Historical profile Organic pioneer Christopher Ingold’s insights into mechanism and reactivity established many of the principles of organic chemistry. John Ridd reveals more about his life and work ROYAL SOCIETY OF CHEMISTRY / LIBRARY AND INFORMATION CENTRE INFORMATION AND LIBRARY / CHEMISTRY OF SOCIETY ROYAL 50 | Chemistry World | December 2008 www.chemistryworld.org Sir Christopher Ingold in Glasgow on the preparation of During those years, there was In short fundamentally changed the gases for use in chemical warfare. another important, more personal approach of chemists to organic This was dangerous work for which Christopher Ingold development in Ingold’s life. In 1922 chemistry. Many have forgotten Ingold was awarded the British established some he published a paper with Edith what a strange and mysterious Empire Medal. He subsequently of the fundamental Hilda Usherwood on the specific subject organic chemistry appeared made no reference to the award or to mechanisms of organic heats of gases and, a year later, they to be in the days before reaction his work during the war. chemistry were married. His wife was herself mechanisms were revealed. Organic Possibly his most a talented chemist but, after a few chemistry is now viewed in a very Award-winning chemistry important work was years, she gave up her research and different way – based on firmly In 1920 Ingold returned to Imperial on the mechanism of supported her husband’s scientific established mechanistic principles College as a demonstrator with his substitution reactions career. – and, although many people have own research laboratory. It was the He described, for At Leeds, Ingold’s interests rapidly contributed to that change, almost beginning of a remarkably active the first time, the two turned to the nature of chemical all chemists would now accept that period of research: he published 12 different forms of bonding. Robert Robinson, who was Ingold was the predominant figure. papers in 1921, 16 papers in 1922, and nucleophilic substitution, then a professor at the University Although this account focuses on his 14 papers in 1923. Most of these dealt SN1 and SN2 of Manchester, UK, had recognised work in organic chemistry, Ingold with classical organic chemistry, His organic chemistry that the current discussions, in terms also made important contributions and some with physical chemistry, textbook soon became an of partial valency and chemical to spectroscopy and inorganic including specific heats and vapour essential reference affinity, lacked any common physical chemistry. pressures. basis and suggested that this could Ingold was born in London on Ingold’s impressive publication be found in the electronic theories 28 October 1893. His father, a silk record led to rapid movement up the of valency put forward by Thomson, merchant, was in very poor health academic ladder – he was promoted Lewis and Langmuir. with tuberculosis; it was for this to a lectureship, gained a DSc (doctor In his 1922 paper, Robinson used reason that the family moved to of science) degree and was awarded Arthur Lapworth’s description of the supposedly gentler climate of the first Meldola Medal in 1922 – an reagents as ‘kationoid’ and ‘anionoid’ Shanklin in the Isle of Wight. But award to commemorate Raphael but added what we would in modern his father died when Ingold was five Meldola, who was president of both terms call inductive and conjugative years old. the Society of Maccabaeans and electron shifts. There are even two After studying at the local school the Royal Institute of Chemistry. of the now common curly arrows to in Shanklin, Ingold moved to the new Remarkably, he was also awarded represent the movement of electrons secondary school at Sandown where a second Meldola Medal in 1923, in a conjugated system. he obtained a county scholarship to and was the only person ever to In his paper on tautomerism study at the new Hartley University receive two medals (the rules were in 1926, Ingold also interpreted College in Southampton. After subsequently changed to make it the results in terms of electron obtaining his BSc degree there, he impossible for an applicant to receive Ingold, Hughes and movements, this time making moved to Imperial College London more than one). In 1924, he was Ingold’s wife Hilda at extensive use of curly arrows. The and, in 1914, joined the research elected to fellowship of the Royal a UCL dinner marking paper contains one reference to group of Jocelyn Thorpe, a new Society and accepted the position Ingold’s receipt of the Robinson’s work published in the professor of organic chemistry. In of professor of chemistry at Leeds Longstaff medal from the same year, but was the start of the 1915, he was asked to carry out work University, UK. Chemical Society long-standing controversy between www.chemistryworld.org Chemistry World | December 2008 | 51 Historical profile Robinson and Ingold – Robinson and substituent effects. Robinson’s considered that insufficient bitterness over the way in which recognition had been given to his his presentation of the electronic earlier ideas. theory was supplanted by that of Ingold continued for the rest of his Opposing conventions life. In his autobiography, Robinson Ingold continued to develop the maintained that the electronic theory of electronic effects in theory was his most important organic chemistry, making a clear contribution to knowledge. distinction between polarisation and In August of 1930, Ingold moved polarisability effects and introducing from Leeds to a professorship at the concept of mesomerism University College London and – equivalent to the concept of remained there until his death 40 resonance between valence bond years later. In the same year, he ROYAL SOCIETY OF CHEMISTRY / LIBRARY AND INFORMATION CENTRE INFORMATION AND LIBRARY / CHEMISTRY OF SOCIETY ROYAL structures – as the permanent was joined by Ted Hughes, a young consequence of tautomeric electron postdoctoral worker who had just displacements in a molecule before taken his PhD with H B Watson at a reaction. Bangor. This was the start of a long Ingold’s terminology differs from collaboration which lasted until that of Robinson, and this is also Hughes’s death 33 years later. true of his description of reagents After arriving at University – Ingold used the terms electrophilic College, Ingold began kinetic and nucleophilic in place of and mechanistic studies. As with kationoid and anionoid on the basis his studies of substituent effects, that whether a reagent is electron- Ingold introduced a language attracting or electron-repelling is for mechanistic studies which not simply dependent on its charge. eventually became accepted. He The two scientists also disagreed first grouped organic reactions on the sign to be attached to according to the underlying substituent effects. Ingold electronic processes involved. Thus designated the effects of electron- the reactions of hydroxide ions and donating substituents as positive To write up their results, they had Sir Robert Robinson amines with alkyl halides together and those of electron-withdrawing to choose one or the other, and quite (above) was bitter that with the reactions of amines with substituents as negative. Shortly quickly Ingold’s approach became his electronic theory was alkyl ammonium ions were termed afterwards Robinson proposed the one generally accepted. One supplanted by Ingold’s ‘nucleophilic substitution at a the opposite sign convention. reason for the preference may have saturated carbon atom’ because, Ingold’s ideas were set out in his been that more people read Ingold’s although the reactions appear article in Chemical Reviews in article in Chemical Reviews than very different in the reagents and 1934 and Robinson set out his own read the reprints of Robinson’s charges, they all involve the attack alternative system in two lectures lectures at the Royal Institute of of a nucleophile and the departure published together by the Institute Chemistry. But perhaps the main of a leaving group with the bonding of Chemistry in 1932. reason is that much of Robinson’s electrons. So, in the early 1930s, chemists interest moved from electronic Ingold made a further distinction were faced with two versions of theories to what he considered by investigating the kinetics of an electronic theory of organic to be other major challenges these nucleophilic substitutions. chemistry with many similar – particularly biosynthesis – while He found two basic forms: in one, features but using a quite different Ingold maintained a rapid rate of the rate of the reaction depended terminology and sign convention. publication in the area of mechanism on the concentration of both the nucleophile and the organic molecule it was attacking. In the Substitution mechanisms other, however, increasing the Ingold described, for the first time, the two where a nucleophile attacks and a leaving group concentration of the nucleophile different forms of nucleophilic substitution SN1 departs simultaneously, always inverts the 3D made no difference to the reaction and SN2. arrangement of atoms neighbouring the reaction rate, which only depended on the This mechanistic distinction has an centre – rather like an umbrella turning inside out. concentration of organic substrate. important bearing on the stereochemistry of The SN1 reaction, however, can either invert or As Ingold worked out, that was the substitution. In two series of papers, Ingold retain the starting arrangement, since the planar because in the first kinetic