Hi Mohammad, Since you did not mention the reaction conditions it is hard to say. I guess, you need to remove the liberated water that may involve in the equilibration of the imine to the ketone. You could use molecular sieves (4 A) to remove the water. Besides, you need to use excess amount of the amine (or use triethylamine in addition) to scavenge HBr that'll form upon displacement of the bromine.

Thanks

Hi Mohammad,

Are you sure in your byproduct is -OH group and not ethylamine?

Well to increase yield of ketimine use pure ketone and ethylamine if both liquid, if not use a very dry solvent along with dehydrating agent (dessicant) e.g anhydrous mgso4, dry molecular sieves.

If your ketimine is solid store in super dry conditions if liquid distill it as soon as it is formed by kugelrohr distillation.

For further assistance plz consult my recently published on propargylamine, go through the supporting info

http://onlinelibrary.wiley.com/doi/10.1002/ejoc.201701567/abstract

Hi Mohammad, Since you did not mention the reaction conditions it is hard to say. I guess, you need to remove the liberated water that may involve in the equilibration of the imine to the ketone. You could use molecular sieves (4 A) to remove the water. Besides, you need to use excess amount of the amine (or use triethylamine in addition) to scavenge HBr that'll form upon displacement of the bromine.

Thanks

You have 2 problems the first is related to the structure of the substrate, having a good leaving group (Br) within the ketone functional group. the second is related to the presence and the formation of the water in the medium. Attempt dry conditions at low temperature.

I think use of large excess ethyl amine may solve it. The halogen is likely to be replaced with -OH. It is difficult to prevent but even then the alpha hydroxy ketone will be converted to alpha hydroxy imine with excess amine. The intermediate 1-ethylamino-1-hydroxyderivative formed can form an epoxide intermediate by NGP of -OH group produced which then can rearrange to alpha hydroxy imine via ring opening to form the product (Scheme enclosed). The alpha hydroxy ketone can form by direct displacement/substituent of alpha "Br" by water which is expected to be converted to the product in presence of excess amine. To remove water the reaction may be tried with excess amine in dry dichloromethane with anhyd. MgSO4 at room temperature or at 40-50 oC

Use some levis acid like Acetic acid.

Use amine 1.3 eq with 0.3 eq AcOH under reflux condition. Try to get solvent which have less water.Better use cyclohexane. Do reaction under Dean-Stark apparatus

Hope your reaction will go 100 %.If you will use water even after reaction you will get starting Ketone.

use mild organic base in imine synthesis strong bae will cause hdrolysis

Three questions:

1) How is there enough water to hydrolyze 100% of the bromide? EtNH2 is commonly sold as a 70% aqueous solution. That works out to 12.6 M EtNH2 and 13.5 M H2O. If you used this, it would mean there is more than a mole equivalent of water at the start and at least two eq by the end of your reaction. Have you tried with 97% or better EtNH2? If not, use redistilled water-free amine and follow the earlier advice of M.T. Rahman about 4A molecular sieves. Also, sieves out of the bottle don't work well if at all. They need to be dried at high temperature (> 400 C) or medium high temperature (> 200 C) under vacuum.

2) Are you making the bromoketone from cyclopentyl 2-thiophene ketone?(Ignore the probably-incorrect nomenclature & call it CpTK)

3) If so, have you looked into brominating the imine* of CpTK? This would avoid the problem of water from the imine-forming step reacting with the bromide (which has not yet been made at this stage.)

*There is a review in Organic Preparations and Procedures International, 1979, 11, 115-199 (N.D. Kimpe). N-bromo succinimide or else CuBr2 might be good reagents.

Since the reaction requires water to produce the alcohol product, I don't think dry or dehydrating conditions are likely to give the desired product. Forced dehydration is more likely to lead to the enone. I would conduct the solvolysis of the bromide first, giving the "byproduct" alpha-hydroxyketone, and then subject that material to imine formation.

Azeotropic removal of water is not an option with a low-boiling reactant like ethylamine. If you can obtain anhydrous ethylamine, you should try using it as the solvent for imine formation. Simple mass action should drive the formation of the desired imine, but you can add molecular sieves to further push it to completion. A sealed flask or Carius tube will permit moderate heating.