Azido-amides

Conversion of Amides to cx-Azido Amides Azidation or Azido-de-hydrogenation... 

On the basis of the same principle, we developed a three-component synthesis of macrocycles starting from azido amide (46), aldehyde (47) and a-isocyanoaceta-mide (48) (the cx-isocyanoacetamides are easily available, see [84—86]) bearing a terminal triple bond (Scheme 11) [87]. The sequence is initiated by a nucleophilic addition of isonitrile carbon to the in situ generated imine 50 led to the nitrilium intermediate 51, which was in turn trapped by the amide oxygen to afford oxazole 52 (selected examples [88-94]). The oxazole 52, although isolable, was in situ converted to macrocycle 51 by an intramolecular [3+2] cycloaddition upon addition of Cul and diisopropylethylamine (DIPEA). In this MCR, the azido and alkyne functions were not directly involved in the three-component construction of oxazole, but reacted intramolecularly leading to macrocycle once the oxazole (52) was built up. The reaction created five chemical bonds with concurrent formation of one macrocycle, one oxazole and one triazole (Scheme 15). 

Pyridazine, 4-amino-5-formyl-3,6-dimorpholino-synthesis, 3, 346 Pyridazine, 4-amino-3-halo-reaction with potassium amide, 3, 29 Pyridazine, aryl-synthesis, 3, 28 Pyridazine, arylthio-synthesis, 3, 27 Pyridazine, 3-azido-... 

A solution of the 2-azido ester or amide (ca. 2 g) in a mixture of MeOII (95 mL) and sodium-dried THF (95 mL) was photolyzed under N2 in a Hanovia photochemical reactor (110-W medium-pressure Hg lamp with a Pyrex filter). The reaction was monitored by observing the rate of disappearance of the absorption band (Nf) at 2140 cm 1 (irradiation times of 3-5 h were generally required). When the reaction was complete the solvent was removed in vacuo and the brown residual oil chromatographed on alumina [petroleum ether (bp 60-803C)/benzene 7 3]. Further elution with benzene followed by removal of the solvent gave the product (the esters as pale yellow oils, the amides as crystalline solids), which were further purified by vacuum distillation or by recrysiallization. 

Azido-l, 4-benzodiazepin-2-ones 43 arc obtained from 1,4-benzodiazepin-2-ones by treatment with potassium bis(trimethylsilyl)amide, followed by 2,4,6-triisopropylbenzencsulfonyl azide. The azides are reduced to the corresponding amino compounds 44 by the action of triphenyl-phosphane in aqueous tetrahydrofuran. No further details were reported.429... 

Oxamic Acid Azide (Azido Oxamate, Oxamido-azide, Oxamidsaureazid or Oxalsaure-amid-azid in Ger). H2N.CO.CO.N3, mw 114.02, N 49.11%, OB to C02 —42.09%, crystals from acet+petr eth mp, explds violently ca 115° or on rubbing. Can be prepd by treating the hydrazide of oxamic acid with Na nitrite in w Refs 1) Beil 2, (244) 2) T. Curtius, JPraktChem [2] 91, 426 (1915) 3) Urbanski 3... 

This lactamization process can be promoted by enzymes such as pancreatic porcine lipase. Reduction of co-azido carboxylic acids leads to macrocyclic lactams. Although treatment of carboxylic acids with amines does not directly give amides, the reaction can be made to proceed in good yield at room temperature or... 

Reaction of N,N-dimethylaniline with 1-cyanobenziodoxol 1783 to afford N-methyl-N-cyanomethylaniline 1784 in 97% yield has been discussed in Section 12.1 [31]. Analogously, oxidation of dimethylaniline with iodosobenzene and trimethylsilyl azide 19 at 0°C in CDCI3 gives the azido compound 2040 in 95% yield, iodobenzene, and HMDSO 7 [194, 195] (Scheme 12.56). Likewise, the nucleophilic catalyst 4-dimethylaminopyridine (DMAP) is oxidized, in 95% yield, to the azide 2041, which is too sensitive toward hydrolysis to 4-N-methylaminopyri-dine to enable isolation [194, 195]. Amides such as 2042, in combination with tri-... 

Sulfosuccinimidyl-2-(7-azido-4-methylcoumarin-3-acetamide)ethyl-l,3 -dithiopropionate (SAED) is a photoreactive heterobifunctional crosslinking agent that also contains a fluorescent group (Thermo Fisher). The sulfo-NHS ester end of the reagent reacts with primary amines in proteins and other molecules to form stable amide linkages. The photoreactive end is an AMCA... 

Figure 11.22 Azido-sialic acid-containing glycans can be labeled in vivo with biotin-PEG-phosphine using the Staudinger ligation reaction, which forms an amide bond.

Figure 17.19 An azido-sialic acid derivative that gets incorporated into glycans in cells can be labeled specifically with a biotin-phosphine tag using the Staudinger ligation process. The result is an amide bond linkage with the glycan.

Figure 17.24 The traceless Staudinger reaction can be used to form larger peptides from smaller peptides, if one contains an azido group at the N-terminal and the other one contains a phosphine ester at its C-terminal. The reaction gives a native peptide (amide) bond with loss of the phosphine group.

Figure 18.11 NHS-PEG4-azide can be used to modify an amine-containing molecule to create an amide derivative terminating in azido groups. The azide modifications then can be used in a click chemistry reaction that forms a triazole linkage with an alkyne-containing molecule. Alternatively, the azide derivative can be used in a Staudinger ligation reaction with a phosphine derivative, which results in an amide bond linkage.

The photochemical reaction can also proceed via the triplet state and in this case no cyclization is observed. Especially when acetophenone is added as a triplet sensitizer, 41 is not formed. Remarkable is the observation that in the presence of anthracene or pyrene as triplet quencher, the yield of the cyclization product 41 was not enhanced and that nitrene insertion into CH bonds of anthracene or pyrene was observed. When the photochemical cyclization reaction was performed with the tosyl azide derivative 42a or the azido nitrile derivative 42b (Scheme 6), only low yields of the tricyclic amide 41 (32% from 42a, 9% from 42b, respectively) were obtained <2001JCS(PI)2476>. 

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