Nucleophilicity parameters for strong nucleophiles in dimethyl sulfoxide. A direct alternative to the s(E + N) equation T. William Bentley To cite this version: T. William Bentley. Nucleophilicity parameters for strong nucleophiles in dimethyl sulfoxide. A direct alternative to the s(E + N) equation. Journal of Physical Organic Chemistry, Wiley, 2011, 24 (4), pp.282. 10.1002/poc.1747. hal-00625939 HAL Id: hal-00625939 https://hal.archives-ouvertes.fr/hal-00625939 Submitted on 23 Sep 2011 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Journal of Physical Organic Chemistry Nucleophilicity parameters for strong nucleophiles in dimethyl sulfoxide. A direct alternative to the s(E + N) equation For Peer Review Journal: Journal of Physical Organic Chemistry Manuscript ID: POC-10-0063.R2 Wiley - Manuscript type: Research Article Date Submitted by the 30-Apr-2010 Author: Complete List of Authors: Bentley, T.; UW Swansea, Chemistry nucleophilicity scales, Swain-Scott equation, nucleophiles, Keywords: benzhydrylium cations, quinone methides http://mc.manuscriptcentral.com/poc Page 1 of 35 Journal of Physical Organic Chemistry 1 2 3 4 Nucleophilicity parameters for strong nucleophiles in dimethyl 5 6 sulfoxide. A direct alternative to the s(E + N) equation 7 8 9 10 11 12 T. William Bentley* 13 14 15 16 17 18 A scale of nucleophilicityFor Peer(N′′′) for relatively Review strong nucleophiles (e.g. carbanions 19 20 21 and amines), spanning over 5 orders of magnitude was constructed directly from 22 23 experimental rate constants for reactions of 34 nucleophiles with a benzhydrylium 24 25 + cation, (lil)2CH (log k = N′′′ in dimethyl sulfoxide at 20 ˚C). The equation log k = 26 27 28 (E′′′ + sEN′′′ +c), where E′′′ is an electrophilicity parameter, sE is a Swain-Scott type 29 30 of response parameter (to variation in nucleophilicity) for the electrophile, and c is a 31 32 residuals term, is used to correlate second order rate constants for reactions of 33 34 35 nucleophiles with other benzhydrylium cations, quinone methides (QM) and 36 37 Michael-acceptor electrophiles. Contrary to published claims (Mayr et al. Angew 38 39 40 Chem. Int. Edn. 2002, 41, 92, and later work), sE increases as the reactivity of the 41 42 QM decreases. The N′′′ scale was extended a further 3 orders of magnitude by an 43 44 extrapolation involving a QM electrophile. In contrast, published procedures 45 46 47 involve over 40 reference electrophiles and over 100 adjustable parameters obtained 48 49 from the equation log k = sN(E + N), where k is the rate constant, and sN is a 50 51 nucleophile parameter. Values of N – N′′′ in DMSO increase by 8 log units, as the 52 53 54 reactivity of the nucleophile increases, because N is a floating scale whereas N′′′ is a 55 56 fixed scale. 57 58 59 60 1 http://mc.manuscriptcentral.com/poc Journal of Physical Organic Chemistry Page 2 of 35 1 2 3 * Chemistry Unit, Grove Building, Swansea University, Singleton Park, Swansea SA2 4 5 6 8PP, Wales, UK 7 8 Email: [email protected] 9 10 11 12 13 KEYWORDS: nucleophilicity scales, Swain-Scott equation, nucleophiles, 14 15 benzhydrylium cations, quinone methides 16 17 18 For Peer Review 19 20 INTRODUCTION 21 22 23 24 25 26 The general equation (1) has recently been proposed to correlate logarithms of rate 27 28 constants (log k) at 20 ˚C for a huge range of reactions of electrophiles (electrophilicity E) 29 30 and nucleophiles (nucleophilicity N); in Eqn (1), s is referred to as a ‘nucleophile- 31 N 32 [1,2] 33 specific’ parameter and sE as an ‘electrophile-specific’ parameter. It is then assumed 34 35 that sE = 1 for many reactions, so ‘deriving’ Eqn (2) which had already been used in plots 36 37 38 of log k vs. E to evaluate values of sN (from slopes) and N (from the intercept on the 39 [3,4] 40 abscissa) for over 100 nucleophiles. 41 42 43 Originally[1-4] the symbol s was chosen for Eqn (2), but it is not the same as the s (or 44 45 [5] 46 sE) parameter in the well established Swain-Scott equation (3). Consequently sN is 47 48 more appropriate than s for Eqn (2). Equation (4) fits many cation – anion 49 50 recombinations,[6] and the absence of an response parameter is consistent with the 51 52 [1,2] 53 assumption that sE = 1. In Eqns (3) and (4), n or N+ quantify nucleophilicity, and k0 54 55 refers to a reference reaction, so relative rates are correlated. 56 57 58 59 60 2 http://mc.manuscriptcentral.com/poc Page 3 of 35 Journal of Physical Organic Chemistry 1 2 3 log k = s s (E + N) (1) 4 E N 5 6 log k = sN (E + N) (2) 7 8 log k/k0 = sn (3) 9 10 11 log k/k0 = N+ (4) 12 13 14 15 The question ‘How constant are Ritchie’s constant selectivity relationships’ was the 16 17 [7] 18 title of a recent Forpaper, concluding Peer that sEReview is constant if anomalous data for water are 19 20 excluded. Recognising this problem earlier, Ritchie proposed[6] that the reference 21 22 nucleophile (rate constant k0) be hydroxide, instead of water which was chosen in earlier 23 24 [8] [6] 25 work in line with Eqn (3). There are various N+ scales, and ideally the reference 26 27 electrophile should be specified when N+ correlations are reported. 28 29 Published work[3,4] on N scales uses values of E for a ‘basis set’ of 23 reference 30 31 32 electrophiles; the electrophilicities of seven benzhydrylium cations, ranging in values of E 33 34 from 0 to 6 were defined by rate constants for reactions with 2-methylpent-1-ene,[3] and 35 36 37 values of E down to -10 (along with N values for 38 nucleophiles) were then obtained by 38 [3] 39 a multi-parameter extrapolation procedure (MPC1, Scheme 1). Plots of log k vs. E for 40 41 individual nucleophiles then gave new values of N. This complex procedure (upper half 42 43 44 of Scheme 1) leads to a floating scale when sN ≠ 1, referring to dichloromethane (DCM) 45 46 as solvent at 20 ˚C: (i) which deviates from a fixed scale by 5 orders of magnitude; (ii) in 47 48 which none of the >200 parameters are defined by directly-determined experimental 49 50 [9] 51 data. 52 53 54 55 56 57 58 59 60 3 http://mc.manuscriptcentral.com/poc Journal of Physical Organic Chemistry Page 4 of 35 1 2 3 IN OUT 4 Experimental Calculated 5 Computation 6 kinetic data data 7 8 extrapolate k 9 define s = 1 E from 0 to 6 + Ar CH+ 10 2 define E = 0 11 at low temp 12 13 200 data points MPC1 38 N values 14 + 15 16 E values data for log k vs. E 16 individual plots 17 nucleophiles additional 18 For PeerN values Review 19 solvent changes from dichloromethane to DMSO 20 E values data for MPC2 of 1a - 1f 21 reaction of 22 2a - 2g (key 23 carbanions) E values of key with 1a - 1m quinone methides 24 1g - 1m 25 N values of 26 MPC3a key carbanions 27 data for various general types MPC3b 28 of electrophiles 29 MPC3c additional 30 E values 31 data for log k vs. E 32 individual 33 nucleophiles plots 34 additional 35 N values 36 37 38 39 40 Scheme 1. An outline of the data processing by multi-parameter correlations (MPC) and 41 42 log k vs. E plots, previously employed to obtain E and N values from Eqn (2); MPC1 is in 43 44 Reference [3] and MPC2 is based on References [11, 12]; there are 6 MPC3 correlations 45 46 47 (3a, 3b etc) in References [13 – 18] 48 49 50 51 An alternative design was reported recently;[9] two benzhydrylium cations were 52 53 54 chosen to define N′ and N′′ directly from experimental data (Eqns (5) and (6)), and the 55 56 57 58 59 60 4 http://mc.manuscriptcentral.com/poc Page 5 of 35 Journal of Physical Organic Chemistry 1 2 3 two fixed scales were linked by the formula N′ – N′′ = 6.6. To avoid complications from 4 5 [10] [9] 6 solvent effects, only kinetic data in DCM were evaluated. 7 8 9 10 11 log k = N′ for decay of 1n, at 20 ˚C (5) 12 13 log k = N′′ for decay of 1a, at 20 ˚C (6) 14 15 16 17 18 To furtherFor extend the Peer N scale to reactions Review of carbanions and other nucleophiles in 19 20 dimethyl sulfoxide (DMSO), six cations (1a – 1f) and seven quinone methides (QM, 1g – 21 22 1m) were chosen[11,12] as reference electrophiles (the codes 1a – 1m in Scheme 2 are the 23 24 [11] 25 same as in the key paper ). Kinetic data for reactions of these electrophiles with key 26 27 nucleophiles (Scheme 3) underwent another correlation (MPC2, Scheme 1), further 28 29 extrapolating the E scale from -10 to -18.[11] The derived N values were then the input for 30 31 [13- 32 MPC3a, MPC3b etc, characterising E values for other electrophiles from E = -8 to -23.