Sodium Hydride Research Articles

Controlled and diastereoselective synthesis of α-(3-hydroxy-2 oxoindolin-3-yl)-β-aminopropanoates

An efficient synthesis of non-natural, diastereoselective, α-hydroxyoxoindolin appended β-aminoester derivatives has been demonstrated from unprotected Morita-Baylis-Hillman (MBH) adducts of oxindole via simple aza-Michael addition strategy. The judicious choice of sodium hydride and bulky 2,4,6-triisopropylbenzenesulphonamide provided a controlled and diastereoselective addition products with MBH adducts of oxindole for the first time.

Transesterification instead of N‐Alkylation: An Intriguing Reaction

AbstractAn intriguing transesterification reaction is reported here for the first time. Different carbocyclic N‐1 alkoxycarbonyl methyl substituted hydantoins were treated with alkyl halides and sodium hydride as a base, in the presence of N,N‐dimethylformamide. Under these typical N‐alkylation reaction conditions, hydantoin alkyl acetates were also isolated, along with the expected N‐alkylated products. Additional experiments were also performed to investigate the role of N,N‐dimethylformamide in the transesterification reaction and a possible mechanism is also proposed.

Controlled Reduction of Carboxamides to Alcohols or Amines by Zinc Hydrides

AbstractNew protocols for controlled reduction of carboxamides to either alcohols or amines were established using a combination of sodium hydride (NaH) and zinc halides (ZnX2). Use of a different halide on ZnX2 dictates the selectivity, wherein the NaH‐ZnI2 system delivers alcohols and NaH‐ZnCl2 gives amines. Extensive mechanistic studies by experimental and theoretical approaches imply that polymeric zinc hydride (ZnH2)∞ is responsible for alcohol formation, whereas dimeric zinc chloride hydride (H−Zn−Cl)2 is the key species for the production of amines.

Controlled Reduction of Carboxamides to Alcohols or Amines by Zinc Hydrides.

New protocols for controlled reduction of carboxamides to either alcohols or amines were established using a combination of sodium hydride (NaH) and zinc halides (ZnX2 ). Use of a different halide on ZnX2 dictates the selectivity, wherein the NaH-ZnI2 system delivers alcohols and NaH-ZnCl2 gives amines. Extensive mechanistic studies by experimental and theoretical approaches imply that polymeric zinc hydride (ZnH2 )∞ is responsible for alcohol formation, whereas dimeric zinc chloride hydride (H-Zn-Cl)2 is the key species for the production of amines.

Novel Synthesis and Biological Evaluation of the First Pyrazole Thioglycosides as Pyrazofurin Analogues

This study reports a novel and efficient method for the synthesis of the first reported novel class of pyrazole thioglycosides 6a–h. These series of compounds were designed through the reaction of sodium 2-cyano-3-oxo-3-(4-substitutedphenylamino)prop-1-ene-1,1-bis(thiolate) salts 2 with hydrazine hydrate in ethanol at room temperature to give the corresponding sodium 5-amino-4-(substitutedphenylcarbamoyl)-1H-pyrazole-3-thiolates 3a–d. The latter compounds were treated with protected α-D-gluco- and galacto-pyranosyl bromides 4a,b in DMF at ambient temperature to give in a high yields the corresponding pyrazole thioglycosides 6a–h. Treatment of pyrazole salts 3a–d with hydrochloric acid at amobient temperature afforded the corresponding 3-mercaptopyrazole derivatives 5. The latter compounds were treated with peracetylated sugars 4 in sodium hydride in ethanol at ambient temperature to tolerate the S-glycosyl 6a–h compounds. Ammonolysis of the pyrazole thioglycosides 6a–h afforded the corresponding free thioglycosides 7a–h. The toxicity and antitumor activities of the synthesized compounds were studied.

REACTION OF ACETONE WITH DIETHYL OXALATE FOLLOWED BY AZOCOUPLING

Condensation of acetone with diethyl oxalate in presence of sodium hydride followed by the action of a mixture of arylamine, hydrochloric acid and sodium nitrite in neutral medium in an equimolar ratio yields 3-arylhydrazono-2,4-dioxopentanoates. The method proposed is simple and convenient, it makes possible to obtain a variety of previously unknown 3-arylhydrazono-2,4-dioxoalkanoates. The target compounds are obtained with the yield of more than 35%, and it favours to produce single crystals for study of the crystal structure of the synthesized compounds by X-ray diffraction analysis. It was found that in the crystalline state synthesized compounds form the E-isomer. The structural features of 3-arylhydrazono-2,4-dioxopentanoates obtained are established by IR and NMR 1H spectroscopy. In the NMR 1H spectra, the signals of the proton-containing groups of 3-arylhydrazono-2,4-dioxopentanoates with comparable integral intensity values are detected in the expected region. In a weak field (15.00 - 15.08 ppm) signals of NH-protons are observed, which indicates the intramolecular hydrogen bond. It is shown that the ratio of reagents and pH of the medium affects the direction of further azocoupling by diazonium salts after acetone treated with diethyl oxalate. Thus, 1,5-diaryl-3-acetylformazanes were isolated in the alkaline medium with double excess of aryldiazonium chlorides by 35 – 37% yield. The identity of synthesized compounds is confirmed by thin layer chromatography, and their structure is proved by IR and NMR 1H spectroscopy data. The proposed structure of the isolated 1,5-diaryl-3-acetylformazans is the most preferred and characteristic of most formazans. NH-proton signals are observed in a weak field at 15.87 ppm. and 16.0 ppm the resulting 1,5-diaryl-3-acetylformazans, which indicates the formation of the hydrogen bond -NH ... N = N-type in the six-membered chelate cycle with the possibility of proton transfer.

The Employment of Sodium Hydride as a Michael Donor in Palladium‐catalyzed Reductions of α, β‐Unsaturated Carbonyl Compounds

AbstractSodium hydride was employed as a Michael donor under the catalysis of PdCl2 for 1,4‐conjugate reductions of α, β‐unsaturated carbonyl compounds, which features operational simplicity, mild conditions and high atom‐economy. The merits of NaH as a reductant were demonstrated by the one‐pot or cascade reactions for the syntheses of complex molecules.magnified image

Synthesis, X-ray crystal and monoamine oxidase inhibitory activity of 4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine 5,5-dioxides: In vitro studies and docking analysis

We report the synthesis and biological evaluation of two new series of 2-amino-6-benzyl-4-phenyl-4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxides and 2-amino-6-methyl-4-phenyl-4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxides. The synthetic methodology involves a multistep reaction starting with methyl anthranilate which was coupled with methane sulfonyl chloride. The product of the reaction was subjected to N-benzylation and N-methylation reactions followed by ring closure with sodium hydride resulting in the formation of respective 2,1-benzothiazine 2,2-dioxides. These 2,1-benzothiazine precursors were subjected to multicomponent reaction with malononitrile and substituted benzaldehydes for the synthesis of two new series of pyranobenzothiazines (6a–r and 7a–r). The synthesized compounds were screened as selective inhibitors of monoamine oxidase A and monoamine oxidase B. The in vitro results suggested that compound 6d and 7q are the selective inhibitors of monoamine oxidase A, however, the selective and potent inhibitors of monoamine oxidase B included compounds 6h and 7r. Moreover, some dual inhibitors were noticed like 7l having more inhibitory activity towards both the isozymes. Moreover, the binding modes of the selective and potent inhibitors of monoamine oxidase A and B were investigated by molecular docking analysis. The results suggested that the synthetic derivatives may be potential towards the monoamine oxidase isozymes.

Reaction engineering approach to the synthesis of sodium borohydride

A mathematical model for the synthesis of sodium borohydride (NaBH4) from finely dispersed solid sodium hydride (NaH) and dissolved trimethyl borate (B(OH)3) in inert mineral oil was developed. The model is based on a plausible reaction mechanism of dissolved and adsorbed trimethyl borate on the surface of sodium hydride, where the reaction is presumed to take place. The surface reaction between sodium hydride and trimethyl borate leads to the formation of main (NaBH4) and side products (methoxy borohydrides), which was verified by chemical analysis of sodium borohydride and methanol in the water extract of the oil phase. Extensive kinetic experiments in a laboratory-scale isothermal and isobaric slurry reactor enabled a detailed kinetic analysis of the data, including the derivation of a mathematical model for the formation of sodium borohydride in a semibatch slurry reactor. The kinetic model was verified with experimental information and can be used as an element for process design.

A Simple and Convenient Strategy for the Synthesis of Novel Ten, Twelve, and Fourteen‐membered Phosphorus Macrocyclic Compounds

Synthesis of the title compounds 4(a–i) was accomplished through a two‐step process. The synthetic route involves the cyclization of equimolar quantities of 2,2′‐methylene(methyl)bis(4,6‐di‐tert‐butyl‐phenol) (1) with tris‐(2‐chloro‐ethyl) phosphite (2a), tris‐(2‐bromo‐ethyl) phosphine (2b), and tris‐bromo methyl phosphine (2c) in the presence of sodium hydride in dry tetrahydrofuran at 45–50°C. They were further converted to the corresponding oxides, sulfides, and selenides under N2 atmosphere by reacting them with hydrogen peroxide, sulfur, and selenium, respectively (4a–c, 4d–f, and 4g–i). But the compounds 6a,b were prepared by the direct cyclocondensation of equimolar quantities of 1 with (2‐chloro‐ethyl)‐phosphonic acid dibromomethyl ester (5a) and (2‐chloro‐ethyl)‐phosphonic acid bis(2‐bromo‐ethyl) ester (5b) in the presence of sodium hydride in dry tetrahydrofuran at 45–50°C in moderate yields. All the newly synthesized compounds 4(a–i) and 6(a–b) exhibited moderate in vitro antibacterial and antifungal activities.

Synthesis and structure of some substituted 2-amino-4-aryl-7-propargyloxy-4H-chromene-3-carbonitriles

A series of 2-amino-7-hydroxy-4H-chromene-3-carbonitriles 4a-l were synthesized through three-component reaction using sodium carbonate as a catalyst. The reaction was carried out in 96% ethanol-water medium (1:20 ratio in volume). Propargyl ether compounds 5a-l of these chromene-3-carbonitriles were successfully synthesized from corresponding hydroxyl chromene derivatives by reaction with propargyl bromide. Two different procedures were applied in this process: the procedure that used potassium carbonate in dried acetone and the procedure that used sodium hydride in dried DMF. The latter gave the ethers 5a-l in higher yields. The single-crystal X-ray structure of propargyl ether 5g has been recorded.

Synthesis, Characterization, and Catalytic Activity of Heteroleptic Rhodium Complex for C–N Couplings

We have reported synthesis of complex [Rh(COD)(L{Me})Cl] (III), where L{Me} (II) is N-(1-methylpyridin-4(1H)-ylidene)benzamide and COD is 1,5-cyclooctadiene. Monodentate ligand L{Me} was synthesized by deprotonation of [HL{Me}][OTf] (I) with sodium hydride. [HL{Me}][OTf] was synthesised by methylation of N-(pyridin-4-yl)benzamide (HL) with methyl triflate. All the three synthesized compounds were characterized by FT-IR, NMR (1H and 13C), elemental and MS analyses. The structure of complex I was further explored with single crystal XRD and computational studies. Complex I was found as a good catalyst for C–N coupling reactions. Molecular docking revealed strong binding of rhodium complex with myoglobin.

Synthesis and antimicrobial screening of novel 1,3-dioxolanes linked to N-5 of 5H-[1,2,4]triazino[5,6-b]indole-3-thiol

Synthesis of 1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-1H-indole- -2,3-dione (10) was achieved by coupling 1H-indole-2,3-dione (16) with (R)- -(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (15) in the presence of sodium hydride in dry N,N-dimethylformamide at room temperature in a closed Erlenmeyer flask. Condensation of 10 with hydrazinecarbothioamide in water afforded the thiosemicarbazone derivative 17; its subsequent cyclization with potassium carbonate in water gave the corresponding thione 18 in good yield. The 3-allylthio and 3-benzylthio derivatives 20 and 21 were also prepared by alkylating thiol 19 with alkyl halides in aqueous sodium hydroxide or coupling of 3-(allylthio/benzylthio)-5H-1,2,4-triazino[5,6-b]indoles (23 and 24) with compound 15 in NaH/DMF. Compound 20 was isomerized to a mixture of geometrical isomers (E/Z)-5-[(2,2-dimethyl-1,3-dioxolan-4-yl)- methyl]-3-(prop-1-en-1-ylthio)-5H-1,2,4-triazino[5,6-b]indoles (25 and 26), evidenced by their 1H- and 13C-NMR spectra taken in deuterodimethyl sulfoxide. Structural elucidation of the synthesized compounds was realized using FT-IR, 1H-NMR, 13C-NMR, mass spectrometry and elemental analysis. The newly synthesized compounds were found to possess moderate inhibitory activity against the fungus Candida albicans compared to clotrimazole as reference control. Compounds 10, 17, 19, 20, 21, 23 and 24 had mean growth inhibition zones (IZ) and minimal inhibitory concentrations (MIC) in the range of 12?15 mm and 31.25?200 ?g mL-1, respectively, with inhibition levels in the range 70.58?88.23 %. Compound 19 exhibited moderate activity against Gram-positive bacteria Staphylococcus aureus relative to imipenem as the standard drug. All compounds were inactive against Escherichia coli and Pseudomonas aeruginosa.

Synthesis, Structure, and Biological Activity of Magnesium(II), Zinc(II), Cobalt(II), and Copper(II) Bis(4-aryl-1-ethoxy-1-oxobutane-2,4-dionates)

The condensation of aryl methyl ketones with diethyl oxalate in the presence of metallic sodium or sodium hydride gave sodium 4-aryl-1-ethoxy-1,4-dioxobut-2-en-2-olates, and metal exchange of the latter with magnesium(II), zinc(II), cobalt(II), and copper(II) salts afforded the corresponding metal bis(4-aryl-1-ethoxy-1-oxobutane-2,4-dionates). The obtained complexes were tested for antibacterial activity against gram-positive and gram-negative bacteria by the agar diffusion method.

Thermal Stability and Thermoelectric Properties of NaZnSb.

A layered Zintl antimonide NaZnSb (PbClF or Cu2Sb structure type; P4/nmm) was synthesized using the reactive sodium hydride NaH precursor. This method provides comprehensive compositional control and facilitates the fast preparation of high-purity samples in large quantities. NaZnSb is highly reactive to humidity/air and hydrolyzes to NaOH, ZnO, and Sb in aerobic conditions. On the other hand, NaZnSb is thermally stable up to 873 K in vacuum, as no structural changes were observed from high-temperature synchrotron powder X-ray diffraction data in the 300–873 K temperature range. The unit cell expansion upon heating is isotropic; however, interatomic distance elongation is not isotropic, consistent with the layered structure. Low- and high-temperature thermoelectric properties were measured on pellets densified by spark plasma sintering. The resistivity of NaZnSb ranges from 11 mΩ∙cm to 31 mΩ∙cm within the 2–676 K range, consistent with heavily doped semiconductor behavior, with a narrow band gap of 0.23 eV. NaZnSb has a large positive Seebeck coefficient (244 μV∙K−1 at 476 K), leading to the maximum of zT of 0.23 at 675 K. The measured thermoelectric properties are in good agreement with those predicted by theoretical calculations.

Preparation of Amphiphilic Poly(ethylene glycol)-b-poly(γ-butyrolactone) Diblock Copolymer via Ring Opening Polymerization Catalyzed by a Cyclic Trimeric Phosphazene Base or Alkali Alkoxide

Biobased poly(γ-butyrolactone) (PγBL) as a fully biodegradable and bioabsorbable biomaterial has shown superior properties compared to those of other aliphatic polyesters. It is of great importance to prepare amphiphilic block copolymer containing PγBL block to make ordered nano-objects for biomedical applications such as drug delivery systems. However, such an amphiphilic copolymer containing PγBL segment was never successfully prepared mostly due to the synthetic challenges of ring-opening polymerization (ROP) of nonstrained γ-butyrolactone (γBL) monomer. Here, we reported the first preparation of amphiphilic poly(ethylene glycol)- b-poly(γ-butyrolactone) (PEG- b-PγBL) diblock copolymer by using PEG as a macroinitiator. We applied two types of bases to initiate the ROP of γBL. An organic cyclic trimeric phosphazene base (CTPB) was first applied to activate the terminal hydroxyl group of PEG as macroinitiator for ROP of γBL. On the other hand, sodium hydride was used to activate the hydroxyl group of PEG to form sodium alkoxide as an initiating system for ROP of γBL. Both catalytic/initiating system showed moderate control on ROP of γBL and successfully produced PEG- b-PγBL diblock copolymers with varied molecular weights and relatively narrow molecular weight distributions. The effects of catalytic systems, activation temperatures, and monomer concentrations on γBL conversion and molecular weight of PEG- b-PγBL were carefully explored. The thermal properties and phase behaviors of obtained PEG- b-PγBL were also investigated.

Synthesis and coordination chemistry of sterically hindered cobalt(II) β-ketoiminate complexes

The reactions of cobalt(II) chloride with α,β-unsaturated-β-ketoamines, CH3C(O)CHC(NHR)CH3, where R = -phenyl, HLPh; R = -mesityl, HLmes; R = -2,6-diisopropylphenyl, HLdipp, and sodium hydride in THF solvent under anaerobic conditions affords brown or orange crystals of Co(Lph)2, Co(Lmes)2 and Co(Ldipp)2, respectively. In THF/acetonitrile solvent mixture, the complexation reactions are not successful as unreactive salts containing networks of acetonitrile-coordinated sodium cations and the respective anions are formed. One of them, the sodium salt of HLdipp, is isolated and characterized as [Na(Ldipp)(CH3CN)]4. Single-crystal X-ray diffraction data for the cobalt(II) complexes reveal that the metal centers assume distorted tetrahedral geometries. The degree of distortion increases with the size of the substituents present in the phenyl groups: Co(Lph)2 < Co(Lmes)2 < Co(Ldipp)2. Crystallographic data measured at 296, 200, 150 and 100 K for Co(Ldipp)2 reveal that it exists as two geometrical forms, namely, distorted tetrahedral and distorted square-planar. The data also indicate that the pseudo-tetrahedral to distorted square-planar transition is favored at lower temperatures. Electrochemical data measured in THF and DCM solvents reveal the likely presence of Co(II)-solvent interaction in Co(Lph)2 and Co(Lmes)2 and no such interaction in Co(Ldipp)2. Magnetic susceptibility data for Co(Ldipp)2 in the 4–300 K temperature region reveal spin-crossover at ca. 130 K. Qualitatively, the magnetic and crystallographic data complement each other with respect to the presence of the high spin pseudo-tetrahedral and low spin pseudo-square planar geometries.

Synthesis and biological activity of 5-vinyl- and 5-allyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles

A synthetic approach to the vinylation and allylation of tetrahydro-γ-carbolines with alkane dimethyl sulfonates in the presence of sodium hydride was developed. The effect of the synthesized 5-vinyl- and 5-allyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles on acetylcholinesterase, butyrylcholinesterase, and carboxylesterase activity, mitochondrial functions, and tubulin polymerization was investigated, and their antioxidant activity was evaluated.

Synthesis and photophysical properties of azuleno[1′,2′:4,5]pyrrolo[2,1-b]quinazoline-6,14-diones: Azulene analogs of tryptanthrin

Azulene analog of tryptanthrin, azuleno[1′,2′:4,5]pyrrolo[2,1-b]quinazoline-6,14-dione, was successfully prepared by the condensation reaction of azuleno[2,1-b]pyrrole-2,3-dione with isatoic anhydride in the presence of sodium hydride or diisopropylethylamine (DIPEA). Its 2-halo derivatives were also obtained in high yields by the condensation reaction with 5-haloisatoic anhydrides in the presence of DIPEA. Reactivity toward electrophilic reagents was revealed by halogenation with N-bromosuccinimide (NBS) or N-iodosuccinimide (NIS) to afford 12-halo derivatives in high yields. Among the halo derivatives, 2-iodo and 12-iodo derivatives were reactive enough to afford phenylethynyl derivatives under Pd-catalyzed Sonogashira cross-coupling conditions. Within the phenylethynyl derivatives, only 12-phenylethynyl derivative was transformed into its 1,1,4,4-tetracyanobutadiene (TCBD) derivative by the reaction with TCNE. Amphoteric redox properties of the novel azulene analogs of tryptanthrin were characterized by spectroscopic and voltammetric analyses.

Mechanism of \u03b5-caprolactone polymerization in the presence of alkali metal salts: investigation of initiation course and determination of polymers structure by MALDI-TOF mass spectrometry

Various alkali metal salts were applied as initiators for ε-caprolactone anionic ring-opening polymerization in tetrahydrofuran at room temperature. It was observed that potassium methoxide (MeOK), potassium isopropoxide (i-PrOK) and potassium tert-butoxide (t-BuOK) nonactivated or activated by 18-crown-6 (18C6) initiated polymerization mainly by deprotonation of the monomer. In the case of potassium hydride (KH), its basicity increased with the ability of the ligand for cation complexation. For example, KH without ligand or with weak ligands for K+ as 12C4 reacted exclusively by ring opening. However, in the presence of strong ligands, as 15C5, 18C6 or cryptand C222, basicity of H− increased with the ability of the ligand for cation complexation. In the last case, ~ 32% of the monomer was deprotonated. In these systems, gaseous H2 evolved during the initiation. Deprotonation of the monomer by some initiators resulted in macromolecules with reactive aldehyde group or lactone ring as starting groups. They took part in the reaction with potassium alkoxide active centers of growing chains leading to the formation of branched poly(ε-caprolactone)s. Sodium hydride (NaH) was inactive, but in the presence of 15-crown-5 or 18-crown-6 initiated polymerization exclusively by ring opening. MALDI-TOF mass spectrometry supported with 13C NMR and SEC was used for analysis of the polymers obtained. Mechanism of the studied processes was proposed and discussed.