Derivatives of Amino Alcohols and Amino Phenols

A group of compounds called catecholamines (from the name catechol that means 1,2-dihydroxybenzene) represents biogeneous amines dopamine, noradrenaline (norepinephrine), and adrenaline (epinephrine). These substances are also known as remedies that stimulate adrenoreceptors.

The prefix nor- designates in the IUPAC nomenclature the absence of the methyl group when a trivial name is employed.

These and subsequent compounds of basic nature, as well as compounds with acidic nature, are often used as salts (usually as hydrochlorides and sodium or other salts, respectively). These details are omitted mostly for simplicity, in structures given in this section.

p-Aminophenol is a toxic matter but its N-aceylated derivative Paracetamol (Panadol, Tylenol, Efferalgan, and many other synonyms), is used as antipyretics and anesthetics.

Derivatives of Amino Acids

Some esters of p-aminobenzoic acid are widely used as local anesthetics. The oldest of them is the ethyl ester, or Anesthesin (Benzocaine) which is known for

more than a hundred years. More effective are an ester Procaine and its soluble salt Novocain. The related compound an amide Novocainamide also has an anesthetic effect but rather it is known as an antiarrhythmic drug.

Among aliphatic amino acids, there should be mentioned Aminalon (Gammalon, GABA) and related compounds Phenibut and Picamilon that possess a nootropic activity. One of the most effective anesthetics Lidocaine (Xylocaine) is a derivative of glycine, the simplest amino acid.

Derivatives of Salicylic Acid

Acetylsalicylic acid (Aspirin and over sixty other synonyms) is the first synthetic antipyretic and anesthetic applied since the close of the 19th century. It is, undoubtedly, the most widely used derivative of salicylic acid, both by itself and in combination with other drugs.

Further derivatives are Oxaphenamide (Osalmid), a cholagogue, and p-Aminosalicylic acid (PAS-acid), a tuberculostatic drug.

Derivatives of Sulfanilic Acid (Sulfa Drugs)

Sulfa drugs were among the first synthetic antibacterial remedies. They are derivatives of sulfanilic acid, or p-aminobenzenesulfonic acid. Its amide, sulfanilamide, is the parent compound of all the sulfa drugs. In spite of the simple structure, it was found to be effective (by the trade name Streptocide white) against some bacterial infections.

Over 10,000 analogues of sulfanilamide were synthesized within a short time after its discovery. The best therapeutic results were obtained by variations in the

amide portion of the molecule, especially by introducing various heterocycles as the R substituent in the general formula. Dozens of sulfa drugs are still used, though more effective remedies appeared.

Additional Problems

6. Write the structural formulas for the following compounds and classify them as polyor heterofunctional ones, if any:

(a) anisole (methoxybenzene);(c) ethyl lactate; (e) p-toluic acid (4-methylbenzoic acid);

(b) 2-chlorobutanoic acid;(d) iodoform (triiodomethane); (f) xylitol (1,2,3,4,5-pentanepentol).

7. Write equations for reactions of p-aminobenzoic acid with the following compounds: (a) sodium hydroxide; (b) hydrogen chloride; (c) acetic anhydride. What is the mechanism for the latter reaction?

8. Explain why β-amino and δ-amino acids produce quite different products on heating. Illustrate this by the examples of 3-amino- and 5-aminopentanoic acids.

9. Write equations for the formation of γ-butyrolactone and γ-valerolactam from the corresponding hydroxy or amino acid. How would you perform hydrolysis of these products?

10. What would you predict as the product obtained on heating ε-amino acids (by the example of 6-aminohexanoic acid)? Compare the result with that for γ-amino acid.