Azines cycloaddition reactions

Burger s criss-cross cycloaddition reaction of hexafluoracetone-azine (76S349) is also a synthetic method of the [CNN + CC] class. In turn, the azomethines thus produced, (625) and (626) (79LA133), can react with alkenes and alkynes to yield azapentalene derivatives (627) and (628), or isomerize to A -pyrazolines (629) which subsequently lose HCF3 to afford pyrazoles (630 Scheme 56) (82MI40401). 

The first example of a cycloaddition reaction of a multiple bond to a diene was reported in 1917 Surprisingly, it was found that benzal azine adds to 2 equivalents of several unsaturated systems, when offered in excess, to yield bicyclie compounds. This reaction was named criss-cross" cycloaddition [190], Exploitation of the preparative potential of criss-cross cycloaddition began only in the early 1970s, when hexafluoroacetone azine became available on a larger scale [191,192] The study of this reaction proved to be an impetus tor the development of azine chemistry [183, 193]... 

The reaction of several substituted imidazo[4,5-c/]-, pyrazolo[3,4-r/]- and triazolo[4,5-zf]pyrid-azines 3 with ynamines, in competition with [4 + 2] cycloaddition, leads to [2 + 2] derivatives 4, which rearrange to l,2-diazocines5.7 8 The reaction seems to be sensitive to the substituents, as replacement of the electron-withdrawing group R on the pyridazine ring of the pyrazolo compound (A = N, B = CH) by chlorine completely inhibits both the [4 + 2] and [2 + 2] cycloaddition reactions. The X-ray structure of the imidazo derivative 5 (R = Ms, A = CH, B = N) reveals a tub conformation of the eight-membered ring. 

Jug and co-workers investigated the mechanism of cycloaddition reactions of indolizines to give substituted cycl[3,2,2]azines <1998JPO201>. Intermediates in this reaction are not isolated, giving evidence for a concerted [8+2] cycloaddition, which was consistent with results of previous theoretical calculations <1984CHEC(4)443>. Calculations were performed for a number of substituted ethenes <1998JPO201>. For methyl acrylate, acrylonitrile, and ethene, the concerted [8+2] mechanism seems favored. However, from both ab initio and semi-empirical calculations of transition states they concluded that reaction with nitroethene proceeded via a two-step intermolecular electrophilic addition/cyclization route, and dimethylaminoethene via an unprecedented two-step nucleophilic addition/cyclization mechanism (Equation 1). 

Thione S-imides, such as the fluorenethione S-tosylimide (68), have been known for about ten years. Saito and co-workers93 have studied the cycloaddition reactions of 68 with compounds containing homonuclear and heteronuclear double bonds. In almost every case the imide (68) reacted as a 1,3-dipole with alkenes, for example, isothiazoline derivatives (such as 69) were formed and with azines the 1,2,4-thiadiazolidine derivatives (70) were produced.93... 

On the basis of available experimental data, it is impossible to choose a definite pathway of elimination of silanol. However, study of silylation of methyl P -nitropropionate (411) with BSA in the presence of trapping agents rigorously proved that silyl nitronate D is initially formed. This compound can be detected in the [3 + 2]-cycloaddition reaction with methyl acrylate product (413). If silylation of AN (411) is performed in the presence of ethyl vinyl ether, a-nitrosoalkene E can be successfully trapped in as heterodiene a Diels-Alder reaction. Dihydroox-azine (414) is formed, and its silylation affords isolable product (415). 

HMO-treatment reveals a closed-shell system for the dianion of 6, thus indicating stabilization for isoelectronic cycl[2,2,2]azines with an additional nitrogen atom in a peripheral position, e.g., 7. Compounds of this type can be prepared by cycloaddition reactions. 

Cycloaddition reactions represent another route to pyrazoles from enamines. For example, azine (101) and enamines react via a [2 + 2]-cycloaddition with the formation of azetidines that undergo acid hydrolysis... 

Cyclocondensations of NADH analogues with / ara-benzoquinone are described in [368, 369]. For example, upon addition of dihydropyridine 338 to an acetonitrile solution of 339 in the presence of scandium trifluoromethane-sulfonate, the cycloaddition reaction occurs efficiently at room temperature, yielding cycloadduct 340 [368] (Scheme 3.113). This reaction passes via formation of a complex between azine and scandium trifluoromethanesulfonate. 

Azine approach. Saturated ring systems with a bridgehead nitrogen atom are best prepared from 3,4,5,6-tetrahydroazine 1-oxides. The latter can be classified as nitrones and as such will undergo 1,3-dipolar cycloaddition reactions. 

Azine approach. Pyridine TV-oxides undergo 1,3-dipolar cycloaddition reactions with aryl isocyanates. The first formed 1,2-dihydropyridines are unstable and rearrange at once to the 2,3-dihydropyridines (287). From 3-picoline 1-oxide both the 6-methyl and 7a-methyl isomers are formed. The adduct (288) from 3,5-dibromopyridine 1-oxide reacts further to eliminate HBr, thereby giving the fully aromatic system (79CPB2261). 

Azine approach. Examples of this heterocyclic ring system have been prepared from 3,4-dihydroisoquinoline azomethine imines (706) and sulfenes by 1,3-dipolar cycloaddition reactions. The products are l,5,6,10b-tetrahydro-3H-[l,2,3]thiadiazolo[4,3-a]isoquinoline 2,2-dioxide derivatives (707) (75JOC2260). 

Azine approach. 1 -Pyridinimines undergo 1,3-dipolar cycloaddition reactions with thiones. In the reaction between 2-isoquinolinimine and carbon disulfide the mesoionic thiadiazole (716) is formed the formation of (716) involves a secondary dehydrogenation of the initial adduct. With diphenyl thionocarbonate, phenoxy group expulsion is succeeded by cyclization leading to the adduct (717) (62TL387). 

The so-called criss-cross additions of azines involve a sequence of two 1,3-dipolar cycloaddition reactions, as exemplified by the reactions of hexafluoroacetone azine and benzaldazine with DMAD and phenyl isocyanate (Scheme 9) (76S349). 

Diazoacetic acid silyl esters can be prepared by fra t-esterification of tert-butyl diazoacetate with trialkylsilyl triflate <1985JOM33>. Analogously prepared (alkenyloxy)silyl 203 and (alkynyloxy)silyl diazoacetates 206 underwent silicon-tethered 1,3-dipolar cycloaddition reactions as shown in Scheme 37 and Equation (38). Compound 205 resulted from a lateral criss-cross cycloaddition of the intermediate azine 204, which was formed from two molecules of 203 by diazo + diazo or diazo + carbene reaction <2000T4139>. On the other hand, when silyl diazoacetates 206 were kept in xylene at 142 °C for 1 h, bicyclic pyrazoles 207 were obtained (Equation 38). 

Since the criss-cross cycloaddition reaction is a sequence of two [3 + 2] cycloaddition steps, the reaction of hexafluoroacetone azine with a,a>-diolefins offers access to a new class of trifluoromethyl-substituted heterocyclic macromolecules. Polymers with interesting structures and properties become available by criss-cross polymerization (88MI3 89MI2 90MI2). 

The Diels-Alder adduct isolated from the reaction of hexafluoro-acetone azine and 2,3-dimethyl-1,3-butadiene at elevated temperatures [75JCS(P1)1411] in fact is the result of a two-step process, namely of a [3-1-2] cycloaddition reaction and a subsequent [3.2] sigmatropic rearrangement [82JFC( 19)589]. 

A specific type of [3 -I- 2] cycloaddition reaction is the crisscross cycloadditioii between the electron-deficient hexafluoroacetone azine (6) and an electron-rich, terminal alkene or al-kyne. - Reactions can be performed under thermal or photochemical conditions and 2 1 adducts are obtained in good yields. 

CSI also reacts with diaryl azines (83) to afford the bicyclic triazolotriazolones (84), which are probably formed by 1,3-dipolar cycloaddition of CSI (two equivalents) to the azine (Scheme 39). Phenyl isothiocyanate undergoes a similar 1,3-dipolar cycloaddition reaction with a diaryl azine (83) to give the adduct (85) (Scheme 40). The main difference is that phenyl isothiocyanate is much less reactive than CSI, and consequently the cycloaddition requires more drastic conditions, namely prolonged boiling in xylene. 

Tominaga and coworkers 22 prepared dimethyl dibenzo[a,/t]cycl[3.2.2]azine-l,2-dicar-boxylate (553) by an [8 -I- 2] cycloaddition reaction of l-cyanoisoindolo[2,l-o]isoquinoline (552) with dimethyl acetylenedicarboxylate (57), followed by elimination of HCN. A small amount of acetic acid was added to improve the yield of the reaction from 1% to 26%. The double adduct 554 was isolated in minor amounts (equation 159). 

Hexafluoroacetone azine undergoes cycloaddition reactions with various electron-rich olefins or 1,3-dienes at moderate temperature to givepyridazines [Eq. (6)]. Depending on the structure and the quantity of the olefin employed and the temperature, other mono or bicyclic heterocycles can be formed. 

Fluoroalkylketenimines may be obtained from fluorinated alkenes and 60 undergoes a series of cycloaddition reactions, including formation of the quinoline derivative 61.149 Hexafluoroacetone azine (62) also reacts with acetylenes150 and the formation of pyrazoles (63) has been formulated as involving the quite novel migration of a trifluoromethyl group. 

Indole has also been used as a dienophile in cycloaddition reactions with 1,2,4-triazines.414 Depending on the substituents bound to the heterocyclic system / - or y-carbolines (33-89% or 6-22% yield, respectively), benzo[/][l,7]naphthyridines (2-50%) or 5-(indol-3-yl)-l,2,4-tri-azines are isolated (60-64%). 

In addition to intermolecular cycloaddition reactions of 1,2,4,5-tetrazines with various dienophiles, intramolecular cycloaddition reactions with alkene367 and acetylene 360 367 dienophiles or nitrile groups355-356 have also been reported. By this method condensed pyrid-azines 15 or 1,2,4-triazines 16 (see Section B.2.2.1.3.) are obtained. In most cases the side chain is bound to the 1,2,4,5-tetrazine ring by a heteroatom (O, S or In ). In a few cases the side chain is bound by a carbon atom or contains an additional heteroatom. The general reaction scheme is shown. 

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