Synthesis, Chemical

the planned production of complex compounds from simpler compounds based on a knowledge of the reactants’ chemical structure and reactivity. Chemical synthesis usually implies a sequence of several chemical processes (steps).

In the early period in the development of chemistry, chemical synthesis was carried out mainly for inorganic compounds and was fortuitous in nature. The synthetic production of complex substances became possible only after knowledge had been gained on the composition and properties of the substances, knowledge derived from the development of organic and physi-cochemical analysis. Of cardinal importance were the first syntheses of organic compounds, namely, oxalic acid and urea, by F. Wôhler in 1824 and 1828. Attempts to synthesize analogues of complex natural compounds in the mid-19th century, when a unified theory on the structure of organic compounds did not exist, indicated only the possibility, in principle, of synthesizing such compounds as fats (P. E. M. Berthelot) and carbohydrates (A. M. Butlerov). Indigo, camphor, and other relatively simple compounds were subsequently synthesized in accordance with a theory, as were more complex molecules, such as certain carbohydrates, amino acids, and peptides.

In the 1920’s, the work of R. Robinson on the preparation of a series of complex molecules by paths that imitated those governing the formation of the molecules in nature proved to be of seminal importance to the methodology of chemical synthesis. A rapid development of chemical synthesis began in the late 1930’s, first in the area of steroids, alkaloids, and vitamins and then in the area of isoprenoids, antibiotics, polysaccharides, peptides, and nucleic acids. R. B. Woodward made significant contributions to the development of fine organic synthesis in the 1940’s through 1960’s, carrying out the synthesis of a series of important natural compounds, including quinine, cortisone, chlorophyll, tetracycline, and vitamin B,₂. An example of the great advance in chemical synthesis is seen in the first complete synthesis of the gene of the alanine transfer-ribonucleic acid of yeast, which was carried out in 1970 by H. G. Khorana and his colleagues.

The development of organic synthesis is proceeding in a number of directions. One of these involves the production of industrially important products (polymers, synthetic fuels, dyes), another the preparation of various physiologically active substances for medicine, agriculture, food processing, and perfumery. A third branch is concerned with establishing the structure of complex natural compounds and obtaining molecules with unusual structures for testing and refining theories of organic chemistry. A fourth branch seeks to expand the number of reactions and methods that can be used in chemical synthesis. Included in this category is the use of catalysts and high energies and the broader use of microorganisms and purified enzymes under rigidly controlled conditions. In the 1970’s, computers have been used for optimizing the results of multi-step chemical syntheses.

The development and perfection of certain methods used in synthesis has permitted the preparation of many important chemical products on an industrial scale. In inorganic chemistry, these products include nitric acid, ammonia, sulfuric acid, sodium carbonate, and various coordination compounds. There is also large-scale production of the organic substances used in various branches of the chemical industry, as well as of the products of fine organic synthesis (hormones, vitamins).