1,6- Naphthyridine

January 18, 2021
I’m one of six members of a heterocyclic family.
What molecule am I?

Naphthalene is an aromatic organic compound that consists of two fused benzene rings. Diazanaphthalenes have the naphthalene structure with nitrogen atoms in place of two of the CH groups. There are two structural classes of diazanaphthalenes: benzodiazines, in which both nitrogen atoms are in the same ring, and naphthyridines, with one nitrogen atom in each ring.

Six naphthyridine isomers exist, based on the positions of the nitrogen atoms; they can be in the 1,5, 1,6 (shown here), 1,7, 1,8, 2,6, or 2,7 positions. All are white solids with a surprisingly wide span of melting points: 1,6-Naphthyridine’s is the lowest at <40 ºC; 2,6-naphthyridine’s is the highest at 114–115 ºC.

Quinoline derivatives such as naphthyridines that have nitrogen atoms in the 1-position are usually synthesized via the Skraup reaction, in which an aminopyridine and a glycerol derivative are heated in the presence of an oxidizing agent (e.g., nitrobenzene) and sulfuric acid. This is often a violent, runaway reaction, so it is perhaps fortunate that the synthesis of 1,6-naphthyridine from 4-aminopyridine was not originally successful.

Refinements of the Skraup reaction, however, did eventually lead to preparations of 1,6-naphthyridine in modest yields. One modification used 4-aminopyridine-N-oxide as the starting material; the resulting 1,6-naphthyridine-N-oxide was then reduced to the free base.

1,6-Naphthyridine and some of its derivatives have been reported to have medicinal, electronic, and catalytic properties. But none of these investigations has yet resulted in any practical applications.

1,6-Naphthyridine hazard information

Hazard class*,** Hazard statement
Acute toxicity, oral, category 4 H302—Harmful if swallowed Chemical Safety Warning
Serious eye damage/eye irritation, category 1 H318—Causes serious eye damage Chemical Safety Warning

*Globally Harmonized System of Classification and Labeling of Chemicals.  Explanation of pictograms. 
**Some safety data sheets classify as “not a hazardous substance or mixture”.

MOTW update

1,4-Dioxane was the Molecule of the Week for August 5, 2019. Dioxane is a valuable solvent that has many industrial and laboratory uses. In 2019, it came under regulatory pressure because it is a possible carcinogen and has been found in drinking water and groundwater in several states. On December 31, 2020, the US Environmental Protection Agency released a hastily compiled risk assessment of dioxane that pleased neither environmentalists, state attorneys general, nor the chemical industry. Among the report’s other shortcomings, EPA ignored drinking-water exposure; environmentalists and regulators say that this is dioxane’s greatest threat to the general population.

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1,6-Naphthyridine 
fast facts

CAS Reg. No. 253-72-5
SciFinder
nomenclature
1,6-Naphthyridine
Empirical formula C8H6N2
Molar mass 130.15 g/mol
Appearance White to pale yellow or light brown solid or liquid
Melting point 31–38 ºCa
Water solubility Unreported

a. Wide range of values reported.

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