O-Quinol

Hydroxyprotoberberine 59a and ( )-corytencine (98) led to 13-acetoxy compounds 104,105, and 107 moreover, the 2,3,9,10,12-pentaoxy-genated protoberberine 108 was also obtained from 98 via the p-quinol acetate 106 through a retro-Mannich reaction followed by recyclization (74,75). Oxidation in dichloromethane instead of acetic acid proceeded differently, namely, 97 and 98 led to pentaoxygenated protoberberines 103 and 109 by introduction of an acetoxyl group at C-4 and C-12, respectively, via o-quinol acetates (76). 

In a continuing study of the synthesis of aporphines via o-quinol acetates, 1,2-diacetoxyaporphines of the type (32) were obtained in good yields by treatment of solutions of the o-quinol acetates (31), in acetonitrile, with concentrated sulphuric acid in acetic anhydride.45... 

FIGURE 9. Marcus analysis of electron transfer reactions between MADH and amicyanin. Values of kn Twere determined for the reactions of different redox forms of MADH with amicyanin shown in Figure 8 0-quinol (A), O-semiquinone ( ), N-semiquinone ( ). Rate constants were also obtained for the reverse reactions of the O-quinol (A) and O-semiquinone ( ). The solid line represent fits to Eqs. 4 and 5, which are superimposible. 

In addition to these reactions typical of the (n,nr ) state, 6-acetyloxycy-clohexadienones (o-quinol acetates) form phenols from the state. 

Figure 7.50. Schematic state correlation diagram for o-quinol acetate photoreactions. Wavy arrows designate physical as well as chemical radiationless processes (by permission from Quinkert et al., 1986).

A preference of 1,4-addition by the alkylmagnesium halide species rather than the dialkylmagnesium species, was observed during the reactions of di-/-propylmagnesium and /-propylmagnesium bromide in diethyl ether with the o-quinol acetate 40 [53]. Between concentrations of 0.06 and 0.24 M in diethyl ether, only 2% of 1,4-addition product 41 was observed with the dialkylmagnesium species. However, at 0.24 M concentration of... 

Quite often the products of the benzoin condensation are unstable to oxygen and lead to a-diketones. This is the case in intramolecular condensations when the initial product is an o-quinol, which is easily oxidized to the quinone. 4-Substituted tetramides can be prepared by the reaction of an aromatic aldehyde with oxalaldehyde in the presence of cyanide ion, via the benzoin condensation (Scheme 8). ... 

The migration of oxygen from a quaternary center in a cyclohexadienone may be preferred to a carbon shift, when present as an ether or ester function rather than free hydroxy. Thus the p-quinol acetate (117) yields the orcinol monoacetate (118 79%) on treatment at room temperature with trifluoroacetic anhydride, and the p-quinol ether (119) forms the resorcinol diethyl ether (120 71%) in ethanolic sulfuric acid. In the second case, hemiketalization must intervene also some methyl shift (12%) is observed. With the quinol (121), treatment with acetic anhydride-sulfuric acid leads to the lactone (122) acetylation or lactonization probably precedes oxygen shift. A number of related examples can be found in the steroid area. - Thermal 1,3-shifts of p-quinol acetates can also be induced acetate (117) yields catechol acetate (123 50-60%, 45 °C) by way of isomerization of the first-formed acetate (124). In the o-quinol acetate series, 1,2-acetoxy shift is seen in (125) (126 92%) and in (127) (128 90%), both in... 

A number of o-quinol diacetates have been prepared and they rearrange smoothly to triacetoxyben-zenes o — o migration is preferred unless the latter position is blocked or sterically crowded, when acetoxy shift is directed to another aryl site. The range of possibilities is indicated by the conversions of the o-quinol diacetates (131)-(134) to the 1,2,3- or 1,2,4-triacetoxybenzenes (135)-(138), in 56-90% yields. 

The conventional dienone-phenol rearrangements of o-quinol acetates are described above. An alternative mode of restructuring to an aromatic system has been observed, exemplified by the quantitative conversion of the 2,4-dienone (155) on heating at 110 C in acetic acid to the benzylic acetate (156). The related 2,4-dienone (157) rearranges at 70-80 °C in dimethyl sulfoxide-sodium bicarbonate to the... 

Dunethylphenol (206) underwent NaI04 oxidation in 1 1 EtOH-HiO containing p-benzoquinone resulting mainly in the formation of a 1 1 adduct 603 (68%) together with the o-quinol dimer 604 (6%) (Scheme 115) °. ... 

Aspersitin (855) is a fungal metabolite of Aspergillus parasiticus NRRL 3260. This metabolite was synthesized successfully by Btichi and coworkers . The key compound (856), prepared from dimethylphloroglucinol in 5 steps, was treated with Pb(OAc)4 in AcOH to afford the corresponding o-quinol acetate 857 in 93% yield. Further treatment of 857 with NFLjOH-MeOH provided two 1 1 diastereomers of 855. 

Dimethylphenol (206) was treated with NaBiOs in benzene to afford polyphenylene oxide (659) and 3,3, 5,5 -tetramethyldiphenoquinone (207) in 74 and 12% yields, respectively . This result is similar to that of Mn02 oxidation (see Scheme 126). In contrast, the use of AcOH instead of benzene as a solvent provided the corresponding quinol acetate 864 and 207 in 38 and 15% yields, respectively (Scheme 174) °. Oxidation of 2,4,6-tri(tert-butyl)phenol (73) with NaBiOs in AcOH afforded the p-quinol acetate (865) as a major product (62%) and the o-quinol acetate (866) as a minor product (22%). In contrast, Pb(OAc)4 oxidation of 73 in AcOH provided 866 as a main product (60%) (see Scheme 170). Oxidation of alkoxyphenols and other phenols has also been studied . ... 

Since many isoquinoline alkaloids incorporate a guiacol moiety, we first tried to oxidize the most accessible 6-methoxy- and 7-methoxy-l,2,3,4-tetrahydroisoquinolinols (types A and B) with LTA. Later, tetrahydro-isoquinolinols of type C were also used. In spite of Wessely s statement (16) that LTA oxidation of both vanillin and isovanillin affords the corresponding o-quinol acetates, for a while we were able to obtain not the o-quinol acetate 2 from corypalline (1) but the p-quinol acetate 3 (17). At the outset of our study (IS), LTA oxidation of isocorypalline (4) gave no isolable o-quinol acetate 5, 4-acetoxyisocorypalline (6) being isolated instead. 

On the other hand, the o-quinol acetate 81 derived from 77 when treated with concentrated sulfuric acid in methanol unexpectedly afforded two diastereomeric mixtures of p-quinol methyl ethers 93 and 4-methoxylated compound 94 in 40 and 12,4% yield, respectively (49) (Scheme 11). Treatment of 92 with acetic anhydride containing concentrated sulfuric acid ensured cyclization to give ( )-(9-acetylthaliporphine (13) in 60% yield. Similarly, ( )-O-acetyldomesticine (22) was also prepared in 71.8% yield from the p-quinol methyl ether 95, which was formed together with 96 on LTA oxidation of 78 (50). 

LTA oxidation of ( )-laudanine (103) under the above conditions readily gives the o-quinol acetate 104, TFA treatment of which as usual produces two compounds (53,54) one is ( )-A -methyllaurotetanine (39) (17% yield) and the other ( )-l,2,3,4-tetrahydro-I-hydroxy-6,7-dimeth-oxy-2-methylisoquinoline (105) (56% yield) (Scheme 13). The yield of the former was raised to 23% on LTA oxidation of 103 in a mixture of TFA and CHiCL. On the other hand, treatment of o-quinol acetate 104... 

As in the case of 1-benzyl congeners, LTA oxidation in CHaCF of ( )-1,2,3,4-tetrahydro-7-methoxy-1 -(3,4-dimethoxyphenethyl)-2-methyl-isoquinolin-6-ol (172) was found to give quantitatively o-quinol acetate 175, the structure of which was readily determined by spectroscopy. However, treatment of the unpurified o-quinol acetate 175 with acetic anhydride containing concentrated sulfuric acid produced ( )-2-acetoxy-1,10,11-trimethoxy-C-homoaporphine (178) in 25.3% yield, accompanied by a comparable amount of a biphenyl compound (181) (58). The... 

It is noteworthy that when the o-quinol acetate 177 derived from 174 was treated with acetic anhydride containing concentrated sulfuric acid, the product was ( )-C-homoaporphine 180, whose stereostructure was confirmed to be 186 by X-ray crystallographic analysis of a methiodide of 180 (59). Furthermore, 186 was heated at 60°C to give a more stable stereoisomer, which should be 187. 

Recently, we found that TFA treatment in CH2CI2 of o-quinol acetates 66 and 69 derived from 64 and 65 at low temperatures gave the corresponding ( )-morphinandienones 220 and 221 besides ( )-apor-phines 68 and 70 (Scheme 23). The ratio of morphinandienone and aporphine was approximately 1 1 in the reaction of o-quinol acetates 66 and 69 in acetonitrile at -25°C for 5 min (43). 

Benzene ring acetoxylation via the o-quinol acetate has been developed in our laboratory (113,114). LTA oxidation in CH2CI2 of isocorypalline (4) gave o-quinol acetate (5) (Scheme 1), treatment of which with acetic anhydride including concentrated sulfuric acid afforded 5-acetoxy-6- )-acetylisocorypalline (438) in 19.4% yield. Hydrolysis of 438 with concentrated hydrochloric acid in methanol afforded a 5,6-diol hydrochloride, methylation of which with diazomethane led to tehaunine (439) in 22.1% yield. Similarly, ( )-7V-methylsalsoline (440) and ( )-I,2,3,4-tetrahydro-7-methoxy-l-(4-methoxybenzyl)-2-methylisoquinolin-6-ol (441) were transformed to ( )-C>-methylgigantine (444) and ( )-tetrahydrotakatonine (445) in 4 and 0.48% yield, respectively, via 442 and 443 (Scheme 59). 

Recently, Gozler et al. (123) proposed the stereostructure 1,4-ci s-l,2,3,4-tetrahydro-4,6-dihydroxy-7-methoxy-l-(3,4-dimethoxyben-zyl)-2-methylisoquinoline (446) for (-l-)-roemecarine. However, the stereostructure was revised to 449 based on the synthesis of 446 (124). Namely, two epimeric acetates, ( )-l,4-(ij- and ( )-l,4-/r zi.v-4-acetoxy-l,2,3,4-tetrahydro-6-hydroxy-7-methoxy-1 -(3,4-dimethoxybenzyl)-2-methyliso -quinolines (447 and 448), previously prepared via a thermal isomerization of the corresponding o-quinol acetates (19), were used for synthesis of ( )-roemecarine and its epimer (Scheme 60). Hydrolysis of 447 and 448 with 5% methanolic potassium hydroxide proceeded with retention of the configuration at C-4 to give the authentic ( )-1,4-c/.v- and ( )-i,4-tran.s-diols 446 and 449. As a result, structure 446 was inconsistent with natural roemecarine on the basis of H-NMR spectral comparison, while 449 was identical with the alkaloid with respect to spectroscopic data. 

Oxidation of 5-hydroxyisoquinolines 107a,b,c with LTA in dichloromethane gave the o-quinol acetate 108 which was converted with trifluoroacetic acid to the 3-hydroxyhomoaporphine 109 (64,65). Treatment of o-quinol acetate 111 prepared from 6-hydroxyisoquinoline 110 with acetic anhydride in the presence of an acid (concentrated sulfuric acid, boron trifluoride, or trifluoroacetic acid) gave the 2-hydroxyhomoaporphine 112 (66). 

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