Structure Elucidation and Synthesis of Hygrine

Hygrine is a natural occurring alkaloid mainly found in coca leaves, from which cocaine is also derived. It is a simple pyrrolidine alkaloid with the molecular formula C₈H₁₅NO. It was first isolated by Carl Liebermann in 1889. Hygrine is a thick yellow oil with a pungent taste and odour. Its molar mass is 141.21 g/mol and has a boiling point of about 193° - 195° C in its pure form. Hygrine is used as a local anaesthetic, sedative, hypnotic, laxative and diuretic. IUPAC name of Hygrine is 1-(1-methylpyrrolidin-2-yl)acetone.

Structure Elucidation of Hygrine

1. Elemental analysis and molecular weight determine the molecular formula of hygrine is C₈H₁₅NO.
2. By the normal reactions, viz, formation of an oxime and oxidation to an acid (hygrinic acids, C₆H₁₁NO₂) having lesser number of carbon atoms, hygrine is found to possess a ketonic group.
3. Similarly, by the normal tests particularly Herzig Meyer reaction, hygrine is found to have one —NCH₃ group.
4. Hygrine on oxidation with chromic acid gives hygrinic or hygric acid, which on heating yields carbondioxide and N-methyl-pyrrolidine.

The easy removal of carbon dioxide from hygrinic acid to form N-methylpyrrolidine indicates by analogy with the α-amino acid that the hygrinic acid is N-methylpyrrolidine-2-carboxylic acid which is further proved by its synthesis (Willstatter, 1990).

5. On the basis of the above results, hygrine may be formulated either as (A) or (B).

Out of these two structures, hygrine was found to be (B) on the basis of its synthesis especially that gives by Hess.

Synthesis of Hygrine

Synthesis of Hygrine by Hess(1913)

Hess synthesised hygrine from pyrrylmagnesium bromide in the following steps-

Synthesis of Hygrine by Sorm(1947)

Sorm synthesised hygrine from N-methylpyrrole in the following steps-

Source: Chemistry of Organic Natural Products Vol.-1 O. P. Agrawal