A Study of the Regiochemistry in the Synthesis of Pyrano[3,4-c]pyridines

2021 ◽  
Vol 25 ◽  
Author(s):  
Samvel N. Sirakanyan ◽  
Domenico Spinelli ◽  
Victor A. Kartsev ◽  
Athina Geronikaki ◽  
Elmira K. Hakobyan ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Reaction Products ◽  
Pyran Ring ◽  
Acylation Reaction ◽  
Reaction Conditions ◽  
Acyl Chlorides ◽  
Alkyl Groups ◽  
Biological Studies ◽  
Physicochemical Methods ◽  
Derivatives Of

Aims: Biological studies have shown that some condensed derivatives of pyrano[3,4-c]pyridines 6 exhibited pronounced biological activity. Considering these results, the principal aim of this work is to study the regiochemistry of the synthesis of pyrano[3,4-c]pyridines 6, optimize the reaction conditions, and increase the previously observed low yields of pyrano[3,4-c]pyridines. Background: Several years ago, a method for the preparation of 6-oxopyrano[3,4-c]pyridines 6 starting from 2,2-dimethyltetrahydro-4H-pyran-4-one 1 was developed. In this study, we have separated and identified only the most expected reaction products of 6-oxopyrano[3,4-c]pyridines 6. On the basis of this datum, we suggested that the enamines 2 and 3 reacting with acyl chlorides were not acylated at C-3 and that 5-acylpyran-4-ones 4 were the only products of the reaction. We have justified this result by considering the steric effects exerted by the two methyl groups present in the pyran ring. Moreover, we did not identify the products at the second reaction center: that is, the isomeric compounds 7. This result was justified considering the different reactivity of aliphatic and cyclic ketone groups. Objective: The main objectives of this work are as follows: a) implementation of the reaction of 2,2-dimethyltetrahydro-4H-pyran-4-one 1 with morpholine; b) acylation of the obtained enamines 2 and 3 with acyl chlorides under Stork conditions; c) synthesis of pyranopyridines 6–8 based on β-diketones: 3-acylpyran-4-ones 4 and 5-acylpyran-4-ones 5; d) confirmation of the structure of the obtained compounds. Method: For the synthesis of pyrano[3,4-c]pyridines, known methods were used. Thus, the reaction of starting 2,2-dimethyltetrahydro-4H-pyran-4-one 1 with morpholine in benzene led to the formation of isomeric enamines 2 and 3. Then, they were acylated with acyl chlorides under Stork conditions with the formation of two β-diketones: 3-acylpyran-4-ones 4 and 5-acylpyran-4-ones 5. Finally, in order to obtain the aimed pyrano[3,4-c]pyridines 6, the obtained β-dicarbonyl compounds 4 and 5 (as a mixture of isomers) were reacted with 2-cyanoacetamide in ethanol in the presence of diethylamine, according to the Knoevenagel condensation. The structure of the obtained compounds has been unambiguously confirmed by using a wide spectrum of physicochemical methods (NMR, IR, X-ray structural and elemental analysis) and, in the instance of compounds 7, also by an alternative synthesis. Results: Starting from the 2,2-dimethyltetrahydro-4H-pyran-4-one 1, a series of new and already known 6-oxopyrano[3,4-c]pyridines 6 were synthesized. As a result of the study of the regiochemistry in the synthesis of pyrano[3,4-c]pyridines, out of the four possible isomer pyranopyridines 6−9, we have succeeded to identify three of them (6−8). Thus, isomer pyranopyridines 7 and 8 were identified in the mixture with the main compounds 6. Moreover, isomeric pyrano[3,4-c]pyridines 8 were detected when alkyl groups are present in the starting compounds 4 and 5, while isomeric pyrano[4,3-b]pyridines 7 were detected in the case of the presence of aromatic groups. Unfortunately, we have not been able to isolate compounds 7 and 8 in the pure state from the reaction mixtures. Currently, we have not been able to detect and identify isomeric pyrano[4,3-b]pyridines 9. On the whole, we have been able to increase the effectiveness of the synthesis of pyrano[3,4-c]pyridines 6, increasing their yields by ≈ 5–15%. Conclusion: As a result of our investigation, we have found that the acylation reaction of enamines 2 and 3 and the cyclization reaction of β-diketones 4 and 5 are not regioselective. Therefore we can state that enamines 2 and 3 can be acylated at both C-3 and C-5 with the formation of a mixture of 3-acylpyran-4-ones 4 and 5-acylpyran-4-ones 5. Their condensation with 2-cyanoacetamide led to the formation of mixtures of regioisomeric pyranopyridines 6−8. In conclusion, as a result of our present research, we can say that we have been able to increase the effectiveness of the synthesis of pyranopyridines, largely improving our previous results։ Other: Currently, we are working to look for the fourth isomeric pyrano[4,3-b]pyridines 9 by using the most modern and fine methods. Moreover, we hope that we would be able to separate the mixtures of pyranopyridines 6–8 so that they can be used for further syntheses.

scholarly journals SYNTHESIS AND RESEARCH OF NITROGEN-CONTAINING XANTHANE GUM DERIVATIVES

2020 ◽  
Vol 9 (5(74)) ◽  
pp. 57-62
Author(s):  
O.R. Ahmedov ◽  
N.Sh. Rahmatova ◽  
H.S. Talipova ◽  
Z.S. Alihonova ◽  
A.S. Turaev
Keyword(s):  
Xanthan Gum ◽  
Condensation Reaction ◽  
Oxidation States ◽  
Reaction Products ◽  
Scanning Calorimetry ◽  
Quantitative Content ◽  
Degree Of Oxidation ◽  
Physicochemical Methods ◽  
Aldehyde Groups ◽  
Derivatives Of

This study presents the results concerning the synthesis of nitrogen-containing derivatives of xanthan gum. The authors obtained xanthan gum derivatives with various oxidation states through the preliminary reaction of periodic oxidation of the polysaccharide. Through the physicochemical methods of analysis, the structure and established quantitative content of aldehyde groups in the macromolecular chain of the polysaccharide were proved. It was possible to carry out a condensation reaction with guanidine and to synthesize new macromolecular derivatives in the presence of reactive aldehyde groups in the structure of xanthan gum. The synthesized derivatives were further investigated through IR spectroscopy, thermogravimetry, differential scanning calorimetry, and elemental analysis for nitrogen content. Furthermore, it is found that the amount of guanidine and the degree of substitution in the synthesized compounds are 15.3-39.0% and 34-85 mol.%. Finally, when using modified xanthan gum with a different degree of oxidation it is possible to vary the quantitative content of guanidine and the degree ofsubstitution in the reaction products.

scholarly journals The interaction of piperylene and its chlorine derivatives with aromatic amines

2019 ◽  
Vol 58 (4) ◽  
pp. 22-33
Author(s):  
Akhat G. Mustafin ◽  
◽  
Yury S. Zimin ◽  
Ildus B. Abdrakhmanov ◽  
Vakil M. Sharafutdinov ◽  
...  
Keyword(s):  
Aromatic Amines ◽  
Lewis Acids ◽  
Direct Interaction ◽  
Reaction Products ◽  
Alkyl Groups ◽  
Reaction Proceeds ◽  
Optimal Reaction Temperature ◽  
Derivatives Of ◽  
Optimal Reaction ◽  
Fold Excess

The article considers the possibility of introducing a pentenyl radical into the structure of aromatic amines by the interaction of the latter with piperylene and its chlorine derivatives, 4-chloro-2-pentene and 3,4-dichloro-2-pentene. Direct alkenylation of aniline with piperylene in the presence of Lewis acids leads to C-alkenyl arylamines. The most effective catalyst is AlCl3. Along with the expected 2- and 4-(1-methyl-2-butenyl) anilines, the formation of 2,4-di- and 2,4,6-tri-(1-methyl-2-butenyl) anilines is observed, the latter being virtiually the only product in the reaction with a 5-fold excess of piperylene. In addition to Lewis acids, H3PO4 deposited on kieselguhr or silica gel, as well as polyphosphoric acid, were used to catalyze this reaction. Under the action of these catalysts, ortho- and para-alkenylated anilines are mainly formed, and the yield of the ortho-isomer, reaching 34%, always exceeds the yield of the para-product. It is possible that, under these conditions, N-alkenylation occurs simultaneously with direct C-alkenylation followed by an amino rearrangement. The yield of the 2,4-dialkenyl product does not exceed 8%, and trialkenylated aniline is completely absent. The optimal reaction temperature is in the range of 180-200 °C, at higher temperatures the yield of the target products decreases due to the polymerization of piperylene. Various aniline derivatives are also involved in the reaction with piperylene. When one of the ortho positions in the arylamine molecule is occupied, as in ortho-toluidine or in 2-chloroaniline, a mixture of the three products is formed in comparable amounts. The reaction of meta-toluidine with piperylene also leads to the mixture of three products, and the substitution does not affect the 2-position between the amino and methyl groups. If both ortho-positions are occupied, as in 2-methyl-6-ethylaniline, the reaction is quite successfully under way in the para-position (yield is 61%). To increase the selectivity of the process, the alkylation of aromatic amines is best carried out not by piperylene, but by its chlorine derivatives. The reaction of aniline with 4-chloro-2-pentene takes place in the environment of triethylamine and leads to N-(1-methyl-2-butenyl) aniline with a yield of 80%. Other primary and secondary arylamines react in the same way. The reaction with 3,4-dichloro-2-pentene proceeds under more severe conditions. If the reaction of aromatic amines with 4-chloro-2-pentene is carried out not in triethylamine medium, but in an excess of arylamine itself as a solvent, then not N- but C-substituted products are formed. The reaction proceeds as a consequitive-simultameous process. In the first stage, N-alkenylation occurs with the formation of N-(1-methyl-2-butenyl) arylamine followed by an amino rearrangement of Claisen under the catalytic action of evolved HCl. Alongside with the obvious predominance of ortho-substituted arylamine (64-82%), para-isomers and, in some cases 5-12% of 2,4- or 2,6-disubstituted compounds were found in the reaction products. The amino rearrangement in the interaction of arylamines with 3,4-dichloro-2-pentene proceeds with exceptional ortho-selectivity. Alkyl groups at nitrogen and ortho positions accelerate, and ortho-chloro, para-methyl, 2,4-dimethyl substituents slow down the process, while the meta-methyl group has no significant effect. The same dependence was observed in the case of 4-chloro-2-pentene. Thus, pentenyl fragment can be introduced in various ways into the structure of aromatic amines: by direct interaction with piperylene in the presence of catalysts, N-alkenylation of 4-chloro-2-pentene and 3,4-dichloro-2-pentene in triethylamine medium and reaction of arylamines with chlorine derivatives of piperylene, accompanied by an amino rearrangement of Claisen.

scholarly journals ALTERNATIVE METHODS OF SYNTHESIS OF NOVEL HETEROSYNTHONES – FUNCTIONALIZED HYPOXANTHINE PYRIMIDINES

2021 ◽  
Vol 26 (2(78)) ◽  
pp. 32-39
Author(s):  
V. M. Povstyanoy ◽  
T. A. Yuyrova ◽  
A. N. Retchitskiy ◽  
A. A. Krysko
Keyword(s):  
Wide Spectrum ◽  
Physiological Activity ◽  
Biginelli Reaction ◽  
Aromatic Aldehydes ◽  
13C Nmr Spectroscopy ◽  
Alternative Methods ◽  
Reaction Products ◽  
Optimal Method ◽  
Methylene Bridge ◽  
Derivatives Of

It has been known that derivatives of dihydropyrimidine and xanthine possess the physiological activity of the wide spectrum of action. The combination of the specified heterocyclic fragments within one molecule can lead to the increase of its known types of biological activity as well as to the discovery of novel types of activity. We have previously reported the synthesis of intermediates, which consist of functionalized dihydropyrimidines, connected via a methylene bridge with the halogen substituted derivatives of the ophylline, 3-methylxanthine and imidazole. It was also observed that these compounds would react with N‑nucleophiles with the formation of various branched and cyclic products. The aim of this work was to determine the optimal conditions for obtaining heterocyclic products as a result of conjugation of bromomethyldihydropyrimidine and hypoxanthine at the positions C6 and C1 via a methylene bridge. It is important to note, that the latter can be widely modified by using structurally diverse aromatic aldehydes during the synthesis of dihydropyrimidine core by using Biginelli reaction, which explains structural diversity of the reaction products. After having tried various reaction conditions, we have concluded that the optimal method for obtaining the products entailed keeping equimolar ratios of bromomethyl substituted dihydropyrimidines and 1-potassium‑2-chloro‑7-methylhypoxanthine in dry ethanol for 4 hours. The ester group at the C5 of dihydropyrimidine ring and a chlorine leaving group at C2 of hypoxanthine fragments of the molecule allow to consider these structures as pro missing synthons for farther synthesis of condensed pyrimidine and xanthine systems. The structures of novel compounds have been confirmed with the methods such as HPLC/MS, 1H, and 13C NMR spectroscopy.

scholarly journals Synthesis of Epoxyperoxides and Peroxide Derivatives of -D-Galactopyranose Based Thereon

2020 ◽  
Vol 14 (4) ◽  
pp. 439-447
Author(s):  
Roman Fleychuk ◽  
◽  
Lidiya Vuytsyk ◽  
Ananiy Kohut ◽  
Orest Hevus ◽  
...  
Keyword(s):  
Thermal Analysis ◽  
Kinetic Parameters ◽  
Reaction Products ◽  
Reaction Conditions ◽  
Derivatives Of ◽  
Complex Thermal Analysis

New epoxide-containing peroxides have been synthesized via the interaction between epichlorohydrin and ditertiary -hydroxyalkyl peroxides. The effect of reaction conditions on both the yield and composition of the reaction products has been established. Through the reactions of either the synthesized epoxide-containing peroxides with 1,2;3,4-di-O-isopropylidene--D-galactopyranose or 6-O-glycidyl-1,2;3,4-di-O-isopropylidene--D-galactopyranose with the -hydroxyalkyl peroxides, new peroxide derivatives with ditertiary and primary-tertiary peroxide groups have been synthesized successfully. The decomposition of the developed substances has been studied by complex thermal analysis and the kinetic parameters of the thermolysis have been determined.

scholarly journals Optimization of Reactions Opening Cyclic Ring of Pentose Sugar Derivatives through Dithioacetalisation Reactions

2017 ◽  
Vol 17 (2) ◽  
pp. 79
Author(s):  
Nuriman Nuriman
Keyword(s):  
Reaction Time ◽  
Ring Opening ◽  
Solvent Mixture ◽  
Reaction Products ◽  
Reaction Conditions ◽  
Ring Opening Reaction ◽  
Pentose Sugar ◽  
Sugar Derivatives ◽  
Derivatives Of ◽  
Better Than

Ring-opening reaction of cyclic pentose sugar derivatives of 2,3,4-Tri-O-benzyl- D-xylopyranoseto derivatives of acyclic 2,3,4-Tri-O-benzyl-D-xylose-Dipropyl dithioacetal been done andoptimized. The reaction was performed using a precursor propanathiol with concentrated HCl.Optimization of reaction conditions was conducted by varying propanathiol concentration,reaction time and optimization of the reaction temperature which the product ioslation conductedusing a variety of solvents. The results of this reaction was obtained 2,3,4-Tri-O-benzyl- Dxylose-Dipropyl dithioacetal with the highest randemen (97%), better than the previous reactionthrough propanathiol excessive concentration, reaction time of 2 hours and the temperature of thereaction at room temperature. Product Isolations using solvent dikloromathane more effectivethan the use of other organic solvents. Purification of reaction products is done through a columnchromatography using a solvent mixture of 20% ethyl acetate-hexane.Keywords: Optimization, Cyclic Ring, Dithioasetalisasi 

Cleavage of the Epimines of 1,6-Anhydrohexoses with Fluoride Anion

2005 ◽  
Vol 70 (12) ◽  
pp. 2075-2085 ◽  
Author(s):  
Jiří Kroutil ◽  
Klára Jeništová
Keyword(s):  
Fluoride Anion ◽  
Ring Cleavage ◽  
Protecting Group ◽  
Reaction Conditions ◽  
Aziridine Ring ◽  
Cleavage Reactions ◽  
Derivatives Of ◽  
Fluoro Derivatives

Aziridine ring cleavage reactions of five N-nosylepimines (2-6) having D-talo, D-galacto, D-manno, and D-allo configurations with potassium hydrogendifluoride under various reaction conditions have been performed. The cleavage regioselectively afforded diaxial isomers of vicinal amino-fluoro derivatives of 1,6-anhydro-β-D-gluco- and mannopyranose 7-11 in 51-94% yields. Removal of 2-nitrobenzenesulfonyl protecting group with benzenethiol has been attempted in the case of compound 10.

scholarly journals Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

2016 ◽  
Vol 12 ◽  
pp. 2588-2601 ◽  
Author(s):  
Vladimir A Stepchenko ◽  
Anatoly I Miroshnikov ◽  
Frank Seela ◽  
Igor A Mikhailopulo
Keyword(s):  
Purine Nucleoside Phosphorylase ◽  
Reaction Conditions ◽  
E Coli ◽  
No Formation ◽  
Structural Peculiarities ◽  
Substrate Properties ◽  
Nucleoside Phosphorylases ◽  
Derivatives Of

The trans-2-deoxyribosylation of 4-thiouracil (4SUra) and 2-thiouracil (2SUra), as well as 6-azauracil, 6-azathymine and 6-aza-2-thiothymine was studied using dG and E. coli purine nucleoside phosphorylase (PNP) for the in situ generation of 2-deoxy-α-D-ribofuranose-1-phosphate (dRib-1P) followed by its coupling with the bases catalyzed by either E. coli thymidine (TP) or uridine (UP) phosphorylases. 4SUra revealed satisfactory substrate activity for UP and, unexpectedly, complete inertness for TP; no formation of 2’-deoxy-2-thiouridine (2SUd) was observed under analogous reaction conditions in the presence of UP and TP. On the contrary, 2SU, 2SUd, 4STd and 2STd are good substrates for both UP and TP; moreover, 2SU, 4STd and 2’-deoxy-5-azacytidine (Decitabine) are substrates for PNP and the phosphorolysis of the latter is reversible. Condensation of 2SUra and 5-azacytosine with dRib-1P (Ba salt) catalyzed by the accordant UP and PNP in Tris∙HCl buffer gave 2SUd and 2’-deoxy-5-azacytidine in 27% and 15% yields, respectively. 6-Azauracil and 6-azathymine showed good substrate properties for both TP and UP, whereas only TP recognizes 2-thio-6-azathymine as a substrate. 5-Phenyl and 5-tert-butyl derivatives of 6-azauracil and its 2-thioxo derivative were tested as substrates for UP and TP, and only 5-phenyl- and 5-tert-butyl-6-azauracils displayed very low substrate activity. The role of structural peculiarities and electronic properties in the substrate recognition by E. coli nucleoside phosphorylases is discussed.

Nitroxides as reaction intermediates

1982 ◽  
Vol 60 (12) ◽  
pp. 1414-1420 ◽  
Author(s):  
Hans Gunter Aurich
Keyword(s):  
Electron Spin Resonance ◽  
Electron Spin ◽  
Isopropyl Alcohol ◽  
High Reactivity ◽  
Reaction Intermediates ◽  
Reaction Products ◽  
Nitronyl Nitroxide ◽  
Reaction Conditions ◽  
Spin Resonance ◽  
Secondary Reactions

Vinyl nitroxides 4 are obtained by oxidation of the nitrones 3, as was shown by esr studies and by identification of the reaction products. The formation of 4d–f is even observed in oxidation of the hydroxylamines 1d–f, nitroxides 2d–f and nitrones 3d–f being the intermediates. The high reactivity of the vinyl nitroxides 4 at their β-position is illustrated by the reactions of 4a with various compounds affording the nitroxides 7–10, respectively. Compound 4c reacts with its precursor 3c to give 11, 12, or 13, depending on the reaction conditions. From oxidation of 3a, c, and e the dimerization products 5a, c, and e, respectively, could be isolated. Whereas further oxidation of 5d yields 6d, the acyl nitroxides 14a and c are formed in the oxidation of 5a and c, respectively.The formation of quinone 23 in the reaction of 2-methyl-2-nitrosopropane with potassium tert-butoxide in isopropyl alcohol in the presence of oxygen is discussed. The nitroxide 20 has been detected in the reaction mixture. Imines 24 react with nitrosobenzene giving nitroxides 26. These are further oxidized by nitrosobenzene to afford nitrones 27. Whereas 27a and b could be isolated, 27c and d undergo further reaction yielding the diimines 30c and d along with dinitrone 29.The formation and reactions of imino nitroxides 31 and of the nitronyl nitroxide 41 are discussed. Electron spin resonance studies revealed the high reactivity of the imidazolyl-1,3-dioxides 46 and the imidazolyl-1-oxides 50, which easily form radicals 47–49 and 51, respectively, which are derived from secondary reactions.

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