One-step synthesis of a new heterocyclophane family

Role of hydroxyl groups on the aromatic ring in the reactivity and selectivity of the reaction of β-phenylethylamines with non-enolizable aldehydes

“…The HOMO orbital of phenylethylamine 1 shows the amine group as the site of greatest nucleophilicity; upon reaction with formaldehyde, the 1,3,5-triphenylhexahydro-1,3,5-triazine 4 was obtained, the product of reacting three moles of phenylethylamine with three moles of formaldehyde [15]. The HOMO orbital of the phenylethylamine 2 shows the carbons ortho to the phenolic hydroxyl (C-3 and C-5) as sites of greater nucleophilicity; the reaction with formaldehyde at one of these carbons, through a Mannich-type aromatic condensation, produces azacyclophane-type macrocyclic [11]. The HOMO orbital of the phenylethylamine 3 shows carbon 6 as the position of greatest activation, and against formaldehyde, it produces the respective tetrahydroisoquinoline 6 through a Pictet-Spengler reaction (Scheme 1) [10].…”

“…This reaction did not produce the expected THIQs but instead led to the formation of benzoxazinephane-type macrocyclic compounds (2 units of 3,4-dihydro-2H-1,3-benzoxazine bonded by ethylene bridges) through a double Mannich-type aromatic reaction [11].…”

L-Tyrosine isopropyl ester

“…For the n-butyl analogue, see: Qian et al (2006). For macrocyclization of tyrosine alkyl esters with formaldehyde, see: Quevedo & Moreno-Murillo (2009); Nuñ ez-Dallos et al (2012). For a related structure of tyramine, see: Quevedo et al (2012).…”

An unexpected route for the synthesis of a new spiroheterocyclic system from ninhydrin

“…When the reaction is performed between dopamine and formaldehyde, the corresponding 1,2,3,4-tetrahydroisoquinoline is obtained by a Pictet-Spengler reaction; when the reaction is performed between tyramine and formaldehyde, an azacyclophane is obtained by a double aromatic Mannich reaction; and when the reaction is performed between phenylethylamine and formaldehyde, a triple amine-aldehyde condensation leads to the corresponding hexahydro-1,3,5-triphenyl-1,3,5-triazine. [1][2][3] On the other hand, ninhydrin 1 is a highly electrophilic tricarbonyl compound derived from indane. The electrophilic character is high due to the presence of three consecutive electron-withdrawing groups, the most electrophilic of which is carbon 2.…”