Azulene derivatives, synthesis

This chemistry has been used to synthesize cyclopentanoid derivatives used in the synthesis of sarko-mycin and brefeldin A.22 Azulene derivatives were also synthesized using this chemistry (Scheme 14).23... 

There are general reviews on heterocyclic syntheses by cycloaddition reactions of isocyanates and on the use of heterocyclic cations in preparative organic chemistry. More specific topics are 5-hydroxymethylfuran-2-carb-aldehyde, isobenzofurans and related ort/io-quinonoid systems, the conversion of 2//-cyclohepta[Zj] furan-2-one (1) into derivatives of azulene, the synthesis of indoles from o-alkylphenyl isocyanides, and abnormal Fischer indolization reactions of o-methoxyphenylhydrazones. Two reviews on isoindoles have appeared and a lecture on highly conducting charge-transfer complexes that are based on heterocyclic selenium and tellurium donors has been reprinted.Recent advances in the chemistry of imidazole and in the use of nitro-imidazoles as radiosensitizers have been summarized. There have been reviews on benzimidazole A -oxides and on dihydrobenzimidazoles, benzimidazolones, benzimidazolethiones, and related compounds. Other topics are synthetic applications of 1,3-dithiolium and 1,3-oxathiolium salts and of isoxazoles, the chemistry of benzisoxazoles, 2-amino-oxazoles, 5-oxazolones (2), furoxans, benzofuroxans, and related systems, the synthesis of five-membered meso-ionic compounds, and tetrazoles. ... 

Olefin cyclization (3, 305-307 4, 531-532 5, 696-697). A key step in a novel synthesis of ( )-longifolene (6) from (1) involves the acid-catalyzed cycUza-tion of (2) to (3) with TFA at 0°. The original paper suggests a mechanism for the cychzation of (2) mainly to the bicyclic product (3) rather than to a hydro-azulene derivative. ... 

Irradiation of chlorobenzene solutions of [Pd(PPh3)4] produces trans-[PdCl2(PPh3)2] and a mixture of chlorobiphenyls, and irradiation of 2-amino-5-iodo-3-(N-methyl-N-tosylamino)pyridine in benzene solution gives 2-amino-3-methylamino-5-phenylpyridine by simultaneous phenylation and tosyl removal. This reaction is a key step in the synthesis of the food-borne carcinogen 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine. Substituted 1,2 -biazulenes have been prepared by photolysis of 2-diazo-l,3-dicyanoazulen-6(2H)-one in the presence of azulene derivatives. ... 

A new synthesis of the hydroazulenone (119) has been reported, from the bicyclic dione (116) (Scheme 6)." Initial conversion of (116) into the spiro-oxiran (117) by Corey s reagent (Mc2S—CH2) is followed by BF3-Et20-catalysed rearrangement via the carbo-cation (118) to the azulene derivative (119). 

This reaction has a limited use in organic synthesis, specifically for the azulene derivatives. 

A sequential one-pot synthesis of functionalized 6-oxa-2,2a,ll-triazadibenzo[c,d, ]azulene derivatives 211 was reported. These novel diben-zoxadiazepine-fused heterocycles may present core structures for biologically active molecules (14RA50947). 

For some examples (a) C. Cui, C. Zhu, X.-J. Du, Z.-P. Wang, Z.-M. Li, W.-G. Zhao, Green Chem. 2012, 14, 3157-3163. Ultrasound-promoted sterically congested Passerini reactions under solvent-free conditions, (b) K. Sato, T. Ozu, N. Takenaga, Tetrahedron Lett. 2013, 54, 661-664. Solvent-free synthesis of azulene derivatives via Passerini reaction by grinding. 

In 1977, Houk reported a new general synthesis of azulene 4 by using the [6+4] cycloaddition of thiophene-5,S-dioxides 184 and 109 [112]. This reaction provides the azulene nucleus in a single step. Several azulene derivatives 187 and 188 were prepared the substituents of the formed azulenes are derived from those of the thiophene-5,5-dioxides 185 and 186 (Scheme 6.48) [113]. 

SCHEME 23 Synthesis of 2,5-disubstituted-l,3,4-oxadiazole-contatning azulene derivatives. 

This principle can be illustrated by the synthesis of the carbon-14-labeled azulene derivative an advanced intermediate in the preparation of an anti-inflammatory... 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

The condensation of a vinylogous formamide with an enamine has been applied to an aza azulene synthesis (351). The point of attachment of the aldehyde to the enamine in condensations with indolenin derived poly-enamines was found to favor the second double bond (352,353). 

During the 1950s and 1960s Hafner used Konig salts, derived from the reaction of A -methyl aniline with Zincke salt 1, for azulene synthesis. The Zincke reaction also achieved prominence in cyanine dye synthesis and as an analytical method for nicotinamide determination. ... 

Of the fundamental nonalternant hydrocarbons, only two prototypes were known about fifteen years ago azulene (XI, Fig. 5), the molecular structure of which was determined by Pfau and Plattner and fulvene (XIX) synthesized by Thiec and Wiemann. Early in the 1960 s many other interesting prototypes have come to be synthesized. Doering succeeded in synthesizing heptafulvene (XX) fulvalene (XXI) and heptafulvalene (XXIII). Prinzbach and Rosswog reported the synthesis of sesquifulvalene (XXII). Preparation of a condensed bicyclic nonalternant hydrocarbon, heptalene (VII), was reported by Dauben and Bertelli . On the other hand, its 5-membered analogue, pentalene (I), has remained, up to the present, unvanquished to many attempts made by synthetic chemists. Very recently, de Mayo and his associates have succeeded in synthesizing its closest derivative, 1-methylpentalene. It is added in this connection that dimethyl derivatives of condensed tricyclic nonaltemant hydrocarbons composed of 5- and 7-membered rings (XIV and XV), known as Hafner s hydrocarbons, were synthesized by Hafner and Schneider already in 1958. 

To facilitate parallel synthesis and purification of triazolyl derivatives of sugars, the products are tagged with an azulene chromophore. For this purpose, guajazulene, an inexpensive azulene, is converted to propargylic ester 1094 and reacted with mannose derivative 1095 to provide a mixture of regioisomers 1096 (44%) and 1097 (32%). Separation of the products can be easily achieved by chromatography because they are visible on the column (Scheme 181) <2006EJ01103>. 

Trimethylpyrylium perchlorate is a very versatile and useful starting material. Thus its reaction with cyclopentadienyl-sodium has made 4,6,8-trimethylazulene 12 easily available for general studies of the properties of azulenes 18 and for the synthesis of related compounds.14 In addition, pyrylium salts are readily converted to a variety of pyridine derivatives 9 15 as well as to derivatives of nitrobenzene16 and phenol.9 17,18 It is clear that its value as a starting material is such that it is receiving wide use. 

Azulene-substituted methyl cations were prepared as illustrated in Figure 7. The hydro derivatives (7a-d) became good precursors for the methyl cations. These derivatives were readily obtained by the reaction of azulenes 6a-d with 1-formyl compounds 5a-d under acidic conditions. The synthesis of the tri(l-... 

The tri(azulenyl)methane derivative 24+ including a 6-azulenyl group was prepared by the reaction of azulene 6b with diethyl 6-formylazulene-l,3-dicarboxylate. Synthesis of 24+ was accomplished by hydride abstraction with DDQ. Cation 24+ was isolated as a hexafluorophosphate salt by treatment with aqueous HPF6. The new salt is a stable, deep-green colored crystals, that can be... 

According to theoretical calculations,16 synthesis of an azulene analogue formally derived by replacing two C=C double bonds in the seven-membered ring by two sulfur atoms seems feasible (cf. 112). 

The product of this synthesis is an especially useful, highly functionalized hydroazulene that is not available commercially. We have used it as a synthetic precursor to homoazulene,5 and to a variety of homoazulene derivatives,6 bridged homotropylium cations,7 and azulene quinones.8 It could undoubtedly serve as a precursor to numerous natural products. The cyclization reaction tolerates electron-donating substituents3 9 but not halogens10 on the aromatic ring. 

Highly strained substrates can be transformed into even more strained isomers by ODPM rearrangement. This has been shown by Murata et al. for the synthesis of a valence isomer of azulene [45]. Albeit the photochemical reaction yielded only 20-25% of the bicyclo[1.1.0]butane derivative 15, the synthesis of the precursor cyclobutene (14) is straight-forward from the bicyclo[3.3.0]octenone 13 (Sch. 18). This substrate has obviously a diverse reactivity pattern when directly excited, however, triplet sensitization reduces these competitive pathways because alkene excitation is excluded. Also benzo-annulated azulene valence isomers were generated by this approach [46]. 

Another intriguing example is a synthesis of azulene that utilises the bis(dimethylamine) derivative of glutaconaldehyde produced with loss of 2,4-dinitroaniline from l-(2,4-dinitrophenyl)pyridinium chloride (Zincke s salt). ... 

Synthesis of azulenes by condensation of cyclopentadienes with derivatives of glutaric dialdehydes. 

The Wittig reaction has been used to construct the side-chain in a synthesis of (-)-sirenin (208), a water mold sperm-attacking hormone.ii The intermediate (206) was generated, without competing formation of the structural isomer (207), by reaction of the ylide (205) with (204) under salt-free conditions in DME. Standard Wittig methods have been used to construct the side-chain in an enantioselective synthesis of (+)-(7 , 9Z)-methyl trisporate (209) and its (9E)-isomer.l 12 The reaction of triphenyl-(vinylimino)phosphorane derivatives (210) with tropones provides a convenient synthesis of 1-aza-azulenes (211) and (212) in either one or two steps (Scheme 28).H The mechanism of the one-step reaction was investigated using deuterium-labelled tropane derivatives. 

Sulphur.—Desulphurizations. Pyrolyses of cyclic bis-sulphones can be used to obtain large-ring cyclophanes (e.g. Scheme 24)/ Sulpholenes undergo pyrolysis or LiAlH4-promoted SO2 elimination to give dienes, and this approach has been used in the synthesis of azulenes. A related reaction gives Dewar-benzene derivatives. ... 

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