Studies of the rotational barrier energy of the amide bond using quantum computing and nuclear magnetic resonance (NMR) are focused mainly on its use as a model of the peptide bond. The results of these studies are valuable not only in terms of the fundamental conformational properties of amide bonds, but also in the design of molecular machines, which have recently attracted interest. We investigate the fluxionality of the amide and enamide bonds of compound 3-[(E)-(dimethylamino)methylidene]-1,1-dimethylurea using advanced dynamic NMR experiments and a theoretical evaluation of the density functional theory (DFT) calculation. The dynamic NMR study shows restricted rotation around the amide group (16.4 kcal/mol) and a very high barrier around the enamine group (18.6 kcal/mol). In a structurally similar compound, (E)-3-(dimethylamino)-N,N-dimethylacrylamide (N atom is replaced by CH), the amide barrier is 12.4 kcal/mol and the enamine barrier is 11.7 kcal/mol. The DFT studies of both compounds reveal the electronic origin of this phenomenon. Theoretical calculations reveal the origin of the higher enamine barrier. The better delocalization of the lone pair of electrons on the end nitrogen atom into the antibonding orbital of the neighboring C-N double bond leads to the better stabilization of the ground state, and this leads to a greater increase in the enamine barrier.

The Michael addition of enaminoesters to coumarins leads to the formation of the rearranged adduct 1 whose structure has been previously elucidated by X-ray crystallographic analysis. Now, N- and/or O-carbamoylation of the 6-amino-2-pyridone 1 by treatment with phenyl isocyanate in a molar ratio of 1:1 and 1:2 gave N-mono- (2a) or N,O-bis-(phenylcarbamoyl) (3) derivatives, respectively. Further transformations of the corresponding new 2-pyridone derivative 2a into the O-acetyl derivative 2b and the chromeno[3,4-c]pyridine 4 are reported as well.

By treatment of ethers of phenol, resorcinol, 2-napththol, alkylanisoles 10, 13, 15, 17, 20, 22, 24, 28 with formic acid/borontrichloride the aromatic aldehydes 11, 14, 16, 18, 21, 23, 25, 26, 29 can generally be prepared in low yields. The formylation reactions proceed between -20 and -10 degrees C within 20 min in 1,2-dichloroethane, chlorobenzene, or methylene chloride as solvents when formic acid and borontrichloride are used in excess [molar ratio of aromatic compound to HCOOH to BCl3 =1:1.2-1.7:1.6-1.8]. The more strongly activated 3,5-dimethoxyphenol (33) is formylated by formic acid/borontrichloride to give the aldehyde 34 with an acceptable yield. The reactions of resorcinol dimethylether with formic acid in the presence of super acids (mainly trifluormethansulfonic acid) in chlorobenzene or nitromethane deliver the aldehyde 21 only in small amounts.

In the reaction of 4‐chlorocoumarin‐3‐carbaldehyde with malononitrile in the presence of piperidine, a piperidinium salt of a novel tricyclic chromeno[3,4‐c]pyridine derivative was isolated instead of the expected “ tert ‐amino effect” product. When hexamethyleneimine (azepane) was used as a base, the corresponding azepanium salt (same anion) was obtained. Both structures have been formulated on the basis of their spectral (IR, NMR, MS) behavior and elemental analyses. In addition, the structure of the piperidinium salt was confirmed by means of X‐ray crystallographic analysis.

AbstractThe Michael addition of enaminoesters to coumarins (1) does not lead to the formation of simple adducts3but to the rearranged 4-aryl-2-pyridone4a. Now,N-carbamoylation of the 6-amino-2-pyridone4awith alkyl isocyanates and further transformation of the corresponding novel ureido-2-pyridone derivatives6a–ginto chromeno[3,4-c]pyridines5d,gandO-acetyl derivatives7a–gare reported. All newly synthesized compounds were characterized by means of1H/13C NMR, MS, IR spectra and elemental analysis. The structure of the ureide6fand of theN-cyclohexyl-O-acetyl derivative7gwere additionally confirmed by crystal structure determinations. Acute toxicity after intraperitoneal administration, blood clotting time, analgesic activity and the effects on the hexobarbital sleeping time were tested on laboratory animals (compounds4a,6a,6c,6dand6g).

1,3-Dimethylthymine can be prepared in a single-step reaction by heating a mixture of N-methylpropionamide and the Bredereck-Simchen reagent [tert-butyloxy-bis(dimethylamino) methane].

1,3-Dimethylthymine can be prepared in a single-step reaction by heating a mixture of N-methyl-propionamide and the Bredereck-Simchen reagent [tert-butyloxy-bis(climethylamino) methane].

In the reaction of 4-chlorocoumarin-3-carbaldehyde with malononitrile in the presence of piperidine a crystalline piperidinium salt of a novel tetracyclic chromeno[4,3,2-de]-1,6-naphthyridine-2-carboxylic acid was isolated instead of the expected product of the "tert-amino effect". The structure of this piperidinium salt and its corresponding acidic form was characterized through spectral methods (IR, NMR, MS) and elemental analysis. In addition, the structure was established by means of X-ray crystallographic analysis. A theoretical multistep mechanism for this one-pot synthesis is discussed.

Tris(chloromethyl)amine (4) can be prepared by chloromethylation of urotropin with paraformaldehyde or 1,3,5-trioxane and ethyl-trichlorosilane in good yields. Photochlorination of tris(chloromethyl)amine affords tris(dichloromethyl)amine (2). Both reactions can be performed on large scale.

Reactions of 4-hydroxycoumarin (1a) and 4-chlorocoumarin-3-carbaldehyde (1b) with amino alcohols or alkylene diamines led to the formation of the corresponding N-substituted 4-aminocoumarins 3, 5 and 6. However, 4-hydroxycoumarin-3-carbaldehyde (8) reacted with 2-aminoethanol and ethylenediamine to give N-substituted 3-(aminomethylene)-chromane-2,4-diones 9a, b. The structure and the E-configuration of compound 6 were proven by X-ray crystal structure analysis. Products 9a, b displayed signals of both E- and Z-isomers in their NMR spectra. All novel products have been characterized by means of spectral (IR, NMR, MS) data and elemental analyses

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

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.

N, N, N´, N´-Tetraalkyl-chloroformamidinium chlorides 6 are prepared from N, N, N´, N´-tetraalkylureas 5 and phosgene in acetonitrile. The iminium salts 6 react with primary and secondary amines in the presence of triethylamine to give N, N, N´, N´, N´´-pentasubstituted and N, N, N´, N´, N´´, N´´- hexasubstituted guanidinium salts 7 and 8, respectively, Treatment of the guanidinium salts 7 with sodium hydroxide in excess affords the N, N, N´N´, N´´-pentasubstituted guanidines 9a - 9aa. Additionally, the N, N, N´, N´, N´´-pentasubstituted and N, N, N´, N´, N´´, N´´-hexasubstituted guanidinium salts 7l´, 7p´ and 8a - c can be obtained from the reaction mixtures by addition of stoichiometric amounts of sodium hydroxide. A modified method is described for the preparation of guanidinium salts possessing dialkylamino substituents consisting of two long-chain alkyl groups (>C14). Some guanidines 9 were alkylated with allyl chloride and bromide, ethyl bromide, butyl bromide, benzyl bromide and chloride, dimethyl sulfate, diethyl sulfate, and methyl methansulfonate to give the corresponding guanidinium salts 11 - 15. By alkylation of the N, N, N´, N´, N´´-pentasubstituted guanidine 9v with triethyloxonium tetrafluoroborate the guandinium tetrafluoroborate 16a is accessible. N-Functionalized guanidinium salts 17 - 18a - c result from the reaction of N, N, N´, N´, N´´-pentasubstituted guanidines with ethyl bromoacetate and bromoacetonitrile, respectively, and subsequent anion exchange with sodium tetraphenylborate. N, N, N´, N´-Tetramethylguanidine (21) adds to ethyl acrylate to give the labile guanidine 22, which forms the guanidinium salt 23a on treatment with methyl iodide. Zwitterionic guanidinium salts 25 result, when N, N, N´, N´, N´´-pentasubstituted guanidines are treated with sultones 24.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Generally, arylmethylene-cyanoacetic acid derivatives react with enols and aromatic or heteroaromatic hydroxy compounds to afford 2-amino-4H-pyran derivatives of type 6. In contrast, a ring closure with the nitrogen atom of the thiadiazole ring occurs when 2-phenacyl-1,3,4-thiadiazoles (1a-d) act on derivatives of arylmethylene-cyanoacetic acid giving rise to the formation of 7H-[1,3,4] thiazolo[3,2-a] pyridine derivatives 5a-r. The same products are obtained if 2-phenacyl-1,3,4-thiadiazoles react with aromatic or heteroaromatic aldehydes and cyanoacetic acid derivatives. The constitution of the novel compounds 5 has been confirmed by an X-ray analysis of 5a.

Some novel 1,2-fused 5H-chromeno[4,3-b]pyridin-5-ones (5a,b) and a 6H-benzo[h][1,6]naphthyridin-5-one (5c) have been synthesized starting from the 4-chlorocoumarin-3-carbaldehyde (1a) or its N-methyl-2-quinolone analogue (1b) via subsequent Knoevenagel condensation and ring closure reaction known as the 'tert-amino effect'. These are rare examples of the tert-amino effect occurring at 2-pyrone and 2-pyridone ring. An unusual intramolecular redox reaction of the iminium ion 6, reported earlier, most probably follows analogous mechanism as the tert-amino effect reactions leading to 5.

Aryl formates are prepared in a two step one-pot procedure from phenols. Firstly the formylating reagent triformamide (1b) is generated from sodium diformamide (2) and methanesulfonyl chloride in situ, which reacts with phenols 4a - f to give aryl formates 5a-f in good yields. Triformamide, prepared in situ, transforms anisole in the presence of aluminum chloride to the N-(diarylmethyl)formamide 7.

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Coumarin and its analogs are considered privileged scaffolds in the current synthetic and pharmacological research. The chemical behavior of enaminocarbaldehydes of the coumarin moiety under intramolecular Wittig reaction conditions in the presence of triphenylphosphine and dimethyl or diethyl acetylenedicarboxylates has been studied, resulting in the isolation of a series of dimethyl and diethyl 5-oxo-1,2-dihydro-5H-chromeno[4,3-b]pyridine-2,3-dicarboxylates in good to high yields.

The course of condensation reactions of alkyne carboxylic acid orthoamides 17a,b is strongly influenced by the nature of the solvent used. Non-acidic or at least low-acidic polar solvents possessing high ET(30) values are best suited for these reactions. The condensation reactions can also be catalyzed by boric acid esters. Bicyclic boric acid esters such as 25 and 27, derived from trioles, are the most effective catalysts. The use of these catalysts allows to prepare conveniently 5,5-bis(dimethylamino)butadienes 18a,b from the acetophenones 16a,b and the orthoamides 17a,b. (c) 2007 Elsevier B.V. All rights reserved.