Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

Regioselective manipulation of hydroxyl groups via organotin derivatives

Indoles, both naturally occurring and synthetic, exhibit wide-ranging biological activity. Unusual and complex molecular architectures occur among their natural derivatives. As a result, this important ring system continues to attract attention from the international chemical community, and new methodologies for the construction of this ever relevant heteroaromatic ring continue to be developed. Unfortunately, many methods frequently start from ortho-substituted anilines, thereby greatly restricting the availability of starting materials. A more general approach would start from a mono-functionalized arene such as an aniline or halobenzene, followed by cyclization with C–C or C–N bond formation to an unactivated C–H bond. Such methods are the subject of this perspective.

http://www.chtf.stuba.sk/~szolcsanyi/education/files/Chemia%20heterocyklickych%20zlucenin/Prednaska%202/Doplnkove%20studijne%20materialy/Indole/Indole%20synthesis%20%96%20something%20old,%20something%20new.pdf

Indole synthesis – something old, something new

Crystal Structure of Hck in Complex with a Src Family–Selective Tyrosine Kinase Inhibitor

Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Heterocyclic compounds and uses thereof

1-Alkyl-5-amino-3-aryl-4-cyanopyrazoles, useful intermediates for fused heterocyclic systems, are synthesised by a one-pot three-step procedure from acid chlorides, malononitrile and alkylhydrazines. The regiochemistry of the hydrazine incorporation was proved in each case by X-ray crystallography and NMR spectroscopy.

One-pot synthesis of tetrasubstituted pyrazoles—proof of regiochemistry

Synthesis of organophosphorus compounds via silyl esters of phosphorous acids

Synthesis of the bacterial coenzyme methoxatin

Primary aromatic amines condense with
4,5-dichloro-1,2,3-dithiazolium chloride 1 to give high yields of the
N-aryl imines 2 which on heating give 2-cyanobenzothiazoles 3,
thus providing a simple two-step route to these heterocycles from the
appropriate aniline. This thermolysis is favoured by electron donating
substituents in the aniline ring, and retarded by electron withdrawing
groups in favour of a second pathway in which both dithiazole sulfur atoms
are lost to form cyanoimidoyl chlorides 4. This is the sole pathway when
both aniline ortho positions are substituted. Analogous
N-alkyl imines 5, prepared from the salt 1 and the
bis(trimethylsilyl) derivatives of the amine, also decompose with loss of
both sulfur atoms as singlet diatomic sulfur, S2.
4-Chloro-5-methylimino-5H-1,2,3-diathiazole 5a does this at
140–150 °C and the S2 generated is intercepted
with 2,3-diphenylbutadiene, 2,3-dimethylbutadiene and norbornene to give
16a, 16b and 17 respectively.

Conversion of imino-1,2,3-dithiazoles into 2-cyanobenzothiazoles,cyanoimidoyl chlorides and diatomic sulfur

The 3-β-D-ribofuranoside 6 of the new imidazo[2,1-f][1,2,4]triazine 27 is isomeric and isoelectronic with the nucleoside deaminoformycin 1 which is a good inhibitor of adenosine deaminase (ADA) while its 5′-monophosphate 2 is a good inhibitor of adenosine 5′-monophosphate deaminase (AMPDA). The 6-methylsulfanyl derivative 7 of 6 is synthesized by condensation of the monocyclic 1,2,4-triazine 9 with bromo aldehyde 10, which is accompanied by cyclization to give the protected C-nucleoside 21; the 8-methylsulfanyl group of 21 is removed by replacement by hydrazine and oxidation. The 1,2,4-triazine 9 cyclizes similarly with chloroacetaldehyde or its dimethyl acetal to give 6,8-bis(methylsulfanyl)imidazo[2,1-f][1,2,4]triazine 17, which is converted into the parent heterocycle 27 by two routes, and into mono- and di-substituted derivatives (19, 20, 24, 25, 28–30) of the new ring system. Riboside 7 is an inhibitor of mammalian ADA (IC50 40 µM).

Charles W. Rees

Papers

One-pot synthesis of tetrasubstituted pyrazoles—proof of regiochemistry

Synthesis of organophosphorus compounds via silyl esters of phosphorous acids

Synthesis of the bacterial coenzyme methoxatin

Conversion of imino-1,2,3-dithiazoles into 2-cyanobenzothiazoles,cyanoimidoyl chlorides and diatomic sulfur

Synthesis of C-ribosyl imidazo[2,1-f][1,2,4]triazines as inhibitors of adenosine and AMP deaminases