academy of Science: Vol. 45 , Article 28. Available at: http://scholarworks.uark.edu/jaas/vol45/iss1/28 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. 45 [1991], Art. 28 PREPARATION OF A SERIES OF N-PHENYLAMIDES OF 5-BROMO-6-CHLORONICOTINIC ACID AND 5-BROMO-2-CHLORONICOTINIC ACID FRANK L SETUFF and JODY Z. CALDWELL Department of Chemistry University of Arkansas at Little Rock LittleRock, AR 72204 ABSTRACT A series of N-phenylamides of 5-bromo 6-chloronicotinic acid and 5-bromo-2-chloronicotinic acid were synthesized by treatment of their freshly prepared acid chlorides with the appropriately ringsubstituted anilines. Thirty new compounds were prepared, and their structures were ascertained by elemental analyses and spectroscopic techniques. Spectroscopic trends in the infrared spectra of the two series were examined in an attempt to correlate structural and electronic effects to hydrogen bonding tendencies. INTRODUCTION Inconnection with our continuing search for dihalonicotinic acid derivatives with potential pesticidal, hcrbicidal, and fungicidal activity (Setliff et al., 1989), we have prepared a series of N-phenylamides of 5bromo-6-chloronicotinic acid (I) and 5-bromo-2-chloronicotinic acid (II) (Setliff, 1970). These compounds, with the dihalopyridine moiety on the carbonyl side of the amide function, exhibit a reversal of the amide linkage in comparison to previously reported benzamide and phenylurea halopyridine derivatives (Setliff and Palmer, 1987; Setliff and Rank in, 1988; Setliff etal., 1989). Thirty new N-phenylnicotinamides were synthesized with a variety of electron releasing groups and electron withdrawing groups present on the benzene ring. Having available two such closely related series of compounds, we also sought to look for any trends in their infrared spectra which could be related to the electronic effects of the benzene ring substituents. form (10.0 mL). A solid precipitate formed, and the resulting reaction mixture was heated under reflux for one hour and 30 minutes then cooled to room temperature. The solid precipitate was collected by vacuum filtration, dried and weighed, and the chloroform filtrate was saved. MATERIALS ANDMETHODS Acids Iand IIwere prepared as previously reported (Setliff, 1970). The substituted anilines employed were fresh practical grade samples from either Aldrich Chemical Company or Eastman Organic Chemicals. Allliquid anilines were freshly distilled. Allsolid anilines were used without further purification with the exception of 4-chloroanilinc and 4methoxyaniline which were recry stallized from mclhy lcyclohexane. Melting points are uncorrected and were determined using a MelTemp IIcapillary melting apparatus. Infrared spectra were obtained on samples prepared as potassium bromide disks using a Perkin-Elmer 1430 spectrophotometer equipped with a Model 7300 data station. Proton nuclear magnetic resonance spectra were obtained using an AC-FBrucker 200 MHzFT spectrometer with deuterated dimethyl sulfoxide as the solvent and tetramethylsilane as the internal standard. Allelemental analyses were performed by Desert Analytics Organic Microanalysis, Tuscon, Arizona. The N-phenyl-5-bromo-6-chloronicotinamide compound series (DT) and N-phenyl-5-bromo-2-chloronicotinamide compound series (TV) were obtained by heating a chloroform solution of the freshly prepared acid chlorides with an excess amount of the appropriately substituted anilines. or II(0.50 g; The reaction sequence is depicted in Figure 1. Dihaloacid I 0.0021 mol) was stirred and heated under reflux with thionyl chloride (3.0 mL) for 30 minutes then cooled to room temperature. The acids completely dissolved to yield a transparent yellow solution. Excess thionyl chloride was removed from this solution under reduced pressure on a rotary evaporator (oil bath 50-60 *C). The residual viscous acid chloride was taken up in chloroform (2.0 mL) and to this mixture was added a solution of the appropriately substituted aniline (0.0050 mol) in chloro- 92 Figure 1. A) Preparation of the 5-bromo-6-chloronicotinamides and B) the 5-bromo-2-chloronicotinamides Isolation and purification of the amide products varied according to their chloroform solubilities. Some of the amides were extremely chloroform-soluble as evidenced by the weight and water solubility of the amine hydrochloride isolated from the reaction mixture. In these instances, purification procedure A was employed as follows: The chloroform filtrate from the reaction mixture was washed with water (2x10 mL) followed by 10% hydrochloric acid (2x10 mL) and then evaporated to yield the crude amide product, which was subsequently recrystallized from aqueous ethanol. Several amide products were insoluble in chloroform and precipitated together with the amine hydrochlorides. These compounds were purified by procedure B as follows: The precipitate from the reaction mixture was stirred magnetically in water (150 mL) to dissolve the amine hydrochloride. The residual crude amide was collected by filtration and recrystallized from aqueous ethanol. In a few instances, the amide product was partially soluble in chloroform and was distributed between the precipitated solid and the chloroform filtrate. Purification procedure C was employed in these cases as follows: The reaction mixture precipitate was stirred magnetically in water (150 mL), and the undissolved amide product was collected by filtration. The original chloroform filtrate was washed with water (2 x 10 Proceedings Arkansas Academy of Science, Vol. 45, 1991 Published by Arkansas Academy of Science, 1991 92 Journal of the Arkansas Academy of Science, Vol. 45 [1991], Art. 28 Franklin L.Setllff and Jody Z.Caldwell mL) followedby 10% hydrochloric acid (2 x 10 mL) and then evapo (...truncated)