1,n-Diamines. Part 3: Microwave-assisted synthesis of N-acyl-N′-arylhexahydropyrimidines and hexahydro-1,3-diazepines

Microwave-Assisted Syntheses of Bioactive Seven-Membered, Macro-Sized Heterocycles and Their Fused Derivatives

“…In this preparation, 2,2,6-trimethyl-4H-1,3-dioxin-4-one 89 (the so-called diketene acetone adduct, DDA) and linear bisamines 90 were condensed at 130 °C under MW-irradiation in solventfree conditions (Scheme 14). Orelli and co-workers [39,40] have developed a synthetic route to a series of 1,3-diazepines starting from the N-arylputrescine derivative 85, which is quantitatively converted into the key aminoamides 86 by means of conventional acylation reactions. In marked contrast to conventional cyclodehydration reactions leading to seven-membered amidines, which require long reaction times and drastic heating, the MW-assisted cyclodehydration of 86 using a CHCl 3 solution of ethyl-polyphosphate (PPE), a mild "Lewis acid" irreversible dehydrating reagent, leads to corresponding 1-aryl-2-alkyl-1H-1,4,5,6-tetrahydro-1,3-diazepines 87 in 8 min at 100˝C with good yields (42%-90%) (Scheme 13).…”

An Efficient Synthesis ofN-Alkyl-N-arylputrescines and Cadaverines

“…[2][3][4][5][6][7][8] In addition, such compounds represent key intermediates for acyclic and heterocyclic polyamine derivatives. [9][10][11][12] The methods usually employed for the synthesis of symmetrically N,N -disubstituted 1,n-diamines involve functionalization of the parent diamine but cannot be applied to unsymmetrical derivatives, which require more elaborate strategies. 9,[13][14][15] In particular, selectively N-substituted putrescines and cadaverines present a challenge, since the available methods for di-and trimethylenediamines are not generally suitable for their higher homologues.…”

Synthesis of 5-Hydroxydihydropyrimidine Derivatives and the Influence of Intramolecular Hydrogen Bonding on Their NMR Properties and Conformational Preferences of the Hydroxyl Group

“…The synthesis of compounds 2a-g using the same method as described above was not possible because all attempts to obtain the corresponding macrocyclic aminal 1,3,7,9,13,15,19,21-octaazapentacyclo[19.3.1.1 3,7 .1 9,13 .1 15,19 ]octacosane-5,11,17,23-tetraol (5) were unsuccessful. Although hexahydropyrimidines are traditionally synthesized from condensations of alkyl diamines and aldehydes, 5 in a recent study, 6 Farrell et al succeeded in the synthesis of six new hexahydropyrimidine derivatives using a three-component Mannichtype reaction involving 1,3-diaminopropane, paraformaldehyde and 2,4-substituted phenol, with excellent yields using two synthetic protocols: neat reactions in pressure flasks and reflux reactions in methanol solutions.…”