[7521-41-7]  · C6H6N2O  · 2-Aminonicotinaldehyde  · (MW 122)

(1,8-naphthyridine synthesis; Friedländer synthon; b-amino aldehyde)

Alternate Name: 2-amino-3-pyridinecarbaldehyde.

Physical Data: yellow solid, sublimes readily, mp 98-99 °C.

Solubility: ether, ethyl acetate: good; dichloromethane: poor.

Preparative Methods: the reagent is best when freshly prepared. A multistep procedure starting from 2-amino-3-picoline has been improved upon by a simple two-step approach. Sulfamation of nicotinamide with ammonium sulfamate (both commercially available) provides 2-(3-pyridyl)pyrido[2,3-d]pyridimine which may be hydrolyzed in 2 N HCl to provide the reagent (eq 1).1 Substituted derivatives of the reagent may be prepared via a similar intermediate.2

Handling, Storage, and Precautions: the reagent is somewhat more stable than 2-Aminobenzaldehyde and may be stored for up to several months at 0 °C under an inert atmosphere. Sublimation is a convenient method for the separation of higher oligomers which may accumulate during storage. Use in a fume hood.

1,8-Naphthyridine Synthesis.

The Friedländer condensation of 2-aminonicotinaldehyde with various ketones provides a convenient one-step access to the 1,8-naphthyridine nucleus. Other naphthyridine isomers are available from related pyridine o-aminoaldehydes.1b The reaction is generally carried out by combining the reactants in ethanol, adding several mL of saturated methanolic KOH and refluxing for 1-4 h. Appropriate diketones will afford two sequential condensations. Reactions with the three isomeric cyclohexanediones are regiospecific and proceed in the direction predicted by the more active methylene position (eq 2).3-5

Related Reagents.

(Z)-b-Aminoacrolein; 2-Aminobenzaldehyde; 1,3-Cyclohexanedione; Quinoline.

1. (a) Caluwe, P. T 1980, 36, 2359. (b) Cheng, C.-C.; Yan, S.-J. OR 1982, 28, 37. (c) Thummel, R. P. SL 1992, 1.
2. Majewicz, T. G.; Caluwe, P. JOC 1974, 39, 720.
3. Evens, G.; Caluwe, P. JOC 1975, 40, 1438.
4. Majewicz, T. G.; Caluwe, P. JOC 1975, 40, 3407.
5. Thummel, R. P.; Lefoulon, F.; Cantu, D.; Mahadevan, R. JOC 1984, 49, 2208.

Randolph P. Thummel

University of Houston, TX, USA

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