Indian Journal of Chemistry Vol. 35A, November 1996, pp. 979-982

Notes

The lFER correlations for SN2 reactions to a great deal in understanding reaction mechan- of phenacyl bromide isms and throw light on the nature of transition 4 7 states. However, limited work has been done .5. on the application of LFER to reactions of phen- S John Winston, P Jayaprakash Rao* B Sethuram & TNavaneeth Rao acyl bromide. Here we report the reactions of Department of Chemistry, Osmania University, phenacyl bromide with a variety of , Hyderabad 500 007, India viz., CO}-, HCO;, OH-, CH3COO-, N;, SOi-, Received 15 March 1996; revised 1 May 1996 ph enoxide, imidazole, , and thiou- rea and discuss the correlation of rate data with The second order rate constants for the reaction of phenacyl bromide with a number of nucleophiles, viz., different LFERs.

COj-, HCOi, OH-, CH3COO-, N}-, SO~-, phenox- ide, imidazole, pyridine, aniline and thiourea have Experimental been measured in 60% acetone - 40% water(v/v) sol- Phenacyl bromide was prepared in the labora- vent medium at different temperatures. The correla- tory by standard procedure" and the purity was tion of the rate data with different linear free energy established by spectral and analytical data. All relations (LFER), viz., the Bronsted equation, the other compounds, viz., sodium carbonate, sodium Swain-Scott equation and the Edwards equation has bicarbonate, sodium hydroxide, sodium acetate, been attempted. The applicability of Bronsted equa- sodium azide, sodium sulphate, phenol, imidazole, tion and Swain-Scott equation has been found to be pyridine, aniline and thiourea were either of high- unsatisfactory and the reasons are discussed. The est purity or purified before use. All the reactions correlation with Edwards equation has been found to were carried in 60% acetone-40% water (v/v) me- be quite good as evidenced from the multiple regres- dium. The kinetics of most of the reactions were sion analysis of the data which yielded the values' a = followed by the volumetric procedure as reported 1.48 and ~ = 0.439 (R2 = 89.7%). The activation parameters for all the reactions have been calculated by Mishra et al.'. Wherever the volumetric proce- and presented. dure was unsuitable, the reactions were followed conductometrically using a DIGISUN conduc- tometer. In these experiments the reaction mix- Phenacyl halides differ from alkyl halides in hav- ture was taken in a double-walled glass container ing a carbonyl group adjacent to the methylene so that water at a given temperature could be cir- carbon bearing the halogen. The high reactivity of culated. The reaction vessel was covered with a phenacyl halides compared to simple alkyl halides stopper fitted with a conductivity cell (EUCO is due to the stabilization of SN2 transition states make). The reactions were followed by noting the by delocalization. This is believed to be caused by conductance of the solution at regular time inter- overlap of the orbital on the carbon atom, at vals. The conductance increases as the reaction which displacement takes place, with the rt-orbital proceeds due to the formation of bromide. All the of the carbonyl group. However, the enhanced reactions were run in duplicate and the rate con- reactivity of phenacyl bromide in nucleophilic stants were reproducible to within ± 5%. Simple substitution reactions has been attributed by For- and multiple regression analyses were carried out ster and Laird J to the combination of field and by the least squares method on a PCI AT 386 conjugative effects. Two types of mechanisms DX. have been proposed in the literature/ - 5 for the SN2 reactions involving phenacyl bromide-the Results and discussion first one is the normal direct displacement me- The bimolecular reactions of phenacyl bromide chanism without carbonyl participation and the and the various nucleophiles were carried out in second one is with carbonyl participation involv- 60% acetone-40% water (v/v) medium at ing a bridged transition state. It has also been 25,30,35 and 40°C. The reactions can be repre- pointed out that a saturated carbon and a carbo- sented by Eq. (1). nyl carbon show different orders of nucleophilic reactivities in SN2 reactions". It is well known that Y- + PhCOCH2Br --+ PhCOCtIz Y + linear free energy relations (LFER) complement Br- ... (1) 980 INDIAN J CHEM. SEe. A, NOVEMBER 1996 r )' Table I-Second order rate constants and activation parame- philes using the Bronsted equation". The Bronst- ters for the reaction of phenacyl bromide with various nucleo- ed equation is a quantitative relationship between philes rates and acid- equilibrium constants and it is [Phenacyl bromide] = 2.5 x 10-3 M; [] = 2.5 x the earliest known LFER. For general acid-base 10-3 M the Bronsted relationship may be ex- : 60% acetone - 40% water (vIv) pressed by Eq. (2). Nucleophile 103 k(M-1 S-I) !!.H" -!!.S# log kA- = j3 pKHA + C ... (2) (kJ mol-I)(JK-Imol-I) where kA - is the rate constant corresponding to 298 303 308 313 K the base A- and KHA is the dissociation constant of the conjugate acid HA. The parameter j3 nor- CO~- 603 853 1039 1378 39.0 ± 2.8 118 ±9.3 nco, 1.59 1.73 1.90 2.13 12.5 ± 0.92 256±3.0 mally has values between 0 and 1; a high value of OH:- 157 263 412 682 72.7 ± 1.4 16.1±4.6 j3 is associated with a large degree of proton CH3COO- 0.5830.857 1.19 1.77 54.2 ± 1.6 125 ± 5.3 transfer to the base and a low j3 value with little N- 61.7 3 101 170 263 73.0 ± 1.4 23.1 ±4.5 bond formation to the base at the transition state. S~- - 0.0240 We have attempted the Bronsted correlation in Phenoxide 650 878 1200 1900 52.1 ± 4.7 73.9 ± 15 our work and the plot of log kA - versus pKHA of Imidazole 4.596.025 7.51 10.4 38.9±2.4 159±7.9 Pyridine 3.62 4.85 6.66 8.53 42.3 ± 1.2 150±4.0 the nucleophiIes is shown in Fig. 1. It can be ob- Aniline 3.35 3.94 4.50 5.62 23.5 ± 2.1 213 ± 7;1 served that the correlation is not good and parti- Thiourea 378 580 830 1290 60.1 ± 1.9 51.3 ±6.2 cularly the points corresponding to OH-, N3- and thiourea are deviating a great deal. Leaving these three points when least squares analysis- is made, where Y- is a nucleophilic species. The second the result is: j3 = 0.532 with r = 0.960. The rea- order rate constants and the activation parameters sons for such an unsatisfactory correlation are for the reactions are presented in Table 1. The quite obvious. Firstly, the nucleophiles employed order of reactivity of the nucleophiles is found to in our study are not a series of closely related be: species. In fact, correlation of nucleophilic substi- phenoxide > CO~- > thiourea > OH-I> N3- tution reactions by the Bronsted equation has > imidazole > pyridine > aniline > HCO) > been argued to be restricted to families of rea-

CH3COO- > SO~-. gents having the same nucleophilic atom'". Secon- While discussing the factors determining nucle- dly, as pointed out earlier, substitutions at a car- ophilic reactivities, three important properties are bon atom depend not only on basicity but also on usually considered. These are basicity, polarizabil- the polarizability of the reagents. The reasons for ity and the presence of unshared pairs of elec- the large deviations observed in the case of OH-, trons on the atom adjacent to the nucleophilic. at- thiourea and N3- could be as follows. The OH - is om, called the alpha effect. Edwards and Pearson" have analysed large experimental data and found PhcnoaidcQ, 2- that different substrates show marked differences 5-0-- 0 Thiourea C03 with respect to susceptibuity toward basicity and polarizability. Substrates which resemble the pro- ton in having a high positive charge and low num- ,4·0 ber of electrons in the outer orbitals of the central ..go atom depend on basicity. Substrates with low pos- +: 3-0- o Imidazole itive charge and with electrons in the outer orbi- '" 00 Pyridine tals of the central atom depend on polarizability. Aniline

The reactivities of substrates of aliphatic tetrahe- 2·0 dral carbon, aromatic carbon and trivalent nitrog- en depend on both basicity and polarizability. It is interesting to discuss the reactivity of phenacyl, 1·0 bromide towards various nucleophiles in the light i of this background.

It is to be noted that basicity and nucleophilic- 6 I 10 12 14 16 ity are closely related because of the fact that sub- pKHA- stitution reactions are generalised acid-base reac- Fig. 1-Bronsted plot-plot of 5 + log k versus pKHA ([phenacyl tions. The rate data of several SN2 reactions have bromide] = 2.5 x 10-3 M, [nucleophile] = 2.5 x 10-3 M, been correlated with the basicities of the nucleo- T = 308 K) NOTES 981 known to undergo a high degree of solvation in hydroxylic II and this could result in its (I) 5 lower reactivity. Thiourea has a large polarizabil- Pheno.~ (I) Thiourea (I) _ ity compared to other nucleophiles and this might OH be the overweighing factor for its high reactivity 4 eventhough its basicity is negligibly small. N; has an electronegative atom (N) holding a pair of go electrons adjacent to the nucleophilic site and this :+: 3 on (I) probably leads to its enhanced reactivity, a phen- Pyridine (I) omenon called the alpha effect". (1)- Aniline (I) _ HC0 21-- 3 The applicability of Bronsted equation to nucle- CH3COO ophilic substitution reactions is in fact limited be- cause of the fundamental difference between nu- cJeophilicity and basicity. Basicity is a measure of the affinity of the nucleophile to bond to hydrog- (1)2- en, and some differences from its affinity towards OL- __ S_O~4__~ ~ ~~ 2 3 4 5 carbon may therefore be expected. In this connec- n_ tion the Swain-Scott equation (Eq. 3) might well be considered. Fig. 2-Swain-Scott plot-plot of 5 + log k versus n ([phenacyl bromide] = 2.5 x 10-3 M, [nucleophile] = 2.5 x 10-3 M, log (klk,)) = sn ... (3) T = 308 K) This is an LFER where k is the rate constant for the reaction of a given anion with the substrate, Nuc, + 2e - ~ 2 Nuc -. In Eq. (4), parameters a ko is the rate constant for the reaction of the same and B measure the sensitivity of the reaction to substrate with water, n is the nucleophilicity con- these nucleophilic parameters. Since H; measures stant, and s is the parameter characteristic of the proton basicity and En the electr~n-donation abi!- substrate which measures the susceptibility of the ity, the Edwards' treatment considers nucleophi- reaction rate to changes in the nucleophilic activ- licity as a combination of electron loss and elec- ity. Figure 2 represents the correlation of the rate tron-pair donation. data in our study with the nucleophilicity con- When the rate data in our study have been sub- stants of the various nucleophiles employed. It jected to multiple regression analysis as per. the. can be observed that the correlation is again un- Edwards equation (Eq. 4), the results obtamed satisfactory which suggests that a different set of n are: values may be required. The n values used here a = 1.48, B = 0439 with R2 = 89.7% (n = 7). are those defined by reaction with methyl bro- The currelation is quite satisfactory and the rel- mide and the fact that the correlation with these ative magnitudes of a and B suggest that the reac- values is poor clearly indicates that the carbonyl tions are very sensitive to changes in the ease of group of the phenacyl bromide may be directly or oxidation of the nucleophile compared to changes indirectly involved in the substitution process. in basicity. This type of result that the o.E; term A very useful equation that is discussed while rather than the BHn term mainly contributes to correlating the rate data of SN2 reactions is the the rate constant has been generally observed for I 2.13. Edwards equation This equation attempts to displacement reactions on saturated carbon 10. correlate the rate data with quite independent This could possibly be viewed as support to the properties, viz., the ability of the nucleophile to contention that SN2 reactions of phenacyl bro- be oxidized (electrode potential) and its ability to mide involve direct substitution on the methylene take up a proton(basicity). The Edwards equation carbon; however, the carbonyl group indirectly may be written as aids the reaction through one or more of the pos- log (klko) = a En + B H; ... (4) sible ways as pointed out earlier. where klko is the rate constant relative to water, En and H; are parameters characteristic of the nu- References cleophile. The values of H; and En are calculated 1 Forster W & Laird R M, J chem Sac, Perkin Trans II, using the equations (1982) 135. H; = pKa + 1.74 and En = f!! + 2.60 2 Rath R, Behera G B & Rout M K, Indian J Chern, 6 where pKa refers to the acid ionization constant (1968) 202. 3 Baker J W, Trans Faraday Sac, 37 (1941) 632. of the nucleophile and EJ to the standard elec- 4 Winston S J, Jayaprakash Rao P, Sethuram B & Nava- trode potential for the two-electron half reaction, neeth Rao T, Indian J Chern, 28 A (1989) 520. 982 INDIAN J CHEM. SEe. A, NOVEMBER 1996

5 Srinivasan C, Shunmugasundaram A & Arumugam N, J 9 Bronsted 1 N & Pederson K 1, Z phy Chern, 108 (1924) chem Sac, Perkin Trans JI, (1985) 17. 185. 6 Edwards J 0 & Pearson R G, J Arn chem Soc, 84 (1962) 10 Wells P R, Chern Rev, (1962) 171. 16. 7 Mishra P, Nayak P L & Rout M K, Indian J Chern, 11 11 Bell R P, Acid-base catalysis, (Clarendon press, Oxford) (1973)452. (1941) 92. 8 Blatt "A H, Organic synthesis, Vol n (Wiley, New York) 12 Edwards 1 0, JAm chern Soc, 76 (1954) 1540. (1943)480. 13 Edwards 1 0,1Am chem Soc, 78 (1956) 1819.