Production of Synthetic Indigo

Demand for natural indigo dramatically increased during the industrial revolution, in part due to the popularity of Levi Strauss’s blue denim jeans. The natural extraction process was expensive and could not produce the mass quantities required for the growing garment industry. So, chemists began searching for synthetic methods of producing the dye. Indigo has been prepared by many methods.

In 1865, the German chemist Adolf von Baeyer began working on the synthesis of indigo. He described his first synthesis of indigo in 1878 from isatin, second synthesis from cinnamic acid and third synthesis from 2-nitrobenzaldehyde. But these synthesis routes were not economically feasible for large scale production. Therefore, the search for alternative starting materials continued. The synthesis of N-(2-carboxyphenyl) glycine from aniline provided a new and economically attractive route. This led the development of a commercially feasible manufacturing process by BASF in 1897. The development of different methods of indigo synthesis and the chemical reactions involved are shown in Figure below.

The third indigo synthesis, from 2-nitrobenzaldehyde (1882), was simple and gave a good yield of indigo, but again was economically impractical due to the high cost of the starting material, 2-nitrobenzaldehyde. This route to indigo is shown in Figure below, now commonly called the Baeyer–Drewson process Adolf von Baeyer was awarded the Nobel Prize for chemistry in 1905 in recognition of his works on indigo, among his many other chemical accomplishments. However, economically practical syntheses of indigo were later developed by a Swiss-German chemistry professor, Karl Heumann (1850–1894), and by a German industrial chemist, Johannes Pfleger (1867–1957).

Heumann’s first synthesis, in 1890, used the industrial chemical aniline as a starting material. It was converted into N-phenylglycine, which was internally condensed into indoxyl in molten alkali at ∼300°C. The indoxyl was quickly oxidized by atmospheric oxygen, dimerizing into indigo. Unfortunately, the yield of product was too low by this route to make it commercially attractive.

His second synthesis at the same time used the more expensive fine organic chemical anthranilic acid as the starting material. In the same sort of reactions utilized by his first route, Heumann obtained a high yield of indigo in this alternate procedure. The process was scaled up to an industrial level (several thousands of tons per annum) by BASF and Hoechst in 1897. Thus, commercial production of indigo began in 1897. By 1900, it equaled the yield of farming 250,000 acres of indigo containing plants.

By 1914 BASF was producing 80% of the world’s synthetic indigo, as a result of which Indian exports of natural indigo fell from 187,000 tons in 1895 to 11,000 tons in 1913 (Freeman, 1997). Thus by 1913 natural indigo had been almost entirely replaced by synthetic indigo. In 1901, Pfleger, working for Hoechst, modified Heumann’s first method by adding sodamide (NaNH2) to the alkaline flux. Sodamide is a very powerful dehydrating agent, and it drove the ring closure reaction, to form indoxyl, to completion.

Sodamide reacts with excess water, thus lowering the overall reaction temperature from almost 300 to 200°C. This results in a much more efficient reaction process. Use of the relatively cheap aniline as the starting material and of sodamide as the condensation agent were the two key factors in the economic success of the BASF–Hoechst industrial indigo synthesis. These synthesis routes are shown in Figure’s below.

Improved synthesis of N-phenylglycine

In 1925 BASF researchers devised an improved synthesis of N-phenylglycine from the N-methylolation of aniline with formaldehyde and hydrogen cyanide, followed by saponification of the resulting nitrile intermediate. This modification provided an additional economy in the overall indigo production method. BASF’s indigo capacity could not meet the huge global indigo demand during the 1960s and 1970s. The increasing prices encouraged quite a few competitors to invest in indigo production, particularly in China.