Ammonium cyanate, urea synthesis

The naturally occurring compound urea, CO(NH,), was first synthesized by Friedrich Wohler in Germany in 1828 by heating ammonium cyanate. This synthesis was a significant event because it was the first time that an organic compound had been produced from an inorganic substance. Urea may also be made by the reaction of carbon dioxide and ammonia ... 

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. 

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

The hydroxyl derivative of X-CN is cyanic acid HO-CN it cannot be prepared pure due to rapid decomposition but it is probably present to the extent of about 3% when its tautomer, isocyanic acid (HNCO) is prepared from sodium cyanate and HCI. HNCO rapidly trimerizes to cyanuric acid (Fig. 8.25) from which it can be regenerated by pyrolysis. It is a fairly strong acid (Ka 1.2 x 10 at 0°) freezing at —86.8° and boiling at 23.5°C. Thermolysis of urea is an alternative route to HNCO and (HNCO)3 the reverse reaction, involving the isomerization of ammonium cyanate, is the clas.sic synthesis of urea by F. Wohler (1828) ... 

The term organic chemistry was first used by the Swedish chemist Berzelius in 1807 (Larsson, 1981). He coined the name to describe the chemistry of substances derived from living matter. Berzelius was a staunch believer in the vis vitalis theory, which held that such substances were endowed with a mystical vital force that precluded their synthesis in the laboratory from materials of mineral origin. Ironically, it was a student of Berzelius, Wohler, who heralded the demise of vitalism with his synthesis of urea from ammonium cyanate (Wohler, 1928). In a letter to Berzelius in 1828, Wohler wrote I must tell you that I can make urea without requiring kidneys, or even an animal, whether a human being or a dog . 

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). 

Wohler. Synthesis of urea from ammonium cyanate. Microscopic examination of plant and animal cells by Dutrochet, Schlieden, and Schwann led to acceptance of the cellular origin of all tissues. ... 

Wohler was actually attempting to synthesize ammonium cyanate when he discovered crystals of urea in his samples. He first prepared urea in 1824, but he did not identify this product and report his findings until 1828. In a note written to Berzelius he proclaimed I must tell you that I can make urea without the use of kidneys, either man or dog. Ammonium cyanate is urea. Although Wohlers synthesis of urea signaled the birth of organic chemistry, it... 

WOHLER SYNTHESIS. Classical synthesis of urea by heating an aqueous solution of ammonium cyanate extended to preparation of urea derivatives. 

N-Arylureas are obtained when salts of primary aromatic amines react with solutions of alkali metal cyanates. The process involves the rearrangement of an amine cyanate, and is analogous to Wohlers classical synthesis of urea from ammonium cyanate. 

In an alternative synthesis (Expt 6.96, Method 2), which is also convenient for the synthesis of alkylureas, the amine hydrochloride is heated in aqueous solution with urea. This reaction also probably involves the amine cynate since in aqueous solution urea serves as a source of ammonium cyanate. 

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... 

Historically, the first chemical synthesis of urea by Wohler, from ammonium cyanate in 1828, was a milestone that established a bridge between inorganic and organic chemistry. Urease was the first enzyme ever to be crystallized (6), and it was the first protein shown to contain nickel ions in the active site (7). The first X-ray crystal structure of urease became known in 1995 (8). Significant progress was made since then toward an understanding of its catalytic mechanism, as well as toward the structural and functional emulation of its active site by synthetic model complexes (5, 9). 

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. 

In the synthesis of urea from ammonium cyanate the cyanate may be used as such already prepared or it ma> be obtained from ferro-cyanides or cyanides by the transformations already given (p. 416). 

Alkyl Ureas.—By substituting alkyl amines for ammonia in the reaction for the synthesis of urea from carbonyl chloride, or by using alkyl derivatives of ammonium cyanate (cyanic acid salts of alkyl amines), in the Wohler synthesis, alkyl ureas may be obtained. They are of different t es as illustrated by the following formulas showing their relationship to urea. 

Thiourea (98) was first prepared in 1870 by heating ammonium thiocyanate (99) (Scheme 54). The reaction is analogous to the historic preparation of urea (Wohler, 1828) which involved heating ammonium cyanate. Thioureas generally are stable crystalline solids which are useful in the synthesis of heterocyclic compounds. Symmetrical thioureas (100) may be obtained by the action of amines on carbon disulfide, and the procedure can be extended to the synthesis of cyclic thioureas (101) (Scheme 55). The reaction occurs via the intermediate (102) which on subsequent treatment with either ammonia or an amine yields the corresponding... 

The first synthesis of urea was conducted by Wohler in 1828 via the heating of ammonium cyanate (Eq. 11.55). 

Nitrogen-containing organic compounds are ubiquitous in nature and essential to life. They are also important intermediates and products of the chemical and pharmaceutical industries. As a consequence, chemists have developed a plethora of methods for their generation, starting with the first organic synthesis, Wohler s preparation of urea from ammonium cyanate in 1828.1 There are many reports of the formation of carbon-nitrogen bonds by electrophilic animation of carbanions and enolates in the early literature, but development of this method as a useful synthetic tool, especially for asymmetric synthesis, is of more recent date. 

This reaction is of particular interest as urea was first obtained in this way by Wohler in 1828. The discovery of this synthesis of urea had a marked effect on the development of organic chemistry. It was the first example of the formation in the laboratory from so-called inorganic compounds of an organic compound produced in the body as the result of the vital force. The reaction by which urea is formed from ammonium cyanate has been shown to be a reversible one. Silver cyanate is precipitated when silver nitrate is added to a solution of urea in boiling water. The reaction has been investigated quantitatively in the study of the law of mass action. 

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