Vent for the aminohalogenation of methyl cinnamate (4a). To prove the
Vent for the aminohalogenation of methyl cinnamate (4a). To prove the synthetic worth with the methodology, other typical major or secondary amines, had been tested inside the reaction beneath optimized situations (Table two). The use of aliphatic amines, for example methylamine (Table 2, entry 2), dimethylamine (Table two, entry three) and ammonia solution (Table two, entry four), lead to the formation from the aziridine because the sole solution in 88 , 83 , 91 yield, respectively. Notably, a complicated mixture was obtained when 1,2-ethanediamine was employed within this reaction (Table 2, entry 1).Outcomes and DiscussionAccording for the earlier reports around the derivatization of aminohalogenation reactions, the vicinal haloamines normally underwent elimination or aziridination reactions after they were treated with organic bases (Scheme two) [33-35]. Having said that, when benzylamine was added to haloamine 1a in acetonitrile, the reaction could also proceed smoothly providing a sole product.Scheme 1: An anomalous outcome with benzylamine as organic base.Scheme 2: Transformation of vicinal haloamines by the usage of organic amines.Beilstein J. Org. Chem. 2014, ten, 1802807.Table 1: Optimization of common reaction conditions.IL-3 manufacturer aentry 1 2 3 four 5 6 7 8 9aReactionamount (mL)b 4 four four 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 six 1yield ( )c 83 75 91 93 63 28d 59d 60d 89conditions: 1a (0.5 mmol), solvent (3 mL). bAmount of benzylamine. c Isolated yields. d2 mL triethylamine was added.Table 2: Examination of other organic bases.aentrybase (mL)T ( )time (min)product ( )b 3a 5a1 2 3aReaction1,2-ethanediamine (2) methylamine (two) dimethylamine (two) ammonia option (two)situations: 1a (0.five mmol), acetonitrile (3 mL), base.rt rt rt rtbIsolated30 30 30yieldsplex mixture 88 83After obtaining the optimized conditions, we then combined the aminohalogenation and the therapy of benyzlamine to create a one-pot process with ,-unsaturated esters as starting materials. On the initial reaction step the cinnamic ester underwent a copper(II) trifluoromethanesulfonate-catalyzed aminohalogenation reaction with TsNCl2 as nitrogen source. After being quenched by saturated sodium sulfite, the resulting mixture was stirred with benzylamine. Different ,-unsaturated esters were studied to evaluate the yield and stereochemical outcome of these reactions (Table 3). As shown in Table three, just about all of the tested substrates worked nicely beneath the optimized KDM1/LSD1 drug conditions providing rise to the corresponding ,-diamino ester merchandise, even though the aromatic ring was substituted by robust elec-tron-withdrawing groups (fluoro, Table 3, entries 6, 10 and 12; trifluoromethyl, entry 15) or an electron-donating group (methoxy, Table 3, entry 8). Within the case of ethyl ester, the reaction showed reduce reactivity (Table 3, 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 within this reaction along with a moderate chemical yield (53 , Table 3, entry 13). Notably, when the phenyl was replaced by 1-naphthyl 4n (Table 3, entry 14), it was also effectively performing within this reaction giving rise to the target item in 64 yield. For the substrates with ortho-substituents (Table three, entries 13 and 16), the yields were just a little bit decrease than the yields of your meta- and para-Beilstein J. Org. Chem. 2014, ten, 1802807.Table 3: One-pot reaction.
