Cyril A. Grob died in his home in Basel (Switzerland) on December 15, 2003 at the age of 86. He was born in London (UK) to Swiss parents, studied chemistry at the Eidgenössische Technische Hochschule Zürich (ETH Zürich), and completed his PhD in 1943 under the guidance of Leopold Ruzicka (Nobel Prize in Chemistry 1939) on artificial steroidal antigens. He then moved to Basel to work with Taddeus Reichstein first at the pharmaceutical institute and from 1947 at the organic chemistry institute of the university, where he moved up the academic career ladder to become the director of the institute and holder of the chair there as Reichstein's successor in 1960. He retained this function until he was given emeritus status in 1987. Initially Grob's research focused mainly on natural products, with synthetic studies on biotin, lysergic acid, and the steroid framework. He also completed an elegant synthesis of sphingosin. A research stay with Saul Winstein at the University of California, Los Angeles (1951/52) gave him the critical impetus: After his return to Basel he dedicated himself more and more to the elucidation of reaction mechanisms and structure–reactivity relationships. An investigation of the reductive elimination of bromine from 1,4-dibromides in the presence of zinc led in 1955 to the recognition of heterolytic fragmentation as a general reaction principle.1 The structural and stereochemical prerequisites for a fragmentation to occur were investigated with model compounds, and the fundamental mechanisms of this reaction type were elucidated.2 The heterolytic fragmentation has now entered textbooks under the name of its discoverer. These studies also led to the elucidation of the mechanism of the Beckmann rearrangement. Experimental evidence for vinyl cations as discrete reactive intermediates was also first provided by Grob.3 The inductive substituent effect occupied Grob for many years. Substituted quinuclidines were chosen as model compounds, as they bear the polar functional groups at a clearly defined distance from basic or protonated nitrogen atoms as a result of their rigid molecular framework. Through the exact measurement of protonation equilibria a large number of substituent inductivity constants were determined.41 In solvolytic reactions intermediate carbon-centered cations often undergo rearrangement of the carbon framework with the transfer of charge to neighboring centers. These reactions do proceed via a nonclassic intermediate or transition state, in which a carbon atom is formally bonded to five other atoms. Whether a charge transfer occurs prior to the complete displacement of the leaving group or in a subsequent elementary step was highly controversial for a long time. Grob saw an answer in the determination of the so-called inductivity; that is, the sensitivity of the rate of the ionization process on neighboring substituents. These substituents should influence the incipient charge transfer in the transition state through their inductive effect. A kinetic study showed that the nature of the transition depends on the individual reaction. Only in exceptional cases, for example, for the notorious norbornyl cation, does the nonclassic structure seem to be more stable than one with a localized charge.5 This result was compared in 1983 in a “symposium in print” with the reports by H. C. Brown and G. A. Olah, who had approached this question from different angles with a similar result. As C. Walling, the “arbitrator”, observed, this publication settled peacefully a long and intense controversy.6 Except in kinetic studies, Grob was a forerunner in the field of physical organic chemistry in continental Europe. Students and colleagues at the university and in his working environment profited considerably from this role of his. As a lecturer he had the ability to present complex concepts in a simple, clear, and precise way, and to convince his audience through well thought out arguments. He allowed his numerous co-workers much freedom, but always gave them good advice at the right time. Cyril Grob never acted impulsively, but always calmly and deliberately. He never sought attention in public, but fulfilled his social duties efficiently, reliably, and without a fuss. In this way as dean he directed the affairs of the faculty for a year and presided over the Swiss Chemical Society during a two-year term. With his scientific success came frequent invitations to almost all countries in Europe, as well as the USA and other parts of the world. He always prized these trips very highly as recognition of his scientific achievements. In public Cyril Grob was reserved and he did not particularly enjoy socializing. Only in intimate circles did he shine as a relaxed, witty, cultured, and kind person. However, his scientific interests always came first, not only in his professional but also in his private life.

Angewandte ChemieVolume 116, Issue 34 p. 4492-4492 Nachruf Cyril A. Grob (1917–2003): Fragmentierung und Induktivität Peter Schiess, Peter Schiess pschiess@bluewin.ch Universität BaselSearch for more papers by this author Peter Schiess, Peter Schiess pschiess@bluewin.ch Universität BaselSearch for more papers by this author First published: 25 August 2004 https://doi.org/10.1002/ange.200461144Citations: 2Read the full textAboutPDF ToolsRequest permissionAdd to favorites ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume116, Issue34August 27, 2004Pages 4492-4492 This is the German version of Angewandte Chemie. Note for articles published since 1962: Do not cite this version alone. Take me to the International Edition version with citable page numbers, DOI, and citation export. We apologize for the inconvenience. RelatedInformation

AbstractDie aus den Benzocyclobutenonen 3 und 4 thermisch oder photochemisch erzeugten ortho‐chinoiden Vinylketene 12 und 13 gehen mit dem substituierten Benzochinon 14 eine Cycloaddition zu den isomeren Tetracyclen 15, 16, 19 und 20 ein, die zu den 10‐Desoxydaunomycinon‐Derivaten 23 und 24 oxidiert werden. Eine analoge Cycloaddition der aus den Benzocyclobutendionen 9–11 photochemisch erzeugten Bisketene mit dem enantiomerenreinen AB‐Baustein 29 führt in nur zwei Schritten zu den optisch aktiven, symmetrisch substituierten Daunomycinonen 33–35.

Flash vacuum pyrolysis has been used to prepare a variety of differently substituted derivatives of the benzocyclobutene ring system starting with simple precursors. An analytical gas flow reactor is described which simulates reaction conditions of flash vacuum pyrolysis experiments. This reactor allows to optimise reaction conditions and to obtain structure reactivity correlations for thermolytic gas phase reactions.

Bis(cyclobuta-η6-benzene)metal complexes of chromium(0) (4), molybdenum(0) (14) and tungsten(0) (15) as well as bis([1,2:4,5]-dicyclobuta-η6-benzene)chromium(0) (5) have been prepared by metal atom ligand vapor cocondensation techniques. The 1H NMR coordination shift &δ for the endo- and exo-protons of the cyclobutene ring are discussed in the context of anisotropic shielding in the periphery of bis(η6-arene)chromium. The ESR spectra of the chromium centered radical cations 4+ and 5+ are also reported. In conjunction with hyperfine coupling data for (η12-[2.2]paracyclophane)chromium+ (16+), which also possesses monitor protons at defined positions, and for bis(η6-paraxylene)chromium+ (17+), containing freely rotating methyl groups, the contributions of conformation dependent, and conformation independent pathways of metal ligand electron-spin transfer are assessed.

Bis(cyclobuta-η6-benzene)metal complexes of chromium(0) (4), molybdenum(0) (14) and tungsten(0) (15) as well as bis([1,2:4,5]-dicyclobuta-η6-benzene)chromium(0) (5) have been prepared by metal atom ligand vapor cocondensation techniques. The 1H NMR coordination shift &δ for the endo- and exo-protons of the cyclobutene ring are discussed in the context of anisotropic shielding in the periphery of bis(η6-arene)chromium. The ESR spectra of the chromium centered radical cations 4+ and 5+ are also reported. In conjunction with hyperfine coupling data for (η12-[2.2]paracyclophane)chromium+ (16+), which also possesses monitor protons at defined positions, and for bis(η6-paraxylene)chromium+ (17+), containing freely rotating methyl groups, the contributions of conformation dependent, and conformation independent pathways of metal ligand electron-spin transfer are assessed.

Nicht nur einfache, sondern auch komplizierter gebaute organische Verbindungen reagieren unter den Bedingungen der Gasphasen-Kurzzeitthermolyse, das heisst beim kurzzeitigen Erhitzen auf 300 bis 800°C unter vermindertem Druck, zu einheitlichen Produkten. Die Möglichkeiten und Grenzen dieses präparativ nutzbaren Verfahrens werden dargelegt unter speziellem Hinweis auf die Unterschiede zwischen der Reaktionsweise in der Gasphase und in Lösung. Anwendungen der Thermolysemethode zur Herstellung vielfältig substituierter Derivate des Benzocyclobuten-Ringsystems im präparativen Maßstab stehen im Brennpunkt dieses Fortschrittsberichtes.

Bei der Behandlung mit einer Kalium‐Natrium‐Legierung erhält man aus Benzocyclobuten (I) in Tetrahydrofuran über Zwischenstufen die Folgeprodukte (II)‐(V).

Benzocyclobutene is cleaved by sodium-potassium alloy in THF at a C aryl -CH 2 bond whereby in contrast to the corresponding reaction with lithium a dimeric product, 1-ethyl-9,10-dihydrophenanthrene, is formed.

Angewandte ChemieVolume 95, Issue 3 p. 248-251 Zuschrift Unerwartete Ringöffnung von Benzocyclobutenen bei der Umsetzung mit Lithium in Tetrahydrofuran Prof. Dr. Adalbert Maercker, Prof. Dr. Adalbert Maercker Institut für Organische Chemie der Universität Adolf-Reichwein-Straße, D-5900 Siegen 21Search for more papers by this authorWilli Berkulin, Willi Berkulin Institut für Organische Chemie der Universität Adolf-Reichwein-Straße, D-5900 Siegen 21Search for more papers by this authorProf. Dr. Peter Schiess, Prof. Dr. Peter Schiess Institut für Organische Chemie der Universität St.-Johanns-Ring 19, CH-4056 Basel (Schweiz)Search for more papers by this author Prof. Dr. Adalbert Maercker, Prof. Dr. Adalbert Maercker Institut für Organische Chemie der Universität Adolf-Reichwein-Straße, D-5900 Siegen 21Search for more papers by this authorWilli Berkulin, Willi Berkulin Institut für Organische Chemie der Universität Adolf-Reichwein-Straße, D-5900 Siegen 21Search for more papers by this authorProf. Dr. Peter Schiess, Prof. Dr. Peter Schiess Institut für Organische Chemie der Universität St.-Johanns-Ring 19, CH-4056 Basel (Schweiz)Search for more papers by this author First published: März 1983 https://doi.org/10.1002/ange.19830950320Citations: 8AboutPDF ToolsRequest permissionAdd to favorites ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume95, Issue3März 1983Pages 248-251 This is the German version of Angewandte Chemie. Note for articles published since 1962: Do not cite this version alone. Take me to the International Edition version with citable page numbers, DOI, and citation export. We apologize for the inconvenience. RelatedInformation

Bei der Umsetzung von Benzocyclobuten (I) mit Lithium in (deuteriertem) Tetrahydrofuran (II) werden die Produkte (III)‐(VII) erhalten, deren Bildungsmechanismus diskutiert wird, u. a. durch analoge Umsetzung des Methyl‐Derivates (VIII).

On the Extent of Sigmatropic 1, 5‐Migration of Hydrocarbon Groups in the Thermolytic Skeletal Rearrangement of 5,5‐Disubstituted 1,3‐CyclohexadienesThe uncatalyzed skeletal isomerization of 5, 5‐disubstituted 1, 3‐cyclohexadienes was investigated with the aim to establish the extent to which sigmatropic 1,5‐shifts of hydrocarbon groups are participating in these reactions.Gas phase pyrolysis of 5,5‐diethyl‐1,3‐cyclohexadiene (7) at 460° followed by chloranil aromatization yields only 4% of 1,3‐diethylbenzene resulting from 7 through a 1, 5‐ethyl migration in the primary reaction step. 2, 3‐Dimethylethylbenzene (56%) and 1, 4‐diethylbenzene (4%) are obtained as other C10‐compounds. This shows that isomerization proceeds mainly through a sequence of electrocyclic and 1, 7‐shift reactions. Ethylbenzene (24%) and other aromatic C8‐ and C9‐hydrocarbons are formed to a considerable extent, indicating that C, C‐bond cleavage is a major competing process and that the 1, 3‐diethylbenzene found is the result of a radical recombination reaction and not of a concerted sigmatropic shift of the ethyl group.5‐Methyl‐5‐phenyl‐1, 3‐cyclohexadiene (12) yields 3‐methylbiphenyl (14) and biphenyl upon thermolysis and aromatization. Through 13C‐substitution of the methyl group in 12 it is shown that in solution at 300° skeletal isomerization proceeds through electrocyclic and 1, 7‐H‐shift reactions exclusively. In the gas phase at 500° 4% of the isomerization product is formed by a 1, 5‐shift of a substitutent, presumably of the methyl group, through a dissociative mechanism.Thermolysis of 5, 5‐diphenyl‐1, 3‐cyclohexadiene (22) at 560° in the gas phase leads to 1, 1‐diphenyl‐1, 3, 5‐hexatriene (23) and 1‐vinyl‐4‐phenyl‐1, 2‐dihydronaphthalene (24) through electrocyclic reaction steps. In addition a small amount of m‐terphenyl is obtained at high conversion of 22. This indicates that sigmatropic 1,5‐phenyl migration can participate in product formation only at high temperature and in the absence of other irreversible pathways to stable products.

Nach 94proz. Umsetzung des Esters (Ia) in der Gasphase bei 350‐500°C und 12 Torr enthält das Produktgemisch die Isomere (IIa)‐(Va) sowie das aromatisierte Produkt (VIa).

Uncatalyzed Sigmatropic 1,5‐Shift of Acyl Groups in the Thermolysis of 5‐Acyl‐5‐methyl‐1,3‐cyclohexadienes Four different 5‐acyl‐5‐methyl‐1,3‐cyclohexadienes 1a–d (R = COOCH 3 , COCH 3 , COC 6 H 5 , CHO) have been shown to yield mixtures of 1,3‐disubstituted cyclohexadienes 2–7 and 1,3‐disubstituted aromatic product 8 upon thermolysis at 150–300° in solution and at 350–500° in the gas phase in a flow system. Two reaction pathways (A and B in Scheme 2 ) are considered for the rearrangement of the C‐Skeleton. For the ester 1a 13 C‐isotopic substitution shows that products arise to 75–86% through a 1,5‐sigmatropic shift of the methoxycarbonyl group ( A in Scheme 2 ) and to 14–25% through a sequence of reaction steps involving a 1,7‐H‐shift reaction in an acyclic intermediate ( B in Scheme 2 ). For the more reactive compounds 1b–d isomerization is assumed to follow the 1,5‐sigmatropic pathway exclusively ( A in Scheme 2 ). A kinetic study yields the following sequence for the migration tendency of acyl groups toward sigmatropic 1,5‐shift: COOCH 3 < COCH 3 < COC 6 H 5 < CHO.

On the Fischer‐Indole Reaction. II. Thermal and Acid Catalysed Indolization of 1′‐Alkenyl‐2′‐methyl‐2′‐phenylacetohydrazidesSeven different 1′‐alkenyl‐2′‐methyl‐2′‐phenylacetohydrazides, 6a‐g, have been prepared by treatment of the methylphenylhydrazones 7 of appropriate ketones and aldehydes with acetyl chloride in pyridine. At 170° 6a‐g are transformed into the N‐methylindoles 3a‐g and acetamide in moderate yield. N‐Methylaniline is the other major reaction product indicating that homolytic cleavage of the weak N, N‐bond in 6 is a major primary reaction step. It is likely but not proven that the N‐methylindoles 3 are formed in a reaction sequence initiated by an uncatalysed concerted [3, 3]‐sigmatropic rearrangement.Upon treatment of 6 with 0.5N dichloroacetic acid in anhydrous acetonitrile at room temperature a quantitative conversion to 3 is observed, interpreted as proceeding by a charge induced [3, 3]‐sigmatropic rearrangement of protonated 6 in the rate determining step. The ketone derivatives 6a‐e (R1 = alkyl) react 40‐1000 times faster with acid than the aldehyde derivatives 6f and 6g (R1 = H). This is rationalized as a consequence of the increased basicity of 6a‐e relative to 6f and 6g caused by a steric effect.