5-alkynyl triazoles

The competing pathways, which arise from dehalogenation of the iodoalkyne and the triazole product and lead to 5-proto 41 and 5-alkynyl triazoles 42, are far too slow in the presence of the ligands. 

Alkenyl- and alkynyl-triazoles have received little attention. By analogy with the behaviour of other azoles they are expected to polymerize but to be less reactive in addition reactions than alkenes or alkynes. Although the most promising polymers derived from triazoles are obtained by different methods (see Section 4.12.5.2.3), some information is available on potentially polymerizable vinyltriazole (63MI4120i). The styryltriazole (134) could be oxidized to 3-methyl-l-phenyl-l,2,4-triazole, i.e. without affecting either the triazole or iV-phenyl ring, but hydroxylation of the alkene chain failed (s4JCS4256). 

Figure 17.15 The small carboxylate-alkyne compound 4-pentynoic acid can be used to modify proteins at their amine groups with EDC to provide alkyne sites for click chemistry-mediated conjugation. The subsequent reaction of an azido-PEG-modified gold nanoparticle with the alkynyl-protein in the presence of Cu1+ yields the triazole-coupled protein.

Besides processes (1) and (2), the reader should be aware that nucleophilic attacks on alkynes are treated in other chapters of this book, dealing with rearrangements, cyclizations, polyacetylenes, cyclic acetylenes and perhaps others. A number of publications overlap with ours in different ways and at different levels -. They treat individual alkynes or families " , e.g. acetylene, diacetylenes , acetylene dicarboxylic esters haloacetylenes , alkynyl ethers and thioethers > ynamines , fluoro-alkynes ethynyl ketpnes , nitroalkynes , etc. synthetic targets, e.g. pyrazoles , if-l,2,3-triazoles , isothiazoles , indolizines S etc. reagents, e.g. nitrones , lithium aluminium hydride , heterocyclic A -oxides - , azomethine ylids - , tertiary phosphorus compounds , miscellaneous dipolar nucleophiles - , etc. The reader will appreciate that all of these constitute alternate entries into our subject. 

The first example of an alkynylation of a bicyclic pyridazine derivative was published in 2000 [35]. Collins studied Sonogashira coupling of 7-bromo-6-[(1-methyl-l//-l,2,4-triazol-5-yl)methoxy]-3-phenyl[l,2,4]triazolo[4,3-Z ]pyridazine (165) with propargyl alcohol at 90°C in a sealed tube using Pd(PPh3)4 and Cul in triethylamine. Unfortunately, only a low yield of the reaction product (202) was obtained. 

As another example, poly(glycolide)s have been described that include a polymeric alkynyl-substituted glycoUde (56). The alk-ynyl groups provide reactive sites for further functionalization of the polymer, for example by reaction with azide derivatives. The alkynyl and azide groups react via the click chemistry mechanism to form functional groups covalently bonded to the polymer via a triazole link. The polymers are biodegradable and can be used to deliver drugs or other therapeutic substances at controlled release rates. 

The alkynyl functionality of alkynones 1 is perfectly suited for subsequent copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) in the sense of an MCR (2015ASC(357)617). A microwave-assisted three-component reaction of aroyl chlorides 4, TMS-substituted acetylene (5a), and benzyl azide (10a) consisting of modified Sonogashira cross-coupling I, desilylation, and CuAAC furnishes 4-disubstituted 1,2,3-triazoles 11 in moderate to excellent yields (Scheme 5) (201 OOL(12)4936). 

Cycloaddition of jo-bromobenzenesulfonyl azide to alkynyl ethers affords equilibrium mixtures of triazole and diazocarbox-imidate. In the case of the ether in which both the carbon and the oxygen substituents of the alkynyl ether are methyl, only the triazole is found (eq 8). ... 

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