Subtractive names

In compositional and additive nomenclatures, we build the names more or less from scratch. The more complex the structure, the longer the name. With substitutive nomenclature, we take the names of parent hydrides or functional parents and modify them adding the names of substituent groups. Once again, the complexity of the name increases with complexity of the structure. In case of both skeletal replacement and functional replacement, a small or no increase in structural complexity still leads to longer names.

Yet there are opposite situations.

(a)	(b)

demethylmirtazapine (trivial + subtractive) 1,2,3,4,10,14b-hexahydropyrazino[2,1-a]pyrido[2,3-c][2]benzazepine mirtazapine (trivial) 2-methyl-1,2,3,4,10,14b-hexahydropyrazino[2,1-a]pyrido[2,3-c][2]benzazepine

You might have noticed that, while the substitutive name of (a) is shorter than that of (b), the reverse is true for their trivial names. This is because the structure of mirtazapine (b) contains a methyl group which is lost in (a), hence ‘demethyl’ bit in demethylmirtazapine.

This method of naming is known as subtractive.

Subtractive nomenclature is not, as its name suggests, the opposite of additive nomenclature. For the most part, it is rather the opposite of substitutive nomenclature. This is because the prefix ‘de’, followed by the name of a group or atom other than hydrogen, denotes replacement of that group or atom with hydrogen. Thus ‘demethyl’ means –CH₃ → –H, ‘deamino’ –NH₂ → –H, ‘decarboxy’ –COOH → –H and so on.

(c)	(d)

decarboxytiaprofenic acid (trivial + subtractive) (5-ethyl-2-thienyl)(phenyl)methanone (substitutive) tiaprofenic acid (trivial) 2-(5-benzoylthiophen-2-yl)propanoic acid (substitutive)

Some of the names obtained this way look positively silly: decarboxytiaprofenic acid (c), derived from tiaprofenic acid (c), is not a carboxylic acid and probably should not be named as an “acid” at all.

On the other hand, the prefix ‘dehydro’ denotes the loss — not a substitution! — of a hydrogen atom. It is most often employed “in pairs” to indicate the unsaturation of a carbon—carbon bond, i.e. ‘didehydro’, ‘tetradehydro’ etc. This particular subtractive operation, of course, is the opposite of addition of hydrogens to indicate the saturation of a carbon—carbon bond, as in ‘dihydro’, ‘tetrahydro’ etc.

(e)	(f)

6,7-didehydro-17β-estradiol (trivial + subtractive) estra-1(10),2,4,6-tetraene-3,17β-diol (substitutive) 17β-estradiol (trivial) estra-1,3,5(10)-triene-3,17β-diol (substitutive)

(g)	(h)

benzyne (trivial) 1,2-didehydrobenzene (subtractive) cyclohexa-1,3-dien-5-yne (substitutive) benzene (trivial)

For example, –CH₂–CH₂– → –CH=CH– in (f) → (e) and –CH=CH– → –C≡C– in (h) → (g) result in ‘didehydro’ names, viz. 6,7-didehydro-17β-estradiol (e) and 1,2-didehydrobenzene (g).

The prefix ‘dehydro’ should not — because it can! — be confused with ‘anhydro’, which refers to the formal loss of H₂O from the parent molecule, often with new bond formation, for example 2 –OH → –O– in (j) → (i). One might wonder whether it is a good idea to refer to both atom of hydrogen and molecule of water as ‘hydro’.

(i)	(j)

1,6-anhydro-N-acetyl-β-D-muramic acid (subtractive) N-acetyl-β-D-muramic acid

Most of us would never hear a subtractive name in our life if not for Phoebus Levene who in 1929 discovered 2-deoxy-D-ribose, a component of deoxyribonucleic acid. The prefix ‘deoxy’ denotes replacement of an –OH group by –H, i.e. a formal loss of an oxygen atom.

(k)	(l)

2′-deoxyadenosine (trivial) 9-(2-deoxy-β-D-ribofuranosyl)-9H-purin-6-amine adenosine (trivial) 9-β-D-ribofuranosyl-9H-purin-6-amine

Compare the structure of deoxyadenosine (k), one of the four deoxyribonucleosides found in DNA, with that of adenosine (l). The seemingly minor change, –OH → –H, accounts for many structural and functional differences between DNA and RNA.