Cyclopentene-1,4-dione

All glassware must be washed with acid before use. 

The dihydroxycyclopentene mixture was prepared from cyclopentene and peracetic acid. The mixture contains approximately 70% of 2-cyclopentene-l,4-diol. 

The submitters found a cooling bath composed of a Dry Ice and methanol-water mixture (1 3 by volume) to be convenient. 

At this point in the preparation, an excess of the oxidant should be present. The presence of excess oxidant may be established by diluting 2 drops of the aqueous phase from the reaction mixture with 2 ml. of water and then adding 1 drop of a 0.4% solution of sodium diphenylaminesulfonate in water. A deepening in color is observed if excess oxidant is present. 

This product is sufficiently pure for most applications. Further purification may be achieved either by sublimation of the product at 30-40VO.l mm. or by recrystallization of the dione from diethyl ether at Dry Ice temperatures. The dione decomposes rapidly at temperatures above 40°. An ethanol solution of pure dione, m.p. 35-36°, exhibits a maximum in the ultraviolet at 222 m/i (log 4.16). 

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Water can be added to the mother liquor, and the mixture extracted with chloroform to increase the diazide recovery to nearly quantitative (95-98%). During the course of any purification method that might be employed the diazide should not be heated above 50°, since decomposition occurs quite noticeably at that temperature. It is best to store the pure product below —5° in the dark, since it undergoes a facile photochemical rearrangement to the cyclopentene-dione. 

Diphenyl cyclopropenone also has been reacted with ynamines, e.g. 387249 Since cyclopentene dione 389 was obtained after hydrolytic work-up, amino cyclo-... 

The observed ring expansion of 2-azido-2-phenylindandione (129) and 2,2-diazido-l,3-indandione (130), along with the established propensity of 2,6-diazido- and 2,5-diazido-l,4-quinones to undergo easy, thermally induced ring contractions to 2-cyano-4-azido-l,3-cyclopentene-diones suggested a unique synthetic route to 2-aza-3-cyano-l,4-quinones (75JA6181). 

Nickelacyclopentenediones (89) react with maleic anhydride (MA) or carbon monoxide to give cyclobutenediones (93), oxygen to cyclopentene-diones (94), and geminal dihalides to 95 (Scheme 33). The mechanism of these reactions has been explained. 

Christman et al. (1978) also chlorinated resorcinol, showing that during chloroform formation it underwent ring contraction to produce the unusual cyclopentene-dione 25. Larson and Rockwell (1979) confirmed Rook s and Christman s observations that resorcinol derivatives were active haloform precursors, and also found that even if the 2-carbon of resorcinol was blocked by a carboxyl group (cf. 26), yields of... 

Cyclopentene-l,2-diol, 42, 51 2-Cyclopentene-1,4-dione, 42, 36 2-Cycloeentene-1-one, 42, 38 2-Cycloeentenone, 42,38 Cyclopropane, bromo-, 43, 9 Cyclopropanecarboxylic add, conversion to bromocyclopropane, 43, 9... 

The photo-induced exo selectivity was observed in other classic Diels-Alder reactions. Data relating to some exo adducts obtained by reacting cyclopentadiene or cyclohexadiene with 2-methyl-1,4-benzoquinone, 5-hydroxynaphtho-quinone, 4-cyclopentene-l,3-dione and maleic anhydride are given in Scheme 4.13. The presence and amount of EtsN plays a decisive role in reversing the endo selectivity. The possibility that the prevalence of exo adduct is due to isomerization of endo adduct under photolytic conditions was rejected by control experiments, at least for less reactive dienophiles. 

Utilizing an alternate mode of Diels-Alder reactivity, Harman has examined the cycloaddition reactions of 4,5-T -Os(II)pentaammine-3-vinylpyrrole complexes with suitably activated dienophiles <96JA7117>. For instance, cycloaddition of the p-vinylpyrrole complex 58 with 4-cyclopentene-l,3-dione, followed by DDQ oxidation affords 59, possessing the fused-ring indole skeleton of the marine cytotoxic agent, herbindole B. 

Feringa s group has demonstrated that cyclopentene-3,5-dione monoacetals as 2-47 can also be successfully applied as substrates in an asymmetric three-component domino Michael/aldol reaction with dialkyl zinc reagents 2-48 and aromatic aldehydes 2-49 [17]. In the presence of 2 mol% of the in-sitw-generated enantiomeri-cally pure catalyst Cu(OTf)2/phosphoramidite 2-54, the cyclopentanone derivatives 2-51 were formed nearly exclusively in good yields and with high ee-values (Scheme 2.11). 

The similar insertion of 93 into 1,2-diphenylcyclopropenone results in cy-clobutenones or o- and p-alkoxyphenols [49]. In the reaction of 93 with 1-alkynylcyclobutenols, 2-alkenyl-4-cyclopentene-l,3-diones are obtained via alkyl shift-ring expansion [50]. (Scheme 33)... 

As compounds exhibiting enhancing effects on CL reactions, a variety of phenols, e.g., firefly luciferin and 6-hydroxybenzothiazole derivatives [12,13], 4-iodophe-nol [14], 4-(4-hydroxyphenyl)thiazole [15], 2-(4,-hydroxy-3 -methoxy-benzyli-dene)-4-cyclopentene-l,3-dione (KIH-201) [16], and 2-(4-hydroxyphenyl)-4,5-diphenylimidazole (HDI) and 2-(4-hydroxyphenyl)-4,5-di(2-pyridyl)imidazole (HPI)[17] (Fig. 6A), and phenylboronic acid derivatives, e.g., 4-phenylylboronic acid [18], 4-iodophenylboronic acid [19], and4-[4,5-di(2-pyridyl)-l //-imidazol-2-yl]phenylboronic acid (DPPA) [20] (Fig. 6B), in the luminol/hydrogen peroxide/peroxidase system are well known. Rhodamine B and quinine are used as sensitizers in the CL-emitting reaction between cerium (IV) and thiol compounds. This CL reaction was successfully applied to the sensitive determination of various thiol drugs [21-32],... 

Figure 6 Representative (A) phenol-type and (B) phenylboronic acid-type enhancers for luminol/hydrogen peroxide/peroxidase system. KIH-201, 2-(4 -hydroxy-3 -methoxy-benzylidene)-4-cyclopentene-1,3-dione HDI, 2-(4-hydroxyphenyl)-4,5-diphenylimida-zole HPI, 2-(4-hydroxyphenyl)-4,5-di(2-pyridyl)imidazole DPPA, 4-[4,5-di(2-pyridyl)-lH-imidazol-2-yl]phenylboronic acid).

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... 

The four-, five-, and six-membered analogs (178,180, and 182) were also obtained from the diprotonation of squaric acid (3,4-dihydroxy-3-cyclobutene-l,2-dione, 177), tri-O-protonation of croconic acid (4,5-dihydroxy-4-cyclopentene-l,2,3-trione, 179), and tetra-O-protonated rhodizonic acid (5,6-dihydroxy-5-cyclohexene-l,2,3,4-tetraone, 181), respectively. These ions were prepared in either Magic Acid (1 1 FSOsH-SbFs) or fluorosulfuric acid at low temperature and characterized by NMR. Ab initio/IGLO calculations showed that di-O-protonated squaric acid (178) is planar and aromatic, whereas the polyprotonated croconic and rhodizonic acids (180 and 182) have more carboxonium ion character, and no indication was obtained for any significant contributing homoaromatic structures. 

The double )5-scission pathway becomes dominant in bicyclic systems (Equations (7)-(9) and Scheme 13). Thus, cyclopentene ozonide (69) gives cyclopropane (Equation (7)) <68TL329l>. Photolysis of the ozonide derived from 1,4-benzodioxins (70) provides a method for the preparation of labile o-benzoquinones (71) (Scheme 13) <87JOC56l6>. Photolysis can also provide a route to unstable compounds and transient species such as the aziridine-2,3-dione (72) (Equation (8)), identified at 77 K using infrared spectroscopy <80JA6902>. Relatively unstable azacarbapenems (73) have been prepared by photolysis of tricyclic compounds containing a cyclobutene ozonide (Equation (9)). On silica, the 1,2,4-trithiolane (74) underwent photo-equilibration (Equation (10)) with the 1,3-dithetane (75) and sulfur. 

Madindoline A 6 and B ent-7) are potent inhibitors of interleukin 6. In a total synthesis that also intended to determine relative and absolute configuration of these antibiotics, the densely functionalized cyclopentene-l,3-dione ring of 6 and 7 was elaborated via RCM of diene-diol 1 (Scheme 1). 

Bicyclic 3a//-cyclopentene[8 annulcnc-l,4-(5//,9a//)-dioncs undergo three types of acid-induced transannular reactions (1) Michael addition (5-exo-trig or 6-exo-trig) leading to the tetracyclic diones, (2) 3 + 2-cycloaddition followed by a novel sequential skeletal rearrangement to 2-naphthalenone derivatives, (3) ipso-Friedel-Crafts alkylation accompanied by the rearomatization and the loss of water (Scheme 25). The factors that control the reaction mode of these transannular cyclizations are discussed... 

Die Moglichkeit der Variation sowohl der 1,3-Diketon- als auch der Ole-fin-Komponente macht auch hier die Cycloaddition zu einem wichtigen synthetischen Hilfsmittel. So eroffnet das Additionsprodukt des Enol-acetats des Cyclopentan-l,3-dions an Cyclopenten (Formel 83) (150)... 

T. Hofmann, O. Frank, M. Kemeny, E. Bernardy, M. Habermeyer, U. Weyand, S. Meiers, and D. Marko, Studies on the inhibition of tumor cell growth and microtubule assembly by 3-hydroxy-4-[( )-(2-furyl)methylidene]methyl-3-cyclopentene-l,2-dione, an intensely colored Maillard product formed from carbohydrates and L-proline, in G, 2002, 401-402. 

The CD induced in 2-(2,4,6-cycloheptatrien-l-ylidine)-4-cyclopentene-l,3-dione upon its inclusion in 6-cyclodextrin was used to obtain full assignment of the observed absorption bands [49]. It was concluded that the low energy band system was composed of three electronic transitions, two of which were polarized perpendicular, and one parallel, with respect to the long molecular axis of the solute. The higher energy band system was found to also consist of three allowed electronic transitions, but two of these were polarized parallel, and one perpendicular, to the long axis of the solute molecule. These deductions were supported by a series of CNDO/S-CI calculations performed on the system. A similar approach was taken to assign the polarizations of the various transitions associated with 2-thioxo-l,3-benzodithiole and 2-selenoxo-1,3-benzodithiole [50]. 

An important potential target of asymmetric hydrosilation catalysis is to the reduction of the cyclopenten-l,4-diones, 1, producing the 4-silyloxyeyclopentenones, 2, which are key intermediates in the synthesis of singleisomer prostaglandins (18-22). 

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