1 -Phenyl-1,2,3-triazole Diels-Alder reaction

Synthesis of benzo[c]furans and isoindoles (181) is also possible by the addition of benzyne to the respective monocycles (178), followed by reduction (179 — 180) and pyrolysis. In an alternative procedure, (179) is reacted with 3,6-bis(2-pyridyl)-l,2,4,5-tetrazine, which affords (181) under far less vigorous conditions via a retro Diels-Alder reaction of the intermediate (182). 4-Phenyl-1,2,4-triazoles pyrolyze to form isoindoles (Section 3.4.3.12.2). 

There are several cases of polycyclic triazolines, obtained by azide addition to the strained olefinic bond in bi- and tricyclic systems, that are susceptible to retro Diels-Alder reaction to yield 1-substituted triazoles. A well-established example is the monoadduct from norbornadiene and phenyl azide, which decomposes at 90-100°C to give 1-phenyltriazole and a cyclopentadiene (Scheme 138).2s 97—" 1 47 430 Similarly, the cycloadduct from the reaction of 7-oxabenzonorbornadiene and 1-azidoadamantane, when heated at 110°C, affords good yields of l-(l-adamantyl)-l,2,3-triazole in a retro Diels-Alder reaction.155... 

Iodobenzyl propargyl ether 57 cyclizes with 7t-allylpalladium (Scheme 18) to form after trapping by a secondary amine tetrahydro-2-benzoxepines 58 in 70% yield. The piperidino derivative 58 (R2 = (CH2)5) undergoes Diels-Alder reaction with 4-phenyl-l,2,4-triazole-3,5-dione as dienophile to give a spiro derivative 59 in 44% yield <1996TL6565>. 

Several syntheses of pyridazinopyridazines via Diels-Alder reactions of 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) (27) with functionalized dienes have been described. One example is the reaction of the diene (26) with PTAD (27) to afford the tandem Diels-Alder adduct (30) (Scheme 5) <85JCS(P1)71>. 

Thiophene 1,1-dioxide did not undergo cycloaddition with electron-deficient dienophiles. In most of the cases the dihydrobenzothiophene derivative 109 was obtained as the major product. This shows that self-dimerization is faster than cycloaddition with a different molecule. In the case of dimethyl acetylenedicarboxylate (DMAD) and 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione (PTAD), the Diels-Alder adducts 111 and 112 of 109 were obtained <1997JA9077>. However, cyclopentadiene gave the Diels-Alder adduct 113 with thiophene 1,1-dioxide. The DMAD adduct 111 on thermolysis undergoes a retro-Diels-Alder reaction to give dimethyl phthalate and thiophene 1,1-dioxide. Azulene was isolated in the thermolysis of 108 in the presence of 6-(dimethylamino)-fulvene this was the result of a [4-1-6] cycloaddition of the thiophene 1,1-dioxide formed in the reaction followed by elimination of SO2 and dimethylamine (Scheme 28) <1999BCJ1919>. 

Phenyl- and 4-methyl-3//-1,2,4-triazole-3,5(4//)-diones have most commonly been employed, although a series of 4-substituted analogs (R = CH3, Et, r-Bu, Bn, 4-CH3OC H4, 4-N02C6H4, CSHSCH = N) have been prepared and the substituent and solvent effects in the Diels-Alder reactions with a variety of dienes determined27. The unsubstituted parent compound is less stable and as a result has been less frequently used22-24. 

Diels-Alder Reaction of Simple 1,3-Cycloalkadienes and 4-Phenyl-3//-l,2,4-triazole-3,5(4//)-dione General Procedure25 ... 

Cyclooctatetraene and derivatives thereof in the ground state have a rigid tub-shaped structure where neighboring double bonds are not planar and cannot participate effectively in Diels-Alder reactions. However, the highly reactive 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione adds cyclooctatetraene at 20-25 UC to give the [4 + 2] bicyclic adduct with low yield1,2. 

Aryl-l,l-difluorobuta-l,3-dienes (e.g., 35) react rapidly with 4-phenyl-4//-l,2.4-triazole-3.5-dione (36) in Diels-Alder reactions.88... 

In so far as 4//-pyrazoles can be regarded as azadienes, the most obvious method of achieving 3,5-addition would seem to be through a Diels-Alder reaction. Unfortunately, these pyrazoles normally only react in this way with the most reactive dienophiles (4-phenyl-l,2,4-triazole-3,5-dione and cyclobutadiene ). It has recently been shown, however, that under acid catalysis a much wider range of dienophiles can be used, greatly extending the range of cyclopropyl derivatives that can be made. A typical example of an uncatalyzed reaction is that between 4,4-dimethyl-3,5-diphenyl-4i/-pyrazole and cyclobutadiene which yielded, after deazetization, 3,3-dimethyl-2,4-diphenyltricyclo[3.2.0.0 - ]hept-6-ene... 

Benzylidenecyclopropane, however, reacted with 4-phenyl-4/f-l,2,4-triazole-3,5-dione to give a 1 2 cycloadduct which can be rationalized by a [4 + 2] cycloaddition of the N-N double bond across the diene formed by the exocyclic C-C bond and a C-C bond of the phenyl ring, followed by a Diels-Alder reaction of the cyclohexadiene structure. 

Alkoxythiazoles (68) give an abnormal Diels-Alder reaction with highly reactive dienophiles such as 4-phenyl-3//-l,2,4-triazole-3,5(4/0-dione (PTAD), diethyl azodicarboxylate (dead), or diethyl oxomalonate. As an example, the reaction of (68) with PTAD (69) is illustrated in Equation (17). The product of the reaction (70) is the formal [3-1-2] cycloadduct between (69) and the corresponding nitrile ylide derived by the opening of thiazole ring system. For this abnormal Diels-Alder reaction of thiazoles a stepwise mechanism has been proposed <92BCJ3315>. 

Two of the double bonds of ethyl azepine-I-carboxylate can take part in a Diels-Alder reaction for example, with heterodieneophiles sudi as diethyl azodicarboxylate or 4-phenyl-1,2,4-triazole-3,S dione, the addition proceeds at ambient temperature over 12 weeks. 

Since both oxepin and its valence isomer benzene oxide contain a x-tb-diene structure they are prone to Diels-Alder addition reactions. The dienophiles 4-phenyl- and 4-methyl-4//-l,2,4-triazole-3,5-dione react with substituted oxepins at room temperature to give the 1 1 adducts 7 formed by addition to the diene structure of the respective benzene oxide.149 190,222... 

As l,2,4-triazole-3,5-dione (PTAD) is a stronger dienophile than acetylenic esters, more facile formation of the Diels-Alder cycloadducts was expected. But because it cannot behave as a diene in a reaction with alkynes such as diethyl azodicarboxylate, the formation of dihydrooxadia-zines is excluded. In spite of these characteristics, no Diels-Alder adducts were obtained in the reaction of l-phenyl-4-vinylpyrazole with PTAD in acetone at -80°C and 2,2-dimethyl-4(l-phenylpyrazol-4-yl)-8-phenyl-l,6,8-triaza-3-oxabicyclo[4.3.0]nona-7,9-dione 277 was obtained as a major product. The isolation of the tetrahydrooxadiazine 277 indicates that the 1,4-dipole 278 was formed and trapped with acetone. 

Only the Diels-Alder-ene products are formed from 4-nitro- and 4-/crt-butylphenylethylene with 4-phenyl- or 4-methyl-6 from 2-vinylpyridines and 4-phenyl-7 and from 1-cyclopropyl-l-phenylethylene and 4-phenyl-3//-l,2,4-triazole-3,5(47/)-dione8. From benzylidenecyclopropane the double Diels-Alder adduct 5 was obtained exclusively on reaction with 4-phenyl-3tf-l, 2,4-t riazole-3,5 (4/f)-d ione9. 

The configuration of all the previously described double Diels -Alder adducts has not been determined, although addition of the second diazene group to the cyclohexadiene moiety of the intermediate adducts is expected to occur anti to the cyclohexadiene substituent. In fact, a single an/7-bisadduct 6 was isolated from the reaction of 1,1,4,4-tetraphenyl-1,3-butadiene and 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione and the structure was inferred from H- and 13C-NMR studies10. 

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