Preparation of a Series of Substituted N-Phenyl-5-Bromo-6-Chloro- and 5-Bromo-6-Chloronicotinates of Potential Agricultural Interest

Journal of the Arkansas Academy of Science Volume 45 Article 29 1991 Preparation of a Series of Substituted NPhenyl-5-Bromo-6-Chloro- and 5-Bromo-6-Chloronicotinates of Potential Agricultural Interest Frank L. Setliff University of Arkansas at Little Rock Maximillia M. Muguluma 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.; Muguluma, Maximillia M.; and Caldwell, Jody Z. (1991) "Preparation of a Series of Substituted NPhenyl-5-Bromo-6-Chloro- and 5-Bromo-6-Chloronicotinates of Potential Agricultural Interest," Journal of the Arkansas Academy of Science: Vol. 45 , Article 29. Available at: http://scholarworks.uark.edu/jaas/vol45/iss1/29 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. 29 I PREPARATION OF A SERIES OF SUBSTITUTED N-PHENYL-5-BROMO-2-CHLORO- AND 5-BROMO-6-CHLORONICOTINATES OF POTENTIAL AGRICULTURAL INTEREST I FRANK L. SETUFF, MAXIMILLIAM.MUGULUMA,and JODY Z. CALDWELL Department of Chemistry University ofArkansas at LittleRock LittleRock, AR 72204 ABSTRACT Substituted phenyl esters of 5-bromo-2-chloronicotinic acid and 5 bromo 6-chloronicotinic acid were prepared. The acids were first converted to their respective acid chlorides using thionyl chloride, and the acid chlorides were immediately transformed to the esters by treatment with the appropriately substituted phenol in sodium hydroxide solution. A unique chloride displacement of bromide was observed on attempting to convert 5,6-dibromonicotinic acid to its acid chloride. INTRODUCTION A recent paper (Setliff,et al.) related our continuing interest in the preparation of dihalonicotinic acid derivatives with potential herbicidal, fungicidal, or ascaricidal activity. As an extension of this work, we now describe the preparation of a series of substituted phenyl esters of 5bromo-2-chloronicotinic acid (I) and S-bromo-6-chloronicotinic acid (II) (Setliff, 1970). These compounds comprise the first series of esters with suspected activity synthesized by our group. Br V^',!'' 2 2H .. LNs JJ v N rix"^-W'Is t t t The following procedure was used to prepare the phenyl esters IIIand IV.The dihalonicotinic acid I or II(0.500g; 0.002 mol) and thionyl chloride (3 mL) were stirred under gentle reflux for 30 min. During this time the acid completely dissolved. The reaction mixture was cooled to room temperature, and the excess thionyl chloride was removed under reduced pressure on a rotary evaporator (oil bath SO'C). The residual viscous oil (the acid chloride) was used to prepare the ester without further purification. The appropriate substituted phenol (0.01 5 mol) was dissolved in 5 mL of0.1 Msodium hydroxide, and the resulting solution was added to the acid chloride. The mixture was stirred vigorously at room temperature for one hour « and then a mixture of ce (5 g) and water (20 mL) was added while stirring was continued. Inmost cases the ester precipitated. m some cases precipitation was induced by the addition of 10-15mL of cold ethanol to the ice water mixture. The crude ester was collected by vacuum filtration and washed with cold water, followed by ice cold ethanol, and then recrystallized from a small volume ofethanol. Melting points and yields (overall from the acids) are listed inTables 1and 2. * MATERIALSANDMETHODS The phenyl 5-bromo-2-chloronicotinates (HI) and the phenyl 5bromo-6-chloronicotinates (IV)were generated by treating the acid chlorides of Iand IIwith the appropriately substituted phenol in basic solution. The acid chlorides were prepared in the normal manner from the acids by use of thionyl chloride. The preparative sequence is summarized in Scheme I below. Scheme I v 2) — \~—* / I r—^ OH* HO-^\ VV-R, / uN 1] soci2 2) Y^n C1X^=> . ™'L N-^ \ / ,T Pf . ." ¦ mp °c ir, v, cm ' c^./^ c h n 4.48(4.41) —~ 91 1748 12S7 48.08(48.38) 2.24(2.26) 103 17M 127 41.49(41.49) 1.72(1.68) 4.03(3.88) 120 1734 1282 36.78(36.50) 1.53(1.45) 3.57(3.53) d. OCHj 40 73 1733 1262 45.41(45.48) 2.91(2.60) 4.07(4.01) •¦ NO, 216 1749 1275 40.28(40.59) 1.67(1.47) 7.83(7.62) 81 b'CI 51 42 IV * W™^ •PfV.™ Table 2. Experimental, Infrared, and Elemental Analysis Data for the Substituted Phenyl 5-Bromo-6-chloronicotinates (TV) r % yw. mp °c ir,«, cm ' _____ Elemental Analysis caic'd % (Found %) C=O C-O-Ar C H N ..H 45 123 173. 12.3 46.0.(46.1.) 2.24(2.0.) 4.4.(4.3.) n. ci 43 116 1741 129. 41.49(41.26) 1.72(1.69) 4.03(3.90) 124 1743 1297 3e.78(36.66) 1.53(1.49) 3.57(3.51) d.0CH,M 151 1735 12.4 45.41(45.51) 2.91(2.71) 4.07(4.1.1 •. no, iea 1731 129s 4o.2.(4o.36) 1.67(1.4.) 7.83(7.66) c, Br „ 40 Proceedings Arkansas Academy of Science, Vol.45, 1991 Published by Arkansas Academy of Science, 1991 Eiimanui Analysis Caicd % (Found %) R Acids I and IIwere prepared in our laboratory as previously described from Aldrich (Setliff, ,1970). The substituted phenols were purchased , • }-* ¦ ¦ »i points were taken Chemical company and were technical« grade. Melting Mel"TemP a rata S Were U COrrcCted 1 taken on a D Perkin -Elmer 1430 Spectrophotometer equipped with a Model 7300 data station, and samples were prepared as KBr disks. Proton nuclear magnetic resonance spectra were determined on a Varian EM360 instrument with samples dissolved in deuteriochloroform and with tetramethylsilane as the internal standard. Carbon, hydrogen, nitrogen, elemental analyses were performed by Desert Analytics Inc., Tuscon, Arizona. . *ym. Ca0 C. Br j Br HO-^^-R, OH' R |,| ill P. 11 n a. H (J 1) SOC1 2 Table 1. Experimental, Infrared, and Elemental Analysis Data for the Substituted Phenyl 5-Bromo-2-chloronicotinates (IE) 95 95 ¦ Journal of the Arkansas Academy of Science, Vol. 45 [1991], Art. 29 Preparation of a Series of Substituted N-Phenyl-5-Bromo-2-Chloro- and 5-Bromo-6-Chloronicotinates RESULTS ANDDISCUSSION Five Substituted phenyl esters were prepared from each of the acids I and II.As noted in Tables 1 and 2, overall product yields from the acids are marginally adequate. Longer reaction times and or heating showed no improvement, and in some cases heating only diminished the yields due to saponification of the es (...truncated)