1.3- Cyclohexanedione synthesis

Acceptors. Most common acceptor molecules such as tetracyanoethylene or tetracyanoqurno dime thane ate commercially available. However, TCNQ can be synthesized in high yield by a two-step synthesis involving a condensation of malonitrile with 1,4-cyclohexanedione followed by treatment with an oxidizing agent such as bromine or A-bromosuccinamide in pyridine solvent (23) (Fig. 6). 

The procedure described is essentially that of Belleau and Weinberg and represents the only known way of obtaining the title compound. One other quinone acetal, 1,4,9,12-t6traoxadispiro[4.2.4.2]tetradeea-6,13-diene, has been synthesized by a conventional method (reaction of 1,4-cyclohexanedione with ethylene glycol followed by bromination and dehydrobromination ) as well as by an electrochemical method (anodic oxidation of 2,2-(l,4-phenylenedioxy)diethanol ). Quinone acetals have been used as intermediates in the synthesis of 4,4-dimethoxy-2,5-cyclohexadienone,. syw-bishomoquinone, - and compounds related to natural products. ... 

Chatteijea showed that cyclic ot-halocarbonyls are acceptable substrates for the Feist-Benary furan synthesis by combining 1-chlorocyclohexanone (34) with 1,3-cyclohexanedione (30) to yield octahydrodibenzofuran 35. ... 

Magnus prepared tetrahydrobenzofuran 37 using a Feist-Benary reaction of ethyl 2-chloroacetoacetate (32) and functionalized 1,3-cyclohexanedione 36. Compound 37 was a key synthetic intermediate in Magnus s synthesis of linderalactone, isolinderalactone, and niolinderalactone. ... 

Shortly thereafter, the first synthesis of the parent system 1 was reported, wherein Fischer indolization involving the carbazole derivative 12 furnished the desired product in 51% yield (Scheme 2). This achievement was correlated neatly with an alternative synthesis of 1 in 45% yield via the reaction of 1,2-cyclohexanedione mraiophenyUiydrazone and rtienylhydrazine in refluxing acetic acid, followed by treatment of the mixture with hot concentrated hydrochloric acid (57CIL363). 

In synthesis of the alkaloid tjipanazole E (19b), the required symmetric dichloro-indolo[2,3-fl]carbazole 20a was obtained in a two-step procedure starting fi-om 4-chlorophenylhydrazine hydrochloride and 1,2-cyclohexanedione employing a Fischer indolization. Subsequent attachment of an acetyl-protected glucopyranosyl moiety to one of the nitrogens, followed by cleavage of the protective groups with ammonia in methanol, produced the desired natural product (91X7739). 

The sequence has been applied to the synthesis of 1,4-cyclohexanedione from hydroquinone 10), using W-7 Raney nickel as prepared by Billica and Adkins 6), except that the catalyst was stored under water. The use of water as solvent permitted, after hltration of the catalyst, direct oxidation of the reaction mixture with ruthenium trichloride and sodium hypochlorite via ruthenium tetroxide 78). Hydroquinone can be reduced to the diol over /o Rh-on-C at ambient conditions quantitatively (20). 

L-Glutamine methyl ester was used in the synthesis of the alkaloid histri-onicotoxin ring system. After condensation with 1,3-cyclohexanedione and photocyclization, the intermediate 149 was obtained (86TL5177). 

Cyclic 1,3-diketones can also participate in this MCR. Thus, utilization of two equivalents of 1,3-cyclohexanedione or dimedone instead of (3-ketoesters led to hydrogenated acridine derivatives. However, when only one equivalent of cyclic 1,3-dicarbonyl is used in combination with one equivalent of (3-ketoester, unsym-metric 1,4-DHPs may be obtained (Scheme 3). For example, this reaction was applied to the synthesis of ZD0947, a potassium chaimel opener [20]. 

Bonjouklian and Moore et al. reported the total synthesis of the tjipanazoles D (359) and E (370) to support the assigned structures for these natural products. Condensation of 2 equivalents of 4-chlorophenylhydrazine hydrochloride (1327) with 1,2-cyclohexanedione (1328) in the presence of air and step-wise Fischer indolization provided tjipanazole D (359) in 54% yield. Coupling of 359 with... 

It is a colorless liquid with an oily-fruity odor with floral, petal-like notes. For synthesis, 1,3-cyclohexanedione is reacted with crotyl bromide in the presence of potassium hydroxyde to give the 2-alkenyl-substituted 1,3-diketone. Ring cleavage with sodium hydroxyde leads to the unsaturated keto acid which is reduced with NaBH4 under formation of the title compound [201]. 

Satoh and coworkers further investigated this reaction and found that, in some cases, magnesium /3-oxido carbenoids gave better results. Trapping of the enolate intermediates with several electrophiles was successfully carried out and a new method for the synthesis of one-carbon expanded cyclic a,a-disubstituted ketones from lower cyclic ketones was realized. An example using 1,4-cyclohexanedione mono ethylene ketal (195) as a representative cyclic ketone is shown in Table 15. ... 

A more convergent synthesis of frovatriptan using the methylamino-substituted cyclohexanone equivalent 75 is shown in Scheme 25.° The mono-ketal of 1,4-cyclohexanedione (74) was treated with methylamine in ethanol and then hydrogenated to give 75 as an oil, which was converted to the hydrochlonde salt. The hydrazine of 76, formed in situ by treatment with sodium nitrite followed by reduction of the diazonium salt with sodium dithionite, was reacted with 75 and additional concentrated HCl at 70 °C to deliver racemic frovatriptan (rac-6). 

To achieve synthesis of (-)-arisugacin A [1], (7 J-89 was obtained readily from 2-methyl-l,3-cyclohexanedione 88 in 4 steps with an overall yield of 46%, featuring vinylogous ester formation, Stork-Danheiser double alpha methylation,52,68,69 vinyl Grignard addition followed by acidic work-up,68 and an asymmetric CBS reduction [Scheme 21].70,71... 

One of the few examples of a synthetically useful 6-exo-trig cyclization from 3-aza-6-heptenyl radicals is found in the total synthesis of ( )-melinonine-E (159, Scheme 31) by Bonjoch et al. [66]. The cyclization precursor, a,P-unsaturated nitrile 157 was prepared from 1,4-cyclohexanedione monoethylene acetal (156) and tryptamine in 5 steps with 41% overall yield. Initially, when 157 was treated with 1.1 equiv. of n-BujSnH and 0.1 equiv. of AIBN in toluene for 16 h, the expected cyclization to the 2-azabicyclo[3.3.1]nonane ring took place to give 158 only as a minor product, along with its C(14) chloro- and dichloro-substituted derivatives as major products. An additional treatment of the crude mixture with 2.2 equiv. of BujSnH brought about the reduction of the C-Cl bonds to provide nitrile 158 in 38% yield over... 

A novel process for the construction of benzodihydrofurans via a procedure involving a heteroatom-directed photoarylation provided the basis for another total synthesis of ( )-lycoramine (299) (Scheme 32) (167). Thus, 339, which was obtained from 1,3-cyclohexanedione in two straightforward steps, was converted to 340 by sequential treatment with LiAlH4, methyl chloroformate, and aqueous acid. Epoxidation of 340 with alkaline hydrogen peroxide followed by... 

Monocapped boronic acid adducts of Tc(III) /m(dioxime) (BATO) (X — Cl, Br dioxime = dimethylglioxime, cyclohexanedione dioxime R = CF13, C4Fl9) have been prepared by template synthesis starting with pertechnetate and stannous ion [NBu4][TcOCl4] or M2[TcXO] (M = NH4, X = C1, Br), yielding seven-coordinate... 

The same reaction was later carried out by Greenhill and coworkers240 using two equivalents of a cyclohexanedione derivative and 2-alkylaminoacroleins with the result of isolating unexpected acridinedione derivatives (equation 170). The reaction is explained by loss of the formyl group of aminoacrolein as a formic acid and is reminiscent of the Hantzsch synthesis of 1,4-dihydropyridines. 

Alkylations of nitrophenylacetates, indole, and methyl benzylidene glycinate under dry conditions induced by microwaves have been studied, leading to the synthesis of arenes (66) linked by a long hydrocarbon chain (Abramovitch et al., 1995). Kumar et al. (1999) reported the enviromnental-friendly process for the synthesis of 2-alkylated hydroquinones (67) under microwave irradiation using 1,4-cyclohexanedione and aldehydes catalyzed by KF-AI2O3. An attractive methodology using microwave irradiation is described by Vanelle et al. (1999) for reactions of... 

The Westphal condensation was applied to the synthesis of sempervirine (289) (68JOC3985). Quaternary salt 287 reacted with 1,2-cyclohexanedione in the presence of dibutylamine to give quinolizinium salt 288 (48%), which was hydrolyzed (93%) and decarboxylated (85%) to afford 289. 

Phenols can be partially hydrogenated in the presence of alkali to cyclohexanones. An example is the synthesis of dihydroresorcinol, or l,>cyclohexanedione, by hydrogenation of resorcinol in the presence of Raney nickel and an equimolar quantity of sodium hydroxide (95%). Under these same conditions, pyrogallol furnishes a stable enediolone. ... 

The oximes of ketones with large hydrocarbon radicals like the acetyl-phenanthrenes are readily prepared by die action of hydroxylamine hydrochloride in the presence of pyridine. Special studies have been made for the synthesis of 1,2-cyclohexanedione dioxime as well as the next higher homolog. Dimethylglyoxime, CH,C(=NOH)C(=NOH)CH is... 

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