Azulene derivatives

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

Cyclization of 8-hydrazinO 3-phenyl-l-azaazulenes 69 with triethyl orthoformate gave 4,5-triazabenz[c(f]azulene derivative 70 which was easily hydrolyzed on silica gel and gave (2-chloro-8-imino-3-phenyl-l-aza-l,8-dihydoazulen-l-yl) formaldehyde oxime (87H767) (Scheme 17). 

Finally, the pyrrolo[2,l-/ [l,2,4]triazine moiety was also encountered in azulene derivatives. Reactions of l,8-diamino-3-phenyl-l-azaazulenium salt 54 with triethyl orthoformate and acetic anhydride gave l-phenyl-2a,3,5-mjzjbenzb. //]jzulcncs 55 and 56. The reaction of the same salt with ethyl pymvate gave 4-acetyl-l-phenyl-2a,3,5-triazabenz[c, /]azulene 14 <2000H(53)323>. 

Nair and coworkers have described the [8 + 2] cycloaddition reactions of 2H-cyclohep-ta[fr]furan-2-ones such as 521 in several reports311. The reactions of 521 with alkenes yield azulene derivatives upon extrusion of carbon dioxide. Table 30 summarizes the results of the reactions between 521 and some 6,6-disubstituted fulvenes 522 (equation 151)311b. In the case of 6,6-dialkyl fulvenes 522a-c, the [8 + 2] cycloadducts 523 were the major adducts obtained, the Diels-Alder adducts 524 only being formed in trace amounts. 

When using relation (12c) it was found that the determination of Pa is subject to large errors, as a result of which the p B values naturally became very inacciu-ate (Gold and Tye, 1952b). Plattner and collaborators (1949) also drew attention to this source of error when evaluating partition equilibria of azulene derivatives. 

The figures for seven azulenes are summarized in Table 24. Again, the basicity of the unsaturated system increases with the substitution of methyl groups. The differences are such that Mq (the Hq- value for P = 1) represents a characteristic quantity which is useful for the identification of azulene derivatives, and for testing their purity. 

Approximate pKj, values for some azulene derivatives in HCIO4/H2O (Long cuid Schulze, 1964)... 

Long and Schulze (1961) determined spectroscopically, in perchloric acid, the Hp-value for which the concentration ratio Cah+/ca = 1- This value can be regarded as an approximate uncorrected pAg-value. These investigations were extended to other azulene derivatives, permitting a study of the effect of polar substituents on the basicity (Long and Schulze, 1964). 

Halobenzenes < Benzene derivatives < Condensed aromatics Diphenylpolyenes < Azulene derivatives -Hb... 

However gratifying this rationalization may seem to be in the case of azulene derivatives, it can of course not be used with naphthalene, biphenyl, etc. Here we have to confine ourselves to the statement that nucleophilic photosubstitution preferentially occurs at the positions that are known to be generally the most reactive in thermal reactions also. 

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... 

V,/V-Dimethylaminomethyl-2,3,3 ,12 -tetrahydrodibenzo[A/]furo[2,3- /]oxepine derivatives, for example, 145 (X = F, Cl, Br, OMe, etc.), are described as potent anxiolytic agents <2004CPB262, 2005BML2898, 2005FA241>, dibenzo[A/]thieno[2,3- /]oxepine derivatives are claimed as inhibitors of tumor necrosis factor-cr and interleukin-1 production for the treatment of inflammatory diseases <2004W02004078763>. 8-Oxa-l,2-diazadibenzo[i , ]azulene derivatives (dibenzo[/>,/]pyrazolo[3,4- /]oxepines) were synthesized as inhibitors of tumor necrosis factor-x and interleukin-1 production <2003W02003099822>. 

A strategy to enable multifold switching in macromolecular systems is briefly described below. On the basis of previous work, which showed that switchable and conducting films can be obtained by electropolymerization of 1,3-unsubstituted azu-lenes (Figure 31),[3S] investigations were carried out on DHA/azulene derivatives.1361... 

Similar [3 + 2] annulations of allenylsilanes 86 and propargylsilanes 87 with a, /i-unsaturated ketones, ketones, 7V-acyliminium ions, nitrosonium ions and tropylium cations giving the corresponding cyclopentenes (cyclohexenes), dihydrofurans, 3-pyrrolines, isoxazoles and azulene derivatives, respectively, have been reported (equations 60 and 6i)142.t54,i68-t72>... 

Treatment of 2-(l,2-dibromoethenyl)quinoxalines 57 with Na2CS3 affords thieno[2,3- ]quinoxalines 59. Addition of the thiocarbonate to the side chain generates 58. Intramolecular cyclization of 58 with loss of CS2 and NaBr leads to 59 (Scheme 14) <2001J(P1)154>. Azulenothiophenes 61 are prepared from azulene derivatives 60 by the reaction with thioacetamide (Scheme 15) <2002H(58)405>. Similar reactions of furyl ketones 62 afford thieno[3,4-3]furans 63 <1998JHC71>. 

Figure 4 Carajurone (R=CHs) and the related carajuretin (R=H) result by the very rapid enzymatic aerial oxidation of flavans present in the leaves of Arrabidaea chica. The plant is one of the most used Amazonian medicinal plants and the anti-microbial and other activities may be related to the presence of these red pigment. Some indigenous tribes use them as face paints and carajurone has been commercialised in the past as chica red. Genipa americana fruit juice, by the action of an endogenous glucosidase followed by aerial oxidation, provides another pigment. The juice has multiple medicinal uses probably associated with its antimicrobial action. Here the dye is blue-black and is believed to be an ethylene-bis- -aza-azulene , derived by condensation of the genipin monomer with primary amines. ...

Irradiation of / -bis(phenylethynyl)benzene (372) gives one azulene derivative 373 and a naphthalene derivative 374. Formation of 374 can be accounted for in terms of a bicyclobutane intermediate similar to 371. Cleavage of bonds corresponding to c and e in 371 and subsequent hydrogen migration would lead to 374 - . 

An azulene (36) having two intramolecularly crossing ethynyl groups was obtained together with its isomer (37) on irradiation of o-diethynylbenzene (35) and no further photochemical reaction was observed . On the other hand, o-bisphenyl-ethynylbenzcne (38) gave an azulenophenalene system, verdene (39), on irradiation . The mechanism of the formation of 39 was considered as a result of further cycloaddition of two triple bonds crossed in an intermediate azulene derivative (40). This photochemical reaction is reminiscent of the Biichi reaction in which diphenyl-acetylene yields an azulene system. 

Allene 68, formed in situ from l-(2,4,6-cydoheptatrien-l-yl)-2-phenyl-acetylene (67) in the presence of DBU in diethyl ether, underwent dimerization to give compounds 69,70, and 71 in 27, 43, and 4% yields, respectively (79CL171). Heating of compound 69 with DBU in benzene afforded a 2 1 isomeric mixture of azulenes 73 and 74 in 90% yield. The formation of the azulene derivatives (73 and 74) probably proceeds via the norcaradiene tautomer (72) of 69 (Scheme 2). 

The azulene derivative, guaiazulene (1,4-dimethyl-7-isopropylazulene), also reacts with COClj to give the expected ketone, (10.3) [1698a] ... 

---