R1, R2, etc.) It is a generic placeholder, the R derived from radical or rest, which may replace any portion of the formula as the author finds convenient. The first to use this symbol was Charles Frédéric Gerhardt in 1844. The symbol X is often used to denote electronegative substituents such as the halides. Statistical distribution One cheminformatics study identified 849,574 unique substituents up to 12 non-hydrogen atoms large and containing only carbon, hydrogen, nitrogen, oxygen, sulfur, phosphorus, selenium, and the halogens in a set of 3,043,941 molecules. Fifty substituents can be considered common as they are found in more than 1% of this set, and 438 are found in more than 0.1%. 64% of the substituents are found in only one molecule. The top 5 most common are the methyl, phenyl, chlorine, methoxy, and hydroxyl substituents. The total number of organic substituents in organic chemistry is estimated at 3.1 million, creating a total of 6.7×1023 molecules. An infinite number of substituents can be obtained simply by increasing carbon chain length. For instance, the substituents methyl (-CH3) and pentyl (-C5H11). See also Functional groups are a subset of substituents References Organic chemistry Chemical nomenclature