I am doing aldol condensation of cyclicketones with p-Hydroxybenzaldehyde. The reaction yield is found to be very low when I am using base catalysed aldol condensation. I want to know the easiest metod for the aldol condensation of cyclic ketones with 4-Hydroxybenzaldehyde.
you may need to cap the hydroxy group, or use more than 1 eq. to deprotonate. Alternatively, preform an enamine with the cyclic ketone
look at these methods :
http://www.organic-chemistry.org/namedreactions/aldol-condensation.shtm
they are quite good. I tested them in the past.
Base will deprotonate the phenol, rendering the aldehyde unreactive, so a protecting group will be needed. I think a carbonate (benzyloxycarbonyl or trichloroethoxycarbonyl) ought to do the trick.
Yang's suggestion of an examine is a good one, for example, see the first step of Corey's Ginkolide B synthesis (JACS 88, 649). You need to pre-form the examine, otherwise you will probably do a Mannich.
However, the first question is whether you're trying to isolate the a,b-hydroxyketone or the a,b-unsaturated ketone? There are five possible products (sun aldol, anti aldol, E enone, Z enone, and intracyclic enone (by double bond isomerisation).
If you are trying to isolate the hydroxyketone, then the titanium enolate cited by Sebastian Gornicki (organic-chemistry.org link) is probably the way to go, you can probably get away with not protecting the hydroxyl. However, the safest may indeed be to protect it.
Don't use base. Use the excess of p-Hydroxybenzaldehyde as acid:
Djerourou has an interesting idea: combine the ketone with a slight excess of aldehyde, fuse them, and gradually increase the temperature. This assumes you want the benzylidene ketone, and not the aldol product. A large excess of aldehyde might yield the α,α'-bis(benzylidene) product, so you'd want to stay close to the stoichiometric amount.
Protecting the Phenolic -OH group as acetate,p-nitro bezoate or benzyloxy carbonate before proceeding with acid catalysed aldol condensation is advisable.
It is good to protect hydroxy group, converting it to tetrahydropyranyl compound and then is possible to process the reaction in alkaline conditions.
Hi Anju,
Please see the attached paper. In that article, Cross-Aldol condensation of aromatic aldehydes with cyclic ketones in the presence of catalytic amount of iodine at room temperature is reported.
Good luck,
Rmin
Protecting -OH group as tetrahydropyranylderivative is good if the following step does not involve acid catalysed condensation. Protection as p-nitro bezoate mat be a better choice as it is not labile in acid condition.
Dr.ramin has given excellent paper. follow that procedure you will get compound with good yield.
I wonder who downvoted may answer. He need to understand well the nature of aldol condensation. Find in attached a link describing using LDA aldol condensation. I invite him to read well.
Under conditions of kinetic control, the mixed Aldol Addition can be used to prepare adducts that are otherwise difficult to obtain selectively. This process begins with the irreversible generation of the kinetic enolate, e.g. by employing a sterically hindered lithium amide base such as LDA (lithium diisopropylamide). With an unsymmetrically substituted ketone, such a non-nucleophilic, sterically-demanding, strong base will abstract a proton from the least hindered side. Proton transfer is avoided with lithium enolates at low temperatures in ethereal solvents, so that addition of a second carbonyl partner (ketone or aldehyde) will produce the desired aldol product.
https://www.google.com.eg/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahUKEwj7kZzR3sXPAhXhIsAKHThdDQYQFggtMAE&url=http%3A%2F%2Fwww.organic-chemistry.org%2Fnamedreactions%2Faldol-addition.shtm&usg=AFQjCNF3vICgO3sfHVRbWJVrYay-MXz2rQ
As well as, the paper provided by Dr. Ramin describe a method using I2 in CH2Cl2 at RT, it is a good method.
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