Quinol acetates synthesis

A full paper has appeared describing the oxidation of 6-hydroxylated tetrahy-drobenzylisoquinolines of type (38) with lead tetra-acetate, to furnish the corresponding ortho-quinol acetates (39), which can readily undergo cyclization to the corresponding aporphines in acid solution. Predicentrine (40), isodomesticine (41), boldine (42), and 2,10-dihydroxy-1,9-dimethoxyaporphine (43) were prepared by such a route, which is, therefore, a practical pathway for the synthesis of 2-hydroxylated aporphines.27... 

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... 

A full paper has appeared describing the synthesis of the aporphines (34) and (35) through treatment of the p-quinol acetate (33) with trifluoroacetic acid.46 The non-identity of (35) with natural lirinine confirmed structure (36) for lirinine. 

Pattenden and coworkers have recently evaluated the relative merits of LTA and electrochemical oxidation of phenolic compounds with particular reference to synthesis of the antiallergic compounds sodium chromoglycate (lOTAL 53) and proxicromil (54), which are used for the prophylactic treatment of asthma. The 2-carboxychromone moieties in the compounds (53) and (54) are synthesized from the appropriate 2, 6 -dihydroxyacetophenones. Oxidation of the 2 -hydroxyacetophenone (55) by LTA in (U-chloromethane gave almost exclusively the quinol acetate (56), which was subsequently converted to the 2, 6 -dihydroxyacetophenone (57), a precursor to proxicromil (54 Scheme 21). By contrast, electro-... 

In the early 1970s, our attention was directed to the Wessely acetoxy-lation (13). LTA oxidation of phenolic tetrahydroisoquinolines was exploited in our laboratory to give the corresponding p-quinol acetates, which were proved to be the reactive intermediates for the aporphine synthesis (14-15)-, that is, when an electron-rich benzene ring was present in a given p-quinol acetate, C-C bond formation occurred intramolecu-larly on its acid treatment. 

Aporphine synthesis via a p-quinol acetate was first achieved in our laboratory (14,15). LTA oxidation in AcOH of ( )-codamine (11) gave a p-quinol acetate (12) (Scheme 2), the structure of which was characterized by spectroscopic means. Treatment of acetate 12 with acetic anhydride in the presence of concentrated sulfuric acid gave ( )-( -acetylthaliporphine... 

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. 

A synthesis of bistetrahydroisoquinolines using p-quinol acetate 3 and 8,8a-epoxy p-quinol 495 was performed (130-132). Reaction of 3 cory-palline (1) (130), isocorypalline (4), and 6- and 7-tetrahydroisoquinolinols (131) and subsequent acetylation gave substituted bistetrahydroisoquinolines 487-492 (Scheme 64). Interestingly, similar treatment of 3 with... 

Discovery of the dienone-phenol rearrangement of quinol acetates has made possible the synthesis of dihydric phenols that were difficult of access by other routes. The starting materials are obtained from phenols and lead tetraacetate, and with acetic anhydride and sulfuric acid (Thiele acetylation) or with boron trifluoride in ether they give, respectively, di- and mono-acetyl derivatives of resorcinol or hydroquinone.309 When treated with lN-sodium hydroxide, 0-quinol acetates of type (1) undergo nucleophilic addition of an OH" ion, giving resorcinol derivatives (2).310 Occurrence of the reaction is considered... 

Scheme 11. Synthesis of the aporphine alkaloids (24) via the p-quinol acetate route (413).

The synthetic method using p-quinol acetates to prepare aporphines has been extended to the synthesis of ( )-kreysigine (220). Treatment with acid of the p-quinol acetate (225a) derived from ( + )-(225) gave ( )-0-acetylkreysigine in 18%yield.2 5... 

Its synthesis has been fully clarified211 . The quinol-ester 5 is the probable primary product. An intramolecular Diels Alder addition leads to 6 and dehydrogenation gives 7. Reduction with zinc/acetic affords the phenanthrol carbonic acid 8. Since these reactions as well as similar reactions using propiolic acid are reported in the literature2U), the experimental details shall not be repeated in this review. The results... 

For the synthesis of 13-hydroxysparteine the starting material was a-picoline iV-oxide (CXVIII) which was nitrated and the nitro group then replaced by benzyloxy. The action of acetic anhydride induced the Boekelheide rearrangement to the acetoxymethyl derivative CXIX. The latter, via the alcohol, the chloride, the cyanide, and the ester, was condensed with ethyl hydroxymethylenepyridylacetate to the quinol-izone CXX, hydrogenation and reduction of which with lithium aluminum hydride gave a separable mixture of hydroxysparteines. The... 

The photochemical addition of ethene at 0°C in methylene chloride to the enedione (77) affords a high yield of the adduct (78). This was converted to the monochloro derivative (79) which also undergoes photoaddition of ethene to yield the Z> adduct (80). This on elimination of HCl yielded the quinol (81) which can be oxidised to the quinone (82). Cycloaddition of alkenes (cyclopentene, cyclohexene, and cycloheptene) has been carried out to the same enedione (77) to yield the adducts (83). lyoda et al. have also described a convenient synthesis of the bicyclo-octanediones(84) by a photochemical addition of alkenes to the enedione (77). The adducts (84) can be reduced by zinc in acetic acid to the desired products. Cycloaddition of ethyne to the same enedione followed by reduction affords the bicyclooctanes (85). The photoaddition of alkenes to the dibromo-enedione (86) is also effective and yields, after reduction, the adducts (87). 

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