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 the methodology, other frequent major or secondary amines, had been tested in the reaction under optimized circumstances (Table 2). The usage of aliphatic amines, for example methylamine (Table two, entry two), dimethylamine (Table two, entry 3) and Estrogen receptor site ammonia answer (Table 2, entry four), cause the formation of the aziridine as the sole product in 88 , 83 , 91 yield, respectively. Notably, a complicated mixture was obtained when 1,2-ethanediamine was made use of within this reaction (Table two, entry 1).Results and DiscussionAccording to the previous reports around the derivatization of aminohalogenation reactions, the vicinal haloamines normally underwent elimination or aziridination reactions once they had been treated with organic bases (Scheme two) [33-35]. Nonetheless, when benzylamine was added to haloamine 1a in acetonitrile, the reaction could also proceed smoothly giving a sole item.Scheme 1: An anomalous outcome with benzylamine as organic base.Scheme two: Transformation of vicinal haloamines by the use of organic amines.Beilstein J. Org. Chem. 2014, 10, 1802807.Table 1: Optimization of common reaction circumstances.aentry 1 two 3 four five 6 7 eight 9aReactionamount (mL)b four 4 four two 0.five 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.five 1 1 1 1 three 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 two: Examination of other organic bases.aentrybase (mL)T ( )time (min)product ( )b 3a 5a1 2 3aReaction1,2-ethanediamine (two) methylamine (2) dimethylamine (two) ammonia answer (2)situations: 1a (0.five mmol), acetonitrile (three mL), base.rt rt rt rtbIsolated30 30 30yieldsplex mixture 88 83After acquiring the optimized situations, we then combined the aminohalogenation along with the treatment of benyzlamine to create a one-pot procedure 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. Immediately after being quenched by saturated sodium sulfite, the resulting mixture was stirred with benzylamine. Numerous ,-unsaturated esters had been studied to evaluate the yield and stereochemical outcome of those reactions (Table 3). As shown in Table 3, nearly all the tested substrates worked well below the optimized conditions giving rise for the corresponding ,-diamino ester solutions, despite the fact that the aromatic ring was substituted by sturdy elec-tron-withdrawing groups (fluoro, Table three, entries six, ten and 12; trifluoromethyl, entry 15) or an electron-donating group (methoxy, Table three, entry 8). Within the case of ethyl ester, the reaction showed reduced 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 within this reaction together with a moderate chemical yield (53 , Table three, entry 13). Notably, when the phenyl was replaced by CK2 site 1-naphthyl 4n (Table 3, entry 14), it was also well performing within this reaction providing rise to the target solution in 64 yield. For the substrates with ortho-substituents (Table three, entries 13 and 16), the yields were a bit bit reduced than the yields of your meta- and para-Beilstein J. Org. Chem. 2014, ten, 1802807.Table 3: One-pot reaction.