Wohler’s synthesis of urea

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 ... 

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. 

The marrying of the fields of coordination chemistry, chemotherapy and enzymology was finally spurred on by the advent of modern instrumental and synthetic techniques, and not least by the dramatic developments in organic synthesis, which was born as a discipline in itself in 1828 with Friedrich Wohler s synthesis of urea from ammonium cyanate. In the course of the development of supramolecular chemistry, enormous progress has been made on quantifying the details of receptors with an affinity for guests which fit inside them. The lock and key image especially has suffered... 

Structural Isomerism.—The phenomenon of the existence of two or more compounds possessing the same composition and empirical formula but which show different physical and chemical properties is known as isomerismy and the compounds themselves are called isomeric compoundsy isomers or isomerides. That the difference is in the structure or constitution characterizes them further as structural isomers and the phenomenon as structural isomerism. The word isomerism was suggested by Berzelius in connection with Wohler s synthesis of urea (p. 429). 

Wohler s Synthesis.—From the preceding discussion of the constitution of urea and of ammonium cyanate (p. 418) we can express the transformation involved in Wohler s synthesis of urea by the following rearrangement. 

Why did Wohler s synthesis of urea from inorganic compounds mean that the theory about organic materials had to be reevaluated ... 

These were pioneer steps indeed, and great strides forward were made in the hundred years between Wohler s synthesis of urea and the isolation of the first crystalline enzyme - also, by some strange chance, one related to urea, urease - by Sumner in America in 1926. But the really explosive growth of biochemistry has had to wait on the consolidation of chemical theory, and the pushing forward of the frontiers of biology to a region where the distinction between it and chemical physiology became obscure. By the... 

Wohler s synthesis of urea was the result of experiments begun in 1823, in which he investigated the salts of cyanic acid, known as cyanates. In 1824 Wohler showed that the empirical formula of silver cyanate was AgNCO. Justus von Liebig, who had studied the compound silver fulminate, had come up with the same formula for an entirely different compound. (These two compounds were structural isomers.) Isomerism was a novel idea at that time, as it was believed that each compound had a unique formula No two compounds could have the same formula. (Berzelius had first described the phenomenon of isomerism in 1831.)... 

The chemical achievements, particularly in synthetic and analytical chemistry, in the 19th century are staggering in number we mention only a few. The growth of organic chemistry after Wohler s synthesis of urea, 1824. The stereochemical studies of van t Hoff, LeBel, and Pasteur. The chemical proof of the tetrahedral arrangement of the bonds about... 

Cities of life in the organic compounds found in animals and plants. Wohler s synthesis of urea an organic compound, from the inorganic compound, ammonium cyanate discredited the theory of the existence of a vital force. 

In 1845, for instance, Adolph Wilhelm Hermann Kolbe (1818-84), a pupil of Wohler s, succeeded in synthesizing acetic acid, an indubitably organic substance. Furthermore, he synthesized it by a method which showed that a clear line of chemical change could be drawn from the constituent elements, carbon, hydrogen, and oxygen, to the final product, acetic acid. This synthesis from the elements or total synthesis is all that can be asked of the chemist. If Wohler s synthesis of urea did not settle the matter of the vital force, Kolbe s synthesis of acetic acid did. 

Chemical synthesis did not seem, at first, a likely source of useful remedies. However, after Wohler s synthesis of urea, in 1828, a whole range of synthetic organic chemicals was introduced into medical practice. After several false starts, some relatively simple substances were adopted as inhalation anaesthetics, namely nitrous oxide, ether, and chloroform (1844-7) which, by giving the surgeon adequate time for his task, initiated a tremendous refinement and extension of the possibilities of surgery. 

The case was strongly made that, in spite of the recent significant achievements in the arena of total synthesis, we still have far to go before we can accomplish practical syntheses of any desired structure, no matter how complicated. We have come a long way from Wohler s synthesis of urea to the Woodward-Eschenmoser synthesis of vitamin B12 and Kishi s synthesis of palytoxin. However, even these monumental synthetic feats are only big steps along the long road toward synthetic perfection. It will probably take another 150 years before chemists will be able to prepare non-biological compounds of... 

Albert Eschenmoser If chemists were successful in documenting experimentally how molecules under well-deHned conditions can self-organize to a level where the phenomenon of life sets in, such a feat would have a great impact on the way people look at our world. It would be a giant step in that process of demystification of Nature which had started with Wohler s synthesis of urea and has continued, in our time, with the synthesis of complex natural products. There are many biologists today who say all this is very simple, life started with RNA, and that s it. It is at this point where we chemists should be very critical. In this context, it is our task to demonstrate experimentally what is possible with organic molecules and what is not. The goal is not to be able to propose how it has happened, not even to propose how it could have happened, it is to demonstrate experimentally that it can happen. 

Wohler s synthesis of urea dispelled the notion that oiganie eompounds were fundamentally different from inorganie compounds—and that they could only be produced by nature. We now know that it is possible to synthesize a wide variety of organie eompounds in the laboratory in fact, many thousands of new organic compounds are produced in researeh laboratories each year. In this chapter, we will consider several types of organic compounds that are important biologically. 

Wohler s synthesis of urea (1828) and Kolbe s synthesis of acetic acid (1845) moved from the scientific scene s vis vitalis theory. Kolbe synthesis is presented here because of its historical importance and also as an extraordinary introduction to the ecological issues of industrial organic synthesis (Scheme 1.16). 

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