Physical organic chemistry Edited by John Murphy Generated on 24 September 2021, 10:07 Imprint Beilstein Journal of Organic Chemistry www.bjoc.org ISSN 1860-5397 Email: [email protected] The Beilstein Journal of Organic Chemistry is published by the Beilstein-Institut zur Förderung der Chemischen Wissenschaften. This thematic issue, published in the Beilstein Beilstein-Institut zur Förderung der Journal of Organic Chemistry, is copyright the Chemischen Wissenschaften Beilstein-Institut zur Förderung der Chemischen Trakehner Straße 7–9 Wissenschaften. The copyright of the individual 60487 Frankfurt am Main articles in this document is the property of their Germany respective authors, subject to a Creative www.beilstein-institut.de Commons Attribution (CC-BY) license. Physical organic chemistry John A. Murphy Editorial Open Access Address: Beilstein J. Org. Chem. 2010, 6, 1025. WestCHEM, Department of Pure and Applied Chemistry, University of doi:10.3762/bjoc.6.116 Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, U.K Received: 01 November 2010 Email: Accepted: 01 November 2010 John A. Murphy - [email protected] Published: 03 November 2010 Guest Editor: J. Murphy © 2010 Murphy; licensee Beilstein-Institut. License and terms: see end of document. Physical organic chemistry – the study of the interplay between I am privileged to act as Guest Editor for this Thematic Series structure and reactivity in organic molecules – underpins of the Beilstein Journal of Organic Chemistry, and hope that organic chemistry, and we cannot imagine organic chemistry as you enjoy the papers that form this issue. I am grateful to the a subject without knowledge of mechanism and reactivity. It is contributors for their contributions. sometimes thought that the golden age of ‘physical organic chemistry’ was in the 20th century, when systematic informa- John A. Murphy tion about mechanism first burst onto the scene. Certainly the impact of early knowledge of mechanism of fundamental ali- Glasgow, November 2010 phatic substitution reactions, among others, was enormous, but our knowledge of reactivity and mechanism has continued to progress and deepen enormously ever since and this has been License and Terms reflected in a number of Nobel Prizes in Chemistry. In an area This is an Open Access article under the terms of the of particular interest to me, the transformation of radical chem- Creative Commons Attribution License istry from being an almost impenetrable area to one that can be (http://creativecommons.org/licenses/by/2.0), which usefully harnessed even in synthetic applications, has been permits unrestricted use, distribution, and reproduction in extraordinary – this transformation has been relatively recent any medium, provided the original work is properly cited. and has been principally dependent on the accurate determin- ation of kinetics of radical reactions. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: Applications to complex reactions in biology, polymer chem- (http://www.beilstein-journals.org/bjoc) istry and electronic materials are ever more prevalent, and add to contributions in ‘small molecule’ chemistry. Novel experi- The definitive version of this article is the electronic one mental techniques combined with the revolution in computa- which can be found at: tional chemistry give new impetus to physical organic chem- doi:10.3762/bjoc.6.116 istry and contribute to its continuing importance, an importance that is reflected in the large number of international meetings in physical organic chemistry in the past two years. 1025 Structure and reactivity in neutral organic electron donors derived from 4-dimethylaminopyridine Jean Garnier1, Alan R. Kennedy1, Leonard E. A. Berlouis1, Andrew T. Turner2 and John A. Murphy*1 Full Research Paper Open Access Address: Beilstein J. Org. Chem. 2010, 6, No. 73. doi:10.3762/bjoc.6.73 1WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, U.K. and Received: 27 April 2010 2PR&D Laboratory Building, AstraZeneca, Silk Road Business Park, Accepted: 09 June 2010 Charterway, Macclesfield SK10 2NA, United Kingdom Published: 05 July 2010 Email: Guest Editor: J. Murphy Jean Garnier - [email protected]; Alan R. Kennedy - [email protected]; Leonard E. A. Berlouis - © 2010 Garnier et al; licensee Beilstein-Institut. [email protected]; Andrew T. Turner - License and terms: see end of document. [email protected]; John A. Murphy* - [email protected] * Corresponding author Keywords: dication; 4-DMAP; electron donor; electron transfer; radical cation; redox; reduction Abstract The effects on the redox properties of modifying the molecular skeleton of neutral bis-2-(4-dimethylamino)pyridinylidene electron donors, derived from 4-dimethylaminopyridine (4-DMAP), have been explored, by varying two parameters: (i) the length of a poly- methylene chain linking the two pyridine-derived rings and (ii) the nature of the nitrogen substituents on the 4 and 4′ positions of the precursor pyridines. Restricting the bridge length to two methylene units significantly altered the redox profile, while changes in the nitrogen-substituents at the 4 and 4′ positions led to only slight changes in the redox potentials. Introduction 1 2 Neutral organic compounds 1 and 4–10 (Figure 1) have valene (TTF, 1, E 1/2 = 0.37 V; E 1/2 = 0.67 V in DCM vs SCE) attracted considerable attention as ground-state electron donors [1], one of the weakest of these donors, reduces arene- [1-38], and many are now being employed as reagents in diazonium salts to aryl radicals [2-12], but is not strong enough organic transformations. Such a range of reagents with different to react with alkyl and aryl halides. The driving force for its redox potentials leads to the expectation of considerable oxidation is the attainment of some degree of aromaticity in the selectivity in their reductions of organic substrates, and evi- formation of its radical cation salt 2 on the loss of one electron, dence is steadily accumulating to support this. Tetrathiaful- and full aromaticity in its dication salt 3 on loss of two elec- Page 1 of 8 (page number not for citation purposes) Beilstein J. Org. Chem. 2010, 6, No. 73. Figure 1: Neutral organic electron donors 1 and 4–10. trons, as well as the stabilization of both the positive charge and to an aryl anion [39]. Whatever about the standard potentials, in radicals by the lone pairs on the sulfur atoms. The effect of practice, the formation of aryl anions is only observed when the aromatic stabilization is enhanced in the extended analogue 4; electron donor has E1/2 = −1 V or is more negative [40]. In line however, unlike TTF, this compound affords only an irrevers- with this, both the imidazole-derived donor 7 (E1/2 = −1.20 V vs ible oxidation Ep = −0.14 V in MeCN (assuming that the SCE in DMF) [22-25] and the 4-dimethylaminopyridine + reported value is measured relative to SHE, that would corres- (4-DMAP)-derived donor 8 [E1/2 (DMF) = −1.69 V vs Fc/Fc ] pond to −0.38 V vs SCE) [13]. Tetrakis-dimethylaminoethene [26-29], which would equate to −1.24 V vs SCE [E 1 2 (TDAE, 5: E 1/2 = −0.78 V; E 1/2 = −0.61 V vs SCE in MeCN) (DMF)Fc/Fc+ = 0.45 V vs SCE] [41] react with aryl iodides to is a stronger reducing agent and converts electron-deficient afford aryl anions. As an indication of their enhanced donor alkyl bromides to the corresponding anions [14-17] and notably properties, these two donors can also cleave appropriate arenes- − the iodide CF3–I to trifluoromethyl anion, CF3, [15] but is not ulfonamides [25], aryl alkyl sulfones [25,26], Weinreb amides powerful enough to react with aryl halides. Despite not experi- [28] and acyloin derivatives [29]. They are also prone to encing any aromatic stabilization on oxidation, the molecule is transfer two electrons rather than one, with the cyclic voltam- such a good donor as a result of the ability of the nitrogen atoms mogram (c.v.) of 8 showing a single 2-electron reversible redox in 5 to stabilize both the positive charge and an unpaired elec- wave [26] while in donor 7 the potentials of the successive elec- tron upon oxidation; this stabilization is greater than is afforded tron transfers are close enough that the c.v. gives the appear- by sulfur in TTF. ance of a single reversible peak, but has a slight shoulder [24]. Molecules 9 (E1/2 = −1.00 V vs SCE in DMF) [30-32] and 10 1 2 Benzimidazole-derived donor 6 (E 1/2 = −0.82 V; E 1/2 = [33,35,37] extend the range of designs of neutral organic elec- −0.76 V vs SCE in DMF) [18-20], combines the stabilization of tron donors, although we are not aware of them being investi- positive charge and of an unpaired electron provided by four gated as yet for the reduction of organic substrates. nitrogens, with aromatic stabilization in its oxidised forms. This exceptional donor has the power to reduce aryl iodides (E0 = In order to design both more potent electron donors, and donors −2.2 V) to aryl radicals, but not to aryl anions [21]. This is para- with calibrated and targeted properties, the factors that drive the doxical in view of the standard potential of the second step; E0 electron transfer(s) need to be clearly understood, and this paper = 0.05 V vs SCE in MeCN for the conversion of an aryl radical now probes two factors that could impact on that. Page 2 of 8 (page number not for citation purposes) Beilstein J. Org. Chem. 2010, 6, No. 73. Results and Discussion chain – a longer chain should afford greater flexibility and Donor 8 has a number of attractive features.