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Bosch began his industrial career in Ludwigshafen, where he improved the process for making phthalic anhydride (a chemical precursor for the alkyd resins used in paint). Later, he reinvestigated some work done by Wilhelm Ostwald (1853-1932) on catalysis of the ammonia equilibrium. In this investigation, he found that Ostwald's results were in error.

Continuing research on nitrogen fixation, Bosch studied the formation of cyanides and cyanamides from reactions of carbides with nitrogen. Calcium cyanamide is able to react with steam to form ammonia, and this process was used for manufacturing ammonia.

Beginning in 1909, Bosch worked on scaling up Fritz Haber's ammonia synthesis. The result was that after a remarkably short time of four years, BASF had developed and brought onstream a synthetic ammonia plant at Oppau (near Ludwigshafen) in 1913. In 1917, a second, larger plant was opened at Leuna (near Leipzig). These plants supplemented the ammonia produced from the cyanamide process and helped to reduce Germany's dependence on imported nitrates from South America.

After the start of World War I, the ammonia became a vital raw material for the production of nitric acid, and hence the explosives like TNT (trinitrotoluene) and cordite, for which nitric acid is needed. Bosch was promoted to managing director at BASF in 1919, and when Interessen Gemeinschaft Farben (I. G. Farben) was founded in 1925, he became a director there. I. G. Farben was organized as a chemical cartel to market and control prices of chemical products, mainly dyes. . .

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