SINGLY PROTECTED 2,2' -DIHYDROXYBIARYLS

Abstract

Novel singly protected 2,2′-dihydroxybiaryls, electrochemical process for preparation of singly protected 2,2′-dihydroxybiaryls.

Claims

1. Compound having one of the general structures (I) to (IIb): ##STR00021## where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.1′, R.sup.2′, R.sup.3′, R.sup.4′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —SO.sub.3H, —CN, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; R.sup.5′, R.sup.6′, R.sup.7′, R.sup.8′, R.sup.9′, R.sup.10′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —SO.sub.3H, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; where the alkyl and aryl groups mentioned may be substituted; and, in the formula (I), the two radicals in at least one of the four following radical pairs are not the same radical: R.sup.1 and R.sup.1′, R.sup.2 and R.sup.2′, R.sup.3 and R.sup.3′, R.sup.4 and R.sup.4′, X.sup.2 is selected from: tert-butyl, -methylthioethyl, -trimethylsilyl, -triethylsilyl, -triisopropylsilyl, -tert-butyldimethylsilyl, -tert-butyldiphenylsilyl, -acetyl, -pivaloyl, -benzoic ester, -3-(2-nitrophenyl)acetyl, -oxoacyl, -trifluoromethanesulphonyl, X.sup.2′ is selected from: tert-butyl, -methylthioethyl, -trimethylsilyl, -triethylsilyl, -triisopropylsilyl, -tert-butyldimethylsilyl, -tert-butyldiphenylsilyl, -acetyl, -pivaloyl, -benzoic ester, -3-(2-nitrophenyl)acetyl, -oxoacyl, -trifluoromethanesulphonyl; X.sup.1 is selected from: -trimethylsilyl, -triethylsilyl, -triisopropylsilyl, -tert-butyldimethylsilyl, -tert-butyldiphenylsilyl.

2. Compound according to claim 1, where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.1′, R.sup.2′, R.sup.3′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen.

3. Compound according to claim 1, where R.sup.5′, R.sup.6′, R.sup.7′, R.sup.8′, R.sup.9′, R.sup.10′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen.

4. Compound according to claim 1, where the compound has the general structure (I).

5. Compound according to claim 1, where the compound has the general structure (IIa) or (IIb).

6. Process for preparing 2,2′-dihydroxybiaryls, comprising the process steps of: a1) reacting a compound of the formula (IVa): ##STR00022## with X.sup.11 to give (IVb) ##STR00023## b1) electrochemically coupling: ##STR00024## (IVb) with (V) to give (VI) with use of the compound having the higher oxidation potential in excess: ##STR00025## where R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.11′, R.sup.12′, R.sup.13′, R.sup.14′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —SO.sub.3H, —CN, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; where the alkyl and aryl groups mentioned may be substituted; X.sup.11 is selected from: tert-butyl, -methylthioethyl, -trimethylsilyl, -triethylsilyl, -triisopropylsilyl, -tert-butyldimethylsilyl, -tert-butyldiphenylsilyl, -acetyl, -pivaloyl, -benzoic ester, -3-(2-nitrophenyl)acetyl, -oxoacyl, -trifluoromethanesulphonyl, tetrahydropyranyl, -allyl ether, -benzyl, -p-methoxybenzyl, -3,4-dimethoxybenzyl, -aryl, -methoxymethyl.

7. Process for preparing 2,2′-dihydroxybiaryls, comprising the process steps of: a2) reacting a compound of the formula (VIIa): ##STR00026## with X.sup.12 to give (VIIb): ##STR00027## b2) electrochemically coupling: ##STR00028## (VIIb) with (VIII) to give (IX) with use of the compound having the higher oxidation potential in excess: ##STR00029## where R.sup.11, R.sup.12, R.sup.13, R.sup.14 are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —SO.sub.3H, —CN, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; R.sup.15′, R.sup.16′, R.sup.17′, R.sup.18′, R.sup.19′, R.sup.20′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —SO.sub.3H, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; where the alkyl and aryl groups mentioned may be substituted; X.sup.12 is selected from: tert-butyl, -methylthioethyl, -trimethylsilyl, -triethylsilyl, -triisopropylsilyl, -tert-butyldimethylsilyl, -tert-butyldiphenylsilyl, -acetyl, -pivaloyl, -benzoic ester, -3-(2-nitrophenyl)acetyl, -oxoacyl, -trifluoromethanesulphonyl, tetrahydropyranyl, -allyl ether, -benzyl, -p-methoxybenzyl, -3,4-dimethoxybenzyl, -aryl, -methoxymethyl.

8. Process for preparing 2,2′-dihydroxybiaryls, comprising the process steps of: a3) reacting a compound of the formula (Xa): ##STR00030## with X.sup.12′ to give (Xb); ##STR00031## b3) electrochemically coupling: ##STR00032## (Xb) with (XI) to give (XII) with use of the compound having the higher oxidation potential in excess: ##STR00033## where R.sup.11, R.sup.12, R.sup.13, R.sup.14 are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —SO.sub.3H, —CN, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; R.sup.15′, R.sup.16′, R.sup.17′, R.sup.18′, R.sup.19′, R.sup.20′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —SO.sub.3H, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; where the alkyl and aryl groups mentioned may be substituted; X.sup.12′ is selected from: tert-butyl, -methylthioethyl, -trimethylsilyl, -triethylsilyl, -triisopropylsilyl, -tert-butyldimethylsilyl, -tert-butyldiphenylsilyl, -acetyl, -pivaloyl, -benzoic ester, -3-(2-nitrophenyl)acetyl, -oxoacyl, -trifluoromethanesulphonyl, tetrahydropyranyl, -allyl ether, -benzyl, -p-methoxybenzyl, -3,4-dimethoxybenzyl, -aryl, -methoxymethyl.

9. Process for preparing 2,2′-dihydroxybiaryls, comprising the process steps of: a4) reacting a compound of the formula (XIIIa): ##STR00034## with X.sup.13 to give (XIIIb): ##STR00035## b4) electrochemically coupling: ##STR00036## (XIIIb) with (XIV) to give (XV) with use of the compound having the higher oxidation potential in excess: ##STR00037## where R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19, R.sup.20, R.sup.15′, R.sup.16′, R.sup.17′, R.sup.18′, R.sup.19′, R.sup.20′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —SO.sub.3H, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; where the alkyl and aryl groups mentioned may be substituted; X.sup.13 is selected from: tert-butyl, -methylthioethyl, -trimethylsilyl, -triethylsilyl, -triisopropylsilyl, -tert-butyldimethylsilyl, -tert-butyldiphenylsilyl, -acetyl, -pivaloyl, -benzoic ester, -3-(2-nitrophenyl)acetyl, -oxoacyl, -trifluoromethanesulphonyl, tetrahydropyranyl, -allyl ether, -benzyl, -p-methoxybenzyl, -3,4-dimethoxybenzyl, -aryl, -methoxymethyl.

10. (canceled)

Description

[0128] The invention is illustrated in detail hereinafter by working examples and figures.

[0129] FIG. 1 shows, in schematic form, the electrochemical processes at the anode. This shows the mechanical concept for electrochemical formation of unsymmetric, partly protected dihydroxybiaryl derivatives.

[0130] There is selective oxidation of the phenol component A, which has a lower oxidation potential than B. As a result of the high reactivity of the free-radical species A. formed, the latter is capable of being attacked nucleophilically by component B. The first oxidation potentials of the two substances are crucial to the course of the reaction. The controlled addition of protic additives such as MeOH or water to the electrolyte can enable a shift in precisely these oxidation potentials. Thus, yield and selectivity of the reaction become controllable.

(PG: protecting group)

[0131] FIG. 2 shows the schematic setup of a reaction apparatus in which the coupling reaction to give the corresponding unsymmetric 2,2′-biaryls can be conducted. The reaction apparatus comprises glassy carbon electrodes (5) held with stainless steel clamps (4). A magnetic stirrer bar (6) ensures mixing in the reaction apparatus. A Teflon stopper (2) rests on top of the reaction apparatus, through which stainless steel holders (1) for the electrodes lead. The reaction apparatus, a beaker cell here, has a fitted outlet (3) for a reflux condenser attachment.

[0132] Examples of possible protecting groups:

##STR00019## ##STR00020##

[0133] The introduction of the protecting groups can be effected, for example, as described in P. G. M. Wuts, T. W. Greene “Greene's Protective Groups in Organic Synthesis”, fourth edition, 2007, John Wiley and Sons; Hoboken, N.J.

[0134] The process according to the invention does not have the disadvantages mentioned in the prior art (A. Kirste, B. Elsler, G. Schnakenburg, S. R. Waldvogel, in J. Am. Chem. Soc., 2012, 134, 3571-3576). By virtue of the protecting group already being introduced in the first process step, costly purification steps at the end of the synthesis chain which lead to minimization of product of value are avoided. An additional factor is that the protecting group can be introduced selectively into one phenol. No reaction of any other OH group takes place, since the compound contains only one OH group, in contrast to the later dihydroxybiaryl.