First point of difference rule

Basic IUPAC Organic Nomenclature

First point of difference rule

This is probably the most difficult of the rules associated with nomenclature to master.

The factors that influence the numbering according to the first point of difference rule are :

the principle functional group is given the lowest possible locant.
substituents are then assigned locants based on this numbering scheme in such a way as to give the lowest number at the first difference
In the event that there is no first point of difference in the locants, substituents are numbered based on alphabetisation giving the first substituent the lowest possible number.

NOTE : It is often INCORRECTLY taught in High School that it is the lowest sum of locants that determines the numbering scheme.

Here are some illustrative examples of the first point of difference rule:

2-methylpentane not 4-methylpentane.		Here the methyl group is given the lowest number by numbering as shown.
2,2,4-trimethylpentane not 2,4,4-trimethylpentane		The first difference is in the second locant - by numbering as shown this is kept lower (2- rather than 4-).
2,4,4-trimethylhexane not 3,3,5-trimethylhexane		The first difference is in the first locant - by numbering as shown this is kept lower (2 rather than 3).
1-ethyl-2-methylcyclohexane not 2-ethyl-1-methylcyclohexane or 1-ethyl-6-methylcyclohexane		The numbering is determined by the alphabetisation : ethyl preceeds methyl so ethyl gets the lower number. But then we number counter-clockwise to give the methyl the lower number (2- vs 6-)

pentan-2-ol not pentan-4-ol		Here the principle functional group, the alcohol -OH is give the lowest locant by numbering as shown.
pentan-3-ol no choice !		No matter which way this is numbered, the -OH is at C3.
4-methylpentan-2-ol not 2-methylpentan-4-ol		The first difference is in the -OH locant - by numbering as shown this is kept lower (2- rather than 4-).
2-methylpentan-3-ol not 4-methylpentan-3-ol		The first difference is in the methyl locant - since the -OH must be at C3 either way, but by numbering as shown the methyl locant kept lower (2- rather than 4-).