Copper‐Catalyzed Trifluoromethylation of Aliphatic N‐Arylhydrazones: A Concise Synthetic Entry to 2‐Trifluoromethylindoles from Simple Aldehydes

The copper‐catalyzed C(sp²) H trifluoromethylation of N,N‐disubstituted hydrazones using the Togni reagent is demonstrated to proceed efficiently for aliphatic aldehyde‐derived substrates. The success of the reactions relied on the choice of the N,N‐diphenylamino group as the terminal hydrazone amino group where N,N‐dialkylamino groups were preferred for (hetero)aromatic aldehyde‐derived substrates. In addition, the trifluoromethylated N‐arylhydrazones are shown to be ideal substrates for Fischer indole synthesis allowing a straightforward, three‐step access to 2‐trifluoromethylindole derivatives from simple aldehydes.

     

Synthesis of Amino Acid Conjugates and Further Derivatives of 3α‐Hydroxylup‐20(;29)ene‐23,28‐dioic acid

Triterpenes of betulinic acid type exhibit many interesting biological activities. Therefore a series of new 3α‐hydroxy‐lup‐20(29)‐ene‐23,28‐dioic acid derivatives 2a—22 with putative pharmacological activities were synthesized. As starting compounds 3α‐hydroxy‐lup‐20(29)‐ene‐23,28‐dioic acid ( 1a ), isolated from Schefflera octophylla, or its 3‐O‐acetyl derivative 1b were used. Mono‐ and diesters ( 2a—b from 1a , and 4d from 4c ) were prepared with CH₂N₂. Oxidation of the isopropenyl side chain with OsO₄ yielded the 20,29‐diols ( 4a—b from 1b , and 19 from 17 ), which were in the case of 4b further transformed to the 29‐norketones 8a/mdash;b . Oxidation of the isopropenyl side chain with m‐chloroperbenzoic acid afforded the 20,29‐epoxide 12 (from 1b ) and the 29‐aldehydes and a‐hydroxy aldehydes ( 13a—c from 2a, 14a—c from 2b , and 16a—c from 15a ). Ring A was modified by a tosylation—elimination sequence using p‐TsCl/NaOAc, which afforded diolefin 15a (from 2a ) with Δ^2,20(29) double bonds or 23‐nor‐Δ^3,20(29)diolefin 17 (from 1a ). Compounds 4b, 4c , and 8a were coupled with L ‐methionin, L ‐phenylalanin, L ‐alanin, L ‐serin, and L ‐glutaminic acid via amide bonds at positions 23 and 28 to afford the amino acid conjugates 5a—7b and 9a—11 .     

Cycloaddition Reactions of 1,3‐Diaza‐2‐azoniaallene Salts and Glycals

The 1,3‐diaza‐2‐azoniaallene salt 3a reacts stereoselectively with glycals ( 5a—e ) to afford pyrano[2,3‐d]‐1,2,3‐ triazolium salts 6a—e . In contrast to other 1,3‐dipolar cycloadditions of glycals reported so far, the stereoselectivity of compounds 6 is not determined by the substituent on C‐3 of the glycal. Both cis ( 6a,b ) and trans ( 6d,e ) substitutions on C‐7 and C‐7a were found for bicyclic compounds 6 (crystal structure of 6a ). Under the influence of acid 6e opens the pyran ring to give the triazolium salt 9 . Addition of antimony pentachloride to a solution of the glycal 5e and the chlorotriazene 2a results in the formation of the pyranotriazene 12 containing two triazene units. In the presence of acid the pyranotriazene 6c reacts with alcohols to afford 2‐hydrazino glycosides 13a,b, 15 , which with zinc dust in acetic acid are reduced to 2‐amino glycosides 14a,b .     

Chiral Lewis Base‐Catalyzed,Enantioselective Reduction of Unprotected β‐Enamino Esters with Trichlorosilane

Catalytic asymmetric reduction of N‐unsubstituted β‐enamino esters represents a major challenge for asymmetric catalysis. In this paper, the first organocatalytic system that could be used for the asymmetric hydrosilylation of N‐unsubstituted β‐enamino esters has been developed. Using N‐tert‐butylsulfinyl‐L ‐proline‐derived amides and L ‐pipecolinic acid‐derived formamides as catalyst, a broad range of β‐aryl‐ and β‐alkyl‐substituted free β‐amino esters could be prepared with high yields and enantioselectivities. The practicality was illustrated by the gram‐scale asymmetric synthesis of ethyl (R)‐3‐amino‐3‐phenylpropanoate and isopropyl (S)‐3‐amino‐4‐(2,3,5‐trifluorophenyl)butanoate. The resulting product can be smoothly transformed to the FDA approved medicines dapoxetine and sitagliptin in a short synthetic route.

     

Synthesis and Characterization of New Aromatic Polyamides with N,N′‐Di(4‐n‐alkylphenyl)benzodiimide Unit on the Main Chain

Summary: New aromatic polyamides containing two n‐alkylphenylimide units fused to the main chain were prepared by the activated polyamidation of 3,6‐di(4‐carboxyphenyl)‐N,N′‐di(4‐n‐alkylphenyl)pyromellitimides ( C _m DA , m = 0, 8, 12, 16) with oxy‐4,4′‐dianiline in a mixture of N‐methylpyrrolidone and pyridine (Py) in the presence of triphenyl phosphite and CaCl₂. The imide‐containing dicarboxylic acid monomers were synthesized by the imidization of 3,6‐di(4‐carboxyphenyl)pyromellitic dianhydride with 4‐n‐alkylanilines. The polymers showed both enhanced thermal stability and excellent solubility due to the presence of thermally stable pendent imido groups and internally plasticizing n‐alkyl chains. Their glass transition temperatures were between 225 and 285 °C and decreased with increasing side chain length. Wide‐angle X‐ray diffraction investigations revealed that all the polymers are amorphous and have typical layered structures formed by n‐alkyl side chains.

     

Darstellung und Atropisomerie von 1‐(2‐Aryl)‐piperidin‐2‐onen

Preparation and Atropisomerism of 1‐(2‐Aryl)‐piperidin‐2‐ones Course and rate of the dehydrogenation of N‐tertiary piperidines dependent on their substitution in 4‐position and on the hydroxy bearing neighbor group were examined, using mercury(II)‐EDTA and the model amino alcohols 1a 1e, 3a 3f, 8a 8f and 10a 10f . The results showed that increasing size of 4‐substituents and neighbor groups too decreased the rate of reaction. The products from the 2‐substituted benzylic alcohols, the 2‐piperidones 7a 7g, 9a 9g and 11a 11g demonstrated atropisomerism. In the case of chiral neighbor groups diastereomeric mixtures were formed.     

Hydrolysis‐improved thermosensitive polyorganophosphazenes with α‐amino‐ω‐methoxy‐poly(ethylene glycol) and amino acid esters as side groups

A series of hydrolysis‐improved thermosensitive polyorganophosphazenes with α‐amino‐ω‐methoxy‐poly(ethylene glycol) (AMPEG) and amino acid esters (AAEs) of ‘N,N‐systems’ was synthesized, and their properties were evaluated in comparison with the thermosensitive polyorganophosphazenes with methoxy‐poly(ethylene glycol) (MPEG) and AAEs of ‘O,N‐systems’, by means of ³¹P NMR spectroscopy, gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). Most of the present polymers showed a lower critical solution temperature (LCST) in the range 32.0–79.0 °C, depending on the kinds of AAE, length of AMPEG and the mol ratio of the two substituents. These polymers exhibited higher LCSTs and faster degradation rates than the MPEG‐based polymers. The aqueous solution of poly(ethyl glycinate phosphazene)‐graft‐poly(ethylene glycol) [NP(GlyEt)_0.94(AMPEG350)_1.06]_n did not show an LCST, which is presumed to be due to its high hydrophilicity, in contrast to [NP(GlyEt)_1.01(MPEG350)_0.99]_n which showing an LCST at 77.5 °C. On the other hand, the polymers with a high content of AAE or with hydrophobic amino acids such as L ‐aspartic acid and L ‐glutamic acid, have shown a similar LCST to those of the MPEG‐based polymers. The half‐lives (t_1/2) for hydrolysis of [NP(AMPEG350)_1.06(GlyEt)_0.94]_n at pH 5, 7.4 and 10 were 9, 16, and 5 days, respectively, which are almost 2.5 to 4 times faster than that of the MPEG‐based polymers. The LCST of the present N,N‐polymers has been shown to be more influenced by salts such as NaCl (‘salting‐out’ effect) and tetrapropylammonium bromide (TPAB) (‘salting‐in’ effect) compared with the ‘O,N‐system’. Such differences of the ‘N,N‐systems’ from the ‘O,N‐systems’ in thermosensitivity, hydrolysis behavior and salt effect seem to be due to the higher hydrophilicity of the amino group in AMPEG. Copyright © 2005 Society of Chemical Industry     

Synthesis of C8‐N‐Arylamine‐Modified 2′‐Deoxyguanosine‐5′‐Triphosphates and Their Effects on Primer Extension by DNA Polymerases

C8‐N‐arylamine adducts of 2′‐deoxyguanosine (2′‐dG) play an important role in the induction of the chemical carcinogenesis caused by aromatic amines. C8‐N‐acetyl‐N‐arylamine dG adducts that differ in their substitution pattern in the aniline moiety were converted by cycloSal technology into the corresponding C8‐N‐acetyl‐N‐arylamine‐2′‐deoxyguanosine‐5′‐triphosphates and C8‐NH‐arylamine‐2′‐deoxyguanosine‐5′‐triphosphates. Their conformation preference has been investigated by NOE spectroscopy and DFT calculations. The substrate properties of the C8‐dG adducts were studied in primer‐extension assays by using Klenow fragment exo^? of Escherichia coli DNA polymerase I and human DNA polymerase β. It was shown that the incorporation was independent of the substitution pattern in the aryl moiety and the N‐acetyl group. Although the triphosphates were poor substrates for the human polymerases, they were incorporated twice before the termination of the elongation process occurred; this might demonstrate the importance of C8‐N‐arylamine‐2′‐deoxyguanosine‐5′‐triphosphates in chemical carcinogenesis.     

Copper(II)‐Catalyzed Reactions of Dimethylformamide with Phenylacetonitrile and Sulfur to Form N,N‐Dimethylthioamides

Novel copper‐catalyzed three‐component reactions of phenylacetonitrile, sulfur and DMF (dimethyformamide) for the selective preparation of N,N‐dimethylthiobenzamide and N,N‐dimethyl‐2‐phenylethanethioamides in yields of up to 96% are described.

     

Combination of UDP‐Glc(NAc) 4′‐Epimerase and Galactose Oxidase in a One‐Pot Synthesis of Biotinylated Nucleotide Sugars

The enzymatic epimerization of uridine 5′‐diphospho‐α‐D ‐glucose (UDP‐Glc, 1 ) and uridine 5′‐diphospho‐N‐acetyl‐α‐D ‐glucosamine (UDP‐GlcNAc, 2 ) and the subsequent oxidation of uridine 5′‐diphospho‐α‐D ‐galactose (UDP‐Gal, 3 ) and uridine 5′‐diphospho‐N‐acetyl‐α‐D ‐galactosamine (UDP‐GalNAc, 4 ) were combined with chemical biotinylation with biotin‐ε‐amidocaproylhydrazide in a one‐pot synthesis. Analysis by CE and NMR revealed a mixture (1.0:1.4) of the biotinylated nucleotide sugars uridine 5′‐diphospho‐6‐biotin‐ε‐amidocaproylhydrazino‐α‐D ‐galactose (UDP‐6‐biotinyl‐Gal, 7) and uridine 5′‐diphospho‐6‐biotin‐ε‐amidocaproylhydrazino‐α‐D ‐glucose (UDP‐6‐biotinyl‐Glc, 9 ), respectively, in a reaction started with 1 . One product, uridine 5′‐diphospho‐6‐biotin‐ε‐amidocaproylhydrazino‐N‐acetyl‐α‐D ‐galactosamine (UDP‐6‐biotinyl‐GalNAc, 8) was formed when the reaction was initiated with 2 . It could be demonstrated for the first time that a UDP‐Glc(NAc) 4′‐epimerase (Gne from Campylobacter jejuni) and galactose oxidase from Dactylium dendroides can be used simultaneously in enzymatic catalysis. This is of particular interest since the coaction of an enzyme demanding reductive conditions and an oxygen‐dependent oxidase is unexpected.     

Improved conversion of 6‐endo‐tosyloxybicyclo[2.2.2]octan‐2‐ones into 6‐exo‐acetoxy and 6‐exo‐benzoyloxybicyclo[2.2.2]octan‐2‐ones

The reaction conditions for the conversion of 6‐endo‐tosyloxybicyclo[2.2.2]octan‐2‐one ( 7b ) into 6‐exo‐acetoxy ( 8b ) and 6‐exo‐benzoyloxybicyclo[2.2.2]octan‐2‐one ( 8a ), respectively, were improved. Thus known 6‐endo‐tosyloxy‐bicyclo[2.2.2]octan‐2‐ones (+)‐(1RS,6SR,8SR,11RS)‐11‐[(4‐toluenesulfonyl)oxy]tricyclo[6.2.2.0^1,6]dodecan‐9‐one ( 1a ), 13‐methyl‐15‐oxo‐9β,13b‐ethano‐9β‐podocarpan‐12β‐yl‐4‐toluenesulfonate ( 3a ), and methyl (13R)‐16‐oxo‐13‐[(4‐tolylsulfonyl)oxy]‐17‐noratisan‐18‐oate ( 5 ), were converted,in comparable yields, as previously recorded, but much shorter times, into (+)‐(1RS,6SR,8SR,11SR)‐11‐(benzoyloxy) tricyclo[6.2.2.0^1,6]dodecan‐9‐one ( 2 ), 13‐methyl‐15‐oxo‐9β,13β‐ethano‐9β‐podocarpan‐12α‐yl benzoate ( 4 ), and methyl (13S)‐13‐(benzoyloxy)‐16‐oxo‐17‐noratisan‐18‐oate ( 6 ), respectively.     

Synthesis of 20‐O‐linked 20(S)‐Camptothecin Glycoconjugates: Impact of the Side Chain of the Ester‐linked Amino Acid on Epimerization During the Acylation Reaction and on Hydrolytic Stability of the Final Glycoconjugates

To improve solubility and tumor selectivity of 20(S)‐camptothecin the synthesis of 20‐O‐linked glycoconjugates 11A — G is described. Particular focus of the paper is the utilization of N‐tert‐butoxycarbonyl protected amino acid N‐carboxy anhydrides (UNCAs) 2a — f for an efficient acylation of the sterically hindered and deactivated tertiary 20‐hydroxy group of 20(S)‐camptothecin 1 . Depending on the solvent and on the side chain of the amino acid different extents of epimerization of the amino acids during the coupling reaction are observed; however, the epimers can easily be separated after removal of the tert‐butoxycarbonyl protecting group and camptothecin amino acid conjugates 4B — E with L‐ and D‐ configured amino acids, respectively, are obtained. Particularly, bulky and β‐branched amino acids can be attached to camptothecin in high yields and with low epimerization. Starting from the camptothecin amino acid conjugates 4B — E the synthesis of the glycoconjugates 11A — G is straightforward following standard procedures. The glycoconjugate hydrochlorides 11A — G show good water solubility (> 5mg‐ ml) and hydrolytic stability of the ester bond which again depends on the side chain of the amino acid residue linked to camptothecin. Particularly, glycoconjugates 11B — E with a bulky and β‐branched amino acid at the ester linkage show high hydrolytic stability in aqueous solutions with less than 2.5% of 20(S)‐camptothecin cleaved within 24 h. These results provide a basis for the selection of appropriate spacer groups for delivery systems of 20(S)‐camptothecin for therapeutic use.     

Ring‐Opening of N‐tert‐Butanesulfinylethynylaziridines with Lithium Tris(dimethylphenylsilyl)zincate: Stereoselective Access to 4‐Amino‐1‐allenylsilanes

The ring‐opening of N‐tert‐butanesulfinylethynylaziridines with lithium tris(dimethylphenylsilyl)zincate is reported. The reaction is demonstrated to be both stereoselective and stereospecific and to proceed through an anti‐S_N2′ process. Further deprotection of the nitrogen atom under mild conditions allows access to 4‐amino‐1‐(dimethylphenylsilyl)allenes with high yields and levels of stereoselectivity.

     

Synthese von Hetaryl‐pyridiniumsalzen und kondensierten 3‐Amino‐pyrid‐2‐onen

1‐(3‐Coumaryl)‐pyridinium salts 3 and 1‐(3‐coumaryl)‐tetrahydrothiophenium salts 5 were synthesized from 2‐acylphenyl chloro‐ or bromoacetates 2 . 2‐Chloro‐N¹‐(3,4‐dimethoxyphenyl)‐acetamide and substituted 2‐chloro‐N¹‐(2‐thienyl)‐acetamides 8 react with acetyl chloride and pyridine to yield the quinolinyl‐ and (thieno[2,3‐b]pyridin‐5‐yl)‐pyridinium salts 10 . Fused thieno[2,3‐b]pyridin‐ones 19 were formed from N‐chloroacetyl‐2‐aminothiophen‐3‐carbonitriles 16 with pyridine via Thorpe‐Ziegler cyclization and followed by cyclodehydrogenation. In presence of pyridine alkyl 2‐chloro‐acetylaminobenzoates 21 yield 3‐(1‐pyridinio)‐quinoline‐4‐olates 23 . Zincke‐cleavage of 10 and 23 with hydrazinium hydroxide leads to fused 3‐amino‐pyridine‐2‐ones 11 and 3‐amino‐4‐hydroxy‐quinoline‐2‐ones 24 , respectively. Oxazoloquinolines 25 were synthesized from 24 with acetic anhydride.     

Synthesis and spectroscopic investigation of cationic donor‐(π‐bridge)‐acceptor dye, 4‐[N‐(5,6,7,8‐tetrahydroisoquinolinium‐5‐ylidene)methyl]‐N,N‐dialkylaniline iodide

The synthesis and fundamental spectroscopic properties of eight hemicyanine (HC) dyes are presented. The dyes were prepared by the condensation of N‐methyl‐5,6,7,8‐tetrahydroisoquinolinium iodide with p‐(N,N‐dialkylamino)benzaldehydes. The compounds were characterised by nuclear magnetic resonance spectroscopy and their purity was checked with the use of thin‐layer chromatography. The spectroscopic properties of the dyes were determined in three organic solvents. The electronic absorption spectra of the dyes demonstrate moderate sensitivity to the nature of the substituent present in the aromatic ring and low solvent polarity dependence. In contrast to this, the positions of fluorescence bands are affected by the structure of an electron donor and solvent polarity. The 4‐[N‐(5,6,7,8‐tetrahydroisoquinolinium‐5‐ylidene)methyl]‐N,N‐dialkylaniline iodides were applied as fluorescent probes for the monitoring of the progress of free radical polymerisation. The study on the changes in the fluorescence intensity and spectroscopic shifts of the dyes was carried out during thermally initiated polymeriszation of methyl methacrylate. The purpose of these studies was to find a relationship between the changes in the shape and intensity of probe fluorescence and the degree of monomer conversion into polymer.     

Chemoenzymatic Preparation of Enantiopure Homoadamantyl β‐Amino Acid and β‐Lactam Derivatives

Racemic cis‐10‐azatetracyclo[7.2.0.1^2,6.1^4,8]tridecan‐11‐one was prepared from homoadamant‐4‐ene by chlorosulfonyl isocyanate addition. The transformation of the β‐lactam to the corresponding β‐amino ester followed by Candida antarctica lipase A‐catalyzed enantioselective (E>>200) N‐acylation with 2,2,2‐trifluoroethyl butanoate afforded methyl (1R,4R,5S,8S)‐5‐aminotricyclo[4.3.1.1^3,8]undecane‐4‐carboxylate and the (1S,4S,5R,8R)‐butanamide with>99% ee at 50% conversion. Alternatively, transformation of the β‐lactam to the corresponding N‐hydroxymethyl‐β‐lactam and the following Pseudomonas cepacia (currently Burkholderia cepacia) lipase‐catalyzed enantioseletive O‐acylation provided the (1S,4S,6R,9R)‐alcohol (ee=87%) and the corresponding (1R,4R,6S,9S)‐butanoate (ee>99%). In the latter method, competition for the enzyme between the (1R,4R,6S,9S)‐butanoate, 2,2,2‐trifluoroethyl butanoate and the hydrolysis product, butanoic acid, tended to stop the reaction at about 45% conversion and finally gave racemization in the (1S,4S,6R,9R)‐alcohol with time.     

Synthesis and structural characterization of novel chiral nanostructured poly(esterimide)s containing different natural amino acids and 4,4′‐thiobis(2‐tert‐butyl‐5‐methylphenol) linkages

Pyromellitic dianhydride (benzene‐1,2,4,5‐tetracarboxylic dianhydride) (1) was reacted with several amino acids in acetic acid and the resulting imide‐acid [N,N′‐(pyromellitoyl)‐bis‐L ‐amino acid diacid] (4a–4d) was obtained in high yield. The direct polycondensation reaction of these diacids with 4,4′‐thiobis(2‐tert‐butyl‐5‐methylphenol) (5) was carried out in a system of tosyl chloride(TsCl), pyridine, and N,N‐dimethyl formamide (DMF) to give a series of novel optically active poly(esterimide)s. Step‐growth polymerization was carried out by varying the time of heating and the molar ratio of TsCl/diacid, and the optimum conditions were achieved. These new chiral polymers were characterized with respect to chemical structure and purity by means of specific rotation experiments, FTIR, ¹H‐NMR, X‐ray diffraction, elemental, and thermogravimetric analysis (TGA) field emission scanning electron microscopy (FE‐SEM) techniques. These polymers are readily soluble in many polar organic solvents like DMF, N,N‐dimethyl acetamide, dimethyl sulfoxide, N‐methyl‐2‐pyrrolidone, and protic solvents such as sulfuric acid. TGA showed that the 10% weight loss temperature in a nitrogen atmosphere was more than 390°C; therefore, these new chiral polymers have useful levels of thermal stability associated with good solubility. Furthermore, study of the surface morphology of the obtained polymers by FE‐SEM showed that each polymers exhibit nanostructure morphology. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

GluN2B‐Selective N‐Methyl‐d‐aspartate (NMDA) Receptor Antagonists Derived from 3‐Benzazepines: Synthesis and Pharmacological Evaluation of Benzo[7]annulen‐7‐amines

Given their high neuroprotective potential, ligands that block GluN2B‐containing N‐methyl‐D ‐aspartate (NMDA) receptors by interacting with the ifenprodil binding site located on the GluN2B subunit are of great interest for the treatment of various neuronal disorders. In this study, a novel class of GluN2B‐selective NMDA receptor antagonists with the benzo[7]annulene scaffold was prepared and pharmacologically evaluated. The key intermediate, N‐(2‐methoxy‐5‐oxo‐6,7,8,9‐tetrahydro‐5H‐benzo[7]annulen‐7‐yl)acetamide ( 11 ), was obtained by cyclization of 3‐acetamido‐5‐(3‐methoxyphenyl)pentanoic acid ( 10 b ). The final reaction steps comprise hydrolysis of the amide, reduction of the ketone, and reductive alkylation, leading to cis‐ and trans‐configured 7‐(ω‐phenylalkylamino)benzo[7]annulen‐5‐ols. High GluN2B affinity was observed with cis‐configured γ‐amino alcohols substituted with a 3‐phenylpropyl moiety at the amino group. Removal of the benzylic hydroxy moiety led to the most potent GluN2B antagonists of this series: 2‐methoxy‐N‐(3‐phenylpropyl)‐6,7,8,9‐tetrahydro‐5H‐benzo[7]annulen‐7‐amine ( 20 a , K_i=10 nM ) and 2‐methoxy‐N‐methyl‐N‐(3‐phenylpropyl)‐6,7,8,9‐tetrahydro‐5H‐benzo[7]annulen‐7‐amine ( 23 a , K_i=7.9 nM ). The selectivity over related receptors (phencyclidine binding site of the NMDA receptor, σ₁ and σ₂ receptors) was recorded. In a functional assay measuring the cytoprotective activity of the benzo[7]annulenamines, all tested compounds showed potent NMDA receptor antagonistic activity. Cytotoxicity induced via GluN2A subunit‐containing NMDA receptors was not inhibited by the new ligands.     

Reaktion von Acetophenonmonomethyl‐ und ‐dimethylhydrazonen mit dem Vilsmeier‐Reagenz; Bildung von Pyrazol‐4‐carbiminiumsalzen: ein Beitrag zum Mechanismus

Reactions of Acetophenonmonomethyl‐ and ‐dimethylhydrazones with the Vilsmeier‐Reagent; Formation of Pyrazol‐4‐carbiminium Salts: A Contribution to the Mechanism Kira discovered the formation of ( 4e ) N,N‐Dimethyl‐N‐[1,3‐diphenylpyrazol‐4‐ylmethylen]ammonium perchlorat by the reaction from acetophenonphenylhydrazone 1e with the Vilsmeier‐Reagent 2 . On the example of the Acetophenonmonomethylhydrazone 1a we represent the mechanism of this reaction. 1a reacts with the Vilsmeier‐Reagent 2 firstly to 3a (scheme 1). 3a is formylated in the secondary step by 2 on the methyl group of the acetophenon part followed of a ring conclusion to the pyrazol 4a containing a carbiminium group in position 4 as substituent. 3a doesN′t react to 6a directly. Hydrolysis of 4a gives 5a . We found moreover, that acetophenondimethylhydrazones 8 react with 2 to 4 , too (scheme 2, eq 2). But here the proton of the methylamino group in 1 is occupied by the methyl group in 8 . Therefore, the reaction starts in this case with an attack on the methyl group of the acetophenon part followed of the ringconclusion to the intermediate 6 accompanied of the eli‐mination of the methyl group. In the last step the not isolated pyrazol 6 is formylated by 2 in 4‐position to 4 . In a secondary reaction from 8 with 2 the compounds 9 are formed (scheme 2, eq. 3). 9 are intermediates in the reaction from 8 to 4 only in a small extent.     

Synthesis of 5‐(1H‐Tetrazolyl)‐1‐hydroxy‐tetrazole and Energetically Relevant Nitrogen‐Rich Ionic Derivatives

Sodium 5‐cyanotetrazolate sesquihydrate ( 1 ) was prepared from sodium azide and two equivalents of sodium cyanide under acidic conditions. Sodium 5‐cyanotetrazolate sesquihydrate ( 1 ) reacts with hydroxylammonium chloride to form 5‐aminohydroximoyl tetrazole ( 2 ). 5‐Aminohydroximoyl tetrazole ( 2 ) is treated with sodium nitrite and hydrochloric acid to form 5‐chlorohydroximoyl‐tetrazole ( 3 ). The chloride azide exchange yields 5‐azidohydroximoyl‐tetrazole monohydrate ( 4 ). When compound 4 is treated with hydrochloric acid, 5‐(1H‐tetrazolyl)‐1‐hydroxytetrazole ( 5 ) is obtained in good yield. Compound 5 can be deprotonated twice by various bases. Different ionic derivatives such as bis(hydroxylammonium) ( 6 ), bis(hydrazinium) ( 7 ), bis(guanidinium) ( 8 ), bis(aminoguanidinium) ( 9 ), bis(ammonium) ( 10 ), and diaminouronium ( 11 ) 5‐(1‐oxidotetrazolyl)‐tetrazolate were synthesized and characterized. With respect to energetic use salts 6 and 7 are most relevant. Compounds 3 – 9 and 11 were characterized using low temperature single‐crystal X‐ray diffraction. All compounds were investigated by NMR and vibrational (IR, Raman) spectroscopy, mass spectrometry and elemental analysis. The thermal properties were determined by differential scanning calorimetry (DSC). The sensitivities towards impact ( 4 : 4 J, 5 : 40 J, 6 : 12 J, 7 : 40 J), friction: ( 4 : 60 N, 5 : 240 N, 6 : 216 N, 7 : 240 N), and electrical discharge ( 5 : 0.40 J, 6 : 0.75 J, 7 : 0.75 J), were investigated using BAM standards and a small scale electrostatic discharge tester. The detonation parameters of 5 – 7 were calculated using the EXPLO5.06 code and calculated (CBS‐4 M) enthalpy of formation values.