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 common major or secondary amines, have been tested in the reaction beneath optimized conditions (Table two). The use of aliphatic amines, such as methylamine (Table 2, entry two), dimethylamine (Table 2, entry 3) and ammonia answer (Table 2, entry four), cause the formation of your aziridine because the sole solution in 88 , 83 , 91 yield, respectively. Notably, a complex mixture was Histamine Receptor supplier obtained when 1,2-ethanediamine was utilised within this reaction (Table 2, entry 1).Final results and DiscussionAccording towards the preceding reports around the derivatization of aminohalogenation reactions, the vicinal haloamines ordinarily underwent elimination or aziridination HSF1 site reactions after they were 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 solution.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, ten, 1802807.Table 1: Optimization of standard reaction conditions.aentry 1 2 three four 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.five 1 1 1 1 3 six 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)solution ( )b 3a 5a1 2 3aReaction1,2-ethanediamine (two) methylamine (2) dimethylamine (2) ammonia answer (2)situations: 1a (0.5 mmol), acetonitrile (3 mL), base.rt rt rt rtbIsolated30 30 30yieldsplex mixture 88 83After obtaining the optimized circumstances, we then combined the aminohalogenation plus the remedy of benyzlamine to develop a one-pot procedure with ,-unsaturated esters as beginning materials. On the initial reaction step the cinnamic ester underwent a copper(II) trifluoromethanesulfonate-catalyzed aminohalogenation reaction with TsNCl2 as nitrogen supply. Right after being quenched by saturated sodium sulfite, the resulting mixture was stirred with benzylamine. Many ,-unsaturated esters have been studied to evaluate the yield and stereochemical outcome of those reactions (Table 3). As shown in Table three, pretty much all of the tested substrates worked nicely beneath the optimized situations giving rise for the corresponding ,-diamino ester solutions, despite the fact that the aromatic ring was substituted by powerful elec-tron-withdrawing groups (fluoro, Table three, entries 6, 10 and 12; trifluoromethyl, entry 15) or an electron-donating group (methoxy, Table 3, entry eight). In the case of ethyl ester, the reaction showed lower reactivity (Table three, entry 2), 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 three, entry 13). Notably, when the phenyl was replaced by 1-naphthyl 4n (Table three, entry 14), it was also nicely performing in this reaction providing rise to the target item in 64 yield. For the substrates with ortho-substituents (Table 3, entries 13 and 16), the yields have been a little bit reduce than the yields of the meta- and para-Beilstein J. Org. Chem. 2014, ten, 1802807.Table three: One-pot reaction.