Urea, Wohler’s synthesis

Mono-substituted and unsymmetrical di-substituted ureas may be prepared by a modification of Wohler s urea synthesis, salts of primary or secondary amines being used instead of the ammonium salt for interaction with potassium cyanate. Thus when an aqueous solution containing both aniline hydrochloride and potassium cyanate is heated, aniline cyanate is first formed, and then C,HjNH,HCl -h KCNO = C,H6NHj,HCNO -h KCl C,HsNH HCNO = C.H NHCONH, by the usual molecular rearrangement is converted into monophenyburea. 

The first major theory of organic chemistry to follow Wohler s urea synthesis was his establishment, with his friend Jnstns von Liebig (1803-1873), of the concept of the multi-atom organic radical - benzoyl, described in the landmark paper of 1832 (15). The definition of a radical was further clarified by Liebig in his 1837 paper, where he defined a radical in terms of three major characteristics (16) ... 

P. J. Ramberg., The death of vitalism and the birth of organic chemistry Wohler s urea synthesis and the disciplinary identity of organic chemistry , Ambix, 2000, 47, 170-195. 

Wohler wrote to Berzelius I can make urea without the necessity of kidney, or even an animal, whether man or dog. However, he made no claim to have disproved vitalism, and both the ammonia and the cyanic acid that he used had been derived from natural sources. The importance of Wohler s urea synthesis was that both ammonium cyanate and urea had the same composition, and it therefore provided an early example of isomerism. 

Wohler s urea synthesis discredited the vital force theory, and his success prompted other chemists to attempt to synthesize organic compounds. Today, organic compounds are being synthesized in thousands of laboratories, and most of the synthetics have never been isolated from natural sources. 

Organic compounds share one unique feature They all contain carbon. Therefore, organic chemistry is defined as the study of carbon-containing compounds. There are a few exceptions to this definition a small number of carbon compounds— such as CO, CO2, carbonates, and cyanides—were studied before Wohler s urea synthesis. These were classified as inorganic because they were obtained from nonUving systems, and even though they contain carbon, we still consider them to be a part of inorganic chemistry. 

Although chemical transformations in aqueous solutions are known, in general, the poor solubility of organic compounds in water avoids the use of aqueous solvents in chemical reactions. Some early examples of reactions in aqueous medium can be traced back to the Wohler s urea synthesis in 1828 [70] and the Baeyer-Drewsen indigo synthesis in 1882 [71], MCR protocols, as already stated, are very important for developing new pharmaceuticals and libraries of medicinal scaffolds. However, few examples for MCRs in water as the solvent have been reported in the literature. In this section, we will discuss some selected MCRs in water ... 

Wohler s classical synthesis of urea from ammonium cyanate may be carried out by evaporating solutions of sodium cyanate and ammonium sulphate ... 

Ammonia and primary and secondary amines can be added to isocyanates to give substituted ureas. Isothiocyanates give thioureas. This is an excellent method for the preparation of ureas and thioureas, and these compounds are often used as derivatives for primary and secondary amines. Isocyanic acid (HNCO) also gives the reaction usually its salts (e.g., NaNCO) are used. Wohler s famous synthesis of urea involved the addition of ammonia to a salt of this acid. "... 

Wohler s urea to the synthesis of Vitamin Bi2 by Robert B. Woodward [1.3] and Albert Eschenmoser [1.4] assisted by a hundred or so collaborators ... 

Thus, in little more than three decades after Wohler s accidental synthesis of urea, it was learned that living organisms exhibited a unique capacity to distinguish a molecule from its mirror image. So profoundly indicative of Life is the handedness of carbon-containing molecules that a search for the existence of Life in outer space once centered on finding such optically active molecules in matter-... 

Indeed, the period from Wohler s accidental synthesis of urea in 1828 to the Biotechnological Revolution of today presents a remarkable pilgrimage with the potential for dramatic and constructive consequences for individual health and societal development. 

The important process of synthesis was not first distinguished according to the nature of the product (natural or artificial). Synthesis was thought to be merely total or partial. Substances were made from elements (commonly C, H, O) or from other, simpler compounds. Wohler s laboratoiy synthesis of urea in 1828, a substance made previously only by the action of a living organism, was... 

Wohler s synthesis of urea by which a product of the living cell was first prepared artificially more than a century ago is the prototype of many addition reactions which take place with the reactive molecules of cyanic acid and its esters, as well as with the series of analogous thio-compounds. In these reactions NH3 is added to the C = N double bond ... 

Wohler s preparation of urea from ammonium cyanate, which could in principle be derived totally from inorganic constituents, is cited as an early demonstration (1828) that living cells were not obligatorily required for the synthesis of natural products. I can prepare urea without requiring a kidney or an animal—either man or dog. Three years after the death of Pasteur the finding by Hans and Edouard Buchner (1897) that fermentation still occured in a cell-free extract from yeast and so did not require the presence of organized cells, was virtually the final nail in the coffin for vitalism and an essential preliminary to the study of intermediary metabolism (Chapter 4). 

The idea of describing the chemical reactions that are germane to the origin of life has a long history - particularly if one starts from Wohler s experiments in 1828 on the synthesis of urea, as recently proposed by Bada and Lazcano (2003). Wohler s reaction was a fortunate accident, in the sense that the German chemist did not have in mind any ambitious Faustian dream. In what follows some basic notions... 

The material in this chapter traced the history of organic chemistry from Wohler s synthesis of urea through Kekule s structure of benzene. The millions of organic chemicals known to exist can be classified into a relatively small number of families, each defined by a common functional group. During the last century, chemists have discovered how to mimic nature to synthesize organic chemicals. A multitude of familiar products are natural or synthesized organic chemicals. 

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