- Synthesis of 3-alkyl-6-methyl-1,2,4,5-tetrazinesviaa Sonogashira-type cross-coupling reaction
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1,2,4,5-Tetrazines have become extremely useful tools in chemical biology. However, the synthesis of some challenging substrates such as asymmetrically disubstituted alkyltetrazines is still a limitation for the widespread use of this class of compounds. Herein we describe an efficient route to these compounds based on the Sonogashira coupling of 3-bromo-6-methyl-1,2,4,5-tetrazine and 3-bromo-6-phenyl-1,2,4,5-tetrazine with terminal alkynes. The preparation of the starting reagents has also been optimized. The alkynyl products have been used as intermediates for the synthesis of dialkyl-tetrazines through a sequence of hydrogenation and re-oxidation with unprecedented yields. The synthetic applicability of this new approach is showcased through the preparation of several unnatural amino acids bearing alkynyl- and alkyl-1,2,4,5-tetrazine fragments.
- Ros, Enric,Prades, Amparo,Forson, Dominique,Smyth, Jacqueline,Verdaguer, Xavier,Pouplana, Lluís Ribas de,Riera, Antoni
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p. 11086 - 11089
(2020/10/05)
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- A New Synthesis of 6-(Alkyl)amino-3-aryl(alkyl)-1,2,4,5-tetrazines
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A new method for the preparation of 6-(alkyl)amino-3-aryl(alkyl)-1,2,4,5-tetrazines is described.Dissolving 3-aryl(alkyl)-1,2,4,5-tetrazines in liquid ammonia or a primary aliphatic amine at -35 deg C to -40 deg C, followed by addition of potassium permanganate gives the title compounds in reasonable to excellent yields.
- Counotte-Potman, Anda,Plas, Henk C. van der
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p. 123 - 127
(2007/10/02)
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