[zq]

I tried to react a benzyl bromide (containing an amide group in the molecule) with an aliphatic alcohol in the presence of NaH to make an ether but it did not work. It seems the bromide (with the amide moiety) is not stable to basic conditions. Any suggestions how to make this ether?

[macman104]

Reverse it.  Put the OH on the benzene, and react that with the alkylbromide.

[g-bones]

I agree with pmgb.  the phenolic hydrogen will be more acidic because it can be delocalized into the aromatic ring.  you can even use a weaker base than NaH such as K2CO3 (less precautions for sure haha).  the alkylbromide will still be very reactive because it is a primary alkyl halide.  i have performed a similar reaction with great yields. 

[agrobert]

Generate the alkoxide in solution.  Then add the benzyl bromide dropwise in a concentrated solution of the same solvent.  I don't understand these other suggestion above because with phenol you do not get the same connectivity.  But you may try to convert your bromide into an alcohol and then attack an aliphatic halide in the same matter.

[lutesium]

You cannot make a benzylic ether by using benzylic halides + alcohols. You must use a molecule that has O directly bonded to the benzene ring + R-X and be more logicial on your selection of the base NaH is far too powerful for this type of reaction. It'll work but why don't you use a base that works the same way as it does but much easir to work with? If your substrate is water soluble you can use NaOH if its Ethanol soluble KOH if its acetone soluble K2CO3. But in here as you'll use a R-X to create your ether you can use   Et-OH + KOH or Acetone + K2CO3 + PTC (if needed).

Hope this helps! Good luck!


Lutesium...

[macman104]

I agree with pmgb.

You mean, macman104?

Generate the alkoxide in solution.  Then add the benzyl bromide dropwise in a concentrated solution of the same solvent.  I don't understand these other suggestion above because with phenol you do not get the same connectivity.  But you may try to convert your bromide into an alcohol and then attack an aliphatic halide in the same matter.

What?  How would you not get the same connection?  Benzylbromide + 1-propanol gives the same product as phenol + 1-bromopropane...

Converting your bromide into an alcohol and attack on an aliphatic halide...how is that different than phenol and an aliphatic bromide?

Besides, lutesium is right.  You cannot have a aliphatic "o" attack the benzyl bromide.  It is an Sn2 attack that is not possible on the benzylbromide.

[g-bones]

sorry macman104

[lutesium]

And one more note on the selection of the base. If your substrate is neither soluble in H2O Et-OH or acetone you can use DMF + Sodium Carbonate.


Lutesium...

[agrobert]

I think you all are confused benzyl bromide is

http://en.wikipedia.org/wiki/Benzyl_bromide

with a methylene group.  This is one of the best reagents for S_N2 with any nucleophile and an alkoxide is a great nucleophile if generated properly.  Phenol plus alkyl halide will not give you the same connectivity.  And you need NaH or stronger base to deprotonate an alkyl alcohol or amine.

Now if the OP meant bromobenzene he should clarify.

[Borek]

Oops, sorry Agrobert - some misclicking on my side, no changes to your post

[macman104]

Wow...I can't believe I completely missed that.  You are correct Agrobert, my apologies.

[zq]

Thank you all for your reply. The problem is that my benzyl bromide contains a 3,4-dihydroquinolin-2(1H)-one system (6 membered lactam ring). I think the lactam is not stable towards base (NaH, K₂CO₃). It might be getting hydrolyzed. So I was looking for a procedure which uses less basic conditions to do the etherification (benzyl bromide + aliphatic alcohol). I think I found one that uses Ag₂O as the reagent (Organic Syntheses 1990, Collective volume 7, p. 386).

[lutesium]

Ohhh god how could I miss that? Sorry!


Lutesium...

[agrobert]

Thank you all for your reply. The problem is that my benzyl bromide contains a 3,4-dihydroquinolin-2(1H)-one system (6 membered lactam ring). I think the lactam is not stable towards base (NaH, K₂CO₃). It might be getting hydrolyzed. So I was looking for a procedure which uses less basic conditions to do the etherification (benzyl bromide + aliphatic alcohol). I think I found one that uses Ag₂O as the reagent (Organic Syntheses 1990, Collective volume 7, p. 386).

Good luck. Let us know how it goes