Klaus Banert

Synthesis and screening of some novel fused thiophene and thienopyrimidine derivatives for anti-avian influenza virus (H5N1) activity.

Several derivatives containing dihydronaphtho, naphtho[2,1-b]thiophene and thieno[2,3-d]pyrimidine ring systems were prepared starting from 2-amino-4,5-dihydronaphtho[2,1-b]thiophene-1-carbonitrile (1). Structure characterization of the thioxo derivative 7 was also performed and its reaction with some chloro and bromoalkyl reagents was studied. Moreover, the prepared products were tested for antiviral activity against H5N1 virus [A/chicken/Egypt/1/2006 (H5N1)] by determination of both EC50 and LD50 and confirmed by plaque reduction assay on MDCK cells. Compounds 5, 7 and 8 showed the highest effect compared with the other tested compounds.

Azido-1,2,3-triphenylpropenes of Varying Stabilities: A Corrigendum of Structure Assignment

A reinvestigation of the reaction between 2,3-diphenyl-2H-azirine (1) and phenyldiazomethane (2) has shown that a literature report has to be corrected since no vinyl azide 4 but rather the allylic compound 3-azido-1,2,3-triphenyl-1-propene (3) is produced. This stable substance, which can also be prepared by substitution reactions of allylic bromide (E)-10 or from alcohol (E)-11, may be separated into its geometrical isomers (E)-3 and (Z)-3, although these equilibrate through rapid [3,3] sigmatropic migration of the azido group. Attempts to synthesize 4 by dehydration of azido alcohols 7 using methanesulfonyl chloride and sulfur dioxide or by elimination of hydrogen chloride from azides 15 led only to 3 and 2-benzyl-2,3-diphenyl-2H-azirine (14). This heterocycle, which can also be prepared by Neber rearrangement, has been found to be the thermal and photochemical decomposition product of the unstable vinyl azides 4. However, dehydrations of 7 using thionyl chloride at low temperature have led to the first isolation of 1-azido-1,2,3-triphenyl-1-propenes (4). Starting with 3 and various other allylic azides, rearrangement reactions involving sigmatropic shift of the azido group or photochemical cis-trans isomerization have been investigated, as have base-catalyzed (prototropic) rearrangements to give vinyl azides.

Experimental and Theoretical Studies on the Synthesis, Spectroscopic Data, and Reactions of Formyl Azide

Tothebestofourknowledge,however,spectroscopicprooforany other indication for the existence of formyl azide (3a)isstill missing. There may be two reasons why 3ahas not beengenerated experimentally. Quantum chemical calculationspredicted activation energies for the process 3a!4a thatwere significantly lower than those of the Curtius rearrange-ment reactions of acetyl or benzoyl azide (differences of 3.4–4.9 and 6.5–10.5 kcalmol

Extremely Simple but Long Overlooked: Generation of α-Azido Alcohols by Hydroazidation of Aldehydes†

of 1 with hydrazoic acid to prepare a-azido alcohols 2 is completely unknown. Attempts to generate 2 by methanolysis of silyl ethers 3 led only to 1. a-Azido alcohols of type 2 have been discussed as short-lived intermediates in the solvolysis of diazides 4, which also yielded the final products 1. Protonation of 2 at N-a leads to an intermediate that is generally accepted to explain the mechanism of the Schmidt reaction. Recently, in situ formation of azidomethanol (2a) was postulated in the reaction of formaldehyde and sodium azide in the presence of acetic acid. This reaction was completed by copper(I)-catalyzed cycloaddition at terminal alkynes to give 1,2,3-triazoles. In all of these cases, there is no spectroscopic proof of intermediates 2, whereas compounds of types 3 6] and 4 and also a-azido ethers 5 9] can be prepared easily from precursors 1 or the corresponding acetals or enol ethers and then isolated and characterized. This led to the presumption that hydrazoic acid does not react with aldehydes readily. Since we did not question this statement or at least did not doubt the elusiveness of a-azido alcohols 2, we obtained evidence for these compounds incidentally. By treatment of triazide 7 with anhydrous hydrogen halide, we prepared azidochloromethane (8) and azidobromomethane (9) besides diazide 10 (Scheme 2). The desired products are inter-

Syntheses and Diels-Alder reactions of 2-alkylazo-substituted 1,3-butadienes☆

Abstract 1-Alkyl-1-(2,3-butadienyl)hydrazines 1b,d—g can be oxidized under mild conditions to yield 1-alkyl-2-(1-methylen-2-propenyl)diazenes 3. These E-configurated azo compounds are precursors for rapid inter- and intramolecular [4+2] cycloadditions to give the heterocyclic products 4 and 6–10.

Elusive ethynyl azides: trapping by 1,3-dipolar cycloaddition and decomposition to cyanocarbenes

Although they decompose rapidly to produce cyanocarbenes, ethynyl azides were generated from (chloroethynyl)arenes and trapped for the first time by 1,3-dipolar cycloaddition at cyclooctyne.

Synthesis of new bi-2H-azirin-3-yl compounds from diazides

Abstract Starting with 2,3-diazido-1,3-butadienes 4 or 10 successive loss of molecular nitrogen by thermolysis or photolysis leads to new bi-2H-azirin-3-yl compounds 2 or 3.

Synthesis of New Vinyl Thiocyanates by [3,3] Sigmatropic Rearrangement of Isothiocyanates

Propargyl isothiocyanates 3 and buta-2,3-dienyl isothiocyanates 20 were prepared conventionally from amines and thiophosgene, or by a new, one-pot procedure using nucleophilic substitution to generate azides, which in turn served as the starting materials for a Staudinger reaction, followed by treatment of the resulting iminophosphoranes or iminophosphates with CS2. Equilibration, through a [3,3] sigmatropic rearrangement, of 3 and the allenyl thiocyanates 4 was established by flash vacuum pyrolysis or by thermolysis in solution. Even the reversible isomerization of the parent compounds 3f and 4f favors the allenyl thiocyanate. In the case of 20, an irreversible rearrangement reaction gave high yields of 2-thiocyanatobuta-1,3-dienes 21. A sequence of two [3,3] migration steps transformed 1,4-diisothiocyanatobut-2-ynes 3m and 3n into 2,3-dithiocyanatobuta-1,3-dienes 21m and 22, respectively. These reactions demonstrate that the [3,3] sigmatropic rearrangement of mustard oils, to afford high yields of thiocyanates bearing the thermodynamically less stable functional group, is possible if the conversion gives rise to a more stable carbon skeleton. The equilibration of 1-thiocyanatopent-2-en-4-ynes 12 and 1-thiocyanatopenta-1,2,4-trienes 14 could be explained by tandem [3,3]−[3,3] sigmatropic rearrangements through short lived 3-isothiocyanatopent-1-en-4-ynes 13. Thiocyanato-substituted vinylallenes 4k and 14 tended to electrocyclize to give cyclobutenes 7 and 15, respectively. Thiocyanates 21a, 21b, 21m and 14a, which exhibit a buta-1,3-diene structure, could be used in Diels−Alder reactions to afford the cycloadducts 25a, 25b, 26a, 26m, 28m, 29m, and 30.

Synthesis of 1,2‐Difunctionalized 1,3‐Butadienes through a Sequence of Sigmatropic Rearrangements

Just by the introduction of isomerizable groups and successive [3,3] or [2,3] rearrangements, the diols 1 can be transformed into the new synthetic building blocks 2. The conversion often proceeds with high stereoselectivity or even stereospecificity, and in some cases in a one-pot reaction. X, Y=NHCOCCl3 , N3 , P(O)Ph2 , 4-SO2 C6 H4 Me, S(O)Ar, SCOR.

The first direct observation of an allylic [3,3] sigmatropic cyanate–isocyanate rearrangement

Abstract Evidence is presented that the [3,3] sigmatropic rearrangement of simple allyl cyanates to give allyl isocyanates proceeds much more rapidly than the analogous reaction of propargyl cyanates. Nevertheless, a substituted allyl cyanate is isolated for the first time, and the activation parameters of its [3,3] sigmatropic isomerization are measured.