Vent for the aminohalogenation of methyl cinnamate (4a). To prove the
Vent for the aminohalogenation of methyl cinnamate (4a). To prove the synthetic value on the methodology, other frequent key or secondary amines, were tested in the reaction under optimized conditions (Table two). The usage of aliphatic amines, which include methylamine (Table two, entry two), dimethylamine (Table two, entry 3) and ammonia solution (Table 2, entry 4), bring about the formation with the aziridine because the sole item in 88 , 83 , 91 yield, respectively. ALK6 Purity & Documentation Notably, a complex mixture was obtained when 1,2-ethanediamine was used in this reaction (Table two, entry 1).Results and DiscussionAccording towards the prior reports around the derivatization of aminohalogenation reactions, the vicinal haloamines generally underwent elimination or aziridination reactions after they have been treated with organic bases (Scheme 2) [33-35]. Nonetheless, 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 two: CYP51 Accession Transformation of vicinal haloamines by the use of organic amines.Beilstein J. Org. Chem. 2014, ten, 1802807.Table 1: Optimization of standard reaction circumstances.aentry 1 two 3 4 5 6 7 eight 9aReactionamount (mL)b 4 4 four 2 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) 0.5 0.5 1 1 1 1 3 6 1yield ( )c 83 75 91 93 63 28d 59d 60d 89conditions: 1a (0.five 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)item ( )b 3a 5a1 two 3aReaction1,2-ethanediamine (2) methylamine (2) dimethylamine (two) ammonia option (two)conditions: 1a (0.5 mmol), acetonitrile (3 mL), base.rt rt rt rtbIsolated30 30 30yieldsplex mixture 88 83After obtaining the optimized conditions, we then combined the aminohalogenation plus the treatment of benyzlamine to develop 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. Following being quenched by saturated sodium sulfite, the resulting mixture was stirred with benzylamine. A variety of ,-unsaturated esters were studied to evaluate the yield and stereochemical outcome of those reactions (Table three). As shown in Table 3, almost all of the tested substrates worked nicely under the optimized circumstances providing rise to the corresponding ,-diamino ester goods, even though 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 3, entry two), and 70 chemical yield was obtained comparing to 79 yield from methyl ester (Table 3, entry 1). A cinnamic ester with double-substituted aromatic ring 4m was also tolerated in 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 properly performing within this reaction providing rise for the target solution 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 with the meta- and para-Beilstein J. Org. Chem. 2014, ten, 1802807.Table 3: One-pot reaction.