Triazole-oligomers by 1,3-dipolar cycloaddition

A variety of triazole-oligomers have been prepared under microwave and conventional conditions from novel alkynes and azides.


Introduction
Triazole-oligomers prepared by 1,3-dipolar cycloadditions of azides to alkynes 1 are new binder cure systems in the initial stage of development for high-energy explosive and propellant formulations. 2Structural features such as the length of chains between the triazole cross-links significantly impact the mechanical properties of the rubber matrices produced by the triazolecured polymers.Previous reports on the synthesis of oligomers with 1,2,3-triazole subunits include 1,3-dipolar cycloadditions of dialkynes and diazides, 3a,b dialkynes and monoazides, 3c diazides and monoalkynes, 3d or tris-alkynes and diazides.3e The kinetics of 1,3-dipolar cycloaddition can be controlled by selecting the appropriate functionalities on the alkyne and the azide; reactions are faster with electron-withdrawing substituents on the alkyne while their presence on the azide has the opposite effect.1e Previously utilized activating substituents on the alkyne mainly include alkoxycarbonyl, 4 carboxyl, acyl, cyano, aryl, haloalkyl, trimethylsilyl, phenylsulfonyl or phosphonate. 5e have studied 1,3-dipolar cycloadditions between a variety of organic azides and alkynes to develop strategies for low-temperature (~ 50 o C) synthesis of oligo-triazoles as binder The hexa-azide core 6 was prepared by the reaction of 4b and 3,5-bis(azidomethyl)phenol 7, which was synthesized in four steps from commercially available 5-hydroxyisophthalic acid (8).Thus, methyl ester derivative 9 was obtained quantitatively by refluxing 8 in methanol in the presence of a catalytic amount of H 2 SO 4 . 6Treatment of 9 with LiAlH 4 provided 3,5-bishydroxymethylphenol (10) in 80% yield.Subsequent hydroxyl to bromine conversion using HBr gave the bis-bromo derivative 11 in 93% yield; 11 was completely converted into 3,5bis(azidomethyl)phenol (7) using NaN 3 .The reaction of tribromide 4b (1 equiv) and bis-azide 7 (3 equiv) in the presence of K 2 CO 3 furnished the desired hexa-azide core 6 in 79% yield (Scheme 2).Preparation of di-carboxyl azides.Reaction of dicarboxylic acid 12a,b with thionyl chloride and subsequent treatment of the acid chloride intermediate with sodium azide gave the dicarboxyl azides 13a,b following the literature method (Scheme 3). 7However, products 13a,b showed spontaneous decomposition when stored at room temperature; successful dipolar cycloaddition reactions could not be carried out.

Scheme 6
Preparation of long-chain di-alkynes.The polyethylene glycol (E300) 22a was reacted with propiolic acid in the presence of a catalytic amount of p-TsOH in refluxing toluene to give the di-alkyne 23a in 98% yield. 10 Similar reactions of polyethylene glycols (E600) 22b and (E900) 22c with propiolic acid gave the corresponding di-alkynes 23b and 23c in 99 and 98% yields, respectively (Scheme 7).E300, E600 and E900 are mixtures of polyethylene glycols, and their structures are most probable representatives based on average molecular weight.

Scheme 11
Bistriazoles from long chain di-alkynes and benzyl azide.The mixture of di-alkyne 23a (1 equiv) and benzyl azide (2.5 equiv) was irradiated under microwaves at 120 W power and at 55 o C reaction temperature under solvent-free conditions for 1 h.The 1 H NMR spectrum of the crude reaction mixture showed signals corresponding to the triazole proton at 8.01 and 8.17 ppm and those from benzylic protons on the N atom of the triazole ring at 5.58 and 5.91 ppm.Further irradiation of the same reaction mixture at 120 W and 85 o C for 1 h resulted in complete reaction as indicated by disappearance of the acetylenic proton signal at 2.95-2.98ppm.We also tried the above reaction under thermal conditions.Thus, 1 equiv of diacetylene 23a was mixed with 2.5 equiv of benzyl azide without any solvent and the resulting mixture was stirred for 2 h at 50-60 o C (oil bath temperature).The 1 H NMR spectrum of the reaction mixture indicated complete reaction, since the signals from acetylene 23a had disappeared to be replaced by the signals from triazole protons (8.01 and 8.17 ppm).The bistriazole 29 was formed in quantitative yield as a mixture of regioisomers in 1:3 ratio.Similar reaction of dialkynes 23b and 23c with benzyl azide gave the corresponding bis-triazoles 30 and 31 (Scheme 12).

Scheme 12
Triazoles from ortho-and para-substituted diazidopropanol derivatives.Reaction of orthosubstituted diazidopropanol derivative 20 with ethyl propiolate (32) under solvent-free microwave irradiation at 50 o C and 60 W for 1 h gave a viscous material.TLC showed the presence of small amounts of starting materials.After repeated purification by column ARKAT chromatography on silica-gel, the desired triazole 33 was obtained in 34% yield with 80% purity as indicated by 1 H NMR (Scheme 13).

Scheme 13
Reaction of para-substituted diazidopropanol derivative 21 with ethyl propiolate (32) in toluene at 50 o C resulted in the formation of triazole 34 as a semi-solid that was recrystallised to give a white powder containing a mixture of six isomers (as indicated by TLC) in 91% yield.After fractional recrystallization of this mixture, we isolated a single regioisomer 34a in 46% yield (Scheme 14).

Scheme 15
Triazole from activated acetylene core.We prepared tris-triazole 36 by the reaction of activated acetylene core 27 and benzyl azide at 50-60 o C for 8 h.The crude material from the 1,3-dipolar cycloaddition reaction contained a mixture of regioisomeric triazoles, the major isomer 36 was separated in 45 % yield by recrystallization (Scheme 16).

Scheme 16
The structure of 36 was unambiguously established by single crystal X-ray crystallography (Figure 1), which confirmed the overall structure and the regiochemistry of the cycloaddition.In the solid state the molecule exists in a relatively compact conformation.The planes of the triazole rings are twisted relative to the plane of the central triazine ring at angles between 24.3 and 48.3 o , with two of the benzyl substituents above the plane of the central ring and the other on the opposite side.

Conclusions
Various azides and alkyne compounds were prepared and their 1,3-dipolar cycloaddition reactions studied under microwave and conventional conditions.The main aim of the study was to complete the triazole formation at the lowest possible temperature.It has been found that the cycloaddition reactions of azides with alkynes substituted with electron-withdrawing groups are fast and take place at low temperatures (~ 50 o C), under microwave or conventional conditions.

Figure 1 .
Figure 1.Perspective view of the X-ray crystal structure of 36.Hydrogen atoms have been omitted for clarity.

Scheme 3 Issue in Honor of Prof. Edmunds Lukevics ARKIVOC 2006 (v) 43-62 ISSN 1424-6376 Page 46
8eaction of oligoethylene glycol 14a with TsCl in the presence of Ag 2 O, KI and K 2 CO 3 gave the corresponding tosylate 15a in 55% yield which was converted to the di-azide 16a using NaN 3 in 91% yield.8Similarly, starting from the oligoethyleneoxide glycol 14b and 14c, we prepared the tosylate 15b and 15c in 93 and 96% yield respectively which on reaction with NaN 3 gave the corresponding oligoethyleneoxide diazide 16b and 16c in 80 and 85% yield (Scheme 4).