Hydrazones intramolecular reactions

Ring transformation involving the intramolecular reaction of a hydrazone or in situ formed hydrazone also appeared. The transformation of 6-methyl-2//-pyran-2,3,4-trione 3-arylhydrazones 332 into l-aryl-6-methyl-4-oxo-l,4-dihydropyridazine-3-carboxylic acids 333 is an example of the former (Scheme 82). Compound 332 are formed via reaction of 4-hydroxy-6-methyl-27/-pyran-2-one 331 with substituted benzenediazonium chlorides. These are normally not isolated and immediately used further <2005EJM1325>. An example where a hydrazone is formed in situ is the reaction of 2-amino-5-aryldiazenyl-4-oxo-6-phenyl-4//-pyran-3-carbonitriles 334 with H2SO4 in glacial acetic acid, yielding 2-aryl-6-benzoyl-3-hydroxy-5-oxo-2,5-dihydropyridazine -carbonitriles 335 (Scheme 83) <2001T6787>. 

Intramolecular reactions of carbenes with alkenes have been exploited in synthesis. The sesquiterpene cycloeudesmol was prepared using, as a key step, the intramolecular cyclopropanation of the diazoketone 122 (4.97). The cyclopropana-tion reaction occurs stereoselectively to give the tricyclic product 123, which was subsequently converted into the natural product. A synthesis of sesquicarene was achieved using the copper(I)-catalysed decomposition of the diazo compound 125, itself prepared by oxidation of the hydrazone 124 (4.98). 

SCHEME 10.50 Intramolecular reaction of hydrazones with cyclopropanes. 

TABLE 10.16 Intramolecular Reaction of Hydrazones with Cyclopropanes... 

In situ formed iminiums were also able to react with alkyltins in an intramolecular fashion, leading to the formation of cyclopropane [265] or cyclopentane rings (Scheme 6.30). Similarly, the intramolecular reaction of y-alkoxystarmane with hydrazones, activated by a Lewis acid, was used to prepare 5- or 6-membered /3-amino cyclic ethers, for which the trans preference for the cyclization was consistent with an acyclic transition state [266]. 

Double intramolecular /zcfcro-Diels-Alder reaction of 1,3-diynil-bis-a,)S-unsaturated hydrazones 139 and 140 is a good example of a thermal multiple Diels-Alder reaction and is a particularly attractive route to annelated pyridines [123]. The initial cycloadduct readily aromatizes by the loss of dimethylamine (Scheme 2.52) under thermal reaction conditions. 

Another sequence involving an anionic and a Pd-catalyzed step was described by the groups of Rossi and Arcadi [477]. These authors prepared substituted tetrahy-dro-2H-pyrrolo[3,2-c]pyrazolones 2-934 starting from hydrazones 2-932 and aryl-halides or alkenyl triflates 2-933 (Scheme 2.208). The first step is the formation of a pyrazolone. There follows cleavage of the urea moiety with piperidine and an inter-as well as an intramolecular Heck-type reaction with 2-933. 

Other multi-heteroatom systems. Triheterocycles with a tetrazine as the central ring can be prepared by a base-induced intramolecular condensation reaction of the hydrazone-substituted pyrimidone shown in Equation (79) C1997JCM154, 1997JRM1041>. 

Hydrazones are also useful substrates in the preparation of pyrazoles. Reaction of N-monosubstituted hydrazones with nitroolefins led to a regioselective synthesis of substituted pyrazoles <060L3505>. lf/-3-Ferrocenyl-l-phenylpyrazole-4-carboxaldehyde was achieved by condensation of acetylferrocene with phenylhydrazine followed by intramolecular cyclization of the hydrazone obtained under Vilsmeier-Haack conditions <06SL2581>. A one-pot synthesis of oxime derivatives of l-phenyl-3-arylpyrazole-4-carboxaldehydes has been accomplished by the Vilsmeier-Haack reaction of acetophenone phenylhydrazones <06SC3479>. 

The formation of derivatives of 2,3,6,8-tetraazabicyclo-[3.2.1]3-octene (425) arises from an intramolecular nucleophilic addition to the nitrone group of hydra-zone (424). Compound (424) was prepared by reaction of 2-acyl-3-imidazoline-3-oxides (423) with hydrazine. From the cis- and frans-derivatives (424), exo- and enr/o-isomers (425) were obtained (Scheme 2.197). The reaction of intramolecular cyclization does not occur in cases with monosubstituted hydrazones (316). 

Depending on the nature of the substrates, selectivity could be completely reversed between the two isomeric products. For example, switching R1 group between Buc and Ph gave high yields of the first and second product structures, respectively. The authors noted that the reaction did not proceed if the imine contained an ortho-MeO group at R2 or if the imine was replaced with an aldehyde, oxime, or hydrazone. The catalytic cycle is initiated by C-H activation of the imine, that is, the formation of a five-membered metallocycle alkyne insertion affords the intermediate drawn in Scheme 69. It is noteworthy that this is the first report of catalytic synthesis of indene derivatives via a C-H insertion mechanism (C-H activation, insertion, intramolecular addition). 

An unusual one-pot intramolecular sulfoxide alkylation-elimination reaction was found by Gibson et al. <2001SL712>. These authors found that treatment of 459 with potassium bis-trimethylsilylamide resulted in a ring closure to 460 in acceptable yield. Furthermore, Batori and Messmer found an effective method for preparation of [l,2,3]triazolo[l,5- ]pyrimidinium salts <1994JHC1041> oxidative cyclization of hydrazones 461 by 2,4,4,6-tetrabromo-2,5-cyclohexadienone gave rise to the quaternary salts 462. Under certain reaction conditions, the formation of 6-bromo-salts 462 (R6 = Br) was also experienced. As neither the starting compound nor the quaternary triazolopyridinium salt underwent bromination in this position, the authors assumed that this bromination process occurred on one of the intermediates in the course of the above-mentioned cyclization reaction. 

Intramolecular addition of trialkylboranes to imines and related compounds have been reported and the main results are part of review articles [94, 95]. Addition of ethyl radicals generated from Et3B to aldimines affords the desired addition product in fair to good yield but low diaster control (Scheme 40, Eq. 40a) [96]. Similar reactions with aldoxime ethers [97], aldehyde hydrazones [97], and N-sulfonylaldimines [98] are reported. Radical addition to ketimines has been recently reported (Eq. 40b) [99]. Addition of triethylborane to 2H-azirine-3-carboxylate derivatives is reported [100]. Very recently, Somfai has extended this reaction to the addition of different alkyl radicals generated from trialkylboranes to a chiral ester of 2ff-azirine-3-carboxylate under Lewis acid activation with CuCl (Eq. 40c) [101]. 

Ring-chain equilibria involving cyclic tautomer formation by intramolecular reversible amidrazone NH-group addition to the C=0 bond were observed (85KGS849 86ZOR500) in solutions of the products formed in the reactions of pentane-2,4-dione and its 3-methyl derivatives with benzamidrazinium iodides. The ring-chain equilibrium was detected only in solutions of iodides or picrates. The free bases exist as the open-chain tautomers, like the hydrazones or enhydrazines. In contrast with the acyl-... 

Reduction of unsaturated aromatic aldehydes to unsaturated hydrocarbons poses a serious problem, especially if the double bond is conjugated with the benzene ring or the carbonyl or both. In Clemmensen reduction the a,)8-unsaturated double bond is usually reduced [160], and in Wolff-Kizhner reduction a cyclopropane derivative may be formed as a result of decomposition of pyrazolines formed by intramolecular addition of the intermediate hydrazones across the double bonds [280]. The only way of converting unsaturated aromatic aldehydes to unsaturated hydrocarbons is the reaction of... 

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