[290-87-9]  · C3H3N3  · 1,3,5-Triazine  · (MW 81.09)

(C1 electrophile; formylating agent;2 methylenating and aminomethylenating agent;3 in combination with cyclic amines, dehydro-Mannich bases4,5 are formed)

Alternate Name: s-triazine.

Physical Data: mp 80-82 °C (very pure: 85-86 °C); bp 114 °C; d 1.38 g cm-3.

Solubility: sol alcohol, ether, most organic solvents; 1 g dissolves freely in 10 mL methanol.

Form Supplied in: white solid; widely available.

Handling, Storage, and Precautions: very volatile; hygroscopic and very sensible to solvolysis in water, alcohols, and solvents with OH groups. Distillation over sodium for purification has to be done cautiously to avoid overheating at the end, otherwise triazine-sodium compounds are formed which can lead to explosive decomposition of triazine.1

Formylating Agent.

In Gattermann's aldehyde synthesis, Hydrogen Cyanide can be replaced by 1,3,5-triazine. Under the action of Hydrogen Chloride, the triazine undergoes an electrophilic attack on aromatic compounds. The intermediate aldimine hydrochlorides are hydrolyzed to the aldehydes (eq 1).2 Nucleophilic arenes such as furans, pyrroles and polyhydroxybenzenes need no catalyst,2a,b while phenols and alkylbenzenes require Aluminum Chloride.2b,c Formylation of 2-hydroxydeoxybenzoins and cyclocondensation with Boron Trifluoride Etherate affords isoflavones.6

Methynylating Agent.

Although the triazine ring is aromatic, it is nonetheless very susceptible to nucleophilic attack. Two molecules of a primary amine H2NR can add to each carbon atom, leading to ring cleavage, release of ammonia, and 3 equiv of a disubstituted formamidine, RHN-CH=NR. 1,3,5-Triazine is a synthetic equivalent for Formic Acid, formamide, or trialkyl orthoformates. As the only byproduct is gaseous ammonia, contamination of the main product is avoided; yields are good and the products pure. The starting materials can also be mixed and melted for reaction. Reaction of aliphatic or aromatic diamines with triazine leads to heterocyclic compounds (eq 2); 2-aminophenols and thiophenols may also be used.7

Acidic a-methylene compounds such as malonic acid derivatives can also be used. The electron-rich nitrogen atom of the triazine can abstract a proton and the resulting carbanion can add to the triazine carbon. The intermediate aminomethylene compound may recyclize to produce 4,5-disubstituted pyrimidines (eq 3).8

1,3,5-Triazine can aminomethylenate aromatic or heterocyclic amines, thus introducing a =CH-NH2 group. The formamidine may react further (eq 4),3 e.g. to 4-aminoquinazolines. Other compounds which have CH acidic protons that can be aminomethylenated include derivatives of malonic acid9 or barbituric acid10 and cyclopentadiene (gives pentafulvenes).11 Pyrazolinones can also condense to the bispyrazolinones.12

When the auxiliary base required for the aminomethylenation (a cyclic amine) is used as the solvent, a three-component reaction takes place, which can be considered as a Mannich-type condensation. Dehydro-N-Mannich bases are obtained from Cyanamide4a,b or heterocyclic amines4c,d (eq 5). Carbon acidic components yield dehydro-C-Mannich bases.5 1,3,5-Triazines react regioselectively with dienophiles in cycloaddition reactions.13a Pyrimidine annulation occurs with pyrrolidine enamines in an inverse electron demand Diels-Alder reaction.13b

1. (a) Smolin, E. M.; Rapaport, L The Chemistry of Heterocyclic Compounds; Interscience: New York, 1959; Vol. 13, pp 6-16. (b) Grundmann, C. AG 1963, 75, 393; AG(E) 1963, 2, 309. (c) Alekseeva, N. V.; Yakhontov, L. N. Usp. Khim. 1990, 59, 888 (CA 1990, 113, 171 910c).
2. (a) Kreutzberger, A. AG 1967, 79, 978; AG(E) 1967, 6, 940. (b) Kreutzberger, A. AP 1969, 302, 828. (c) Kreutzberger, A. AP 1971, 304, 362.
3. Kreutzberger, A.; Stevens, M. F. G. JCS(C) 1969, 1282.
4. (a) Kreutzberger, A. T 1972, 28, 4877. (b) Kreutzberger, A.; Kreutzberger, E. JHC 1979, 16, 175. (c) Kreutzberger, A.; Uzbek, M. U. AP 1973, 306, 28. (d) Kreutzberger, A.; Meyer, B.; Gürsoy, A. CZ 1974, 98, 160.
5. Kreutzberger, A.; Kreutzberger, E. T 1976, 32, 2603.
6. Jha, H. C.; Zilliken, F.; Breitmaier, E. AG 1981, 93, 129; AG(E) 1981, 20, 102.
7. Grundmann, C.; Kreutzberger, A. JACS 1955, 77, 6559.
8. Huffmann, K. R.; Schaefer, F. C.; Peters, G. A. JOC 1962, 27, 551.
9. Kreutzberger, A.; Kreutzberger, E. AF 1980, 30, 232.
10. (a) Kreutzberger, A. AF 1978, 28, 1684. (b) Kreutzberger, A.; Kreutzberger, E.; Leyke-Röhling, S. AP 1979, 312, 115. (c) Kreutzberger, A.; Kreutzberger, E. AP 1983, 316, 6.
11. Kreutzberger, A.; Kolter, K. LA 1986, 374.
12. (a) Kreutzberger, A.; Kreutzberger, E. T 1975, 31, 93. (b) Kreutzberger, A.; Kolter, K. AP 1986, 319, 18. (c) Kreutzberger, A.; Kolter, K. JHC 1986, 23, 781.
13. (a) Neunhoeffer, H.; Bachmann, M. CB 1975, 108, 3877. (b) Boger, D. L.; Schumacher, J.; Mullican, M. D.; Patel, M.; Panek J. S. JOC 1982, 47, 2673. (c) Taylor, E. C.; Fletcher, S. R.; Fitzjohn, S. JOC 1985, 50, 1010.

Roswitha M. Böhme

University of Bonn, Germany

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