Crum Brown

Crum Brown s rule A guide to substitution in benzene derivatives. This rule states that a substance C Hj A yields the meia disubstituied product if the compound HA can be oxidized directly to HOA otherwise a mixture of the o-and p-compounds will be obtained. Not universally applicable.. Sec Hammick and Illingworth s rules. 

Hydrogen must be considered as a member of Group I in such cases as — CHO the hydrogen must be ignored and only the remaining element considered. See also Crum Brown s rule. 

The student when preparing disubstituted benzenes should bear in mind VorlSnder s Rules of aromatic substitution, which form the most convenient modification of Crum Brown s earlier rules. Vorl5nder stated that if a substance... 

Shortly after the tetravalent nature of carbon was proposed, extensions to the Kekule-Couper theory were made w7hen the possibility of multiple bonding between atoms was suggested. Emil Erlenmeyer proposed a carbon-carbon triple bond for acetylene, and Alexander Crum Brown proposed a carbon-carbon double bond for ethylene. In 1865, Kekule provided another major advance when he suggested that carbon chains can double back on themselves to form rings of atoms. 

Faraday, in 1834, was the first to encounter Kolbe-electrolysis, when he studied the electrolysis of an aqueous acetate solution [1], However, it was Kolbe, in 1849, who recognized the reaction and applied it to the synthesis of a number of hydrocarbons [2]. Thereby the name of the reaction originated. Later on Wurtz demonstrated that unsymmetrical coupling products could be prepared by coelectrolysis of two different alkanoates [3]. Difficulties in the coupling of dicarboxylic acids were overcome by Crum-Brown and Walker, when they electrolysed the half esters of the diacids instead [4]. This way a simple route to useful long chain l,n-dicarboxylic acids was developed. In some cases the Kolbe dimerization failed and alkenes, alcohols or esters became the main products. The formation of alcohols by anodic oxidation of carboxylates in water was called the Hofer-Moest reaction [5]. Further applications and limitations were afterwards foimd by Fichter [6]. Weedon extensively applied the Kolbe reaction to the synthesis of rare fatty acids and similar natural products [7]. Later on key features of the mechanism were worked out by Eberson [8] and Utley [9] from the point of view of organic chemists and by Conway [10] from the point of view of a physical chemist. In Germany [11], Russia [12], and Japan [13] Kolbe electrolysis of adipic halfesters has been scaled up to a technical process. 

Crum Brown A, Frazer TR. On the connection between chemical constitution and physiological action. Part I. On the physiological action of the salts of the ammonium bases, derived from strychnia, brucia, thebaia, codeia, morphia, and nicoti. Trans R Soc Edinburgh 1869 25 151-203. 

In 1868 two Scottish scientists, Crum Brown and Fraser [4] recognized that a relation exists between the physiological action of a substance and its chemical composition and constitution. That recognition was in effect the birth of the science that has come to be known as quantitative structure-activity relationship (QSAR) studies a QSAR is a mathematical equation that relates a biological or other property to structural and/or physicochemical properties of a series of (usually) related compounds. Shortly afterwards, Richardson [5] showed that the narcotic effect of primary aliphatic alcohols varied with their molecular weight, and in 1893 Richet [6] observed that the toxicities of a variety of simple polar chemicals such as alcohols, ethers, and ketones were inversely correlated with their aqueous solubilities. Probably the best known of the very early work in the field was that of Overton [7] and Meyer [8], who found that the narcotic effect of simple chemicals increased with their oil-water partition coefficient and postulated that this reflected the partitioning of a chemical between the aqueous exobiophase and a lipophilic receptor. This, as it turned out, was most prescient, for about 70% of published QSARs contain a term relating to partition coefficient [9]. 

If any two of the quantities a, b, c, d in Eq. (1) are equal, then 0=0. If the values of any two of them are interchanged, 0 changes sign. If a, b, c, d are identified with some property of the ligands, therefore, then is a chiral property of the molecule, and is thus a candidate for an approximate representation of the rotatory power. Crum Brown and Guye identified the quantities a, b, c, d with the masses of the ligands. 

With the exception of some unique symbols of William Higgins in 1789, generally, straight lines appeared in published chemical formulas only when Archibald Couper introduced them in 1858 to indicate valences (units of atomicity, saturation capacity, or quantivalence).77 Whereas innocent accent marks or superscript dashes had been used at midcentury to indicate valence or value, straight lines now suggested a less abstract meaning, despite disclaimers like Alexander Crum Brown s that the lines indicated the "chemical," not "physical," positions of atoms. 78... 

Practitioners of quantum chemistry employed both the visual imagery of nineteenth-century theoretical chemists like Kekule and Crum Brown and the abstract symbolism of twentieth-century mathematical physicists like Dirac and Schrodinger. Pauling s Nature of the Chemical Bond abounded in pictures of hexagons, tetrahedrons, spheres, and dumbbells. Mulliken s 1948 memoir on the theory of molecular orbitals included a list of 120 entries for symbols and words having exact definitions and usages in the new mathematical language of quantum chemistry. 

Dobbin, L., "Daniel Rutherford s inaugural dissertation. Crum Brown s trans-... 

Although the work of Gomberg and those who followed provided good evidence for the existence of arylmethyl radicals, there was still skepticism regarding simple aliphatic radicals such as methyl and ethyl. As noted above, the modern history of these species began with the suggestions of Crum Brown (equation 2). ... 

Statistical and computational methods have been used to quantify structure-activi relationships leading to quantitative structure-activity relationships (QSAR). The concqpt of QSAR can be dated back to the work of Crum, Brown and Fraser from 1868 to 1869, and Richardson, also in 1869. Many notable papers were published in the period leading up to the twentieth century by men such as Berthelot and Jungfleisch in 1872, Nemst in 1891, Ov ton in 1897 and Meyer in 1899 (7). Professor Corwin Hansch is now regarded by many as the father of QSAR, because of his work in the development of new and innovative techniques for QSAR. He and his co-woikers produced a paper that was to be known as the birtii of QSAR, and was oititled "Correlation of biological activity of phenoxyacetic acids with Hammett substituent constants and partition coefficients" (2). 

The obvious resemblance between Cram Brown s formulas and those of Couper, whose brief time at Edinburgh after his return from France overlapped with Crum Brown s student days, raises the equally obvious question of whether or not Crum Brown was acquainted with Couper s formalism for writing chemical structures. His biographer in the Journal of the Chemical Society maintains (60) that although both men were in Playfair s laboratory in 1858 (Couper had returned to Edinburgh in late autumn, 1858, and was offered the position in Playfair s laboratory that December) Cram Brown was not, in fact, acquainted with Couper s work. 

Figure 7. Crum Brown s structural formula for succinic acid.

Hexadecanedioic Acid Monomethylazelate Soda Aromatic Co. (Japan) Not available Crum Brown-Walkerc... 

Sebacid Add Diesters Adipic acid half esters BASF (West Germany) (Japan) (USSR) Past pilot-plant Past pilot-plant Commercial Crum Brown-Walker ... 

---