Volume 67, Issue 4

The reaction of N,N-diaryl-substituted formamides with oxalyl chloride gives rise, instead to the formation of the expected salt-like formamide chlorides, to the formation of corresponding non-ionic N-dichloromethyl-substituted diarylamines. Graphical Abstract On the Formation and 1 H NMR-spectroscopic Characterization of N,N-Diaryl-substituted Formamide Chlorides

The regioselective ipso-formylation of electron-rich, 3,4-push-pull-substituted 2-chlorothiophenes under Vilsmeier-Haack conditions was performed in good yields. The synthetic scope of this new reaction was explored using various halothiophenes, chloroanilines, and 1-methyl-3-chloroindole. In comparison with their structural C-H analogs the chlorinated thiophenes, anilines, and the indole proved to be less reactive toward electrophilic attack by chloromethyleniminium salts. Graphical Abstract Chemistry of Polyhalogenated Nitrobutadienes, Part 11: ipso-Formylation of 2-Chlorothiophenes under Vilsmeier-Haack Conditions

A new synthetic strategy for the preparation of imidazo[1,2-a]pyridines 10 is reported, which is based on the electrocyclization reaction of imino pyridinium salts 7 upon treatment with a strong base. The starting materials are easily prepared from 2-aminopyridine (3) by imine condensation and subsequent alkylation at the pyridine nitrogen atom. The ring closure reaction of the zwitterionic intermediate 8 to give a five-membered ring proceeds in low yield forming first the dihydro compound 9, which under the reaction conditions is transformed into the corresponding aromatic compounds 10 and 11 by air oxidation. The mechanism of the electrocyclization reaction is interpreted in detail by quantum-chemical calculations. Graphical Abstract A Novel Pathway to Imidazo[1,2-a]pyridines. Access through Imino Pyridinium Salts

N,N,N’,N’-Tetramethyl-formamidinium chloride (2a) reacts with elemental sodium in various solvents to give N,N,N’,N’,N’’,N’’-hexamethyl-guanidinium chloride (4a). The reaction of 2a with potassium affords N,N,N’,N’,N’’,N’’,N’’’,N’’’-octamethyl-oxamidinium dichloride (3a). From the reaction of 2a with magnesium in different solvents in general result mixtures of the salts 4a, 3a and N,N,N’,N’-tetramethyl-formamidinium chloride (10a). The composition of these mixtures depends on the solvent and the reaction temperature. Similar results are obtained, when a zinc/copper couple is used instead of magnesium. Very likely from 2a and magnesium or zinc, respectively, organometallic intermediates 11, 12 are formed which could be trapped by aromatic aldehydes and phenylisocyanate. The salt 2a can be reductively coupled by a low-valent titanium reagent to give the oxamidinium salt 3a. Graphical Abstract Orthoamide und Iminiumsalze, LXXIV [1]. Umsetzung von N,N,N´,N´-Tetramethyl-chlorformamidiniumchlorid mit Metallen

The syntheses of the three new guanidine-quinoline hybrid ligands TMGmqu, DMEGmqu and TMG t bqu are reported. Zinc chlorido and triflato complexes with these ligands were obtained and structurally characterised by X-ray crystallography. In the chlorido complexes the zinc atom is coordinated by two chlorido ligands and the bidentate guanidine ligand in a distorted tetrahedron. Using zinc triflate, tetrahedral bis(chelate) complexes are formed, and the triflate anions serve only for charge compensation. All reported complexes show activity in the polymerisation of rac-lactide, with the chlorido complexes only showing a poor activity. With the bis(chelate) triflato complexes a high polymerisation activity with a slight heterotactic bias was observed. Kinetic studies reveal a firstorder chain growth reaction for the lactide polymerisation with all complexes. Graphical Abstract Novel Guanidine-Quinoline Hybrid Ligands and the Application of their Zinc Complexes in Lactide Polymerisation

2-Formyl-1,1,3,3-tetramethylguanidine (1) could be prepared from tris(dimethylamino)ethoxymethane (3a) and formamide (4). Surprisingly, guanidine 1 does not result from the reaction of 1,1,3,3-tetramethylguanidine with formylating reagents such as dimethylamino-methoxy-acetonitrile (8) or the N,N-dimethylformamide-dimethylsulfate adduct (9), rather the isomeric 1,1-dimethyl-3- dimethylaminomethylene-urea (2) is formed. The structure of 2 was confirmed by NMR spectroscopy and crystal structure analysis. Graphical Abstract Orthoamides and Iminium Salts, LXXV [1]. Contribution to the Formation of 2-Formyl-1,1,3,3-tetramethylguanidine and the Isomeric 1,1-Dimethyl-3-dimethylaminomethylene-urea

The synthesis of two new chiral guanidines 5 and 12 and derived guanidinium salts 6, 11, 13 -15 with one and three N-(1-phenylethyl) substituents is described. In both cases, the well-precedented, reliable route via chloro-formamidines was taken. Since direct attachment of the N-methyl-N-(1- phenethyl)-amino group failed, the two-step protocol - introduction of the primary 1-phenethylamino group first followed by N-methylation - was employed. Crystal structures and NMR data reveal, that the sterically highly congested “tris” salt - with formal C 3 symmetry, albeit unsymmetrical in the crystal - constitutes an intriguing structure with two rotamers present in solution. Graphical Abstract Synthesis and Characterization of Chiral Guanidines und Guanidinium Salts Derived from 1-Phenylethylamine

Hexaalkylguanidinium-based room-temperature ionic liquids were investigated as solvents for the cyclopropanation of styrene with diazoacetates catalyzed by Rh 2 (OAc) 4 or [Ru 2 (μ-OAc) 2 (CO) 4 ]n. While the yields of the formed cyclopropanes are much lower compared to the reactions performed in dichloromethane, the diastereomeric ratio is not significantly affected by the change of the reaction medium. Immobilization of the catalysts is only partially successful. In contrast to this intermolecular reaction, the Ru-catalyzed formation of a β -lactam by an intramolecular carbenoid C-H insertion of an α-methoxycarbonyl-α-diazoacetamide occurs in high yield, similar to the Rh 2 (OAc) 4 -catalyzed reaction. The cis → trans isomerization of the resulting 1-tert-butyl-3-methoxycarbonyl-4-phenylazetidin- 2-one is accelerated in the ionic liquid N,N-dibutyl-N’ ,N’-diethyl-N’,N’-dihexylguanidinium triflate. Graphical Abstract Ruthenium- and Rhodium-catalyzed Carbenoid Reactions of Diazoesters in Hexaalkylguanidinium-based Ionic Liquids

Bromination of 1-hydroxyimidazole 3-oxide and 1-hydroxy-2-methylimidazole 3-oxide using bromine in acetic acid gave 2-bromo-1,3-dihydroxyimidazole hydrobromide and 4,5-dibromo-1,3-dihydroxy- 2-methylimidazole hydrobromide, respectively. In contrast, bromination in aqueous mixture (acetic acid, methanol, dimethylformamide, tetrahydrofuran) yielded 2,4,5-tribromo-1-hydroxyimidazole. Crystal structures of four compounds were determined by X-ray diffraction. Graphical Abstract Bromination of 1-Hydroxyimidazoles. Synthesis and Crystal Structures

The synthesis of a pyrazol-3-ylidene palladium complex is described, and results of a single-crystal X-ray diffraction study are presented. The properties of pyrazolium salts as well as of two types of heterocyclic mesomeric betaines, the pseudo-cross-conjugated mesomeric betaine pyrazolium-3- carboxylate and its cross-conjugated analog pyrazolium-4-carboxylate, are compared. Graphical Abstract Synthesis of a Pyrazol-3-ylidene Palladium Complex, Pyrazolium Salts and Mesomeric Betaines of Pyrazole as N-Heterocyclic Carbene Precursors

A synthesis of novel hexacyclic bis-benzimidazoles 6 starting from 2,3-diarylamino-quinoxalines via an oxidative cyclization cascade is described. These very stable and high-melting derivatives are featured by their strong fluorescence in the blue region of the visible spectrum. The cyclization reaction between 2,3-dichloroquinoxaline and 1,2-phenylenediamine did not lead to derivatives of type 6. In this case, only fluoflavine 7 was isolated quantitatively. Graphical Abstract A Surprising Formation of Novel Bridged Bis-Benzimidazoles by Oxidation of Diaminoquinoxalines

An improved procedure for the preparation of trimethoxyacetonitrile (3a) starting from trichloroacetonitrile and sodium methanolate is described. Carbanions, obtained by the action of sodium hydride on nitriles, ethyl acetate and methylketones, react with trialkoxyacetonitriles 3 to give α- imino-orthocarboxylic acid trialkylesters 12, 14 and 20, which form an equilibrium with the tautomeric enamines 13, 15 and 21. The enamines 21 react with N,N-dimethylformamide dimethylacetal (24) to give amidines 25 which are cyclized to pyridinium salts 28 and 29 on treatment with benzyl bromide and acetyl chloride, respectively. The reaction of the enaminonitrile 13a with the orthoamide derivative of phenylpropiolic acid 30 affords the pyridine-2-orthocarboxylic acid trimethylester 31. The N,O-protected 4-hydroxy-piperidine 35 can be deprotonated by means of sec-butyl lithium. The carbanions thus formed are trapped with D 2 O, dimethyl sulfate, phenylisocyanate, CO 2 , and dimethyl carbonate delivering the piperidine derivatives 37 - 41. The heterocyclic orthoester 43 can be prepared analogously from 35 and 3a. The piperidine derivatives 44, 46 and 47 are prepared from the N,O-protected piperidines 39 and 41. Graphical Abstract Orthoamide und Iminiumsalze, LXXVI [1]. Ein weiterer Beitrag zur Chemie der Trialkoxyacetonitrile/ Orthoamides and Iminium Salts LXXVI [1]. A Further Contribution to the Chemistry of Trialkoxyacetonitriles

The stereoselective synthesis of 3-substituted and 3,4-disubstituted piperidine and piperidin-2-one derivatives was achieved starting from 2-pyridone. After N-galactosylation and subsequent O-silylation, nucleophilic addition of organometallic reagents proceeded with high regio- and stereoselectivity at 4-position. Substituents at position 3 were stereoselectively introduced by reaction of electrophiles with amide enolates of the N-galactosyl-2-piperidones. Graphical Abstract Stereoselective Synthesis of 3-Substituted and 3,4-Disubstituted Piperidine und Piperidin-2-one Derivatives