Sequence rule

In organic chemistry, the sequence rule is used to determine the relative priorities of substituents ^{[1] [2]}. This is important when specifying the configuration about a double bond or a stereocentre. For example, a carbon atom bonded to a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom is a stereocenter, and the compound bromochlorofluoroiodomethane can exist as a pair of enantiomers. The four substituents (fluorine, chlorine, bromine, iodine) must be ranked in order of priority. The five sub-rules to the sequence rule are as follows, in order or priority:

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1. The priority of an atom is first determined by its atomic number, thus I > Br > Cl > F. Isotopes of higher mass of an element have higher priority than isotopes of lower mass of the same element, and thus T > D > H. According to the IUPAC nomenclature of organic chemistry, a lone electron pair can be taken to have lower priority than ¹H.

2. If rule 1 fails to establish priority, the comparison is extended through to the atoms bonded to the atoms of identical atomic number and mass. For example, for a stereocenter bonded to a hydrogen atom, a hydroxyl group, a methyl group, and an ethyl group, we need to determine whether ethyl or methyl has higher priority, because the atom with the free valence is carbon in both cases (and we assume that we are ignoring isotopes). What we do then is to find the substituent of highest priority on each of these two carbon atoms and compare them. The carbon with the substituent of highest priority has the higher priority. Thus, the carbon of a methyl group is bonded to three hydrogens while the carbon of an ethyl group is bonded to two hydrogens and a carbon atom. Thus -CH₂CH₃ > -CH₃.

3. When two atoms are linked by a double bond, they are both considered to be duplicated, and in the case of a triple bond, they are both triplicated. For example, -C=O is considered to be -C(O)-O(C) and -C≡N is considered to be -C(N)(N)-N(C)(C). The extra atoms are considered to be bonded to substituents of rock bottom priority.

4. When two substituents are identical (ignoring stereoisomerism), and geometrical isomerism is present, they are compared at the first double bond (the closest to the free valence) exhibiting geometrical isomerism, and the one with a configuration of Z has higher priority than the one with a configuration of E.

5. When two substituents are identical but for stereoisomerism, and no geometrical isomerism is present, they are compared at the first stereocenter (the closest to the free valence). The one with a configuration of R is considered to be of higher priority than the one with a configuration of S.

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