Unusual Reaction of Macrocyclic Uracils with Paraformaldehyde

Abstract

The ability of simple uracils to afford bis(uracil‐5‐yl)methanes upon reaction with paraformaldehyde is well documented. This reaction has been used in the preparation of pyrimidinophanes. The extension of the scope of this reaction to the synthesis of multipyrimidinophanes has been reported. Starting with isomeric pyrimidinophane containing 6‐methyluracil and 5‐methyluracil (thymine) moieties, linearly arranged multimacrocycles were prepared. A completely unexpected result was that the reactions of isomeric pyrimidinophanes containing 6‐methyluracil moieties with paraformaldehyde produced only cyclic‐arranged macrocycles, in particular, cryptand‐like pyrimidinophanes and multipyrimidinophanes with a cyclic topology.

Novel Acetylcholinesterase Inhibitors Based on Uracil Moiety for Possible Treatment of Alzheimer Disease

“…This began with the amination of dibromides 7a – c and was followed by the alkylation of bisamines 8a – c with o -nitrilebenzyl bromide. This strategy was developed for the synthesis of compound 1 [ 25 ] , and the procedure for the synthesis of initial reagents 7a – c , 8a – c is described elsewhere [ 28 , 29 ].…”

“…Synthesis of initial compounds 1,3-bis(4-bromobutyl)-6-methyluracil ( 7a ), 1,3-bis(5-bromopentyl)-6-methyluracil ( 7b ), 1,3-bis(6-bromohexyl)-6-methyluracil ( 7c ) [ 35 ], 1,3-bis(4-ethylaminobutyl)-6-methyluracil ( 8a ), 1,3-bis(5-ethylaminopentyl)-6-methyluracil ( 8b ), 1,3-bis(6-ethylaminohexyl)-6-methyluracil ( 8c ) [ 28 , 29 ], 1,3-bis(5-azidopentyl)-6-methyluracil ( 11 ) [ 30 ], and 1,3-bis(5-bromopentyl)quinazoline-2,4-dione ( 9b ) was carried out as previously reported [ 36 ].…”

6‐Methyluracil Derivatives as Bifunctional Acetylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease

“…The target compounds 3 were synthesized by starting from substituted benzyl bromide 4 and diamines 5 a – c , the latter of which were obtained from dibromides 6 and ethylamine. This step was described elsewhere . Scheme shows the steps leading to bisamines 3 .…”

“…Initial compounds 5 a–c : The syntheses of initial compounds 1,3‐bis(4‐ethylaminobutyl)‐6‐methyluracil ( 5 a ), 1,3‐bis(5‐ethylaminopentyl)‐6‐methyluracil ( 5 b ), and 1,3‐bis(6‐ethylaminohexyl)‐6‐methyluracil ( 5 c ) were reported previously …”

“…Initial compounds 5a-c:T he syntheses of initial compounds 1,3bis(4-ethylaminobutyl)-6-methyluracil (5a), 1,3-bis(5-ethylaminopentyl)-6-methyluracil (5b), and 1,3-bis(6-ethylaminohexyl)-6-methyluracil (5c)were reported previously. [24,25] Synthesis of compounds 3a-k. General procedure:Amixture of diamine 5a-c (5.0 mmol), substituted benzyl bromide 4 (10.0 mmol) and K 2 CO 3 (3.45 g, 25.0 mmol) was stirred in CH 3 CN (150 mL) at 73-78 8Cf or 8h.T he precipitate was filtered off. The solution was concentrated to 10-15 mL and transferred to ac olumn with SiO 2 .T he column was successively washed with petroleum ether (PE), 1:1P E/Et 2 Om ixture and Et 2 O.…”