Vent for the aminohalogenation of methyl cinnamate (4a). To prove theVent for the aminohalogenation of

Vent for the aminohalogenation of methyl cinnamate (4a). To prove the
Vent for the aminohalogenation of methyl cinnamate (4a). To prove the synthetic worth of your methodology, other typical principal or secondary amines, have been tested inside the reaction under optimized situations (Table two). The usage of aliphatic amines, like methylamine (Table two, entry two), dimethylamine (Table two, entry three) and ammonia answer (Table 2, entry 4), result in the formation in the aziridine as the sole product in 88 , 83 , 91 yield, respectively. Notably, a complex mixture was obtained when 1,2-ethanediamine was applied in this reaction (Table 2, entry 1).Outcomes and DiscussionAccording towards the prior reports on the derivatization of aminohalogenation reactions, the vicinal haloMC3R medchemexpress amines commonly underwent elimination or aziridination reactions when they have been treated with organic bases (Scheme two) [33-35]. Nevertheless, when benzylamine was added to haloamine 1a in acetonitrile, the reaction could also proceed smoothly giving a sole solution.Scheme 1: An anomalous outcome with benzylamine as organic base.Scheme 2: Transformation of vicinal haloamines by the use of organic amines.Beilstein J. Org. Chem. 2014, ten, 1802807.Table 1: Optimization of standard reaction conditions.aentry 1 2 3 four 5 six 7 eight 9aReactionamount (mL)b 4 4 4 2 0.5 0.1 0.1 0.1 2solvent CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH2Cl2 CHClT ( ) rt 50 rt rt rt rt rt rt rt rttime (h) 0.five 0.5 1 1 1 1 3 6 1yield ( )c 83 75 91 93 63 28d 59d 60d 89conditions: 1a (0.five mmol), solvent (three mL). bAmount of benzylamine. c Isolated yields. d2 mL triethylamine was added.Table 2: Examination of other organic bases.aentrybase (mL)T ( )time (min)item ( )b 3a 5a1 two 3aReaction1,2-ethanediamine (two) methylamine (two) dimethylamine (two) ammonia answer (two)situations: 1a (0.five mmol), acetonitrile (three mL), base.rt rt rt rtbIsolated30 30 30yieldsplex mixture 88 83After acquiring the optimized conditions, we then combined the aminohalogenation plus the remedy of benyzlamine to develop a one-pot process with ,-unsaturated esters as beginning materials. Around the initial reaction step the eNOS supplier cinnamic ester underwent a copper(II) trifluoromethanesulfonate-catalyzed aminohalogenation reaction with TsNCl2 as nitrogen supply. Immediately after getting quenched by saturated sodium sulfite, the resulting mixture was stirred with benzylamine. Several ,-unsaturated esters have been studied to evaluate the yield and stereochemical outcome of these reactions (Table 3). As shown in Table three, almost all of the tested substrates worked nicely below the optimized situations providing rise towards the corresponding ,-diamino ester products, although the aromatic ring was substituted by strong elec-tron-withdrawing groups (fluoro, Table three, entries six, ten and 12; trifluoromethyl, entry 15) or an electron-donating group (methoxy, Table 3, entry eight). Within the case of ethyl ester, the reaction showed decrease reactivity (Table three, entry two), and 70 chemical yield was obtained comparing to 79 yield from methyl ester (Table three, entry 1). A cinnamic ester with double-substituted aromatic ring 4m was also tolerated in this reaction together with a moderate chemical yield (53 , Table three, entry 13). Notably, when the phenyl was replaced by 1-naphthyl 4n (Table three, entry 14), it was also well performing within this reaction giving rise for the target product in 64 yield. For the substrates with ortho-substituents (Table three, entries 13 and 16), the yields were somewhat bit decrease than the yields on the meta- and para-Beilstein J. Org. Chem. 2014, ten, 1802807.Table three: One-pot reaction.