Triazolines from azides

Potassium/tert-butanol 5-Hydroxy-Zl 2-1,2,3-triazolines from azides and ketones... 

From Azides and x-Acylphosphorus ylids Addition of azides to a-acylphosphorus ylids takes place at room temperature in dichloromethane or at 80°C in benzene, giving triazolines from which a phosphine oxide is spontaneously eliminated. " The ylids exist almost exclusively in the cis-enolate configuration, and a mechanism involving concerted 1,3-dipolar addition has been proposed (Scheme 12) on the basis that there is a low entropy of activation for the reaction, and that the reaction rate is insensitive to changes in solvent polarity. ... 

Analogous methyl azidoformate forms with norbornene a thermal unstable triazoline.251 The decomposition products are 40% aziridine and 55% imide. Furthermore it has been observed that the rate of nitrogen evolution of the triazoline from methyl azidoformate increases threefold when triglyme and 20-fold when dimethyl sulfoxide are substituted for 1,1-diphenylethane as solvents. This fact supports a betaine intermediate in the thermal decomposition reaction. The triazoline from 2,4-dinitrophenyl azide and norbornene could just be isolated, but from picryl azide only the aziridine was obtained.252-254 Nevertheless, the high negative value of the activation entropy (—33.4 eu) indicates a similar cyclic transition state for both reactions. 

Organic azides combine with open-chain and cyclic eno) ethers to give A -triazolines in high yield. The addition is stereospecific cis and the orientation process is determined by electronic effects.145-160 The triazolines are unstable above 100° and can decompose in mainly two ways. 44 Triazolines from the open-chain enol ethers, vinyl butyl ether, /S-ethoxypropene, and a- and /3-methoxystyrene, eliminate alcohol thermally and are converted into 1,2,3-triazoles. For example, the triazoline 67 from /J-ethoxypropene 66 and p-nitrophenyl azide decomposes quantitatively at 150° into l-(p-nitrophenyl)-5-methyl-1,2,3-triazole (68). 

Triazolines from the cyclic enol ethers, dihydrofuran and dihydropyran, decompose at 100-130° into anils and nitrogen. Thus p-bromophenyl azide reacts with dihydropyran (69) to give triazoline 70 which decomposes thermally into the aryl-inline of 5-valerolactone (71). Photochemical decomposition of 70, on the contrary, yields 7-p-bromophenyl-7-aza-2-oxabi-cyclo[4.1.Q]heptane (72) in 67% yield. Scheiner has shown that aziridine 72 is stable at the decomposition temperature of 70, proving that it is not an intermediate in the thermal conversion of 70 to 71. 51... 

A second example is the formation of an endo-triazoline from a chloronor-bornyltriazene compound, apparently by an intramolecular nucleophilic displacement reaction (Scheme 106).373 Direct azide addition to norbornene is known to lead exclusively to the exo adducts (Section II,A,1). 

Imidazolines are well known and certain derivatives, such as efaroxan 27, stimulate insulin secretion by binding to imidazoline I3 receptors <1999ANY(881)217>. Stability decreases as the number of heteroatoms increases 1,2,3-triazolines 28 are formed from azides as 1,3-dipolar cycloadducts but readily form the aromatic 1,2,3-triazole by oxidation or elimination. 

Triazolines formed from azides attached to electron-withdrawing groups are much less stable and the decomposition products are obtained directly. A -Picryl imines were obtained in the reaction of picryl azide with a series of olefins yields were 70% with cyclopen-tene, 58% with cycloheptene and only 20% with cyclohexene. No imine was formed with norbomene . 

Synthesis of triazolines or aziridines from azides by photodecomposition or flash vacuum pyrolysis of 1,2,3-triazolines. 

The synthesis of monosubstituted A -l,2,3-triazolines from 1-arylazo-aziridines (11.1-5) has been reported to give excellent yields (Eq. 9). The starting materials (11.1-5) are often unstable and were isomerized without purification. A more recent report provides a promising alternative and extension for the synthesis of these compounds from dimethyloxosulfonium methylide (11.1-7) (Eq, 10). The use of 4-nitrophenyl- or benzoyl azide produced only triazenes. ... 

C. E. Olsen and C. Pedersen, The preparation of 5-hydroxy-A -l,2,3-triazolines from organic azides and aliphatic ketones. Tetrahedron Lett., (1968) 3805-3809. 

Triazoles from azides and enamines via 5-amino-J -1,2,3-triazolines... 

Trimethylsilylazide attacks citraconic anhydride with regiospecificity and catalytically adds to aldehydes in the presence of ZnCl2-18-crown-6. Silylazides react with vinyl and other alkenylsilanes to give bis(silyl)enamines through the thermal rearrangement of intermediate triazolines. Other azides give silyl-aziridines, which also result when silyl bromoazides, obtained from alkenylsilanes, are reduced with LiAlHi. ... 

Scheme 6.23) (see also Chapter 7). Under these conditions the intermediate triazoline is not isolable the Lewis acid appears to have the dual role of activating the enone and facilitating the decomposition of the triazoline. Triflic acid is a very efficient catalyst for promoting the formation of aziridines from azides and electron deficient alkenes such as but-3-en-2-one (Scheme 6.23). ° The acid appears to activate the alkene to nucleophilic attack by the azide it is not necessary to invoke triazolines as intermediates although they may be involved. 

The interaction of diazomethane with 1-azirines was the first example of a 1,3-dipolar cycloaddition with this ring system (64JOC3049, 68JOC4316). 1,3-Dipolar addition produces the triazoline adduct (87). This material can exist in equilibrium with its valence tautomer (88), and allylic azides (89) and (90) can be produced from these triazolines by ring cleavage. 

Enamines from cyclic ketones give derivatives of triazole 133,134). The enamine (113) reacts with p-nitrophenyl azide to give the triazoline (194), which on treatment with acid gives the triazole (195). 

The reaction of 1-methyl-1,2,3,4-tetrahydropyridine 62 and azides 50a-c in dry ether at 25°C afforded the l-methylpiperidylidene-2-sulfon(cyan)amides 65a-c in good yield (82JHC1259). The reaction proceeds via a triazoline intermediate 63, which loses nitrogen to afford 65. The elimination of nitrogen from triazoline intermediate 63 occurs by two possible mechanisms [68JCS(C)277]. In path A, the 63 could eliminate nitrogen to give first an unstable 2,7-diazabicyclo[4.1.0]heptane... 

Another conceptually unique approach in alkene aziridination has come from Johnston s labs. These workers shrewdly identified organic azides as nitrene equivalents when these compounds are in the amide anion/diazonium resonance form. Thus, when a range of azides were treated with triflic acid and methyl vinyl ketone at 0 °C, the corresponding aziridines were obtained, in synthetically useful yields. In the absence of the Bronsted acid catalyst, cycloaddition is observed, producing triazolines. The method may also be adapted, through the use of unsaturated imi-des as substrates, to give anti-aminooxazolidinones (Scheme 4.25) [32]. 

The nonsymmetrical quinolizidine 373 was obtained from the acyclic symmetrical precursor 372 by means of a reaction sequence comprising azide formation, intramolecular 1,3-dipolar cycloaddition, thermal triazoline fragmentation to a diazoalkane, and Michael addition individual steps, as shown in Scheme 85 <2005CC4661>. 

In reactions with azides, ketones are directly converted to 5-hydroxytriazolines. Ketone enolate 247, generated by treatment of norbornanone 246 with LDA at 0°C, adds readily to azides to provide hydroxytriazolines 248 in 67-93% yield. Interestingly, l-azido-3-iodopropane subjected to the reaction with enolate 247 gives tetracyclic triazoline derivative 251 in 94% yield. The reaction starts from an electrophilic attack of the azide on the ketone a-carbon atom. The following nucleophilic attack on the carbonyl group in intermediate 249 results in triazoline 250. The process is completed by nucleophilic substitution of the iodine atom to form the tetrahydrooxazine ring of product 251 (Scheme 35) <2004JOC1720>. 

Acyl azides 268, derived from furan, thiophene and selenophene, add slowly at room temperature to the strained double bond of 5-methylenebicyclo[2.2.1]hept-2-ene. Two regioisomeric triazolines, 269 and 270, which form in the first step, are unstable and decompose with elimination of nitrogen to provide aziridine derivatives 271. Products 271 are isolated in good yield (73-85%). It is worthy to note that not only the terminal, unstrained double bond in the starting material, 5-methylenebicyclo[2.2.1]hept-2-ene, is unaffected, but also the typical dipolarophiles like esters of crotonic, propiolic and byt-2-ynoic acids do not react with azides 268 under these conditions (Scheme 39) <2002J(P1)1420>. 

Finally (pathway e, Scheme 5.56), triazoline 103 formed by cyclo addition of azide to glycal 1 can be photolytically converted into a 1,2-aziridine intermediate 104, from which 2-benzylamino-2-deoxy-P-glucosides can be formed on addition of an alcohol and catalytic scandium triflate [176]. 

The reaction of ethyl azidoformate (93) with tetramethylallene yielded triazoline 94 and oxazoline 95 [88]. The triazoline 94 was formed by [3 + 2]-cycloaddition of azide 93 to the allene. The oxazoline 95 may result from [3 + 2]-cycloaddition of car-bethoxynitrene (96), which is formed from 93 by nitrogen evolution, to the allene or by the [2 +1] addition of the nitrene and subsequent rearrangement. 

Closure to the triazoline certainly occurs in many systems, since products are isolated which can only have been formed by this route. Occasionally these products include w-triazoles for example, 4-phenyl-triazole is isolated in moderate yield from the reaction of the aldehydes (3) with toluene-p-sulfonyl azide (Scheme 9). ... 

Treatment of the alcohol ( ) with trifluoromethylsulfonic anhydride (triflic anhydride) at -78 C afforded the ester (1 ) which could be isolated and characterized. We knew from previous experience (2J that sulfonyl esters vicinal to an isopropylidene acetal are relatively stable. The triflate T,) reacted cleanly with potassium azide and 18-crown-6 in dichloromethane at room temperature. The crystalline product [68% overall from (1 )] was not the azide ( ) but the isomeric A -triazoline ( )- Clearly the initially formed azide (18) had undergone intramolecular 1,3-cyclo-addition to the double bond of the unsaturated ester (21- ). The stereochemistry of the triazoline (1 ), determined by proton nmr spectroscopy, showed that the reaction was stereospecific. There are several known examples of this reaction ( ), including one in the carbohydrate series ( ). When the triazoline was treated with sodium ethoxide ( ) the diazoester ( ) was rapidly formed by ring-opening and was isolated in 85% yield, Hydrogenolysis of the diazo group of (M) gave the required pyrrolidine ester ( ) (90%). 

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