Triacetonamine (TAA), also known as 2,2,6,6-tetramethyl-4-piperidone, is a key intermediate in the synthesis of HALS (hindered amine light stabilisers); Their ability to effectively inhibit polymer degradation by scavenging free radicals is based on their sterically hindered amine functional groups, which are capable of forming stable N-oxides as active intermediates (the Denysov cycle). TAA is also used in the synthesis of pharmaceuticals, piperidine nitroso radicals and pyrrolidone derivatives. For example, the oxidation of TAA or its derivatives yields the corresponding tetramethylpiperidine-N-oxide, namely TEMPO; the latter can be used as a polymerisation inhibitor, molecular weight regulator or oxidation catalyst[1].

Synthesis of Triacetonamine

Methods for the synthesis of triacetonamine include the ‘one-pot method’, involving the direct condensation of acetone and ammonia (Scheme 1), and a two-step method: first, the synthesis of 2,2,4,4,6-pentamethyl-1,2,5,6-tetrahydropyrimidine (acetopyrimidine, ACTN) at room temperature, followed by the reaction of the isolated ACTN with acetone or water to produce TAA (Scheme 2).

Synthesis Route 2: One-pot method

Acetone and ammonia react directly in the presence of an acidic catalyst (such as NH?Cl or H-Y zeolite) to form TAA in a single step, with water as a by-product.

This reaction is a condensation reaction. Homogeneous catalysts include NH?Cl and NH?NO?; heterogeneous catalysts include H-Y zeolite (HY-6, which has good hydrophilicity, yields the best results). The reaction temperature is 65 °C, with a catalyst-to-acetone mass ratio of approximately 0.02 (homogeneous) or 0.10 (zeolite); the acetone-to-ammonia molar ratio has a significant effect on selectivity, with an optimal value of approximately 10.0.

However, this reaction involves a variety of parallel and sequential reactions, both reversible and irreversible. The main by-products generally include acetylacetoneamine (ACTN), diacetone alcohol (DAA), isopropylaceton (MO), diacetoneamine (DAAM) and the most undesirable irreversible by-product, 2,2,4,6-tetramethyl-2,5-dihydropyridine (TMDP).

Synthesis Route 2: Two-step method

Step 1: Synthesis of ACTN

Acetone reacts with ammonia at low temperature (room temperature) to first form the intermediate 2,2,4,4,6-pentamethyl-1,2,5,6-tetrahydropyrimidine (acetonine, ACTN). This step is typically carried out in the absence of a catalyst or under weakly acidic conditions to maximise ACTN selectivity.

Step 2: Conversion of ACTN to TAA

The isolated ACTN is then reacted with acetone or water and converted to TAA under the catalysis of a Br?nsted acid or Lewis acid (e.g. BF?, CaCl?, NH?Cl, etc.). This reaction can be carried out in three ways: in at least an equimolar amount of water; in an excess of acetone without the addition of water; or using both acetone and water simultaneously.

This reaction avoids the complex side reactions associated with one-pot methods, and the yield of TAA from ACTN is very high.

Reference

[1] GHERARDO GLIOZZI . Towards a more sustainable production of triacetoneamine with heterogeneous catalysis[J]. Journal of Molecular Catalysis A: Chemical, 2014, 393: Pages 325-332. DOI:10.1016/j.molcata.2014.06.023.