Building on the basics of the previous lesson, we will master advanced rules required for entrance examinations and practical work, including compounds with complex functional groups, cyclic compounds, and stereochemical notation.
Basic Knowledge
Priority order when multiple functional groups are present: -COOH > -COOR(ester) > -CONR2(amide) > -CN > -CHO > -CO-(ketone) > -OH > -NH2 > -OR(ether) > C=C > C≡C > -X(halogen) > -R(alkyl). Use the highest-priority group as the principal functional group(suffix), and name the others as prefixes.
Examples of prefixes: -OH=hydroxy hydroxy, -CHO=formyl/oxo formyl/oxo, -CO-=oxo oxo, -NH2=amino amino, -OR=alkoxy alkoxy, -COOH=carboxy carboxy(when outside the parent chain).
Naming cyclic compounds: A benzene ring+substituents. Examples: C6H5-CH3=methylbenzene(common name toluene), C6H5-OH=hydroxybenzene(common name phenol).
Disubstituted benzene: 1,2-(ortho-, o-), 1,3-(meta-, m-), 1,4-(para-, p-).
CIP rules for stereochemical notation(R/S)(Cahn-Ingold-Prelog rules):
① Compare the atomic numbers of the four atoms bonded to the asymmetric carbon and determine their priority(a>b>c>d)
② If the atoms are the same, compare the next atoms; count double bonds as duplicates
③ Place the lowest-priority group(d) toward the back. If a→b→c is clockwise, it is R; if counterclockwise, it is S.
CIP rules(Cahn-Ingold-Prelog rules, comparison of atomic numbers)
R form/S form(clockwise R, counterclockwise S, lowest priority toward the back)
E/Z notation(higher-priority groups on the same side=Z, opposite sides=E)
D/L notation(determined by the highest-position carbon in a Fischer projection, common for sugars and amino acids)
(+)/(-)(sign of optical rotation, +=dextrorotatory, -=levorotatory, determined by measurement)
rac-(racemic mixture, equimolar mixture)
Further Exploration (Principles and Applications)
Example: (2R)-2-hydroxypropanoic acid=D-(-)-lactic acid=muscle lactic acid. CIP priorities at C2: -COOH(O,O,O)>-OH(O,H,H)>-CH3(H,H,H)>-H. With H toward the back, if COOH→OH→CH3 is clockwise, it is R.
D/L notation for sugars(Fischer projection): In a vertical structure with the carbonyl(CHO or CO) written at the top, if the -OH on the lowest chiral center(the carbon immediately below the highest-position carbon in a sugar) is on the right, it is D; on the left, it is L. The configuration of all the carbons in D-glucose is(2R,3S,4R,5R).
D/L notation for amino acids: With the carboxyl group at the top, if NH2 on the α-carbon is on the left, it is L; if on the right, it is D. Amino acids in natural proteins are generally in the L form(except glycine).
These forms of notation are essential in pharmacy and biochemistry, and in most cases only one enantiomer of a drug's active ingredient is approved.
- Always check functional-group priority(-COOH has the highest priority)
- The principal functional group is a suffix; the others are prefixes
- Disubstituted benzene=ortho/meta/para(1,2/1,3/1,4)
- R/S=CIP rules(atomic numbers)→clockwise/counterclockwise
- E/Z=arrangement of higher-priority groups around a double bond
- D/L=common notation for sugars and amino acids, Fischer projection
- Natural amino acids are L; natural sugars are D
Points to Note(Common Confusions and Frequent Mistakes)
① R/S and D/L are independent: L-alanine is the S form, but L-cysteine is the R form because of substituent priorities. ② (+)/(-) and R/S are also independent: D-lactic acid is the R form but is(-) rotating, while L-lactic acid is the S form and(+) rotating(the relationship differs by substance and is determined experimentally). ③ Functional groups have priority in numbering: If an alcohol and an alkene are both present, -OH has priority, so number accordingly→“pent-4-en-2-ol,” for example. ④ Choosing a parent for cyclic and acyclic compounds: If the ring has more carbon atoms, use the cyclic compound as the parent.
Practice
- Give the IUPAC name of the following structure:
HOOC-CH(OH)-CH2-CH3(stereochemical notation is unnecessary). - Draw the structural formula of p-cresol(p-methylphenol).
- Write the structural formula of(S)-alanine using a Fischer projection and include both the R/S and D/L designations.