Aminoacids in the synthesis of heterocyclic systems. The synthesis of methyl 2-acetylamino-3-dimethylaminopropenoate and 2-(N-methyl-N-trifluoroacetyl)amino-3-dimethylaminopropenoate and their application in the synthesis of heterocyclic compounds

Methyl (Z)-2-acetylamino-3-dimethylaminopropenoate (3) was prepared from N-acetylglycine (1), which was converted with N,N-dimethylformamide and phosphorus oxychloride into 4-dimethylaminomethylene-2-methyl-5(4H)-oxazolone (2), followed by treatment with methanol in the presence of potassium carbonate, into 3. The compound 3 was shown to be a versatile reagent in the synthesis of various heterocyclic systems. With N-nucleophiles, such as heterocyclic amines 4, either methyl 2-acetylamino-3-heteroarylaminopropenoates 5 or fused pyrimidinoncs 6 were formed, dependent on the reaction conditions and/or heterocyclic substituents: C-nuclcophiles with an active or potentially active methylene group, such as 1,3-dicarbonyl compounds 7, 8 and 9, substituted phenols 10a,b, naphthols 11, 12a-c, and substituted coumarin 13a, afforded substituted pyranones 20 and 22, and fused pyranones 21, 23–26. The nitrogen containing heterocycles 14–19 produced pyranoazines 27–31 and pyranoazole 32. In all of these systems the acetylamino group is attached at position 3 of the newly formed pyranone ring. The orientation around the double bond for methyl (Z)-2-(N-methyl-N-trifluo-roacetyl)-3-dimethylaminopropenoate (36) was established by X-ray analysis.     

The synthesis of 5-substituted 3-benzoylamino-6-(2-substituted amino-1-ethenyl)-2H-pyran-2-ones and their transformations into 2H-pyrano[3,2-c]pyridine derivatives

A new approach to the 2H-pyrano[3,2-c]pyridine system is described. 5,6-Disubstituted 3-benzoylamino-2H-pyran-2-ones 3a,b , prepared from the corresponding 1,3-dicarbonyl compounds 1a,b and methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate ( 2 ), were converted into 3-benzoylamino-6-(2-dimethylamino-1-ethenyl)-5-ethoxycarbonyl-2H-pyran-2-one ( 4a ) and 5-acetyl derivative 4b . The exchange of the dimethylamino group in 4a,b with aromatic amines 5a-f,m , héteroaromatic amines 5g-i , and benzylamines 5j-l produced 5-ethoxycarbonyl-3-benzoylamino-6-(2-arylamino- or heteroarylamino-or benzylamino-1-ethenyl)-2H-pyran-2-ones 6a-l , and its 5-acetyl analog 6m . The compounds 6 were cyclized in basic media into 2H-pyrano[3,2-c]pyridine derivatives 7a-h . Analogously react also α-amino acid derivatives 8a-c and 11 as nitrogen nucleophiles producing 9a-c, 10 and 12 .     

A synthesis of 1-substituted 5-[2-(acylamino)ethyl]-1H-pyrazole-4-carboxamides

A seven-step synthesis of 1-substituted 5-(2-acylaminoethyl)-1H-pyrazole-4-carboxamides 20 as the pyrazole analogues of histamine was developed. The synthesis starts with a three-step preparation of N(1)-substituted methyl 5-(2-tert-butoxycarbonylaminoethyl)-1H-pyrazole-4-carboxylates 7 from commercially available Boc-β-alanine (1). Subsequent four-step transformation of the key-intermediates 7 into the final products 20 was performed following two complementary reaction sequences comprising acidolytic removal of the Boc group, hydrolysis of the COOMe group, amidations of the COOH group, and acylations of the NH₂ group. The structures of pyrazole derivatives were determined by spectroscopic methods and by X-ray diffraction.     

Parallel synthesis of 3-amino-4H-quinolizin-4-ones, fused 3-amino-4H-pyrimidin-4-ones, and fused 3-amino-2H-pyran-2-ones

On the basis of the enaminone methodology, libraries of 3-amino-4H-quinolizin-4-ones, fused 3-amino-4H-pyrimidin-4-ones, and fused 3-amino-2H-pyran-2-ones were synthesized by the solid-phase and by the solution-phase parallel synthesis. The solution-phase approach turned out to be advantageous over the solid-phase approach. The solution-phase synthesis afforded, in most cases, analytically pure products in high yields, whereas the solid-phase approach gave products in poor yields and in low purity.     

Noise generation by vacuum cleaner suction units: Part I. Noise generating mechanisms - An overview

Among all household appliances, the vacuum cleaner is the most powerful source of noise. The built-in suction unit, consisting of an electric motor and a centrifugal blower, represents the main source of noise; this is partially aerodynamic, mechanical and electromagnetic in origin. The contribution of the particular origin of noise generation to the total noise level depends on the geometry of the suction unit and operating conditions. The operating point of a suction unit built into a vacuum cleaner depends on the amount of dust particles in the dust bag and is constantly changing during operation until it reaches a zero flow rate. There are differences in noise generation at different operating conditions as well as between the suction units having a blower without and with a vaned diffuser. In this part of the paper, an overview of aerodynamic, mechanical and electromagnetic noise origins at different operating conditions is given.     

Noise and synchronization of a single active colloid

A two-state oscillator in a viscous liquid is composed of a micron-scale particle whose intrinsic dynamics is defined by linear potentials that undergo configuration-coupled transitions and is externally driven by a piecewise constant periodic force of varying amplitude and frequency. This elementary example of "active matter" has the minimal elements that allow us to study synchronization in the presence of thermal fluctuations. Experiments reveal the presence of synchronized states (and Arnol'd tongues), which we explain using analytical and numerical calculations. The system maintains synchronization by adjusting the phase between the bead and the clock. We discuss the relevance of this model to synchronization in real-world systems, including the role of thermal noise.     

Parallel synthesis of 7-heteroaryl-pyrazolo[1,5-a]pyrimidine-3-carboxamides

A simple and practical four-step protocol for the parallel synthesis of 7-heteroaryl-pyrazolo[1,5- $a$ ]pyrimidine-3-carboxamides was developed. The synthesis starts with transformation of commercially available 2-acetylpyridine and acetylpyrazine with $N,$ $N$ -dimethylformamide dimethylacetal into the corresponding $(E)$ -3-(dimethylamino)-1-(heteroaryl)prop-2-en-1-ones followed by cyclisation with methyl 5-amino-1 $H$ -pyrazole-4-carboxylate to give methyl 7-heteroarylpyrazolo[1,5- $a$ ]pyrimidine-3-carboxylates. Hydrolysis of the ester group and subsequent amidation of the so formed carboxylic acids with 12 primary and secondary aliphatic amines furnished a library of 24 title compounds in good overall yields and purity.     

A simple metal-free synthesis of 2-substituted pyridine-4,5-dicarboxylates and their N-oxides

Herein a simple, metal-free synthesis of 2-alkyl-, 2-cycloalkyl-, 2-aryl-, and 2-heteroaryl-substituted pyridine 3,4-dicarboxylates and their N-oxides from the corresponding methyl ketones in good to excellent yield, demonstrated with 22 examples in each case, is described. The method complements the current coupling reactions of 2-heterocyclic organometallic reagents.     

Detection of cavitation in situ operation of kinetic pumps: Effect of cavitation on the characteristic discrete frequency component

Cavitation within a pump causes structural vibration with noise, among other by-products. Experiments have shown that there is a discrete frequency or broadband peak within the audible noise spectra, which is in strong correlation with the development of the cavitation process in the pump. Furthermore, the peak of the discrete frequency, or broadband peak, coincides with the net positive suction head (NPSH) critical value, which corresponds to a 3% drop in the total delivery head. Therefore, the discrete frequency tone can be used to detect the incipience of cavitation and its development as well as to determine the NPSH required or critical value with in situ operation of a pump. In this study, we wanted to clarify the mechanism of noise generation, which is responsible for the discrete frequency component and on which cavitation has an important effect. For this purpose, three different measurement methods were used: the first is based on measurement of the sound pressure level (SPL) in the surrounding air, the second is based on measurement of the underwater acoustics and the third is based on measurement of the structural vibration. Experiments have shown that the characteristic discrete frequency tone, which is in close correlation with the cavitation process, is a result of structural vibrations (modes) or resonances caused by implosion of bubbles and bombardment of the inner surfaces of the pump.