Significance We found that the number of new chemical compounds has grown exponentially with a 4.4% annual production rate from 1800 to 2015 not even affected by World Wars. There are three distinct growth regimes: proto-organic, organic, and organometallic, with decreasing variability in the production of compounds over time. Contrary to the belief that organic synthesis developed only after 1828, synthesis had been a key provider of new compounds already at the beginning of the 19th century. By 1900, it became the established tool to report new compounds. We found that chemists are conservative when selecting starting materials and that despite the growing production of new compounds, most of them belong to a restricted set of chemical compositions.