Cyclohexan-1,3-diones

Whilst the solution is still hot, add dilute hydrochloric acid until the stirred solution is just acid to litmus, and then distil off as much ethanol as possible, using the water-bath. Now add more dilute hydrochloric acid to the residual hot solution until it is just acid to methyl-orange. The 5,5-dimethyl-cyclohexan-1,3-dione separates as an oil which solidifies on cooling. Filter the product at the pump, wash it with ice-cold water, and dry it in a desiccator. Yield of the pale cream-coloured crystals, 12 g. m.p. 136-145 (preliminary softening). 

In keeping with the thermodynamic stability of the ene-hydrazine, the mono-phenylhydrazone of cyclohexane-1,3-dione 38 provided only one of two possible isomers 39, or at least, one dominant product 39 on indolization. ... 

Cyclohexen-l-one is easily prepared by a two-step procedure from cyclohexane-1,3-dione.3 It is available from Fluka AG CH-9470 Buchs. 

In a detailed investigation, Turner and coworkers have described the preparation and application of solid-supported cyclohexane-1,3-dione as a so-called capture and release reagent for amide synthesis, as well as its use as a novel scavenger resin [125]. Their report included a three-step synthesis of polymer-bound cyclohexane-1,3-dione (CHD resin, Scheme 7.104) from inexpensive and readily available starting materials. The key step in this reaction was microwave-assisted complete hydrolysis of 3-methoxy-cyclohexen-l-one resin to the desired CHD resin. 

Scheme 7.104 Preparation of resin-bound cyclohexane-1,3-dione (CHD resin).

Scheme 7.106 Preparation of high-loading cyclohexane-1,3-dione scavenger resin (CHD-SR).

In order to explore the potential of CHD resins as scavenger materials, 1-ethyl-3,5-dimethoxycydohexa-2,5-dienecarboxylic acid was anchored to a commercially available trisamine resin (Scheme 7.106), which yielded a high-loading cyclohexane-1,3-dione scavenger resin (CHD-SR) [125]. 

Reaction of 1,3-dicarbonyl compounds with vinyl sulfides gives the corresponding medium- and large-sized ring substituted furans 78 in moderate to good yields. In addition to cyclohexane-1,3-diones, 4-hydroxycoumarins and 4-hydroxyquinone can also be used as 1,3-dicarbonyl components . 

An equilibrium mixture of the cyclohexane- 1,3-dione (42) and its enol form (43) was irradiated in the presence of cyclopentene in MeOH to afford the intermediate (44), which was readily transformed to the tricyclic intermediate (45) and subsequently followed an retroaldolization sequence to give the cyclooctanedione (46) in 90 % yield. When refluxed with titanium trichloride and K metal in THF for 5 min., compound (46) gave the diol (47) 21K... 

Izumi used Pd(OAc)2 to effect the bis-alkoxylation of o-nitrostyrenes to form the corresponding o-nitrophenylacetaldehyde acetals, which, upon treatment with Fe/HOAc/HCl, give a variety of indoles (4-OMe, 5-OMe, 4-Me, 4-C1, 4-C02Me, 6-Me) in 63-86% yields [465]. Mori and coworkers employed a titanium-isocyanate complex to construct tetrahydroindolones 373 from cyclohexane-1,3-diones [466],... 

Alkylation of 2-ethoxycarbonylcyclohexanone, followed by hydrolysis and decarboxylation, has been used as a convenient route to 2-alkylcyclohexanones [74, 92]. Polymer-supported catalysts have also been used [e.g. 93] 2-acylcyclohexanones are C-alkylated at the 2-position almost exclusively, whereas cyclohexane-1,3-dione produces a mixture of mono- and di-C-alkylated products, together with the O-alkylated derivative. In all cases, less polar solvents promote the O-alkylation. 

Nitisinone (59 Qrfadin ) Leptospermone 2-[2-Nitro-4-(trifluoromethyl) benzoyl] cyclohexane-1,3-dione NP-derived Plant Antityrosinaemia Inhibits /5-hydroxyphenyl-pyruvate dioxygenase (HPPD) activity 208-210, 518-524... 

Microbial reduction of prochiral cyclopentane- and cyclohexane-1,3-diones was extensively studied during the 1960 s in connection with steroid total synthesis. Kieslich, Djerassi, and their coworkers reported the reduction of 2,2-dimethylcyclohexane-l,3-dione with Kloeokera magna ATCC 20109, and obtained (S)-3-hydroxy-2,2-dimethylcyclohexanone. We found that the reduction of the 1,3-diketone can also be effected with conventional baker s yeast, and secured the hydroxy ketone of 98-99% ee as determined by an HPLC analysis of the corresponding (S)-a-methoxy-a-trifluoromethylphenylacetate (MTPA ester).(S)-3-Hydroxy-2,2-dimethy1cyc1ohexanone has been proved to be a versatile chiral non-racemic building block in terpene synthesis as shown in Figure 1. 

The tetrahydroquinoline-2,5-dione (46) is obtained when the 2-cyanoethylcyclohexane-1,3-dione is treated with acetyl chloride in chloroform, or phosphorus tribromide in pyridine (76JOC636). In contrast, the cyclohexane-1,3-dione (47) can be converted into an isoquinolin-... 

The first member of the diazaphenalene system (which could be considered to be a benzonaphthyridine) to be synthesized was the 1,6-diazaphenalene (353). This was obtained in six steps starting from the reaction of dimethyl acetonedicarboxylate with cyclohexane-1, 3-dione. The intermediate steps are shown (78H(9)1561, 79H(12)903>. Compound (353) has similar chemical and physical properties to those of imidazole. For a full account of the syntheses and reactions of this ring system the review <83H(20>87) should be consulted. 

The possibility of regioselective angular fusion has been demonstrated in the annelation of two benzo[ ][l,8]naphthyridine units on to a 1,8-naphthyridine nucleus, leading to three isomeric octacyclic compounds (79JOC531). The condensation between two molecules of 2-aminonicotinaldehyde, two of cyclohexane-1,3-dione and one of 4-aminopyrimidine-5-carbaldehyde gave a mixture of the three isomeric products (420), (421) and (422). 

Coupling of compound 228 with dimethylaniline and with 2-naphthylamine afforded the azo derivatives 230 and 231. Compound 228 also coupled with active methylene reagents, such as pyrazolone 234, indan-l,3-dione 236, and cyclohexane-1,3-dione 238, to yield the corresponding arylhydrazones 235, 237, and 239, respectively <2004H(63)1143, 2004BMCL5013> (Scheme 15). 

The facile acid-catalyzed elimination of the elements of water from the carbinols derived from 2-methylindole and 1,3-dicarbonyl compounds, such as ethyl acetoacetate or pentane-2,4-dione, yields the 3-vinylindole derivatives (122) (B-70MI30500). Pyrroles tend to form 2 1 adducts with 1,3-diketones. For example, cyclohexane-1,3-dione produces the bispyrrolyl derivatives (121) (B-77MI30502). 

When an a-chloroaldehyde or an a-chloroketone is condensed with a /3-ketoester, in the presence of aqueous base, a furan is produced bearing an ester substituent at the /3-position. It is thought that the reaction is of the aldol type intermediate dihydrofurans (256) have been isolated in certain cases (Scheme 70) (74BSF519). The condensation of ethyl bromopyru-vate and sodium oxaloacetate follows a similar mechanism (54JOC1671). The one-pot synthesis of 2,4,5-trisubstituted furans (257) from ketones and ethyl 3,4-dibromo-2-butenoate is a useful addition to a well known route (80S52). The analogous reaction of cyclic /3-diketones, i.e. cyclohexane-1,3-dione and 5,5-dimethylcyclohexane-l,3-dione, results in the formation of the condensed furans (258) and (259). These reactions are preformed either in ethanol with sodium ethoxide or in DMF with potassium carbonate. 

A nitrile-stabilized carbanion is also involved in a synthesis of a fused pyranone system (81S225). A range of 2-ureidomethylenecyclohexane-l,3-diones, e.g. (308), react with activated acetonitriles in the presence of a strongly basic catalyst to produce 5-oxo-5,6,7,8-tetrahydrocoumarins (309). Since the substrates are readily available from cyclohexane-1,3-diones by reaction with triethyl orthoformate and a urea, the synthesis is attractive (Scheme 88). Furthermore, it has been applied to a pyran-2,4-dione, whereupon the 2,5-dioxopyrano[4,3-6]pyran (310) is formed. 

The versatility of cyclohexane- 1,3-dione functionalised resins has been illustrated by their syntiietic application as both capture and release reagents and resin scavengers. In addition, CHD resins show considerable potential for further use as linkers in several other solid-phase applications. 

Humphrey, C.E., Easson, M.A.M., Tierney, J.P. and Turner, N.J., Solid-supported cyclohexane-1,3-dione (CHD) a capture and release reagent for the synthesis of amides and novel scavenger resin, Org. Lett., 2003,... 

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