Dehydrogenations with palladium

Recently Swan has employed tetrachloro-o-benzoquinone in the oxidation of the 3,4-dihydro-j8-carbolinium cation 124 to the j8-carbo-linium cation 252. Dehydrogenation with palladium black at 175° or at a higher temperature and with selenium has also been successfully used for the purpose. 

The first example of an indolo[2,3-a]carbazole derivative reported with a reasonably estabhshed structure was the mono N-methylated system 9, prepared via dehydrogenation with palladium on charcoal of the octahydro derivative 10, available via reaction of the aminocarbazole 11 with 2-hydroxycyclohexanone in the presence of a trace amount of anihnium bromide (Scheme 1). An approach toward the parent compound 1 using the same method has also been attempted, although without success (56JCS4783). The utility of this route is impaired by the complexity of the starting material, which requires multistep preparation, and the harsh conditions of the final step. 

An alternative route was later reported by Hall and Plant, who obtained 2 as well as the methyl derivative 110 in low yields, via the reaction of 5-aminotetrahydro-carbazoles with 2-chlorocyclohexanone, followed by dehydrogenation with palladium on charcoal of the intermediate octahydro derivatives 109 or 111 (53JCS116). The octahydro compounds 109 and 111 have also been reported as products from the reactions of suitable 1,3-phenylenediamines and 2-hydroxycyclohexanone in the presence of a catalytic amount of hydrochloric acid (53JCS4114). 

An elegant synthesis of 1,3,7,9-tetramethyldibenzothiophene has been recorded as shown in Eq. (2). Cyclization of the diene (34) to the octahydrodibenzothiophene was accomplished with either aluminum chloride or a mixture of acetic acid and sulfuric acid (90%). Subsequent dehydrogenation with palladium on carbon gave the tetramethyl compound. The NMR spectrum of this compound has been discussed earlier... 

Isoquinoline synthesis Bischler-Napieralski synthesis is used to synthesize isoquinolines. (3-phenylethylamine is acylated, and then cyclodehy-drated using phosphoryl chloride, phosphorus pentoxide or other Lewis acids to yield dihydroisoquinoline, which can be aromatized by dehydrogenation with palladium, for example in the synthesis of papaverine, a pharmacologically active isoquinoline alkaloid. 

This ester cannot be dehydrogenated with palladium-charcoal, selenium, or chloranil 16 similar attempts to aromatize 4,5,6,7-tetrahydrobenzo[c]thiophene have failed.616 Diethyl 4,5,6,7-tetra-hydrobenzo[c]thiophene-l,3-dicarboxylate forms an adduct with maleic anhydride.6... 

The dienophile is the usual sort of unsaturated carbonyl compound—but count the electrons used from the indolizine. The nitrogen lone pair is not used but all the other eight are, so this is a most unusual [2 + 8] cycloaddition. The first formed product is not aromatic (it is not fully conjugated) but it can be dehydrogenated with palladium to make a cyclazine. 

Kaneko (28) followed essentially the method described by Prasad and Swan (25). The ketone XXVIIb was, however, prepared by a different route and its phenylhydrazone on heating with hydrogen bromide in ethanol yielded a bromine-containing product. This was first dehydrogenated with palladium charcoal in -cymene and subsequently de-brominated with palladium charcoal and hydrogen to form fiavopereirine. 

R = H) was dehydrogenated with palladium black in refluxing xylene to give, in 73% yield, 5-methyl-9-phenyl-8-azaharman (163). ... 

Oxidation of diethyl 5,10-dihydrophenazine-l,4-dicarboxylate with sodium dichromate in glacial acetic acid at room temperature or by catalytic dehydrogenation with palladium/calci-um carbonate in refluxing nitrobenzene yields diethyl phcnazinc-l,4-dicarboxylatc. ... 

The acid V was also obtained when deoxynupharidine was dehydrogenated with palladium to C15H19ON and this was oxidized w ith permanganate (15). 

When dehydrogenated with palladium nupharamine (XXXII) is converted to the pyridine derivative (XXXIII) and this can be oxidized with permanganate to pyridine-2,3,6-tricarboxylic acid (XXXIV) which indicates the location of the substituents (35). 

Cocker et al found the tetralin derivative (1) to be dehydrogenated normally by sulfur at 230-240° but to lose the n-buty1 group to give (3) on reaction with selenium at 330-350°. Dehydrogenation with palladium charcoal at 260-280° gave a mixture of (2) and (3). 

Pimaric acid (6) and isopimaric acid (7) differ in carbon skeleton from abietic acid, and the amounts initially present in rosin are lost in the process described for the preparation of dehydroabietic acid. In the step of dehydrogenation with palladium the two acids act as hydrogen acceptors and are converted into a mixture of dihydro-pimaric and dihydroisopimaric acids. Note that pimaric acid and isopimaric acid have been shown to be rearranged to abietic acid by concentrated sulfuric acid. 

A series of these acyclo C-nucleosides (312) were prepared from aldose phthalazin-l-ylhydrazones (311), which underwent facile thermal dehydro-genative cyclization to 312. The cyclization was expedited by catalytic dehydrogenation with palladium on charcoal (81MI5 83MI8 89BCJ2701 91MI9) (Scheme 95). 

Aromatization of the partially hydrogenated pyridine moiety of 1,2,3,4-tetrahydropyrido[2,3-d]pyridazin-5(60)-one and 1,2,3,4-tetrahydropyrido[2,3-<7]pyridazin-8(7W)-one is accomplished by dehydrogenation with palladium on charcoal to give 1 and 2, respectively 75 in the case of 1,3,4,7-tetrahydropyrido[2,3-i7]pyridazin-8(2//)-one, 2 is also obtained by oxidation with chromium(VI) oxide in acetic acid.8 This reagent also aromatizes the diazine side in 7,8-dihydropyrido[2,3-rf]pyridazin-5(67/)-one to give 3, a similar result is also obtained in small yield by air oxidation in the presence of dibenzoyl peroxide.76 The mixture of 5,6- and 7,8-ad-dition products of methylmagnesium iodide to pyrido[2,3-i7 pyridazine is readily aromatized by air to give a mixture of 5-methyl- and 8-methylpyrido[2,3-r/]pyridazine.3 77... 

This preparation is based on a procedure published by the submitters.8, 9 9-Phenylphenanthrene has been prepared previously by the reaction of phenyllithium with 9-chlorophehanthrene,10 by the high-temperature dehydrogenation with palladium on charcoal of the Diels-Alder dimer of 1-phenyl-l,3-butadiene,11 and by the acid-catalyzed cyclization of the alcohol formed from the reaction of 2-biphenylylmagnesium iodide and 2-phenoxy-acetophenone.3... 

The same reagent has been used by Descamps and Binon47 to cyclize amides of the type 21, in which R was phenyl, 4-methoxyphenyl, and 3,4,5-trimethoxyphenyl yields were high (72-86%), and the dihydro compounds were successfully dehydrogenated with palladium-charcoal in xylene (yields 65-70%). Dressier and Joullie4 have employed the Bischler-Napieralski synthesis to prepare more highly substituted thieno[3,2-c]pyridines (25) than those discussed above. The general reaction sequence used is shown in Scheme 9. 

A second route to the 6H-pyrido[4,3-ft]carbazole nucleus of ellipticine involves as a key step the internal condensation of a 2-alkylskatolyl-piperidone. Le Goffic et al. (259) developed this synthesis in the 5,11-bisdemethyl series. When enamine 630 was condensed with 2-methyl-gramine (635), hydrolysis afforded the skatolylpiperidone (636). Cycliza-tion was carried out with glacial acetic acid under reflux, debenzylation with sodium/liquid ammonia, and dehydrogenation with palladium-charcoal to give 637. 

An alternate route from the ketone VII utilized its reaction with formamide and formic acid to give IX which on ring closure with phos-phoryl chloride followed by dehydrogenation with palladium-charcoal gave VIII (R = H). Its conversion to dihj dronitidine was achieved as described above. 

---