Azide condensation reactions

CONDENSATION REACTIONS A. Displacement of Other Functional Groups by Azide Ion... 

In the case of the stepwise synthesis of peptide fragments starting from an amino acid without C-terminal protection, peptide bond forming methods are limited to the mixed anhydride method,the active ester method, and the azide methodJ l Although such peptide fragments can be directly used for the segment condensation reaction, the purification of the products after each coupling reaction is not so easy. 

Activation of the carboxyl group in condensation reactions can occur as an azide or, most common, with dicyclohexylcarbodiimide (DCC) or diisopropyl-carbodiimide. Neutral conditions are applied and no racemization occurs. Application of these condensation reactions is discussed in Section 9.3. 

Click reactions are a variety of condensation reactions in which Cu(I) is used as a catalyst for the synthesis of oligomers or polymers. The starting reactants are typically allgme-azides (125), but thiol-enes (TEC) and other alkenes (Diels-Alder) are also used (128). Several of their properties—selectivity, high yield, mild conditions, for example, room temperature, and fast reactions that proceed via minimal steps— make them desirable for use in green chemistry, a relatively new field that has imde-rgone explosive development in recent years (125,126,128,161). 

The Schotten-Baumann reaction is used in many peptide syntheses. It is usually carried out in the presence of conunon bases to remove the halogen acid. Another reaction also utilized often is an acid azide condensation ... 

Multicomponent approaches toward the formation of more complex phthalazine-containing compounds were reported in 2014. A four-component one-pot condensation reaction was employed by Dabiri and coworkers to generate (1,2,3-triazol-4-yl)methyl-3-amino-5,10-dihydro-5,10-dioxo-lH-pyrazolo[l,2-f)]phthalazine-2-carboxylates 26 (Scheme 18) (14SC2037). Catalyzed by Cu(OAc)2 (10mol%) and sodium ascorbate (20mol%), the reaction of benzaldehyde derivatives (1 equivalent), azides (1 equivalent), prop-2-ynyl-2-cyanoacetate (27) (1 equivalent), and phthalhydrazide (28) (1... 

Apart from condensation reactions, dick reaaions have extensivdy been used for the formation of model networks in recent years. The copper(I)-catalyzed regiospecific (3 + 2] cycloaddition reaction of azides with acetylenes has mainly... 

Basic hydrolysis of the products from the reaction of 3-P-D-ribofuranosyl-adenine with phosphorus oxychloride in trimethyl phosphite gave the cyclic phosphoramidate (620) as well as the expected 5 -phosphate. Phosphoramid-ates e.g. (621)] have been obtained from the reaction between nucleoside 5 -azides and 3 -silylphosphites the silylation reaction and azide condensation were conducted simultaneously (Scheme 95). ... 

Our initial experiments utilized 2 -deoxyadenosine in attempting to acquire knowledge of the reactivity of the 3 -hydroxyl group for condensation reactions with the p-nitrophenyl ester of 3-chloropropionic acid with free imidazole as catalyst. The choice of the 3-chloropropionic acid rested upon the feasibility of converting the halide first into an azide, then an amine, and finally a diazo derivative. 

Cytidine has been converted into l-(5-amino-5-deoxy-j8-D-arabinofuranosyl) cytosine by a sequence of reactions involving A-benzoylation, sulphonation, acetylation, displacement with azide ion, e/c., and l-(3-amino-3-deoxy-jS-D-arabinofuranosyl)-6-azauracil was derived from 2, 3 -di-0-methanesulphonyl-5 -O-trityl-6-azauridine via 2,2 - and 2, 3 -anhydro-nucleosides. Other syntheses have been accomplished by the condensation of an appropriately derivatized amino-sugar with either a pyrimidine or purine derivative for example, the Hilbert route was used to prepare l-(2-amino-2-deoxy-a-D-arabino- and -jS-o-xylo-furanosyl)cytosine. > The reactivity of l,3,4,6-tetra-0-acetyl-2-acyl-amido-2-deoxy-j3-D-glucopyranoses in condensation reactions with 2,6-dichloro-purine, theophylline, and 6-benzylaminopurine was shown to be in the order benzamido > acetamido > phthalimido. 9-(3-Acetamido-2,5-di-0-acetyl-3-deoxy-j8-D-ribofuranosyl)-2,6-dichloropurine has been synthesized and converted into the corresponding 2,6-diamino- and 6-amino-2-chloro(fluoro)-nucleosides. ... 

Hemetsberger and coworkers published in 1969 the special condensation reaction of benzaldehydes 76 with ethyl azidoacetate (77a) in the presence of sodium ethoxide to get moderate to good yields of the a-azidocinnamic esters 79a (Scheme 5.12). The temperature and the reaction time had to be controlled careMly, because the strongly alkaline reaction conditions induced the danger of decomposition of the base-sensitive azides 77 and other unwanted side reactions. Thus, Knittel reported some years later that usage of methyl azidoacetate (77b) and sodium methoxide offers several advantages in the synthesis of vinyl azides 79b. Nevertheless, the Hemetsberger-Knittel reaction can only be... 

Abstract Although the synthesis of 1,4- or 1,5-disubstituted 1,2,3-triazoles has been popularized by the recent developments of metal-catalyzed 3-1-2 cycloaddition of organic azides and terminal alkynes, the preparation of 1,4,5-trisubstituted triazoles is less popular. The focus of this chapter is the synthesis of these heterocycles, using condensation reactions and rearrangements, selective preparation of trisubstituted triazoles from disubstituted precursors, and formal [3-1-2] cycloaddition reactions involving internal alkynes. 

Substituted benzyl azides can also be used in such condensation reactions. Several 5-amino-4-carbamoyl-triazoles 21 were prepared as single isomers by condensation of the corresponding benzyl azides 20 with cyanoacetamide under basic conditions (NaOH/EtOH, reflux) in poor to reasonably good yields (Scheme 6) [11]. 

Dinitroaniline from 3 5-dinItrobenzoic acid. Place a solution of 50 g. of 3 5-dinitrobenzoic acid (Section IV, 168) in 90 ml. of 10 per cent, oleum and 20 ml. of concentrated sulphuric acid in a 1-litre three necked flask equipped with a reflux condenser, mechanical stirrer, adropping funnel, and thermometer (FUME CUPBOARD ). Add 100 ml. of clJoroform and raise the temperature to 45°. Stir rapidly and add 17 -5g. of sodium azide in small portions whilst maintaining the temperature at 35-45°. The reaction is accompanied hy foaming, which usually commences after about 3 g. of sodium azide has been introduced. After all the sodium azide has been added raise the temperature so that the chloroform refluxes vigorously and maintain this temperature for 3 hours. Then cool the reaction mixture, pour it cautiously on to 500 g. of crushed ice, and dilute with 3 litres of water. After 1 hour, separate the yellow solid by filtration at the pump, wash well with water and dry at 100°. The yield of 3 5-dinitroaniline, m.p. 162-163°, is 39 g. The m.p. is unaffected by recrystallisation from dilute alcohol. 

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