i usually have heard about water: t-butanol system but my compound is insoluble in water and is non-polar?
Can be tried in following solvents
a) DMF
b) THF
c) Dioxane
d) Polyethylene glycol with min water
e) Acetonitrile.
Solvent for azide alkyne cycloaddition, you cantry acetonitrile, ethylene glycol, THF or high b.p. solvent DMSO.
This depends on your expectation on regio-selective outcome of the reaction. Even though azide-alkyne Huisgen dipolar cycloaddition reactions are considered as highly regiioselective, if your requirement is entirely 1,4- adduct, go for click chemistry conditions.
The thermal Huisgen 1,3-Dipolar Cycloaddition of alkynes to azides requires elevated temperatures and often produces mixtures of the two regioisomers in case of asymmetric alkynes. Click chemistry (copper-catalyzed variant) follows a different mechanism that can be readily conducted under aqueous conditions, at room temperature conditions. As told before, classic Huisgen 1,3-dipolar cycloaddition often gives mixtures of regioisomers, the copper-catalyzed reaction allows the synthesis of the 1,4-disubstituted regioisomers selectively. However, ruthenium-catalyzed reaction gives the opposite(1,5-) regioselectivity with the formation of 1,5-disubstituted triazoles.
You can also run this reaction under neat(no solvent) conditions at elevated temperatures, but may end up in mixture of 1,4- and 1,5-cycloadducts. A wide variety of solvents can be employed here Polar aprotic solvents such as THF, DMSO, Acetonitrile, DMF as well as non-polar aprotic solvents such as toluene/benzene are commonly used solvents for cycloaddition. Neat solvents or a mixture of solvents may be used based on your regio-chemistry requirements of the product .
The Phenyl acetylenes are insoluble in t-BuOH: H2O, I heated at 50 C, reaction went well and I got very good yields.
Even you can vary the t-BuOH: H2O ratio, you do not have to exactly follow the literature. I mean the organic solvent ratio can be increased for the improvement of solubility. But you must be using catalytic amounts of NaAsc and CuSO4.
You can even use common solvent acetonitrile: H2O system and CuI, DIPEA. same here you can vary the solvent ratio. Wishes!
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