Starting from 1940, the synthesis problem was planned by theoretical principles, and every step of the reaction process was controlled by instruments, which greatly changed the situation of synthetic organic chemistry. The chemistry of natural products has played an extremely important role in promoting this change. Biochemists are interested in vitamins and enzymes, and pharmaceutical industry is interested in some natural substances such as antibiotics, hormones and rotenone alkaloids, which stimulate the synthesis of complex molecules with multiple reaction centers.
The development of organic synthetic chemistry has gone through the following periods:
early stage
For example, Wuzi reaction, Williamson reaction, Parkin reaction, Rosen reaction, Hoffman reaction, Scripps reaction, Frehling reaction, Jacobson reaction, Noel reaction, Mitchell reaction, etc., some established "name" reactions continue to be widely used, and people constantly propose improved methods to expand their applications. Grignard reagent was put forward in 1899 because the discovery of new reactions made it easier to achieve the previous goals and made new synthesis possible, but it did not attract enough attention until the 20th century. Green himself extended this reaction to the preparation of various compounds, and inorganic chemists also used this reaction.
Grignard reagent is easy to react with substances containing substitutable hydrogen or active hydrogen, such as water, alcohol, ammonia, HCl, etc., so it is used to analyze and determine this substitutable hydrogen. This application was first put forward by L Chu Gaeff of St. Petersburg (1872— 1922), and later his student Tserevitinov further developed this application.
Other reactions adopted at the beginning of the 20th century include the aldehyde synthesis of Bouvette, the acid-to-amine reaction of bouchard, the reaction of ullman's aromatic halide and copper converting into hydrocarbons, and ullman's condensation reaction of connecting simple rings into more complex condensed rings. All these reactions can be used for aromatic compounds, which reflect people's close attention to dye chemistry in the first decade of the 20th century. At the same time, Bouvette-Blanc reduction method provides a method to convert acids into corresponding alcohols. The reduction reaction is that of sodium and ethanol in the presence of ester of the acid. The Clementine reaction converts carbonyl to methylene by using zinc amalgam in acid. Hydrogen peroxide in alkaline solution is used in the Darkin reaction, which converts aromatic aldehydes into phenol.
During the First World War, there was no new activity in the field of synthetic chemistry except the Rosenmonde reduction reaction. In this reduction reaction, an acyl group is converted into an aldehyde group by introducing hydrogen into a solution containing a palladium catalyst. The Barbier-Vilander degradation reaction of shortening the chain length of organic acids by one unit was proposed by Barbier in 19 13 and improved by Vilander in 1926. O. Diels (1876-1934) and K. Alder (1902-1958) found another important reaction in 1928 in Kiel. They observed that cis -△4- tetrahydrophthalic anhydride, a six-membered ring compound, can be obtained quantitatively by the violent reaction of butene with maleic anhydride.
Earlier, Melwein was one of the independent discoverers of the Melwein-Pontdorf-Wiley reduction reaction, which was the reaction of reducing carbonyl compounds to alcohols in the presence of aluminum alkoxides. This oxidation reaction is most suitable for converting secondary alcohols into ketones, although it is also used for the oxidation of primary alcohols to some extent.
Catalytic hydrogenation is a useful technique for synthesizing and explaining theoretical problems. At the beginning of the 20th century, Sabatier and Sen Delens first developed it, and it was quickly used in industrial production. Until the end of World War I, the requirement of providing appropriate high pressure delayed the wide application of hydrogenation technology in organic research. It was not until the 1930s that it was applied to many important tasks.
The development of suitable catalysts for hydrogenation reaction is also very slow. At the beginning of the 20th century, Parr proposed a method to prepare platinum catalyst. Other metals, especially nickel, are also used. However, the method of preparing the catalyst is not standardized, so the result is disappointing. 1927M Rani patent is widely used to prepare nickel catalyst, in which aluminum is dissolved and separated by sodium hydroxide. Adams and his colleagues in Illinois reduced metal oxides and used them as catalysts. H adkins of Wisconsin (1892— 1949) and his colleagues first developed copper chromite as an effective catalyst.
middle period
Modern organic synthesis began in the 1940s. Although some difficult syntheses have been completed in the past ten years, for example, the synthesis of thiamine by R.R. Williams and J.K. Klein; Riboflavin synthesis independently completed by P. Kaleel and R. Kuhn; Synthesis of pyridoxine independently completed by S.A. Harris, K.Fox and Kuhn; T. The synthesis of ascorbic acid was independently completed by Reichstein and Kuhn; Three laboratories-Kaleel laboratory, A. Todd laboratory and L. I. Smith laboratory-synthesized α-tocopherol; Hemostatic vitamin K was synthesized by E.A. doisy laboratory and L. Fiscel laboratory; Bachmann, J. W. Cole and A. L. Wirtz completed the synthesis of menadione; Fox, Kuhn and H. Vilander completed the synthesis of pantothenic acid, but these syntheses were somewhat eclipsed by the following total synthesis.
These total syntheses include quinine synthesis by R.B. Woodward and W.E. Doreen, cortisone synthesis by L.H. Saret, patulin and brucine synthesis by Woodward, morphine synthesis by M. Gates and D. Ghinsberg, vitamin H synthesis by Fox, A. Gresner and Subarov in Merck laboratory, folic acid synthesis by C.W. Waller. Carotene synthesis of O. isler, vitamin A synthesis, insulin synthesis of F. Sanger and chlorophyll α synthesis of Woodward and martin strel.
The remarkable feature of these syntheses is that they can be completed quickly after the structures of these compounds are determined. These syntheses show the power of new ideas in the field of organic chemistry. Because before doing experiments, it is often necessary to design the reaction theoretically. These comprehensive achievements reflect the characteristics of science in the mid-20th century-relying heavily on the exchange of ideas. The era of narrow research has given way to the era of comprehensive research.
A particularly important synthetic development that is valuable in both organic research and industrial production is the utilization of microorganisms. Mould and other organisms are widely used to produce antibiotics. Microbes produce antibiotics, but people don't know much about the intermediate process. However, in a series of synthetic operations, microorganisms have been used in a certain step of the reaction. They are especially suitable for this application, because they can carry out stereoselective reactions, and if they pass through pure chemical synthesis reactions, they will produce a mixture of isomers. Vitamin c, 1? Ephedrine, pyridoxal, pyridoxamine, some anthraquinone and some penicillin have been synthesized by suitable microorganisms, and this method has also been used in steroid field.
in the near future
The number of high-level organic synthesis research groups, their great discoveries and the attraction of this field to young and promising scientists far exceeded that of the 1960s. The methodology of chemical synthesis includes some new synthetic processes, important synthetic strategies and highly selective reagents and catalysts. Affinity chromatography and multifunctional liquid chromatography have improved the separation and purification methods of organic compounds, which will greatly accelerate the research of organic synthesis, and thus may solve many more complicated problems.
The application of physical instruments (X-ray crystal diffraction, nuclear magnetic resonance, mass spectrometry) and computers in the accurate determination of structures has greatly accelerated the discovery and identification of new synthetic bioactive molecules and promoted our understanding of the functions of bioactive molecules. This shows that computers have become an important tool for organic synthetic chemists. Computers will not only be used for calculation, but also for solving various problems and teaching each other. Using computer-aided model analysis and synthesis will become a conventional tool in chemistry.