Indian Journal of Chemistry Vol. 45A, May 2006, pp. I 099- 1112

Is electrophilicity a kinetic or a thermodynamic concept?

P K Chattaraj"" *, U Sarkar", DR Roy", M Elango", R Parthasarathib & V Subramanian"·*

"Chemistry Department, Indian Institute of Technology. Kharagpur 721 302. India

bChe mical Laboratory, Central Leather Research In stitute, Adyar. Chennai 600 020, India

Email: pkc @c hem.iitkgp.erne t.in , subuchem @hotmail.com

Received 21 November 2005; accepted 20 March 2006

An understanding of the preci se nature of a chemical reac ti vity descripto r is of utmost interest to quantum chemists. An attempt has been made here to analyze whether the electrophilicity index is a re liable descriptor of the kinetic behavi our or not. Relative experimental rates of Friedel-Crafts benzylation, acetylation and benzoylation reactions correlate well with the corresponding calculated electrophilicity values. Chlorination o f various substituted ethylenes and nitration of toluene and chlorobenzene have been studied as representative examples of e lectrophilic addition and substitution reacti ons, respectively. The correlation is not very good although it improves drastically by re mov ing a few data points to show that the electrophilicity is a kinetic quantity with inherent thermodynamic information. The correlation between the experimental and the calculated activation energies is studied for some Markovnikov and anti-Markovnikov addition reac tio ns and it turns out to be reasonably well. Reaction e lectrophilicity, local e lec trophilicity and activation hardness are used together to provide a transparent picture of reactio n rates as well as the orientation of aromatic el ectrophilic substitution reactions. Ambiguity in the definition of the e lec trophilicity is hi ghli ghted.

Many of the organic reactions can be described in terms of the electro (nucleo) philic addition and substitution. These reactions have got large synthetic potentials and are most widely studied 1

-4

.

Traditionally, the electrophilicity is treated J.4 as a kinetic quantity, which explains the rate of a reaction through its correlation with activation energy or free energy of activation occasionally supplemented by thermodynamic stabilities of various species involved. On the other hand, the nucleophilicity and the basicity are often analyzed at par 1

.4, s ince both involve the amount of electron density present in it and its potential to donate that, although the former correlates with I:!.G+ (a kinetic quantity) and the latter with I:!.G, (an equilibrium or thermodynamic property) . Although, it has been known for a long time that the electrophilicity is a cardinal index of reactivity and selectivity, an acceptable definition of it was lacking. Based on the work of Maynard er a/. 5

, a theoretical definition of electrophilicity has been introduced recently by Parr et a/6

. It may be noted that Maynard et al. 5 and Parr et a/ .6 have prescribed the same definition of electrophilici ty through essentially kinetic (via correlation with reaction rates) and thermodynamic (in terms of the energetically favourable charge transfer processes) routes, respectively and hence it is expected that it will

contain both kinetic and thermodynamic information. This electrophilicity, however, does not correlate well with the electron affinity<' .

Density Functional Theory (DFT)7·8 has been quite

successful in providing theoretical background of popular qualitative chemical concepts. In this context, several reactivity descriptors have been proposed and used to analyze chemical reactivity and site se lectivity . Hardness , global softness. electronegativity and polarizability are the global reactivity descriptors widely used to understand the g lobal nature of molecules in terms of their stability and it is possible to gain knowledge about the react1v1ty of molecules. Atomic charges, Fukui functions (FF) and local softnesses are the local reactivity descriptors, which provide information about the site selectivity . In addition to these reactivity descriptors, Hard and Soft Acids and Bases (HSAB) principle has been employed in number of cases in analyzing both nucleophilicity and basic ity. which encapsulates both thermodynamic and kinetic properties of numerous molecules<J.JO_ A . hard (soft) nucleophile prefers to react with a hard (soft) electrophile for both kinetic and thermodYnamic considerations and for two species of comparable electronegativity values (same strengths of the acids/bases)9

"10

.

1100 INDIAN J CHEM . SEC A, MAY 2006

Zhou and Parr 11 have defined the activation hardness and investigated the electrophilic subst itution of aromatic compounds using that. It is expected that the electro (nucleo) philicity should have both kinetic and thermodynamic requirements. The main objective of the present work is to gain insights into the exact nature (kinetic or thermodynamic) of the electrophilicity index. Different types of Friedel-Crafts reactions like benzylation, acetylation and benzoylation are studied to correlate the ex peri mental rates of those reactions with the corresponding theoretical electrophilicity values. Reliability of calculated activation energies and the problems associated with the definition of electrophilicity for more than one species are also discussed . Chlorination of vanous substituted ethylenes and nitration of toluene and chlorobenzene are taken as the representati ve reactions encompassing the electrophilic addition and substitution, respectively .

Theoretical Various global and local reactivity descriptors used

in the present work are: Activation hardness: Zhou and Parr 11 have

proposed the activation hardness in accordance with the transition state (TS) theory. The activation hardness is defined as :

... (I)

where 11 + is the activation hardness , llR is the hardness

of the reactant and llTS is the hardness of the transition state. Zhou and Parr 11 have shown that smaller the activation hardness , the faster is the reaction.

One of the difficulties associated with the calculation of hardness of the reactants is that the hardness of the chemical species is not additive. The hardness of two chemical species, viz., A, the acceptor and D, the donor is calculated 11 by :

... (2)

where / 0 is the ionization potential of the donor and AA is the electron affinity of the acceptor.

Electrophilicity: Electrophilicity index (co) has been defined by Parr et a/.6 as:

0

J.F (J) =-

21] . .. (3)

In Eq. (3), )..l ==-(! + A)/2 and 11 == (1-A)/2 are the electronic chemical potential and the chemical hardness respectively, approximated in terms of the vertical ionization potential ([) and electron affinity (A). The electrophilicity is a descriptor of reactivity that allows a quantitative classification of the global electrophilic nature of a molecule within a relative scale and effectively is the power of a system to 'soak up ' electrons6

.

The local version of the electrophi licity index has been proposed by employing a resolution of identit/ 2

as:

... (4)

where fk is the Fukui function at atom k in a molecul e and (a=+,- and 0) represents local philic quantiti es describing nucleophilic, electrophilic and radical attacks, respectively. Since electrophilicity measures the energy change of an electrophile as it is saturated with electrons, it may be considered to be an additive parameter. This property of electrophilicity has been used here to define new reactivity quantities such as activation electrophilicity and reaction electrophilicity.

Activation electrophilicity: Consider the following chemical reaction:

A+B ---7 C+D ... (5)

Let coA, cos, coc and co0 be the global electrophilicity indexes of reactants A, B and products C, D respectively. Considering this reaction to proceed via a transition state, it is possible to define activation electrophilicity by:

. .. (6)

where coR= co A + cos. The corresponding activation energy is given by:

... (7)

where ER = EA + Es . coR and ER are the electrophilicity index and energy of reactants respectively , and coTs and ETS are the electrophilicity index and energy of the transi tion state, respectively.

Reaction electrophilicity: Reaction electrophilicity is defined as:

. .. (8)

CHAlTARAJ era/. : IS ELECTROPHILICITY A KI NETIC OR A THERMODYNAMIC CONCEPT? 1101

where COp = coc + coo. The corresponding reaction energy is given as :

... (9)

where Er = Ec + ED, and cop and £p are the electrophilicity index and energy of products, respectively .

For the reactions involvi ng more than one reactant or product , the definition of electrophilicity becomes ambiguous. We consider here some of the probable defi nitions. For a reaction of the type: A+B ----:) TS ----:) C+D we may define the electrophilicity of the reactant as:

w<1l =W +W

R A B ... (lOa)

W~2 ) = W A, if B is common for a series of A type

molecules ... (I Ob)

2 2 (.{) (3) = /J AB - X AB

R 277AB 2ryAB

I . +A where x,\li = mill max

2

I . -A and 17 = min max

AB 2

... (lOc)

. .. (lOd)

... ( lOe)

Three different types of electrophilicity for the products can also be defined accordingly.

Computational details General reaction scheme for all the reactions

considered in the study is presented in Scheme I . All the geometries of the molecules concerned are optimized in gas phase using Becke's three parameter hybrid density functional 13

, B3L YP/6-31 G* which includes both Hartree-Fock exchange and OFT exchange con·elation functionals 14"

15 ustng the Gaussian 98W 16 package. The minimum energy configurations of the reactants, intermediates and products and the saddle point nature of the transition states have been ensured with the help of the cotTesponding calculated vibrational frequencies. The reactants, intermediates and products are assoc iated with zero imaginary frequencies, whereas there is one imaginary frequency for each transition state. Reactivity descriptors like chemical hardness and elcctrophilicity index have been calculated usmg

standard working equations described earlier. AIM

analyses for the rr-complexes are carried out with the help of AIM 2000 software package 17

. The thermodynamic parameters for various reactions have been computed by the standard method impl emented in the Gaussian package 16

• Using the freq keyword, the free energies of vari ous reactions have been computed at T= 298. 15 K. From the calculated free energi es of the transition states ( GTs) and those of reactants (GR), the free energy of acti vation has been

obtained by the equation ilG+= GTS - GR. From the free energies of products (Gp) and the reactants (GR), the free energy of reacti on have been calculated using

the following equation ilG,=Gp-GR.

Results and Discussion

Friedel-Crafts reaction The general reaction scheme is depicted in

Scheme I . Optimized structures of all the molecules involved in the benzy lation, acetyl ation and benzoylation reactions studied here are given in

Fig. 1. Experimental rel ati ve rates ( R = :;:·:::·.:::, ) are

taken from the reported results 18 and are correlated with the calculated electrophilicity values. Table I presents the theoretical co values along with the experimental and calculated In (RR) values.

As we see in Table 2, the experimental In (RR) values for the benzylation, acetylation and benzoylation reactions are not very tightly correlated with thew values. However, the correlation improves significantly (R=0.914, 0.898, 0.992) once we neglect some of the points. Mainly, the nitro- and chloro­subst ituted compounds in the benzylation reactions and highly tluoro-substituted and crowded molecules in the benzoylation reactions exhibit differen t behavior than the rest. It may, however, be noted that there is no a p riori method known to judge those points causing the "discrepancies" and to provide a rati onale for that. Perhaps, it stems fro m the quali ty of the experi ments and/or the definition of e lectrophilicity (to especially take care of the kinetic aspects) and its method of calculation. The situation improves further if the reaction rates are correlated with both the global and the local electrophilicities. The corresponding regression equat ions are as fo llows:

Benzylation: Calculated In (RR ) =- 4.555w - 3.404w;(ITUX) + 14.586

R = 0.922, SD = 0.513 , N = 9

1102 INDIAN J CHEM. SEC A. MAY 2006

Benzylation

R, R, R, R. Rs . I H H N02 H H 2 F H H H H 3 H F H H H 4 H H F H H 5 Cl H H H H 6 H Cl H H H 7 H H Cl H H 8 H H H H H 9 CH, H H H H 10 H CH, H H H II H H CH, H H 12 CH, H CH, H CH, 13 OCH, ..H H H H 14 H OCH, H H H 15 H H OCH, H H 16 OCH, CH, OCH, CH, OCH,

Acetylation Benzoylation

R, R, 0 R, R, R, R. Rs I F H I F F F F F 2 F OCH, 2 N02 H NO, H H 3 Cl CH, R, 3 H N02 H N02 H 4 Cl C2Hs 4 H H N02 H H 5 Cl CH(CH,), 5 F H H F H 6 Cl CH2CI 6 H H H H H 7 Cl CHCI, 7 H H CH, H H

8 H H F H H 9 CH, H CH, H CH, 10 H H OCH, H H

Addition of chlorine to alkenes Cl

Cl I . Cl Cl )' TS2 Cl H H R Cl TS1

H-f-1-R H*R -.H++R CI-CI + >==< -- I -- --H I R H H R H H H ~. H Cl

H H Intermediate Cl

Nitration oftoluene/chlorobenzene (only ortho nitration iJ shown)

R R R o-,o, I &'o, . TS 1 TS 2 .

0 + NO~ - - + H30

~ t H~O #

RzCI , CH 3 ( HONO ~ + H 250 4 ) a-complex

Scheme ;

Acetvlation: Calculated In (RR) =- 0.436cv

+ 0.776W~( Ilnx ' + 4.999

It is not always easy to gather the experimental rates and reaction energies of several reactions to come to a definite conclusion. In order to bypass this problem, we propose to calculate the activation and reaction energies of some reactions. For gaining confidence we first calcu late the activation energies of some Markovnikov and anti-Markovn ikov addition reactions of hydrogen halides to alkenes whose experimental activation energies are knov•n 20

. Table 3 presents the activation and reaction energies as well as the experimental activation energies obtained from a synchrotron radiation experiment211

• A linear correlation of R=0.970 between the experimental and the theoretical activation energies provides confidence

R = 0.919. SD = 0.151, N= 5

Benzoylation: Calcu lated In (RR ) = - 0 .244cv

- 0.862 (Jjklrrux) + 6.678

R = 0.997, SD = 0.072, N = 7

This may allow us to consider the electrophil icity as a kinetic quantity and may be used in estimating the rate of a chemical reaction and consequently the associated Hammett constant and the nucleus independent chemical shift, wherever applicable 19

•

CHATIARAJ el al.: IS ELECTROPHILICIT Y A KJ NETIC OR A TH ERMO DYN AMIC CONCEPT? 1103

Ben::ylution

1

5

9

13

Acetylation

5

2

~) ... ,

:f!J .. . '···= . "' o~

6

10

14

.·_,.}

3

7

~~~­~

11

15

' .. , __ /~:r+·.-. ~ '-< .) ~ . . (,

o~-.,

0= ·~) ·:, =-:-- .. .

.

8

12

.ql ··~ -. ft . ! . 2 3 ~~

6 7

Fig. I ~- Optimized structures o f all the molec ules involved in the Fri ede l-Crafts benzylation, acetylation and benzoy lation reactio ns considered in the study- Conrd.

1104 INDIAN J CHEM, SEC A, MAY 2006

Benzoylation

2 3 4

5 6 7 8

10

Fig. I (Co111d) - Optimi zed structures of all the molecules invol ved in the Friedel-Crafts benzy lat ion. acety lati on and benzoy lation reactions considered in the study.

Table I - Theoretical electrophilicity (w), ca lculated In (RR) and experimental In (RR) values associated with the Friedel-Crafts benzy lation, acetylati on and ben zoy lation reactions

Molecules w (eY) Calculated Experimental Molecules w (eY) Ca lculated Experimenta l ln(RR)" ln(RR) ln (RR)" ln(RR)

Benzylation Acetylation I 5.369 0.2 13 0.9 16 I 2.887 4.465 3.544 2 2.581 2.5 11 1.569 2 2.377 4.576 4.868 3 2.628 2.472 1.526 3 3.073 4.425 4.949

4 2.412 2.650 2.1 63 4 3.03 1 4.434 4.49 1

5 2. 180 2.841 1.526 5 2.92 1 4.458 4.436

6 2.753 2.369 1.856 6 4.289 4.161 4.359

- 7 4.722 4.067 3.940 7 2.726 2.391 1.825 Benzoylation 8 2.396 2.664 1. 84 1 I 5.047 4.445 2.779 9 1.742 3.203 2.950 2 7.540 3.37 1 3.367 10 2.307 2.737 2.054 3 7.280 3.483 3.66 1 II 2.250 2.783 3.367 4 6.9 17 3.639 3.951

12 2. 198 2.826 3.666 5 4.795 4.554 4.566

13 2.086 2.91 8 4.099 6 4.277 4.777 5.034

14 2.111 2.898 2.580 7 4.065 4.868 5. 102 8 4.353 4.744 5.1 36

15 1.945 3.035 4.575 9 2.803 5.4 12 5.278 16 2.09 1 2.9 15 4.9 13 10 3.68 1 5.034 5.451

"Calculated ln(RR) = 4.63765-0.82405 *w for benzy lati on; Ca lculated ln(RR) = 5.09156-0.21697 *w for acetylation; Calculated ln(RR) = 6.6 1966-0.43089*w for benzoy lation

CHA TT ARAJ eta!.: IS ELECTROPHILICITY A KINETIC OR A THERMODYNAMIC CONCEPT? ll 05

Table 2- The correlations between the experimental ln(RR) and calculated e lectrophili city values (eV) for the benzylation, acetylation and benzoylation reactions considered in the study

Axi s With all the points X y N R Regression equation

co Exp ln(RR)" 16 -0.560 Y= (4.638) + (-0.824) X

co Exp ln(RR)b 7 -0.37 1 Y = (5.092) + ( -0.2 I 7) X

co Exp ln(RR)c 10 -0.752 Y= (6.620) + (-0.43 1) X

"Benzylation, b Acetylation, cBenzoylation

Table 3 - Calculated activation and reaction energies and experimental activation energies of Markovnikovm and anti ­Markovnikov" addition of hydrogen halides to alkenes. All the values are in kcal/mol

Reactants Et E, (Exp.) £ *

Ethene:HF 38.3 -23.05 49.1

Ethene:HCI 34.0 -24.59 39.7

Ethene:HBr 28.8 -28.04 35.9

"Propene:HF 41.3 -19 .20 50.5

"Propene:HCI 35.8 -20.95 41.3

"Propene :HBr 30.0 -25.97 34.5

mPropene:HF 34.2 -23.68 44.0

mPropene:HCI 27.7 -23. 19 34.5

"'Propene:HBr 21.4 -29.32 28.8

"2- Methyl Propene: HF 43.7 -16.38 52.8

"2- Methyl Propene:HCI 37. 1 -17.74 41.7

"2- Methyl Propene:HBr 30.5 -23 .60 36.3

m2- Methyl Propene:HF 30.9 -23.58 39.2

m2- Methyl Propene:HCI 22.4 -21.27 28.5

m2- Methyl Propene:HBr 14.1 -29.96 23.9

and helps us to proceed further with the corresponding theoretical quantities for the following reactions. The associated regression equation is:

Thea. (Activation Energy)= 6.659 + 1.022 x Expt. (Activation Energy)

R = 0.970, SD = 2.072, N = 15

Chlorination of various substituted ethylenes

In chlorination of various substituted ethylenes, chlorine acts as an electrophile and n-electrons of the substituted ethylene are the nucleophile and the gas phase reaction proceeds via a cyclic chloronium bridged ion 1.4. The substituted ethylene and chlorine form a n-complex before forming the transition state. The n-electrons attack the chlorine and displace a chlorine ion to form a cationic cyclic chloronium ion as an intermediate. This step proceeds via a transition state that involves breaking of the Cl-Cl bond as well as breaking then-bond in the substituted ethylene in a

With the neglect of some points N R Regression equation

9

5

7

-0.914

-0.898

-0.992

Y= (16.308) + (-5.804) X

Y= (5.463) + (-0.301 ) X

Y= (7. 189) + ( -0.488) X

concerted manner. Formation of chloronium ion is the slow and the rate-determining step. Therefore, the transition state formed in the rate-determining step is of much interest in calculating activation quantities.

Figure 2 presents the structures and selected bond lengths for these transition states. Chlorine (Ch) and substituted ethylenes (CH2CHR) are the reactants. Final anti product is the product considered for calculating reaction quantities. Various substituents on ethylene influence the rate of electrophilic addition to it. It is well known that electron-withdrawing substituents decrease the reactivity whereas electron­donating ones increase the reactivity.

In the present study, the existence of a weak complex between substituted ethylenes and Cl2 have been analyzed with the help of an atoms-in-molecule (AIM) approach developed by Bader and his group21

by locating the critical points at which the gradient of electron density vanishes . The topographical features, i. e. the presence of bond critical points between the C atom and Ch, the value of the electron density at the bond critical points ( p(~) ) and the Laplacian of the

electron density at the bond critical points (\72 p(~))

have revealed the existence of weak complexes before the formation of the transition state. The calculated p(~. ), \72 p(~) and the BSSE corrected interaction

energy (E1m) for various n complexes are shown in Table 4.

The calculated p(~. ) and \72 p(~) values are

correlated with the BSSE corrected interaction energy calculated using the following formula,

Interaction energy correlated well with p(~) and

\72 p(~) with R values of 0.952 and 0.987

respectively. Among all the substituted ethylenes studied, the NOz- and NO-substituents are the most deactivating systems towards an electrophilic addition reaction. For these two cases, the n-complex formation with C[z was not observed.

1106 INDIAN J CHEM, SEC A, MAY 2006

- •. 3.453 I\ ....

2.217 I \ 2.213 •' ••

·~ 'Cl, 1.441 ·=

}

-NHOH

- 3.101 1.142 1 11 . .;;• ••

~-~ .COF

.CH,

· - 3.411 2.122 I 1 2.1; •••

P. f ' · :· .

. .()H

-NHNH,

.CN

·--~ .. ~ 1.893 I 11.916

91·~. :(;. 1..at"·

• - 1-H.S. 1.939 1 \ 1.!113

I '

.COOH

-- ~-,1~8 1.950 I 1 2.029

~ .CHO

.CCH

-NH,

- - ~-11!,1_ 1.!11)9 I \ 1.123

-~ -H

- l.465 ~,' \2.1~; - -~0

o ::-0' 1.442

.CHCH,

Fig. 2- Tran sition state structures and selected bond lengths fo r the chlor inatio n reactio ns considered in the present study (bond leng ths in A).

Table 4 - Electron density ( p( ~ ) ), lap lac ian of the electron

density (V2 p(~)) and BSSE corrected inte raction energy (E; 111 )

for all the n-complexes observed 111 chlorination of variou s substituted e thy lenes

-R

-NH 2

-NHNH2

-O H

-NHOH

-CH,

-C HCH2

-H

-CCH

-CHO

-COOH

-COF

-CN

0.045

0.046

0.029

0.043

0.022

0.023

0.019

0.018

0.014

0.014

0.012

0.012

0.022

0.022

0.019

0.022

0.016

0.016

0.015

0.014

0.011

0.011

0.009

0.010

E;nt

(kcal!mo l)

-60.6

-60.4

-52.4

-59.9

-43.5

-44.1

-31.7

-37.9

-24.6

-25.4

-19.7

-21.8

In order to verify whether e lectrophilicity is a kinetic or a thermodynamic quantity, the activation energy (£+), reaction energy (£,), activation free energy (L'lG :f:) and_ free energy of reaction (L'lG,) are calculated and reported in Table 5. Electrophilicity (w) values of the reactant, the transition state and the product are presented in Table 6 . The resu lts of their correlations with various kinetic and thermodynamic quantities (reported in Table 4) are provided in Table 7 . It is observed that the electrophilicity does not correlate well with all the thermodynamic and the kinetic quantities. However, the correlation improves substantially by neglecting some odd points. Possible linear free energy relationships may also be obtained.

The inter correlation patterns between the kinetic and thermodynamjc sets are also attempted and from the R values (0.869 for E, vs E* and 0.858 for L'lG, vs L'lG+), it becomes transparent that they themselves correlate to some extent among each other.

CHAIT ARAJ eta!.: IS ELECTROPHILICITY A KINETIC OR A THERMODYNAMIC CONCEPT'~ 1107

Using Eqs (I), (6) and (8), activation hardness (11 *), activation electrophilicity (ffi+) and reaction electrophilicity (ffi,) are calculated and they are presented in Table 8. £ * is a predictor of relative rates and it is a kinetic quantity and any other quantity that con-elates well with £ * and t.G+ can BE considered as a kinetic quantity . Hence, an attempt has been made to correlate ffi, and ffi :J: with £ * and t.G+. The poss ible relationships between various quantities with ffi, are given in Table 9. In order to derive information about

the nature of n'. the poss ible linear regress ion with£* and t.G* is also at tempted and are provided in Table 9.

Table 5- Calculated ac ti vati on energy(£"), reaction energy (£,), activation free energy (1'1Ct) and free energy of reaction (1'1C,.) va lues for all the chlorination reactions considered in the study. A lithe values are in kcal/mol

-R £+ £ ,. 1'1Ct 1'1C,.

-NH2 18.6 -49.4 28.8 -36.1

-NHNH2 18.2 -50.8 28. 1 -37.3

-OH 28.0 -49.4 37.9 -35.8

-NHOH 19.9 -50.9 29.7 -37.4

-CH3 32. 1 -49.5 41.0 -35.9

-C HCH 2 33.7 -43.2 42.9 -30.2

-H 36.2 -51.2 45.8 -38 .3

-CC H 38.9 -4 1.2 47.9 -28 .2

-CHO 43.6 -42.9 52.9 -29.9

-COOH 43 .9 -41.6 53.3 -28.6

-NO 47.0 -40.1 56.1 -27.6

-COF 48.4 -39.4 57.8 -26 .6

-CN 49.1 -38.7 57.9 -25.8

-N02 51.1 -40.7 60.6 -27.8

It is evident from Table 9 that reaction electrophilicity exhibits a reasonable linear relationship with £,, £ +, t.G, and t.G*. A drastic improvement is noticed by omitting a few points. It is noticeable that ffi, correlates well with most of the quantities and the reby confirming that L0 1 contains both thermodynamic and kinetic information. However, ffi t does not show any reasonabl e linear relationship with these quantities. It deserves a careful scrutiny. It may be noted that the R values for the plots of£, and t.G, versus ffi, are approximately 0.81 while that of the plots of £ * and t.G+ versus ffi, are roughly 0.89 which confirms the additional thermodynamic information content of ffi,. Similarly,

11 + shows good linear relationship with £ * and t.G+. The R values suggest that the activation hardness is

essentially a kinetic parameter. Therefore, LO, and 11 * together will provide important insights into the thermodynamic and kinetic aspects of any reaction.

Nitration of toluene and chlorobenzene In an electrophilic aromatic substitution reaction.

the e lectrophile replaces a proton from the ortlw, 111 eta or para pos ition or another Lewi s acid leaving group from the ipso position. The electrophile in the nitration reactions is the nitronium ion (N02+) formed via reaction of HN03 and H2S04 . The reac tion 1.

4

proceeds through any of the three possible

intermediates, viz. two types of n-complexes and a CJ­

complex, called a benzenium ion . All of these intermediates are stable species as vindicated by their NMR spectra. It has been long be lieved that the transition states (late) associated with electrophilic

Table 6- Calcu lated electrophi lic ity values of the reactants ( w~ ' . w~2 ' and w~' ' ), the TS (W(TS)) and the product (w(P)) for a lithe

chlorination reactions considered in the study (all the values in eY)

-R (1)0) W L!) w"' w(TS) w(P) R R R

-NH 2 8.876 0.600 0.394 11 .754 2.213

-NHNH2 9.11 3 0.837 0.417 12.483 2.402

-OH 9 093 0.818 0.545 13.735 2.336 - 110H 9.562 1.287 0.532 13.481 2.680

-CH1 9.476 1.200 0.729 11.499 2.203

-CHCH2 10.359 2.084 0.588 17.543 2.630

-H 9.740 1.464 0.844 7.921 2.212

-CCH 10.527 2.252 0.671 19.709 2.808

-CHO 12.093 3.8 17 0.781 17. 152 3.874

-COOH 11 .504 3.229 0.916 14.265 3.221

-NO 14.197 5.921 0561 25.576 6.782

-COF 12.352 4.076 I. Ill 17.420 3.98 1

-CN 11.764 3.488 0.998 2 1.846 3.632

-N02 13.486 5.210 1.043 19.090 5.391

1108 INDIAN J CHEM, SEC A, MAY 2006

Table 7 -The correlations of various quantities for the chlorination reactions considered in the present study

Axis With all the Eoints With the neglect of some Eoints X y N R Regression equation N R Regression equation

w/> E, 14 0.838 Y= (-70.939) + (2.393) X 9 0.941 Y= (-81.692) + (3.567) X WR(2) E, 14 0.838 Y= (-51.133) + (2.394) X 9 0.951 Y= (-53.056) + (3.666) X WR(JJ E, 14 0.619 Y= (-54.399) + (13.090) X 9 0.962 Y= (-58.062) + (17 .630) X WR(I) Et 14 0.873 Y= (-28.050) + (5 .924) X 10 0.946 Y= (-17.635) + (5.266) X WR(21 E* 14 0.873 Y= (20.978) + (5 .925) X 10 0.946 Y= (25.94:1) + (5.266) X WRO) e 14 0.832 Y= (6.128) + (41.748) X 13 0.936 Y= (1.443 ) + (46.290) X WR(II L'.G, 14 0.823 Y= (-56.067) + (2.23 1) X 9 0.942 Y= (-66.295) + (3.354) X WR(2) L'.G, 14 0.823 Y= (-37.604) + (2.231) X 9 0.942 Y= (-38.538) + (3.354) X WR(J) t.G, 14 0.616 Y= (-40.756) + (12.349) X 9 0.962 Y= (-44.151) + (16.636) X WR(I) L'.G t 14 0.876 Y= (-17.326) + (5.805) X 10 0.950 Y= (-8.089) + (5.243) X WR( 2) t.G* 14 0.877 Y= (30.716) + (5.806) X 10 0.950 Y= (35.305) + (5.244) X WR(3) t.G* 14 0.834 Y= (16.18) + (40.888) X 13 0.938 Y= (11.620) + (45.308) X

w(TS) E, 14 0.848 Y= (-59 .086) + (0.886) X 10 0.965 Y= (-65 .224) + (1.235) X w(TS) Et 14 0.648 Y= (10.619) + (1.612) X 9 0.917 Y= (-20.865) + (3.332) X w(TS) t.G, 14 0.844 Y= ( -45.238) + (0.841) X 11 0.952 Y= (-48.600) + ( 1.034) X w(TS) t.G* 14 0.643 Y= (20.873) + ( 1.560) X 9 0.909 Y= (-9.406) + {3.2 13) X w(P) E, 14 0.689 Y= (-53 .203) + (2.496) X 10 0.912 Y= (-64.655) + (6.351) X w(P) E* 14 0.698 Y= (16.414) + (6.017) X 9 0.895 Y= (11.456) + (9.325) X w(P) L'.G, 14 0.673 Y= (-39.509) + (2.324) X 10 0.907 Y= (-50.614) + (6.069) X w( P) t.G* 14 0.702 Y= (26.215) + (5.904) X 9 0.901 Y= (21.03B) + (9.226) X

Table 8 - Calcu lated activation electrophilicity ( w '<' 1 , w ' 121

, w '<JJ ). reaction electrophilicity ( w!' 1, w~21 , w!31

) and ac tivation hardness

( 171 ) of all the chlorination reactions considered in the study. "All the values are in eV

-R w '< 'J w '(2) w '(3) w~l) w!2) (1)~ 31 111

-NH2 2.879 10.761 11.361 -6.662 1.613 1.819 -0.158 -NHNH2 3.369 11 .228 12.065 -6.711 1.565 1.985 -0.081 -OH 4.641 12.37 1 13.189 -6.757 1.518 1.791 0.282 -NHOH 3.919 11.662 12.949 -6.882 1.393 2.148 0.173 -CH3 2.023 9.570 10.770 -7 .273 1.003 1.474 0.696 -CHCH2 7.184 14.871 16.955 -7 .729 0.546 2.042 0.529 -H -1.819 5.612 7.076 -7.528 0.748 1.368 0.655 -CCH 9.182 16.787 19.039 -7.719 0.556 2.137 0.711 -CHO 5.059 12.554 16.371 -8.219 0.057 3.093 0.832 -COOH 2.761 10. 120 13.349 -8.283 -0.008 2.305 1.048 -NO 11.379 19.094 25.015 -7.415 0.861 6.221 0.538 -COF 5.068 12.234 16.3 10 -8.371 -0.095 2.870 1.464 -CN 10.082 17.360 20.848 -8.132 0.144 2.634 1.325 -N02 5.604 12.837 18.047 -8.095 0.181 4.348 1.343

a cv:l.1.3l =Wp -(()~1. 2.3) ; W t( i. 2.3) =WTS -w~I. 2.J)

Table 9- The correlations of various quantities for the chlorination reactions considered in the present study

Axis With all the Eoints With the neglect of some points X y N R Regression equation N R Regression equation

w <'i E, 14 -0.817 Y= (-93.697) + (-6.454) X 12 -0.929 Y= (-94.626) + (-6.581) X w:(2) E, 14 -0.817 Y= (-40.278) + (-6.456) X 12 -0.930 Y= (-40.159) + (-6.583) X w,<J> Er 14 0.608 Y= (-50.909) + (2.310) X 9 0.926 Y= (-63.684) + (9.195) X w<' i E+ 14 -0.893 Y= (-90.201) + (-16.747) X 12 -0.960 Y= (-104.634) + (-18.441) X w:(2) Et 14 -0.892 Y= (48.397) + (-16.749) X 11 -0.971 Y= (46.845) + (-17.642) X w (3) Et 14 0.581 Y= (22 .771) + (5.240) X 10 0.768 Y= (-14.564) + (21.377) X r w <'> t.G, 14 -0.812 Y= (-77.763) + (-6.080) X 12 -0.929 Y= (-78.452) + (-6.185) X

r? w,<-> L'.G, 14 -0.812 Y= (-27.440) + (-6.082) X 12 -0.929 Y= (-27 .264) + (-6.187) X w (3) L'.Gr 14 0.593 Y= (-37.345) + (2.134) X 9 0.926 Y= (-49.823) + (8.834) X r w <'> t.G+ 14 -0.892 Y= (-77.631) + (-16.332) X 11 -0.973 Y= (-86.389) + (- 17.200) X w'(2) t.G+ 14 -0.891 Y= (57.526) + (-16.333) X 11 -0.973 Y= (55.953) + (-17 .201) X r w,m t.G+ 14 0.585 Y= (32.424) + (5.154) X 8 0.854 Y= (-14.824) + (26.911) X

T] :;: E* 14 0.915 Y= (22.340) + (20.949) X !l* L'.Gt 14 0.914 Y= (32.104) + (20.441) X

CHATIARAJ eta/.: IS ELECTROPHILICITY A KINETIC OR A THERMODYNAMIC CONCEPT? 1109

aromatic substitutions resemble the a-complexes more than the two types of n-complexes and the formation of the a-complex is the rate determining step in most cases and is irreversible for all practical purposes in many reactions. This leads to the general

' rules governing these reactions' as: (a) Electron donating (-I) groups increase the rates (activated by stabilizing the TS for the a-complex formation) and direct the electrophile predominantly to the ortho- or the para-positions; and, (b) Electron withdrawing (+I)

groups decrease the rates (deactivate by destabilizing the TS for the a-complex formation) and direct the electrophiles predominantly to the meta-positions. Of course, the resonance effects ( ± M) of the substituents are also to be considered in understanding their effects on rates. It may be noted that in other text books3

.4, electron donating and withdrawing effects are designated as (+1, +M) and (-1,-M) respectively. At high temperature, all groups show preferences towards the meta-positions mainly because of

Nitration olchlorohen=ene

1 "!~ 203 :~!-201 --- .... .201 .--·""'''' .:lot

O-TS1

~1 .220 1.211

M-TS1

M-o~ompl ..

P-TS1

Y'· i .

'

"

P-o-complea

1.10~. -21 1 - - '.212 ; .

i ., '

Nitration of toluene

1 .5t~-21 1 . 1 -~'-.212 ,<"'"'12 _

0. )_· . ....,"':"- .212

J I!

·'-d~- I - ,·.

4 O-TS1 M-TS1 P-TS1

0 -o-complea M-o~omplea

Fi g. 3 - Optimized structures of various transition states TS I and a-complexes associaied wiih the nitration of toluene and ch lorobenzene (bond lengths in A).

Table I 0 - Electrophilicity va lues (W) of different spec ies in vo lved in the nitration o f to luene and chlo robenzene

Toluene w(eV) Ch lorobenzene w(eV)

a-N itration o-TS I +OH- 11.928 o-TS I + OH- 14.688

o-cr-complex + OH' 9.849 o -cr-complex + OH- 13.995

o-TS2 +Or-r -0.062 o-TS2 + 011 0.523

o-P + H20 -23.893 o- P + H20 -22 .866

m-N itrati on m-TSI + OH- 14.205 111-TS I + OH- 21.887

111 -cr-complex + OH- 11 .457 111-cr-complex + OH- 17.447

m-TS2 + OH- 0.418 111 -TS2 + OH- 2.093

m-P + H20 -23.80 1 111-P + H20 -23.538

p-Nitration p -TS I + OH- 9.680 p-TSI + OH- 11.960

p-cr-complex + OH- 8.68 1 p-cr-complex + OH- 10.523

p-TS2 + OH- 0.112 p-TS2 + OH- 1.772

p -P + H20 -23 .872 p-P + H20 -23 .628

1110 INDIAN J CHEM, SEC A, MAY 2006

thermodynamic control. It is expected that the reactions are effectively kinetically controlled at the temperature (298.15 K) in which the free energies are calculated. Partial rate factors are argued l A to be better descriptors of the substituent effects on rates than their relative rates. Both -CH 3 and -CI groups are ortho- and para-directing although the former is activating (-1) and the latter is deactivating (+I) but havi ng pronounced resonance effects . Various transition states and a-complexes associated with the nitration of toluene and ch lorobenzene are presented in Fig. 3. Table 10 reports the electrophi licity values of all the species involved in these reactions. Their relative energies and electrophi licities are provided respective ly in Figs 4 and 5. It is important to note that the transition states and the intermediates are always more electrophil ic than the reactants and the products.

Table 11 presents CD, £, CD+, E+ and 11 + of these species . It is clear from the £+ values that both -CH 3

and -CI wi ll be o-p directing. Although, the f/+ values properly take care of -CH3, it fai ls in case of -Cl. In case of intramolecu lar reactivity, CD, does not correlate well with £ * which may be due to the fact that the reactant is the same in al l cases. However, CD, (like£+)

0 .5 0 5

va lues of the m-products are larger than those of the o-p products in both cases.

The philicity ( w; ) values of toluene and

chlorobenzene are reported in Table 12. They clearly reveal that both -CH3 and -CI are o-p directing and are found to be better descriptors of orientation of aromatic e1ectrophi lic substitutions than r{ The respective Fukui functions will suffice in case the intramolecular reactiv ity is considered . A preliminary report of this work is avai lable in reference 22.

Conclusions In order to test the potential of the electrophilicity

as a descriptor of the ki netic characteristics, Friedei­Crafts benzylation, acetylation and benzoy lation reactions, electrophi lic addition to various substituted ethy lenes and electrophilic aromatic substitution reactions in toluene and chlorobenzcne are studied. It has been observed that if a few systems are neglected the electrophi licity correlates very well with the experimental rates and hence is essentially a kinetic concept, but it has also inherited an adequate amount of thermodynamic informat ion due to their intercorrelations. Different ways of defining electrophi licity for reactants and products are

OS

o-N it roC h lorobe nzene m -N ltro Chlorobe nze ne p7N it roC hloro ben zene

0 .4 " 0 .4

O.J 0 .3 " 0.2 0 .2 0 .2

0.1 0 .1 01

! 0.0 0 .0 0 .0

R TSt <J -CpX TS2 p R TS 1 <J -CpX TS2 p R TS1 a-cpx TS2 p Ill ;;. -0 .1 -01 -0 .1

>-

f 0 .4 o-N itro T olu en e.---------' " m -NitroToluene

" p-NitroToluene • ·----------i •• 0! ... • Q:

02 " 02

• 1 0 .1 0 .1

•• 0 .0 •• R TS1 a-cpx TS2 p R TSt a-cpx TS2 p R TSt <J-cpx TS2 p

-01 -<l1 -0 .1

Reaction co-ord inate Reaction coo rdinate Reaction co o rdinate

Fig . 4 - Relative energies of various reactants. transit ion states, products and a -complexes associated with the nitration of toluene and ch lorobenzene (Here cpx =complex) .

CHATIARAJ eta/.: IS ELECTROPHILICITY A KINETIC OR A THERMODYNAMIC CONCEPT'J I 111

> .!. ~

> .!. 8

" .p-N ~tr~C h lorobe nzene~. o-N itroChlorobenzene m -N itroCh lorobe nze ne

" " > " > .!. .!. . I

" 2 2

" I

1 HNO , • C nlorobenz~ne 1 HN O • C l'llorot!e nune 1 HN O, • Chletobenz e ne .I ,, 2 T$1 + OH 2 TSI • 01-4 2 TS1 • OH

3 n-comptex + OH ,, l,.cornptu• OH " ),.c:ornptu • OH

. 1 4 TS2 + OH • f$2 • OH <I T$2 • OH

5 H ~O • o-Chlorobflnzene S H 0 • m·Chtorob enzene 5 H,O + p-Chl0100enze ne

~ '

R eact ton coorden ate Reactron coordmate Rea ctto n coordtn ale

" o-N itrotoluene m-N itrotoluene ., p-Nitrote luene .. ,, "

-. I / I "

'' I

> .!. >

" 8 "

.!. " 1 HNO J • To lue ne

2 ·A 1 HNO , • To luene '1 HNO _, +Toluene

2 TS1 + OH 2TS1•0H _;! · ·· 2TS 1 •0H

" 3 11-comptex • 0 H

\ 10 3 a-complex + OH

3 o-comple :J + O H 4TS2+0H 4TS2 • 0 H

5 H 0 • m-NrtroTolue ne 4 TS2 + OH

5 H:O • o-Nrtr oToluene 5 H :O + p-NrltoTotuene

Reactron coo rdma te Reactmn coordtnate Reactton coordtnate

Fig. 5- Electrophilic ities of various reactants, transition states. products and a-compl exes associated with the nitration of tol uene and chlorobenzene.

,,

j • /

Table II - Calcul ated reaction electrophilici ty (w,) , reaction energy (£,.) . activation electrophilicity (Wt). activation energy (£t ) and activation hardness (11; ) of various nitrotoluenes and nitrochlorobenzenes

Species w, £, (kcal/mol) w" £+ (kcal/mol) ll t (eY) (eY) (eY)

o-N itrotoluene -0.304 -0.029 -0.110 0.472 0.052 m-Nitrotoluene -0.212 -0.033 -1.764 1.525 0. 125 p-N itrotoluene -0.282 -0.033 0.016 0.244 0.0 18 o-Nitrochlorobenzene -0.415 -O.OI8 -1.629 1.203 0.107 m-Nitroch lorobenzcne 0.05 1 -0.029 9.350 8.720 -0.389 p- Nitrochlorobenzene -0.039 -0.030 -0.574 0.698 0.072

Table 12 -Calculated cv; values (eY) of toluene and chloroben zene

Toluene Chlorobenzene 0.461 0.439

~ 2 0.000 ·~ 2 0. 180 I 3 0.438 I 3 0. 103

~- .:.~-• -~~ 4 0.108 ' 4 0.508 i 5 0.098 .:{~- .:¥~ 5 0.103

. I I . 6 0.146 lJJ 6 0.180 ,:

7 0.156 7 0.437

·4/~ " '31" 8 0.000 '• ,,

8 0.000 3 ' ~ 9 0.000 ~- -~~ 9 0.000 f: 10 0.000 t .• / ?jj 10 0.000

~ ' 1:;) 11 0.026 l II 0.000

~ I 12 0.012 '21 I2 0.000

~ 13 0.008 14 0.043 15 0.000

,, "

·-1112 INDIAN J CHEM, SEC A, MAY 2006

discussed. A linear correlation between the experimental and the calculated activation energies for some Markovnikov and anti-Markovnikov addition of hydrogen halides to alkenes are observed. Reaction electrophilicity complements activation hardness concept in understanding the rates of the electrophilic addition and substitution reactions and to some extent the stability of the associated products as well. Philicity also adequately describes the orientation of electrophilic aromatic substitution reactions.

Acknowledgements We thank CSIR, New Delhi, for financial support

and Prof. A Basak and Prof. D Mal for helpful discussions.

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Phys Chem, 98 (1994) 11623. 16 Gaussian 98, Revision A.5, Frisch M J, Trucks G W &

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22 Chattaraj P K, Sarkar U, El ango M, Parthasarathi R & Subramanian V, Los Ala. Nat. Lab., Preprint Archive, Chem Phys, (2005), 1-38, arXiv: physics/0509089. See also Meneses L, Fuentealba P & Contreras R.. Tetrahedron, 61 (2005) 831 for a related work.