1030 Bull. Koren Chem. Soc. 2013, Vol. 34, No. 4 Bong Re Cho nd Sng Yong Pyun http://dx.doi.org/10.5012/bkcs.2013.34.4.1030 Elimintions from (E)-2,4-Dinitrobenzldehyde O-Aryloximes Promoted by R 3 N/R 3 NH + in 70 mol % MeCN(q). Effects of Leving Group nd Bse-Solvent on the Nitrile-Forming Trnsition-Stte Bong Re Cho nd Sng Yong Pyun,* Deprtment of Chemistry, Kore University, Seoul 136-713, Kore Deprtment of Chemistry, Pukyong Ntionl University, Pusn 608-737, Kore. * E-mil: sypyun@pknu.c.kr Received December 26, 2012, Accepted Jnury 3, 2013 Elimintion rections of (E)-2,4-(NO 2 ) 2 C 6 H 2 CH=NOC 6 H 3-2-X-4-NO 2 (1-e) promoted by R 3 N/R 3 NH + in 70 mol % MeCN(q) hve been studied kineticlly. The rections re second-order nd exhibit Brönsted β = 0.80-0.84 nd β lg = 0.39-0.42, respectively. For ll leving groups nd bses employed in this study, the β nd β lg vlues remined lmost the sme. The results cn be described by negligible p xy interction coefficient, p xy = β/pk lg = β lg /pk BH 0, which describes the interction between the bse ctlyst nd the leving group. The negligible p xy interction coefficient is consistent with the (E1cb) irr mechnism. Chnge of the bse-solvent system from R 3 N/MeCN to R 3 N/R 3 NH + -70 mol % MeCN(q) chnged the rection mechnism from E2 to (E1cb) irr. Noteworthy ws the reltive insensitivity of the trnsition stte structure to the rection mechnism Key Words : Elimintion, E1cb-like nd (E1cb) irr, Leving group nd bse-solvent effect Introduction One of the most importnt problems in the elimintion rections is the borderline mechnism. 1-8 Some yers go, Jencks hs clerly elucidted how the E2 mechnism chnges to n E1cb in lkene-forming elimintions. 3 More recently, we hve reported imine-forming elimintions which proceeded vi competing E2 nd E1 mechnisms. 6 During the lst two decdes, we hve conducted extensive reserch for nitrile-forming elimintion from (E)-O-rylbenzldoximes to investigte the borderline mechnism between E2 nd E1cb. 9-16 Except for few cses, 15,16 however, ll rections proceeded by the E2 mechnism despite the fct tht the rectnts hve syn stereochemistry, poor leving, nd n sp 2 hybridized β-crbon tom, ll of which fvor E1cb or E1cblike trnsition stte. Erlier, we reported tht elimintion rections of (E)-O-pnitrophenyl-2,4-dinitrobenzldoxime with E 3 N/Et 3 NH + in MeCN-H 2 O proceeded by n E2 mechnism. 17 The rte decresed s the mol % of MeCN incresed up to 70% nd then incresed upon further increse in the MeCN content. However, the effect of the solvent on the trnsition stte structure ws not elucidted in detil. More recently, we investigted the elimintion rections of (E)-2,4-dinitrobenzldehyde O-ryloximes promoted by R 3 N in MeCN. 18 The rections proceed by n E2 mechnism. When the β- ryl group ws chnged from Ph to 2,4-dinitrophenyl, the structure of the trnsition stte chnged from E2-centrl to highly E1cb-like. It occurred to us tht the chnge in the elimintion mechnism from E2 to E1cb might be relized, if the rection is conducted in more protic solvent which cn stbilize the crbnion developed in the trnsition stte. In order to explore such possibility, we hve now conducted kinetic study on the elimintion rections of (E)- 2,4-dinitrobenzldehyde O-ryloxime with R 3 N/R 3 NH + -70 mol % MeCN(q) (eq. 1). By compring with the existing dt for (E)-2,4-(NO 2 ) 2 C 6 H 3 CH=NOC(O)C 6 H 3-2-X-4-NO 2 (2) with R 2 NH/R 2 NH 2 + -70 mol % MeCN(q) nd 1-e with R 3 N/MeCN, the effects of leving group nd bse-solvent vritions on the nitrile-forming elimintion ws ssessed. Results (E)-2,4-Dinitrobenzldehyde O-ryloximes 1-e were vilble from previous studies. 18 The rection of 1 with Et 3 N/Et 3 NH + in 70 mol % MeCN(q) produced 2,4-dinitrobenzonitrile in 96% yield. No trce of (E)-2,4-dinitrobenzldoxime could be detected by TLC. For ll rections, the yields of ryloxides determined by the compring the bsorbnce of the infinity smples from the kinetic studies with those of the uthentic ryloxides were in the rnge of 96-98%. The rtes of elimintion rection were followed by monitoring the increse in the bsorption t the λ mx for the ryloxides in the rnge of 400-434 nm s described previously. 9 Excellent pseudo-first order kinetics plots, which (1)
Elimintion, E1cb-like nd (E1cb) irr, Leving Group nd Bse-solvent Effect Bull. Koren Chem. Soc. 2013, Vol. 34, No. 4 1031 Tble 1. Rte constnts for nitrile-forming elimintion from (E)-2,4-(NO 2) 2C 6H 3-CH=NOC 6H 3-2-X-4-NO 2 promoted by R 3N/R 3NH + in 70 mol % MeCN(q) b,c t 25.0 C R 3N d e pk 10 3 k 2, M 1 s 1 f,g When X is CH 3 (1b) H (1) Cl (1c) CF 3 (1d) NO 2 (1e) N(CH 2CH 2OH) 3 15.7 0.149 0.188 2.01 5.63 14.7 EtN(CH 2CH 2OH) 2 16.3 0.713 0.862 8.65 23.7 109 Et 2N(CH 2CH 2OH) 17.7 8.66 7.80 107 246 787 Et 3N 18.5 31.3 33.7 521 1320 4070 [Substrte] = 5.0 10 5 M. b [R 3N]/[R 3NH + ] = 1. c µ = 0.1 (Bu 4N + Br ). d [R 3N] = 2.0 10 3 0.25 M. e pk in MeCN tken from reference 19. f Averge of three or more rte constnts. g Estimted uncertinty, ± 3%. Figure 1. Brönsted plots for the elimintion from (E)-2,4- (NO 2) 2C 6H 3CH=NOC 6H 3-2-X-4-NO 2 promoted by R 3N/R 3NH + in 70 mol % MeCN(q) t 25.0 C. [X = H (1, ), CH 3 (1b, ), Cl (1c, ), CF 3 (1d, ), NO 2 (1d, )]. covered t lest three hlf-lives were obtined. For rections of 1-e with R 3 N/R 3 NH + in 70 mol % MeCN(q), the plots of k obs versus bse concentrtion were stright lines pssing through the origin, indicting tht the rections re secondorder, first order to the substrte nd first order to the bse (Figure Sl-9). The second-order rte constnts (k 2 ) were obtined either from the slopes of stright lines or by dividing the k obs by bse concentrtion. Vlues of k 2 for elimintions from 1-e re summrized in Tble 1. The log k 2 vlues for elimintions from 1-e showed good correltion with the pk vlues of the promoting bses on the Brönsted plot (Figure 1). Similrly, the elimintion rtes determined with different leving groups correlted resonbly well with the leving group pk lg vlues (Figure 2). The β nd β lg vlues re in the rnge of 0.80-0.84 nd 0.39-0.42, respectively. The β nd β lg vlues remined lmost the sme within experimentl error for ll leving Figure 2. Plots log k 2 versus pk lg vlues of the leving group for the elimintion from (E)-2,4-(NO 2) 2C 6H 3CH=NOC 6H 3-2-X-4- NO 2 promoted by R 3N/R 3NH + in 70 mol % MeCN(q) t 25.0 C. [R 3N = N (CH 2CH 2OH) 3 ( ), EtN (CH 2CH 2OH) 2 ( ), Et 2N (CH 2CH 2OH) ( ), Et 3N ( )]. Tble 2. Brönsted β vlues for elimintion from (E)-2,4-(NO 2) 2- C 6H 3CH=NOC 6H 3-2-X-4-NO 2 promoted by R 3N/R 3NH + in 70 mol % MeCN(q) t 25.0 C X = CH 3 X = H X = Cl X = CF 3 X=NO 2 pk lg 21.1 b 20.7 18.1 17.0 16.0 0.80 ± 0.07 0.80 ± 0.03 0.84 ± 0.03 0.82 ± 0.04 0.82 ± 0.08 Reference 19. b Determined from the slope of the plot of vs pk. groups nd bses employed in this study (Tbles 2 nd 3). Discussion Mechnism of Elimintions from 1. The mechnism of elimintion for 1-e promoted by R 3 N/R 3 NH + in 70 mol % MeCN(q) hs been elucidted by the results of kinetic investigtions nd product studies. Becuse the rections Tble 3. Brönsted β lg vlues for elimintion from (E)-2,4-(NO 2) 2C 6H 3CH=NOC 6H 3-2-X-4-NO 2 promoted by R 3N/R 3NH + in 70 mol % MeCN(q) t 25.0 C R 3N N(CH 2CH 2OH) 3 EtN(CH 2CH 2OH) 2 Et 2N(CH 2CH 2OH) Et 3N pk 15.7 16.3 17.7 18.5 β lg -0.39 ± 0.01-0.41 ± 0.03-0.39 ± 0.01-0.42 ± 0.01 Reference 19.
1032 Bull. Koren Chem. Soc. 2013, Vol. 34, No. 4 Bong Re Cho nd Sng Yong Pyun produced only elimintion products nd exhibited secondorder kinetics, ll but bimoleculr elimintion pthwys cn be negted. The (E1cb) ip nd internl return mechnisms were ruled out by the observed generl bse ctlysis with the Brönsted β vlues rnging from 0.80 to 0.84 becuse these mechnisms would exhibit either specific bse ctlysis or Brönsted β vlues ner unity. 1,20,21 Hence, the most likely mechnism for this bimoleculr process is either E2 or E1cb. If the rection proceeds vi crbnion intermedite, the rte eqution cn be expressed s k obs = k 1 k 2 '[B]/(k -1 [BH + ]+k 2 ') (Scheme 1). 1,20,21 The (E1cb) R mechnism requires tht the first step must be reversible, i.e., k 1 [BH + ]>> k 2 ', nd the rte expression cn be simplified to k obs = k 1 k 2 '[B]/k 1 [BH + ]. This would predict tht the k obs should remin constnt regrdless of the buffer concentrtion becuse [B]/[BH + ] = 1.0 is mintined throughout the rection. Hence, the (E1cb) R mechnism is ruled out by the liner dependence of the k obs vlues on the bse concentrtion. On the other hnd, if the rections proceed by the (E1cb) irr mechnism, i.e., k 1 [BH + ] << k 2 ', the rte eqution should become k obs = k 1 k 2 '[B], which is kineticlly indistinguishble from the E2 mechnism. 1,20,21 The distinction between the two mechnisms hs been mde by the interction coefficients. The β nd β lg vlues remined lmost the sme within experimentl error regrdless of the bility of the leving groups nd the bse strength vrition (Tble 2 nd 3). The results cn be described by negligible p xy interction coefficient, p xy = β/ pk lg = βlg/ pk BH 0, which describes the interction between the bse ctlyst nd the leving group. The negligible p xy interction coefficient is consistent with the (E1cb) irr mechnism. 1,20,21 The chnge in the β nd β lg vlues cn be described by the More-O Frrell-Jencks digrm (Figure 3). On the More-O Frrell-Jencks digrm shown in Figure 3, chnge to better leving group will rise the energy of the top edge of the digrm. According to the Hmmond postulte, the trnsition stte on the horizontl coordinte will shift from A to B becuse there is no digonl chrcter. This would predict negligible chnge in β. 2 Similrly, stronger bse rises the energy of the right side of the digrm. The trnsition stte on the horizontl coordinte will then move towrd the right s depicted by shift from A to C, resulting in little chnge in β lg. 2 The negligible interction coefficients re inconsistent with the E2 mechnism for which p xy > 0 is expected but provide strong evidence for the (E1cb) irr mechnism. 1,20,21 Effect of the Leving Group on the Nitrile-Forming Trnsition Stte. Erlier it ws reported tht the elimintion rections of (E)-2,4-(NO 2 ) 2 C 6 H 3 CH=NOC(O)Ar (2) with Figure 3. Rection coordinte digrm for nitrile-forming elimintions. The trnsition sttes for elimintions from 1 nd 2 re indicted s A nd D, respectively. According to the Hmmond postulte, the effect of the chnge to better leving group on A is depicted by the shift from A to B, while the effects stronger bse on A re shown by the shifts from A to C, respectively. R 2 NH/R 2 NH 2 + proceeded vi cyclic trnsition stte. 15 Comprison of the trnsition stte prmeters for elimintions from (E)-2,4-(NO 2 ) 2 C 6 H 3 CH=NOC(O)C 6 H 4-4-NO 2 (2) nd (E)-2,4-(NO 2 ) 2 C 6 H 3 CH=NOC 6 H 4-4-NO 2 (1) revels tht there is lrge difference in the trnsition stte structures, despite the sme leving group pk vlues (Tble 4). The rte of elimintion incresed only slightly, but the β vlue incresed from 0.32 to 0.80, nd β lg vlue incresed from 0.30 to 0.42, respectively, by the chnge in the leving group from 4-nitrobezonte to 4-nitrophenoxide. This result indictes the trnsition stte for 1 is more sensitive to the bse nd leving group vritions. This outcome cn be ttributed to the structures of the leving groups. In the nitrile-forming trnsition stte from 2, the negtive chrge developed t the β-crbon cn be deloclized by the two oxygen toms of the benzote leving group nd stbilized by the intrmoleculr hydrogen bond s depicted in TS1. In contrst, such delocliztion is not possible in TS2. Therefore, Et 3 N-promoted elimintion from 1 should be more sensitive to chnge the leving group nd bse strength vritions, s observed. Scheme 1 Effect of Bse-Solvent. It is well estblished tht R 3 N- promoted elimintion from (E)-2,4-(NO 2 ) 2 C 6 H 3 CH=NOC 6 H 4-4-NO 2 in MeCN proceeds by n E2 mechnism. 18 When the bse-solvent system ws chnged to Et 3 N/Et 3 NH + -70 mol %
Elimintion, E1cb-like nd (E1cb) irr, Leving Group nd Bse-solvent Effect Bull. Koren Chem. Soc. 2013, Vol. 34, No. 4 1033 Tble 4. Trnsition stte prmeters for elimintions from (E)-2,4- (NO 2) 2C 6H 3CH=NOY promoted by bse in 70 mol % MeCN(q) Y = 4-nitrobenzoyl (2) Y = 4-nitrophenyl (1) Bse R 2NH b + /R 2NH 2 R 3N c /R 3NH + pk (YOH) 20.7 d,e 20.7 d,e rel. rte 0.6 1 β 0.32 ± 0.02 0.80 ± 0.03 β lg 0.30 ± 0.01 0.42 ± 0.01 Reference 15. b R 2NH = i-pr 2NH. c R 3N = Et 3N. d pk of the conjugted cid of leving group in MeCN. e Reference 19. Tble 5. Effect of the bse-solvent on the nitrile-forming elimintions from (E)-2,4-(NO 2) 2 C 6H 3CH=NOC 6H 4-4-NO 2 Bse-solvent R 3N-MeCN R 3N/R 3NH + -70 mol % MeCN(q) rel. rte b 1 0.5 β 0.86 ± 0.1 0.80 ± 0.03 β lg 0.46 ± 0.04 0.42 ± 0.01 Reference 18. b R 3N = Et 3N. MeCN(q), the elimintion mechnism chnged to (E1cb) irr s discussed bove. However, there is only modest chnge in the trnsition stte structures, despite the mechnism The rte of elimintion decresed by hlf with the bsesolvent vrition from Et 3 N-MeCN to Et 3 N/Et 3 NH + -70 mol % MeCN(q), indicting decresed bsicity in the queous medium. 22 The extent of the C β -H bond clevge nd N α - OAr bond rupture decresed by the sme vrition of the bse-solvent s reveled by the decrese in the β nd β lg vlues. This result cn redily be ttributed to solvent effect. If the prtil negtive chrge developed t the β- crbon is stbilized by solvtion in more protic 70 mol % MeCN(q), the trnsition stte should be less sensitive to the bse strength vrition. This would predict smller β vlue, s observed. In ddition, the negtive chrge should be trnsferred from the β-crbon towrd the α-nitrogen to form prtil triple bond nd to brek the N α -OAr bond. If smller mount of negtive chrge is trnsferred from the β- crbon, the extent of N α -OAr bond clevge should be smller too. Noteworthy is the smll chnge in the trnsition stte structure ccompnied by the rection mechnism In conclusion, we hve studied elimintion rections from (E)-2,4-(NO 2 ) 2 C 6 H 3 CH=NOC 6 H 3-2-X-4-NO 2 promoted by R 3 N/R 3 NH + -70 mol % MeCN(q). The elimintion rection mechnism chnged from E2 to (E1cb) irr by the chnge in the bse-solvent from R 3 N-MeCN to R 3 N/R 3 NH + -70 mol % MeCN(q). Noteworthy is the smll chnge in the trnsition stte structure ccompnied by the rection mechnism Experimentl Section Mterils. (E)-2,4-Dinitrobenzldehyde O-ryloximes 1 were vilble from previous investigtions. 18 Regent grde cetonitrile nd tertiry mine were frctionlly distilled from CH 2. The buffer solutions of R 3 N-R 3 NH + in 70 mol % MeCN(q) were prepred by dissolving n equivlent mount of R 3 N nd R 3 NH + Cl - in 70 mol % MeCN(q). In ll cses, the ionic strength ws mintined to 0.1 M with Bu 4 N + Br. Kinetic Studies. Rections of 1 with R 3 N/R 3 NH + in 70 mol % MeCN(q) were followed by monitoring the increse in the bsorbnce of the ryloxides t 400-434 nm with UV-vis spectrophotometer s described. 9 Product Studies. The product from the rection of 1 with Et 3 N/Et 3 NH + in 70 mol % MeCN(q) ws identified by using more concentrted solution s described previously. 18 A solution of 0.50 g (1.51 mmol) of 1 nd n excess mount of bse in the pproprite bse (10 ml) ws stirred for 7 h t room temperture. The solvent ws removed in vcuo nd the residue ws extrcted with CH 2 Cl 2 nd wshed thoroughly with wter until ll of the mine, mmonium slt, nd ryloxide were completely removed. The product ws 2,4-dinitrobenzonitrile with mp 104-106 C (lit. 23 mp 104-105 C). The yield of 2,4-dinitrobenzonitrile ws 96%. For ll rections, the yields of ryloxides s determined by compring the bsorbnce of the infinity bsorbnce of the smples from the kinetic studies with those for the uthentic ryloxides were in the rnge of 96-98%. Control Experiments. The stbilities of 1 were determined s reported erlier. 14,24 The solutions of 1 in MeCN were stble for t lest two dys when stored in the refrigertor. Acknowledgments. This work ws supported by the Pukyong Ntionl University Reserch Fund in 2012 (C-D- 2012-0548). Support Informtion Avilble. Observed rte constnts for elimintion from 1-e promoted by R 3 N/R 3 NH + in 70 mol % MeCN(q) nd plots of k obs vs bse concentrtion re vilble on request from the correspondence uthor (9 pges). e-mil: sypyun@pknu.c.kr. References 1. Gndler, J. R. The Chemistry of Double Bonded Functionl Groups; Pti, S., Ed.; John Wiley nd Sons: Chichester, 1989; Vol. 2, Prt 1, pp 734-797. 2. Jencks, W. P. Chem. Rev. 1985, 85, 511. 3. Gndler, J. R; Jencks, W. P. J. Am. Chem. Soc. 1982, 104, 1937. 4. Thibblin, A. J. Am. Chem. Soc. 1988, 110, 1582. 5. Thibblin, A. J. Am. Chem. Soc. 1989, 111, 5412. 6. Cho, B. R.; Pyun, S. Y. J. Am. Chem. Soc. 1991, 113, 3920. 7. Meng, Q.; Thibblin, A. J. Am. Chem. 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1034 Bull. Koren Chem. Soc. 2013, Vol. 34, No. 4 Bong Re Cho nd Sng Yong Pyun 14. Cho, B. R.; Cho, N. S.; Song, K. S.; Son, K. N.; Kim, Y. K. J. Org. Chem. 1998, 63, 3006. 15. Pyun, S. Y.; Cho, B. R. J. Org. Chem. 2008, 73, 9451. 16. Cho, B. R.; Pyun, S. Y. Bull. Koren Chem. Soc. 2010, 31, 1043. 17. Cho, B. R.; Ming Yoon, C. O.; Song, K. S. Tetrhedron Lett. 1995, 36, 3193. 18. Cho, B. R.; Ryu, E. M.; Pyun, S. Y. Bull. Koren Chem. Soc. 2012, 33, 2976. 19. Coetzee, J. F. Prog. Phys. Org. Chem. 1965, 4, 45. 20. Lowry, T. H.; Richrdson, K. S. Mechnism nd Theory in Orgnic Chemistry; Hrper nd Row: New York, 1987; () pp 214-218, (b) pp 591-616, (c) pp 640-644. 21. Sunders, W. H., Jr.; Cockerill, A. F. Mechnism of Elimintion Rections; Wiely: New York, 1973; pp 510-523. 22. Drgo, R. S.; Zoltewicz, J. A. J. Org. Chem. 1994, 59, 2824, nd references cited therein. 23. Dictionry of Orgnic Compounds; Mck Printing Co.: Eston, PA, 1982; Vol. 2, p 2258. 24. Cho, B. R.; Chung, H. S.; Pyun, S. Y. J. Org. Chem. 1999, 64, 8375.