Process for the production of tetraaminobiphenol macrocyclic ligands; and novel tetraaminobiphenol macrocyclic ligands
A process for preparing a tetra-substituted aminobiphenol macrocyclic ligand having the structure (I), including the step of treating a precursor compound having the structure (II) with a compound having the structure R6-L where L is a leaving group (hereafter compound (III)) in the presence of a base.
1. A compound of structure (le)
wherein R 1 and R 2 are independently selected from hydrogen, halide, a nitro group, a nitrile group, an imine group, —NCR 13 R 14 , an amine, an ether group —OR 15 or —R 16 OR 17 , an ester group —OC(O)R 10 or —C(O)OR 10 , an amido group —NR 9 C(O)R 9 or —C(O)—NR 9 (R 9 ), —COOH, —C(O)R 15 , —OP(O)(OR 18 )(OR 19 ), —P(O)R 20 R 21 , a silyl group, a silyl ether group, a sulfoxide group, a sulfonyl group, a sulfinate group or an acetylide group or an optionally substituted alkyl, alkenyl, alkynyl, haloalkyl, aryl, heteroaryl, alkoxy, aryloxy, alkylthio, arylthio, alicyclic or heteroalicyclic group;
R 3 is independently selected from optionally substituted alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene, arylene, heteroarylene or cycloalkylene, wherein alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene and heteroalkynylene, in each case optionally interrupted by aryl, heteroaryl, alicyclic or heteroalicyclic;
R 4 is independently selected from hydrogen, or optionally substituted aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl, heteroaryl, alkylheteroaryl or alkylaryl;
and E is independently selected from NR 5 and NR 6 ,
wherein R 5 is independently selected from optionally substituted aliphatic, heteroaliphatic, alicyclic, alkanoate, arylate, carboxyl, heteroalicyclic, aryl, heteroaryl, alkylheteroaryl or alkylaryl;
or two R 5 species may together be selected from optionally substituted alkylene, alkenylene or alkynylene, bonded to two different N groups of the compound of structure (Ie);
wherein R 6 is independently selected from optionally substituted aliphatic, alicyclic, heteroalicyclic, aryl, heteroaryl, ether, polyether, or optionally substituted alkylaryl or alkylheteroaryl;
with the first proviso that at least one of the species E conforms to the definition given for NR 6 ;
and with the second proviso that the groups R 5 and R 6 are not all identical with each other;
wherein R 9 , R 10 , R 13 , R 14 , R 18 , R 19 , R 20 and R 21 are independently selected from hydrogen or an optionally substituted aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl group and R 15 , R 16 and R 17 are independently selected from an optionally substituted aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl group.
2. The compound according to claim 1 , wherein each occurrence of R 1 and/or each occurrence of R 2 , is the same.
3. The compound according to claim 1 , wherein R 1 is different from R 2 .
4. The compound according to claim 1 , wherein R 1 and R 2 are independently selected from hydrogen, halide, amino, nitro, sulfoxide, sulfonyl, sulfinate, silyl, silyl ether and an optionally substituted alkyl, alkenyl, aryl, heteroaryl, heteroalicyclic, alkoxy, aryloxy or alkylthio or arylthio.
5. The compound according to claim 4 , wherein R 2 is hydrogen or alkyl and R 1 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, alkoxy, aryl, halide, nitro, sulfonyl, silyl or alkylthio.
6. The compound according to claim 5 , wherein R 2 is hydrogen and R 1 is independently selected from t-butyl, n-butyl, i-propyl, methyl, piperidinyl, methoxy, hexyl methyl ether, —SCH 3 , —S(C 6 H 5 ), H, nitro, trimethylsilyl, triethylsilyl, methylsulfonyl (—SO 2 CH 3 ), triethylsilyl, halogen or phenyl.
7. The compound according to claim 1 , wherein R 3 is independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene or heteroalkynylene group which may optionally be interrupted by an aryl, heteroaryl, alicyclic or heteroalicyclic group, or may be a divalent arylene or cycloalkylene group which acts as a bridging group between two nitrogen centres in the compound of structure (Ie).
8. The compound according to claim 7 , wherein R 3 is independently selected from a substituted or unsubstituted alkylene, cycloalkylene, alkenylene, heteroalkylene and arylene.
9. The compound according to claim 8 , wherein R 3 is independently selected from 2,2-dimethylpropane-1,3-diyl, ethane-1,2-diyl, 2,2-fluoropropane-1,3-diyl, propane-1,3-diyl, butane-1,4-diyl, phenylene, cyclohexane-1,4-diyl, cyclohexane-1,2-diyl or biphenylene.
10. The compound according to claim 9 , wherein R 3 is independently selected from 2,2-dimethylpropane-1,3-diyl, ethane-1,2-diyl, 2,2-fluoropropane-1,3-diyl, phenylene, cyclohexane-1,4-diyl, cyclohexane-1,2-diyl or biphenylene.
11. The compound according to claim 1 , wherein R 4 is independently selected from hydrogen, and optionally substituted aliphatic or aryl.
12. The compound according to claim 11 , wherein R 4 is independently selected from hydrogen, and optionally substituted alkyl or aryl.
13. The compound according to claim 12 , wherein R 4 is independently selected from hydrogen, methyl, ethyl, n-propyl, n-butyl, phenyl and trifluoromethyl.
14. The compound according to claim 1 , wherein R 5 is independently selected from optionally substituted alkyl which is optionally interrupted by at least one N atom, or by at least one O atom, or by at least one S atom, optionally substituted alkylthio, alkylaryl, alkylheteroaryl, alkenyl, alkynyl, heteroalkenyl, heteroalkynyl, aryl, alicyclic, heteroalicyclic, heteroaryl, sulfonate, alkanoate (—C(O)—OR 10 ), arylate (arylC(O)O—), aryl-C(O)OR 10 , alkylaryl-C(O)OR 10 , alkyl-C(O)—OR 10 , carbonyl (—C(O)—R 10 ), ether, polyether, alkylarylC(O)O— or carboxyl; or two R 5 groups together comprise an optionally substituted alkylene group bonded to two different N groups on the same macrocycle.
15. The compound according to claim 14 , wherein R 5 is independently selected from optionally substituted alkyl, alkylaryl, alkenyl, alkynyl, sulfonate, alkanoate, aryl-C(O)OR 10 , alkylaryl-C(O)OR 10 , alkyl-C(O)—OR 10 or alkyl-C≡N.
16. The compound according to claim 15 , wherein R 5 is independently selected from methyl, ethyl, propyl, butyl, allyl, propargyl, benzyl, 4-nitrobenzyl, —CH 2 CH 2 —C(O)—OR 10 , —CH 2 CH 2 —C≡N, or —C(1-4)alkylC(O)O—, or benzoate which is unsubstituted or ring-substituted by 1, 2 or 3 C(1-4)alkyl groups.
17. The compound according to claim 1 , wherein R 6 is independently selected from optionally substituted alkyl, alicyclic, alkenyl, alkynyl, alkylaryl, methylpyridine, ether, polyethylene glycol, or polypropylene glycol.
18. The compound according to claim 17 , wherein R 6 is independently selected from an optionally substituted alkylaryl, C(2-10)alkenyl group, C(2-10)alkynyl group, C(1-10) alkyl, allyl, propargyl or benzyl.