Benzofuranols

Arylation of enamines with p-benzoquinones takes a somewhat different course (70). The enamine (16) reacts exothermally with p-benzoquinone in benzene solution to give 2-(dimethylamino)-2,3-dihydro-3,3-dimethyl-5-benzofuranol (92). The reaction of enamines with quinone dibenzenesul-fonimide proceeds similarly (68). The product from the enamine (28) is the tetrahydrocarbazole derivative (93). 

The addition of p-quinone to enamines normally produces furan derivatives, especially when the enamine possesses a 3 hydrogen (see Section III. A). 1,2 Cycloaddition is claimed to take place to give a cyclobutane derivative when p-quinone and an enamine with no jS hydrogens are allowed to react at low temperatures (51). However, little evidence is reported to verify this structural assignment, and the actual structure probably is a benzofuranol (52). Reaction of a dienamine (formed in situ) with p-quinone in the presence... 

FIGURE 6.12 Traditional application of the Mills-Nixon effect theory to a-tocopherol-type henzopyranols and benzofuranols, having an anullation angle sum of (a + (3). 

Dihydro-6- [3-(2-hydroxymethyl)-phenyl-2-propenyl]-5-benzofuranol +0.55 glassy carbon 264... 

Meyers and Novachek described the Stille coupling of a chiral 2-bromooxazoline with a furylstannane to produce furyloxazoline [58]. Liebeskind and Wang conducted a benzannulation of a furylstannane using a Stille coupling with 4-chloro-2-cyclobutenone 62 to elaborate benzofuranol 63 via a dienyl ketene intermediate [59]. 

Merck s L-651,896 (54) was the lead compound from a series of dihydro-benzofuranols [158]. L-651,896 inhibited cRBL (1 //M) as well as platelet 12-LO (5.9 /zM). In zymosan-stimulated mouse macrophages, both LTC4 and PGE2 release were inhibited (0.1 //M and 1.1 //M, respectively) similar potency was seen in rat and human ISN. Potent topical activity in AAE was seen, with LT production and oedema both inhibited at 20-30 nM/ear. LT levels were also reduced in mouse oxazolone contact sensitivity, but in this... 

Oxidative coupling of 2-bromo-4,6-di-im-butylphenol (202, Scheme 51) with potassium hexacyanoferrate(III) in a two-phase system consisting of aqueous potassium hydroxide and benzene affords the dibenzofuranone 203 by the mechanism indicated.The dibenzofuranone 203 is a convenient source of 1-dibenzofuranol (205). On boiling with isopropanol, compound 203 provides the tetra-tert-butyl-l-benzofuranol 204, which may be de-butylated by treatment with aluminum chloride in toluene. 1-Dibenzo-furanol (205) is also obtained by direct treatment of the dibenzofuranone 203 with aluminum chloride in toluene. With boiling methanol, however, compound 203 supplies the methoxy analog 206, which on mild debutylation affords 4-methoxy-1-dibenzofuranol (207). ... 

Bromo- and iododibenzofurans readily form Grignard reagents that undergo the usual reactions. They have been oxidized at low temperature by oxygen to give phenols, usually in low yield.2-Methoxy-dibenzofuran-l-ylmagnesium bromide, however, affords 2-methoxy-l-di-benzofuranol in 71% yield under these conditions. ... 

Chromanol 4 and 2,3-dihydro-benzofuranol 3 were isolated from the crude reaction mixture by column chromatography (petrol/Et20 90/10-80/20). 3-Chromanol 4 (172.2 mg, 70% yield). 

The benzofuran-3-carbaldehyde (398) is the key intermediate in the synthesis of rus-codibenzofuran. Condensation of (398) with Meldrum s acid in the presence of piperidine acetate afforded the arylmethylene derivative (399), which on flash vacuum pyrolysis gave the benzofuranol (400) (Scheme 107) (80AJC1817). 

BENZOFURANOL. 4-BROMO-2-PHENYL-6- ((4-PHENYL-l-PIPERAZINYL) METHYL) -,... 

BENZOFURANOL, 3-CHLORO-4- ((DIMETHYLAMINO)METHYL-2-PHENYL-. HYDROCHLORIDE... 

BENZOFURANOL, 4-( (DIMETHYLAMINO)METHYL)-2-PHENYL-, HYDROCHLORIDE 5-BENZOFURANOL. 4-( (DIMETHYLAMINO)METHYL)-3-PHENYL-, HYDROCHLORIDE 5-BENZOFURANOL, 4-BROMO-6-(DIMETHYLAMINOMETHYL)-2-PHENYL-5-BENZOFURANOL, 2-CHLORO-4- (DIMETHYLAMINOMETHYL)-3-PHENYL-... 

The photocyclization of o-alkoxy phenyl ketones to yield benzofuranols (57 and 58) represents one of the earliest example of 8-H-abstraction from the lowest n, n triplet Wagner et al. [18] have provided detailed photokinetic data studying the photocyclization of a variety of o-alkoxyphenyl ketones 56, and have revealed that quantum efficiency for cyclization for 56d was the lowest (0.023) and that for 56f the highest (1.00). The diastereoselectivity for cyclization of 56 was found to be higher in benzene and lower in polar solvents. From the estimated kH values (0.6-25 x 106 s 1), it was inferred that the low rate constant for 56e (8 x 106 s ) compared to that for 56g (25 x 106s 1) i s due to the alkyl chain in the alkoxy groups that points away from the o-carbonyl moiety in the most populated equilibrium conformations (Table 8.1). 

The synthesis of benzofuranols has been accomplished by reaction of/ -benzoquinones with enamines110,117. For example, when silylenamine 217 was allowed to react with /7-benzoquinone 216, a 1,3-cycloaddition took place to give dihydrofuranol 218, which after treatment with acid was transformed to benzofuranol 219110 (equation 47). 

---