N-alkylation of benzooxazine-3(4H)-one.
I have tried acetone, K2CO3: MeOH KOH/NaOH: K2CO3 in MeOH etc did not find anything working. I want to do reaction with chloroacetic acid or ethyl chloroacetate. Any suggestions?
try sodium hydride in THF, it is similar the alkylation of isatin.
The reaction of anyone depends on the nucleophilic ability and basicity of the anyone.
the diverse anyone show diffrent behaviour.
Meerweins salt (Me3O(+)BF4(-)) should definitely do an alkylation. But I think MeI Cs2CO3 maybe at elevated temperatures should do the trick as well.
Hi,
From my experience, inorganic bases are preferred for O-alkylations using ethyl chloroacetate. I would suggest to try DIPEA in THF as that worked well with both primary and secondary amines in my case. If not try in DMF also.
You can easily do this alkylation with ethyl chloroacetate in DMF containing NaH. You can also try to use acetone/K2CO3, with addition of KI as catalyst to enhance the SN2 reaction.
I did N-alkylation in CH3CN with anhydr. Na2CO3 and ethyl bromoacetate. I also used MeI and anhyd. Na2CO3 in DMF. Both worked well.
Similar reactions worked for me with K2CO3/DMF, NaH/THF at room temperature.
Ethyl bromoacetate is probably the better choice, and DMF as solvent, K2CO3 or NaH. Of course, acetone is easier to work with and so is K2CO3.
Sodium hydride in THF seems to be suitable for your alkylation if you use ethyl chloroacetate.
The N-alkylations procedures were governed by different methods depends on the nature of the NH-substrate. The most useful procedures If chloroacetic acid is used, the reaction could be performed in the use of Na2CO3, K2CO3 or Li2CO3 in DMF, THF, Dioxane or in DMSO. The same reagents were applied in the case of ethyl chloroacetate.
For interestingly, there is an early efficient reported method and gave an excellent yields was simplified in the use of K2CO3/Cu-metal in boiling xylene.
You may try NaH in DMF, zero degree to rt. Use 1eq of NaH and other agent.You will find maximum two spots for N-alklation and c-Alkylated product. You may optimize the conditions by adjusting Temprature . It will work, Inshallah.
Thanks and JazakAllah for suggestions hope one of them may work in our case
Hi Tashfeen,
I would go with the K2co3 or CsCo3/DMF suggestions. However, from a previous life, I would avoid any combination of NaH/DMF -as there are very real hazards (explosion) here. Good luck and regards, John Johnson, Appleton Scientific
Perhaps using NaH as base in DMF; Perhaps with weaker bases can also work after adding catalytic iodide (TBAI, for example).
First of all u react with methyl iodite then methyl group replace by acetate group by chloroformate or acetate
Probably you need to add NaI to your reaction; this will enhance the reactivity of the haloacetate. adding also a tetrabutyl ammonium salt may be beneficial.
First you need to neutralize by NaOH or anhydrous sodium acetate... Then add it dropwise to the other reagent in ethanolic or aqueous medium... Dunkley & Thoman, 2004; Asundaria et al, 2010).
try in NaOAc a s base and EtOH as solvent at 90 oC. I suceeded. But keep reaction monitoring and add excess of abse and alkylaing agent to complete
I think you are building the benzoxazine-3(4H)-one from o-aminophenol and chloroacetic acid and base. Take ethyl chloroacetate excess to get the O- and N- alkylated o-aminophenol and try to cyclize it in a refluxing solvent. There is a good chance of getting the target product.
Reaction with chloroacetic acid or ethyl chloroacetate use Acetone as a solvent & K2CO3 as a base , with NH containing compounds under refluxing condition..However, reaction requires longer time.
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