Demethylation pyridine hydrochloride

Methylation of carbazole phenolic oxygen has been achieved using dimethyl sulfate without reaction at nitrogen. Demethylation of carbazole methyl ethers has been achieved with hydrobromic acid-acetic acid, boron trichloride,and pyridine hydrochloride. Selective demethylation of methoxyl ortho to an aldehydo function has been achieved using boron trifluoride. ° ° Partial demethylation of 1-methoxy-3-formylcarbazole occurred during Wolff-Kischner reduction." ... 

An important extension of this method has made it possible to synthesize polycyclic benzofurans under the influence of various demethylating and dehydrating media.335 For such ring closures, pyridine hydrochloride is especially suitable thus coumestan has been synthesized from 4-hydroxy-3-(2-methoxyphenyl)coumarin.8 4,7-Di hydroxy-3-(2,4-dimethoxyphenyl)coumarin gives coumestol with aniline hydrochloride 336 other polymethoxycoumestans have been obtained with pyridine hydrochloride or with HBr (or HI) and acetic acid.337-339... 

Hydroxybenzo[6]thiophene has been isolated from coal tar.42 It may be prepared from 6-aminobenzo[fr]thiophene by standard procedures.241 6-Methoxybenzo[h]thiophene may be prepared by decarboxylation of the corresponding 2-carboxylic acid,341 and 6-ethoxybenzo[6]thiophene is obtained by reduction of 6-(ethoxy)-thioindoxyl (Section VI, 1,2). 6-Methoxy-5-methylbenzo[6]thiophene is obtained by cyclization of (3-methoxy-4-methylphenylthio)-acetaldehyde dimethyl acetal (Section IV,B).617 The product previously described542 as 6-hydroxy-3-phenylbenzo[6]thiophene has now been shown to be the 2-phenyl isomer.307 6-Methoxy-818 and 6-methoxy-5-methyl-benzo[6]thiophene617 are demethylated by pyridine hydrochloride. 

IV,B).617 On demethylation with pyridine hydrochloride, it affords the free phenol which is reported to be unstable.617 A similar demethylation of 4-ethyl-2,3-dimethyl-7-methoxybenzo[ ]thiophene affords the corresponding phenol.616 7-Hydroxybenzo[6]thiophene undergoes a Bucherer reaction to give 7-aminobenzo[6]thiophene.84... 

The structure of another phenolic base O-demethyllycoramine (300) was deduced from spectroscopic evidence, and this assignment was confirmed by its preparation from lycoramine (299) by demethylation on heating with dry pyridine hydrochloride (63). Other new alkaloids of this family include 2-epi-lycoramine (302) and 79-allylnorgalanthamine (293) (60). 

The acid 350 was demethylated with pyridine hydrochloride, then realkylated with benzyl bromide in aqueous potassium hydroxide to give 351. The latter was converted to the diazoketone 352 by the sequential treatment of 351 with oxalyl chloride and etheral diazomethane. Reaction of 352 with concentrated hydrobromic acid gave the bromoketone 353. The latter was reduced with sodium borohydride at pH 8 -9 to yield a mixture of diastere-omeric bromohydrins 354. Protection of the free hydroxyl as a tetrahydro-pyranyl ether and hydrogenolysis of the benzyl residue afforded 355. The phenol 355 was heated under reflux with potassium m/V-butoxide in tert-butyl alcohol for 5 hr to give a 3 1 epimeric mixture of dienone ethers 356 and 357 in about 50% yield. Treatment of this mixture with dilute acid gave the epimeric alcohols 358 and 359. This mixture was oxidized with Jones reagent to afford the diketone 349. 

Benzoxathiol-2-one formation can in turn be the desired reaction pathway. This compound can be similarly prepared when a methoxy group is present at the 2 position [67]. The cycUsation is carried out using hydroiodic acid or pyridine hydrochloride as demethylating agents (Scheme 25). 

Methylmagnesinm iodide. (For suppliers, see Grignard reagents.) Wilds and McCormack encountered difficulties in attempted demethylation of the ketone (2). The usual, strongly acidic reagents lead to self-condensation even pyridine hydrochloride was unsatisfactory. They then found that the alcoholic precursor (1) can... 

Erdtman and co-workers attempted to demethylate the diphenyl derivative (4) with pyridine hydrochloride, but the reaction was attended with ring closure to... 

Desoxymorphine-D can be prepared by the demethylation of desoxy-codeine-D [xxv] with pyridine hydrochloride at 215° C. [17], by the action of phosphorus tribromide on dihydroallo-i/r-codeine [lxi] [13, 53], and as a by-product in the preparation of desoxycodeino-D from 8-chlorodihydrocodide [13], On methylation it gives desoxycodeine-D [13, 17]. 

Beckmann rearrangement. Aryl alkyl ketone oximes (acetophenone oxime) or diaryl ketone oximes (benzophenone oxime) undergo Beckmann rearrangement when refluxed with anhydrous or hydrated pyridine hydrochloride. If the ketone has a methoxyl group in the para position concomitant demethylation occurs.15... 

This ring is foimed by reaction between a side-chain nitriie and a phenolic group the latter is produced in situ by demethyiation of an ether with pyridine hydrochloride which also acts as a cyclizing agent and demethylates another methoxy group. 

Energetic reduction with lithium aluminum hydride led to the reduction of the carbonyl group with the formation of the correct alcohol epimer, as expected from the steric hindrance presented by the benzene ring, and to removal of the aromatic bromine. This last reaction is a noteworthy example of the removal of aromatically bound halogen without reduction of either an allyhc hydroxyl or a double bond. The codeine so produced (CCCLXXXIII) was then demethylated to morphine (CCCLXXXIV) by short heating to 220° with pyridine hydrochloride. 

Codeine has been demethylated either by reaction with boron tribromide in chioroform at ambient temperature in 91% yield (ref. 164) or by treatment with sodium propylmercaptide in DMF at 125 C in 80% yield (ref. 165) to give morphine, both procedures representing considerable improvements on the former method with pyridine hydrochloride (ref. 166). 

Demethylation-cyclodehydration. Two cases where demethylation of phenolic ethers with pyridine hydrochloride was accompanied by cyclodehydration have been reported. ... 

The substituted naphthalene (available in four steps from 3,4,5-trimethoxybenzaldehyde) reacted with malonic acid and polyphosphoric acid (100°, 15 min) to give the phenalenone (29), which was selectively demethylated to (30) with hydrochloric acid. The demethyl compound formed a dimethylallyl ether (31), which on heating in DMF at 100° gave the yellow trimethyl ether of atrovenetin (16). Demethylation of (16) with pyridine hydrochloride led to the racemic natural product. A more prolonged reaction between (28) and malonic acid in poly-... 

The methylenedioxy group in (—)-j8-hydrastine (23) can be selectively converted to an o-diphenol by treatment with boron trichloride, whereas (9-demethylation without affecting the methylenedioxy function can be accomplished with pyridine hydrochloride in hot pyridine. Boron tribromide cleaves both methylenedioxy and methoxyl groups. Isomerization at C-9 is known to... 

On being heated with pyridine hydrochloride, the tetracyclic ketone (364) is readily isomerized and demethylated to give D-homoequilenin (21) [141]. 

A transition from the D-homoketone (367) to the methyl ether of 8-isoestrone (368) was effected by Johnson s method [84], and the demethylation of (368) with pyridine hydrochloride gave free 8-isoestrone with a yield of about 30% [465]. 

On being heated with pyridine hydrochloride, the methyl ethers (33)-(38) were demethylated to the corresponding isomers of estrone [83, 84]. The constants of all eight theoretically possible racemates of estrone obtained by this and other methods of synthesis and also the arbitrary designations given to them by various authors are shown in Table 8. The racemates of the isomeric estrones are arbitrarily shown in this table by the formulas of the corresponding -enantiomers. 

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