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 principal 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 locant number at the first time there is a 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 locant number

Misconception Alert!
It is often INCORRECTLY taught in High School that it is the lowest sum of locants that determines the numbering scheme.

See here for more discussion on the first point of difference rather than summing locants follow this link.

STUDY TIP
In order to work with the first point of difference rule, try the approach shown below based on the comparision of 1,1,2 vs 1,2,2:

for each possible numbering scheme, list out the locants in numerical order
compare the "lists" to locate the first point of difference, i.e. the first time you encounter a low number
at the first point of difference, select the lower locant choice (mouseover)

example

Here are some illustrative examples of the first point of difference and related rules:

2-methylpentane not 4-methylpentane.		Here the methyl group is given the lowest number by numbering as shown (2- rather than 4-).
2,2,4-trimethylpentane not 2,4,4-trimethylpentane		The first difference is at 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 at 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 first difference is at the second locant (2- rather than 6-) which means 1,2- is preferred over 1,6-. The application of this numbering is then dictated by the alphabetisation : ethyl preceeds methyl so ethyl gets the lower number.

pentan-2-ol not pentan-4-ol		Here the principle functional group, the alcohol -OH is give the lowest locant by numbering as shown (2- rather than 4-).
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-).