Method for preparing cucurbiturils
The invention relates to a method for preparing cucurbiturils. The method comprises reacting an oligomer consisting of 2 to 11 linked glycolurils or glycoluril analogues with one or more compounds selected from glycoluril, glycoluril analogues and/or oligomers of glycoluril or glycoluril analogues, in the presence of an acid, to form a cucurbituril. The method can be used to prepare variably substituted cucurbiturils having specific substituted units at specific locations in the cucurbituril. The invention also provides cucurbiturils prepared by the method of the invention. The invention further provides novel cucurbiturils.
1. A method for preparing a cucurbituril, the method comprising the steps of:
(a) selecting
(1) a compound of the formula (1)
wherein:
for each unit of the formula (A)
in the compound,
R 1 and R 2 may be the same or different and are each a univalent radical, or
R 1 , R 2 and the carbon atoms to which they are bound together form an optionally substituted cyclic group, or R 1 of one unit of the formula (A) and R 2 of an adjacent unit of the formula (A) together form a bond or a divalent radical, and
each R 3 is independently selected from the group consisting of ═O, ═S, ═NR, ═CXZ, ═CRZ and ═CZ 2 , where Z is an electron withdrawing group, X is halo and R is H, an optionally substituted straight chain, branched or cyclic, saturated or unsaturated hydrocarbon radical, or an optionally substituted heterocyclyl radical;
each R 5 is independently selected from the group consisting of H, alkyl and aryl;
R 7 and R 8 may be the same or different and are independently selected from the group consisting of H and —CHR 5 OR 5 , or R 7 and R 8 together form the group —CHR 5 —O—CHR 5 , where each R 5 is independently selected from the group consisting of H, alkyl and aryl;
R 9 and R 10 may be the same or different and are independently selected from the group consisting of H and —CHR 5 OR 5 , or R 9 and R 10 together form the group —CHR 5 —O—CHR 5 , where each R 5 is independently selected from the group consisting of H, alkyl and aryl; and
x is an integer from 1 to 10; and
(2) one or more compounds of the formula (2)
wherein:
for each unit of the formula (A)
in the compound,
R 1 and R 2 may be the same or different and are each a univalent radical, or
R 1 , R 2 and the carbon atoms to which they are bound together form an optionally substituted cyclic group, or R 1 of one unit of the formula (A) and R 2 of an adjacent unit of the formula (A) together form a bond or a divalent radical, and
each R 3 is independently selected from the group consisting of ═O, ═S, ═NR, ═CXZ, ═CRZ and ═CZ 2 , where Z is an electron withdrawing group, X is halo and R is H, an optionally substituted straight chain, branched or cyclic, saturated or unsaturated hydrocarbon radical, or an optionally substituted heterocyclyl radical;
each R 5 is independently selected from the group consisting of H, alkyl and aryl;
R 11 and R 12 may be the same or different and are independently selected from the group consisting of H and —CHR 5 OR 5 , or R 11 and R 12 together form the group —CHR 5 —O—CHR 5 —, where each R 5 is independently selected from the group consisting of H, alkyl and aryl;
R 13 and R 14 may be the same or different and are independently selected from the group consisting of H and —CHR 5 OR 5 , or R 13 and R 14 together form the group —CHR 5 —O—CHR 5 —, where each R 5 is independently selected from the group consisting of H, alkyl and aryl; and
y is 0 or an integer from 1 to 9 and x+y=10 or less;
(b) mixing the compound of formula (1), the one or more compounds of formula (2) and an acid to form a mixture; and
(c) exposing the mixture to conditions effective for the compound of the formula (1) and the one or more compounds of the formula (2) to form a cucurbit[n]uril.
2. A method according to claim 1 wherein R 1 and R 2 are independently selected from the group consisting of —R, —OR, —N 2 where each R is independently selected, —NO 2 , —CN, —X, —COR, —COX, —COOR,
where each R is independently selected,
where each R is independently selected, —SeR, —SiR 3 where each R is independently selected, —SR, —SOR,
—SO 2 R, —S—S—R, —BR 2 where each R independently selected, —PR 2 where each R is independently selected,
where each R is independently selected,
where each R is independently selected, —P + R 2 where each R is independently selected and a metal or metal complex,
wherein R is H, an optionally substituted straight chain, branched or cyclic, saturated or unsaturated hydrocarbon radical, or an optionally substituted heterocyclyl radical, and X is halo.
3. A method according to claim 2 wherein R is H, an optionally substituted C 1-10 alkyl, an optionally substituted C 2-10 alkenyl, or an optionally substituted C 5-10 aryl.
4. A method according to claim 1 wherein the mixture further comprises one or more compounds that can form bridges of the formula —CHR 5 — between compounds of formula (1) and (2).
5. A method according to claim 4 wherein the compound that can form bridges of the formula —CHR 5 — between compounds of formula (1) and (2) is selected from the group consisting of trioxane, optionally substituted 2,3-dihydropyran, optionally substituted 2,3-dihydrofuran, compounds of the formula R 5 COR 5 and compounds of the formula R 5 OC(R 5 ) 2 OR 5 , where each R 5 is independently selected and is H, alkyl or aryl.
6. A method according claim 5 wherein the compound that can form bridges of the formula —CHR 5 — between compounds of formula (1) and (2) is formaldehyde, paraformaldehyde or trioxane.
7. A method according to claim 1 wherein step (c) comprises heating the mixture to a temperature of from 20° C. to 120°C. for a period of time sufficient for the compound of formula (1) and the one or more compounds of formula (2) to form a cucurbit[n]uril.
8. A method according to claim 1 wherein R 7 ═R 8 , R 9 ═R 10 , R 11 ═R 12 and R 13 ═R 14 .
9. A method according to claim 1 wherein Z is selected from the group consisting of —NO 2 , —CO 2 R, —COR, —CN and —CX 3 , where X is halo and R is H, alkyl, alkenyl, alkynyl, aryl, or saturated or unsaturated heterocyclyl.
10. A method according to claim 1 wherein R 3 is ═O.
11. A method according to claim 1 wherein R 5 is H.
12. A method according to claim 1 wherein the mixture further comprises a templating compound.
13. A method according to claim 12 wherein the templating compound is a salt.
14. A method according to claim 13 wherein the anion of the salt corresponds to the anion of the acid in the mixture.
15. A method according to claim 12 wherein the templating compound is selected from ammonium chloride, lithium chloride, sodium chloride, potassium chloride, rubidium chloride, caesium chloride, ammonium bromide, lithium bromide, sodium bromide, potassium bromide, rubidium bromide, caesium bromide, lithium iodide, sodium iodide, potassium iodide, rubidium iodide, caesium iodide, potassium sulfate, lithium sulfate, tetrabutylammonium chloride, tetraethylammonium chloride, o-carborane, thioacetamide, N-(1-napthyl) ethylenediamine, 2,2′-biquinoline, p-bromoanaline, taurine, blue tetrazolium, 2-amino3-methyl benzoic acid, indol-3-aldehyde, cysteine, 4-acetamidoaniline, p-aminophenol, acetamide, 4-aminoacetophenone, 4-dimethylaminobezaldehyde, 2-aminobenzimidazol, bis-(4,4′-bipyridyl)-α,α′-xylene, red phosphorus, and lithium p-toluenesulfonate.
16. The method of claim 15 , wherein the templating compound is 4-dimethylaminobezaldehyde.
17. The method of claim 1 , wherein the acid is selected from the group consisting of sulfuric acid, hydrochloric acid, hydrobromic acid, hydriodic acid, deuterated sulfuric acid, phosphoric acid, p-toluenesulfonic acid and methane sulphonic acid.