4- PHENYL 1,2,4-TRIAZOLINE

Preparation of cholesta-5,7-diene-ia,3/3-diol a solution of 500 mg of the 1,4-cyclized adduct of cholesta-5,7-dien-3/3-ol-ia,2a-epoxideand 4-phenyl-1,2,4-triazoline-3,5-dione in 40 ml of tetrahydrofuran is added dropwise under agitation to a solution of 600 mg of lithium aluminum hydride in 30 ml of THF. Then, the reaction mixture liquid Is gently refluxed and boiled for 1 hour and cooled, and a saturated aqueous solution of sodium sulfate is added to the reaction mixture to decompose excessive lithium aluminum hydride. The organic solvent layer is separated and dried, and the solvent Is distilled. The residue Is purified by chromatography using a column packed with silica gel. Fractions eluted with ether-hexane (7 3 v/v) are collected, and recrystallization from the methanol gives 400 mg of cholesta-5,7-diene-la, 3/3-diol. 

An example of a /zctcro-Diels-Alder reaction in SC-CO2 is the cycloaddition of anthracene with 4-phenyl-1,2,4-triazoline-3,5-dione, carried out at 40 °C and at a pressures between 75 and 216 bar [86]. The rate constant increases with decreasing pressure and the highest reactivity was observed at the critical pressure. The value of the rate constant at the critical pressure was higher than that observed in liquid CHCI3 and MeCN at the same temperature. At higher pressures, the rate is slower than that in the polar solvents, which reflects the apolar nature of SC-CO2 as a solvent. 

In 1974, Vogel and his coworkers62) reported the first synthesis of the syn-benzene bisepisulfide 119 and its thermal behavior. The bisepisulfide 119 is thermola-bile and decomposes at 20 °C with a half-life of about 30 min to form benzene and sulfur as final products. When the reaction was carried out in the presence of 4-phenyl-1,2,4-triazoline-3,5-dione (PTD), 119 gave the product 120 which corres-... 

Methyl-3-(tetramethylcyc opropylidene)propene (176), obtained by isomerization of allene 175 with potassium ferr-butoxide, added to 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD, 177) at room temperature to give the Diels-Alder adduct 178 in 46% yield (Scheme 26) [43]. 

Gycloaddition reactions of betaine 64 with electron-deficient dipolarophiles, such as the extremely reactive 4-phenyl-1,2,4-triazoline-3,5-dione, gave the corresponding cycloadduct 65 isolated in quantitative yield (Equation 8) <1995T6651>. 

The attack from the less-hindered side and in which how the products formed by exo or endo additions vary has attracted great attention and a very interesting case of the reaction between naphthalene derivatives and 4 phenyl-1, 2, 4 triazoline 3, 5 dione (d) acting as dienophile has been reported by B.M. Jacobson in 1973. 

Phenylurazole, from 4-phenyl-l-carbethoxysemicarbazide and potassium hydroxide, 51,122 with /-butyl hypochlorite to give 4-phenyl-1,2,4-triazoline-3,5-... 

The syntheses have been reported of la,3/3-dihydroxy-4,4-dimethylcholesta-5,7-diene (269) and its 3a-epimer, along with the ergostane analogues/ As reported in the preliminary account, 4,4-dimethylcholesta-5,7-dien-3-one underwent the ene reaction with 4-phenyl-1,2,4-triazoline-3,5-dione to give (270) rather than the normal Diels-Alder adduct.Treatment of (270) with acid gave the trienone (271). Treatment of cholecalciferyl tosylate with aq. KHCO3-... 

We were not able to obtain any cycloadduct from unactivated 2-azadienes 139 and esters of acetylenedicarboxylic acid. However, we found that 139 did cycloadd to typical electron-poor dienophiles such as esters of azodicarboxylic acid and tetracyanoethylene (Scheme 62). Thus, diethyl and diisopropyl azodicarboxylates underwent a concerted [4 + 2] cycloaddition with 139 to afford in a stereoselective manner triazines 278 in 85-90% yield (86CC1179). The minor reaction-rate variations observed with the solvent polarity excluded zwitterionic intermediates on the other hand, AS was calculated to be 48.1 cal K 1 mol-1 in CC14, a value which is in the range of a concerted [4 + 2] cycloaddition. Azadienes 139 again reacted at room temperature with the cyclic azo derivative 4-phenyl-1,2,4-triazoline-3,5-dione, leading stereoselectively to bicyclic derivatives 279... 

Substituted l,2,4-triazoline-3,5-diones are excellent dienophiles which react rapidly at room temperature with oxepins, but particularly with the arene oxide valence tautomer. A similar [4 + 2] cycloaddition reaction between the episulfide tautomer of thiepin (44) and 4-phenyl-1,2,4-triazoline-3,5-dione has been reported (74AG(E)736). Benzene episulfide (the valence tautomer of thiepin 44) was generated in situ by thermal decomposition of the diepisulfide (151) at 20 °C and trapped as a cycloadduct at the same temperature (equation 34). A 1,3-dipolar cycloaddition reaction between thiepin (152) and diazomethane has been reported (56CB2608). Two possible cycloadduct products are shown since the final structure has not been unequivocally established (equation 35). 

A product A, C28H30N6O4, was obtained in 87% yield when a mixture of 3,4-di-t-butylthiophene 1,1-dioxide and 4-phenyl-1,2,4-triazoline-3,5-dione (2 eq.) was heated under reflux in toluene for 5 hours. Hydrolysis of A with methanolic potassium hydroxide at room temperature gave an 80% yield of 4,5-di-t-butylpyridazine. 

The first report of reactions of vinylthiophene with azodienophiles appeared in 1974 The reaction between 4-phenyl-1,2,4-triazolin-3,5-dione... 

A comparative study involving singlet oxygen, ozone, and 4-phenyl-1,2,4-triazoline-3,5-dione oxidation of chiral oxazolidinone substituted enecarbamates has shed light on the mechanistic intricacies of the oxidative cleavage of alkenyl double bonds.282... 

In general, reaction of (110) with a wide variety of dienes was quite satisfactory (67JOC330). Only the most unreactive dienes such as hexachl-orocyclopentadiene and hexachlorobutadiene failed to react under the conditions employed. The chief limitation of this dienophile is that the mixture cannot be heated to force reaction without the decomposition of (110). Another important observation was the strong, almost complete preference for undergoing the Diels-Alder-type addition even when other reactions are possible. This may be attributed to the two favorable factors of cis configuration and electron deficiency that are exhibited by 4-phenyl-1,2,4-triazoline-3,5-dione. 

Dimethyloxazolidines have been utilized as chiral auxiliaries for the diastere-oselective functionalization of the optically active tiglic acid derivatives by means of epoxidation with dimethyldioxirane (DMD) or m-CPBA and ene reactions with 02 or 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). In the DMD and m-CPBA epoxidations, high diastereoselectivities but opposite senses of diastereomer selection was observed. In contrast, the stereochemistry of the 102 and PTAD ene reactions depended on the size of the attacking enophile whereas essentially perfect diastereoselectivity was obtained with PTAD, much lower stereoselection was observed with 02. The stereochemical results for the DMD and m-CPBA epoxidations and the PTAD ene reaction are explained in terms of the energy differences for the corresponding diastereomeric transition states, dictated by steric and electronic effects.200... 

Michael addition, on A-2-thiazoline-5-one. with diethylazodicarboxylate, 433 with maleic anhydride, 433 4-phenyl-1,2,4-triazolin-3,5-dione, 433 Microreversibility principle, 85 Miticide, 440 Mitodepressive, 149, ISO Mn complexes, 104 Molecular orbital calculations. 17 and ambident reactivity, 61, 62 and amino-imino equilibrium, 18 and electrophilic substitution, 18 and HSAB, 1 8... 

Where the carbon-carbon double bond is a part of an aromatic system, in general, cyclopropanation of diazoketones results in the formation of unstable cyclopropane adducts. For example, Saba " has shown that in the intramolecular cyclopropanation of diazoketone 57 the norcaradiene ketone 58 can be detected by low-temperature NMR and can be trapped in a Diels Alder reaction with 4-phenyl-1,2,4-triazoline-3,5-dione (equation 69). In addition, Wenkert and Liu have isolated the stable norcaradiene 60 from the rhodium catalysed decomposition of diazoketone 59 (equation 70) Cyclopropyl ketones derived from intramolecular cyclopropanation of hetereoaromatic diazoketones are also known and two representative examples are shown in equations 71 and 12. Rhodium(II) compounds are the most suitable catalysts for the cyclopropanation of aromatic diazoketones. 

A synthesis of 22,23-epoxyergocalciferol from the 4-phenyl-1,2,4-triazoline-3,5-dione adducts (272) employed the K2CO3-DMSO reaction for deprotection of the A -diene cf. ref. 53). The Reporter observes that the assignment of the 22/3,23/3-configuration is dubious in view of earlier work in this area. " Syntheses have been reported for la,25-dihydroxy-24-nor-cholecalciferol, 25-hydroxy-24 -nor- 5,6- frans-cholecalcif erol, and 2 5 -hydroxy- 24a-homo- 5,6-... 

A novel route to the ring b aromatic anthrasteroids (49) from S,7-dienes (50) proceeds in two steps and uses 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) as the oxidant, as is shown in equation (47)7 Addition of PTAD to the steroidal S,7-diene gives an adduct which, when treated with boron trifluoride etherate, rearranges to the anthrasteroid in generally greater than 90% yield. This reaction presumably proceeds through a spirocyclohexa-1,4-diene. 

A special case of these ring transformation reactions is the 5-insertion reaction of 4-phenyl-1,2,4-triazolin-3,5-diones (4 Ph-TAD) [750PP251 81AG832, 81AG(E)797] into uracils, for example, the reaction of 5-(3,5-dioxo-4-phenyl-l,2,4-triazolidin-l-yl)-l,3-dimethyluracils with hydrazine... 

Some unexpected (V-acylations (Scheme 30) came to light in studies of 4-phenyl-1,2,4-triazoline-3,5-dione (76). Addition to vinyl acetate is followed by intramolecular acylation to (94), finally yielding (95) (72JOC1454), while reaction with methanol resulted in a 1,2-dicarboxylic acid (probably through NCH2OH formed by reaction with formaldehyde) isolated as (96) (76cc326). 

The mechanism of this type of reaction has received some attention. ° It has been suggested that these reactions are pericyclic processes, and since N°=N dienophiles have lower lying LUMOs than C=—C compounds, diey are more reactive. Cyclic N—N species have an even lower LUMO energy. However, a recent investigation of the cycloadditions of 4-phenyl-1,2,4-triazoline-3,S-dione (vide infra) indicates that in at least some cases the Diels-Alder reactions involve discrete intermediates. It would appear that a range of mechanisms may be available to azo dienophiles. 

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