Development of Catalyst Technology for Producing Methyl Methacrylate (MMA) by Direct Methyl Esterification

The direct methyl esterification reaction for MMA was commercialized. Precisely synthesized Pd₃Pb₁ catalyst and the catalysis at the proposed reductive oxidation reaction condition (PROC) realized and guaranteed high MMA yield and long catalyst life. Controlled Pd distribution in a catalyst particle drastically decreased Pd loss from the catalyst during reaction. Unit processes are introduced as well.     

铜催化异噁唑还原环清洁高效合成1-氨基-2-乙酰基蒽醌简

以水为反应介质,水合肼为还原剂,研究了痕量铜催化3-甲基蒽醌-[1,2-c]-异噁唑还原开环反应以清洁高效合成1-氨基-2-乙酰基蒽醌,考察了不同种类过渡金属硝酸盐的催化性能,发现Cu（NO₃）₂性能最好. 加入 2.6% 的催化剂和1.3倍的水合肼,在室温反应 2 h,底物转化率和目标产物选择性分别可达到 97.2%和 95%,TON达到38. 产品结构经氢核磁谱和质谱得以确证,主要副产为羟基取代的1-氨基-2-乙酰基蒽醌. 此外,提出了铜催化 3-甲基蒽醌-[1,2-c]-异噁唑还原开环反应合成 1-氨基-2-乙酰基蒽醌的可能反应机理.     

Reductive amination of cyclohexanol/cyclohexanone to cyclohexylamine using SBA-15 supported copper catalysts

Amination of cyclohexanol was investigated in vapour phase over copper catalysts supported on mesoporous SBA-15. The different products identified during reductive amination of cyclohexanol reaction were cyclohexanone, cyclohexylamine, along with small amounts of N-Cyclohexylidinecyclohexylamine and dicyclohexylamine. Among several catalysts tested for the reductive amination, 5% Cu supported on SBA-15 exhibited better catalytic performance than other catalysts with 36% selectivity towards cylclohexylamine at 80% cyclohexanol conversion. The optimum reaction conditions employed to achieve the best catalyst performance were at 250 °C, 0.1 MPa of H₂/NH₃, TOS-10h. The active Cu sites, acidity of the catalyst, and effect of reaction parameters play a pivotal role in the reductive amination reaction. The prepared catalysts were characterized by XRD, BET, SEM, H₂-TPR and NH₃-TPD. The dispersion of Cu, particle size, and metal surface area (m²/g) calculated from pulse N₂O decomposition method. TPR findings reveal the presence of substantially dispersed copper oxide species at lower loadings which is easily reducible than the bulk copper oxide species found at higher Cu loadings. The acidity measurements by NH₃-TPD analysis suggest that the maximum acidic strength was obtained at 5 wt% copper on porous SBA-15, and decreased with Cu loadings. The catalytic properties are well in agreement with the findings of catalysts characterization.     

Synthesis of Heterodinuclear Hemisalen Complexes on a Hexaarylbenzene Scaffold and their Application for the Cross‐Pinacol Coupling Reaction

Intermolecular cross‐pinacol coupling reaction between aliphatic and aromatic aldehydes by using heterodinuclear hemisalen complexes 1 _cis with vanadium(V) and titanium(IV) on a hexaarylbenzene scaffold is reported. Our ligand design is based on the individual activation of two aldehydes by vanadium and titanium, which are positioned with a suitable space on the rigid scaffold. Ligands such as 1 _cis were synthesized by Diels–Alder addition and decarbonylation reaction, followed by condensation of dialdehyde 3 _cis with various aminophenols. The influence of the substituents on the ligands on the pinacol coupling reaction was investigated. As a result, the reductive coupling reaction between aliphatic and aromatic aldehydes by using a catalytic amount of 1 _cis in the presence of Me₃SiCl and Zn provided the corresponding cross‐coupled 1,2‐diol in good yields with high cross‐selectivity.     

Understanding the Mechanisms of Unusually Fast HH,CH,and CC Bond Reductive Eliminations from Gold(III) Complexes

Carbon–carbon bond reductive elimination from gold(III) complexes are known to be very slow and require high temperatures. Recently, Toste and co‐workers have demonstrated extremely rapid C?C reductive elimination from cis‐[AuPPh₃(4‐F‐C₆H₄)₂Cl] even at low temperatures. We have performed DFT calculations to understand the mechanistic pathway for these novel reductive elimination reactions. Direct dynamics calculations inclusive of quantum mechanical tunneling showed significant contribution of heavy‐atom tunneling (>25 %) at the experimental reaction temperatures. In the absence of any competing side reactions, such as phosphine exchange/dissociation, the complex cis‐[Au(PPh₃)₂(4‐F‐C₆H₄)₂]⁺ was shown to undergo ultrafast reductive elimination. Calculations also revealed very facile, concerted mechanisms for H?H, C?H, and C?C bond reductive elimination from a range of neutral and cationic gold(III) centers, except for the coupling of sp³ carbon atoms. Metal–carbon bond strengths in the transition states that originate from attractive orbital interactions control the feasibility of a concerted reductive elimination mechanism. Calculations for the formation of methane from complex cis‐[AuPPh₃(H)CH₃]⁺ predict that at ?52 °C, about 82 % of the reaction occurs by hydrogen‐atom tunneling. Tunneling leads to subtle effects on the reaction rates, such as large primary kinetic isotope effects (KIE) and a strong violation of the rule of the geometric mean of the primary and secondary KIEs.     

Synthesis of pyrazole- and thiazole-annulated 3-R-1,5-dinitro-3-azabicyclo[3.3.1]nonanes

The previously unknown 3-R-1,5-dinitro-3-azabicyclo[3.3.1]nonanes fused to the pyrazole or thiazole rings were synthesized by the reductive cyclization of m-dinitroindazoles and benzothiazoles. The method is based on the reduction of carbon-carbon bonds in the benzene ring, which are activated by the meta-nitro groups, with NaBH₄ followed by the Mannich reaction with formaldehyde and primary amines.     

Reagent-controlled diastereoselective synthesis of (2S,3R)- and (2R,3R)-2,3-diaminobutanoic acid derivatives using proline-catalyzed α-hydrazination reaction

(2S,3R)- and (2R,3R)-2,3-Diaminobutanoic acid (Dab) derivatives were efficiently synthesized from Cbz-(R)-alanine using the proline-catalyzed diastereoselective α-hydrazination reaction and the SmI₂-promoted reductive cleavage of the N-N bond as the key steps.     

利用薯蓣皂甙元完整骨架形式合成1α,25-二羟基维生素D3

首次利用薯蓣皂甙元的完整骨架经16步反应以7.6%的总收率合成了骨化三醇(1α,25-二羟基维生素D₃)的光化反应前体. 3-苄基保护的薯蓣皂甙元经还原开E/F环产生3,16,26-胆甾三醇-3-苄醚(5). 除去化合物5 C-16羟基后, 其C-26羟基经消除和羟基化反应转移到C-25位. 目标分子A/B环结构单元通过薯蓣皂甙元A/B环的官能团转化被构筑. 按照已知的光化反应, (1S,3R)-胆甾-5,7-二烯-1,3,25-三醇能被转化成为1α,25-二羟基维生素D₃.     

Synthesis and applications of 3,4-dihydroxy-2,5-bis-(2′-(4′-substituted-oxazolinyl)) furan

Three 3,4-dihydroxy-2,5-bis-(2′-(4′-substituted-oxazolinyl)) furans were synthesized at 90%–94% yields from reaction of 3,4-dihydroxyfuran-2,5-dicar-boxylic acid or its dimethyl ester with chiral β-amino alcohol via a one-step process. Their chemical structures were determined by ¹H NMR, IR, MS, and elemental analysis. With these chiral bisoxazoline ligands, the asymmetric reductive reaction of β-acetonaphthalene with KBH₄ or NaBH₄ was preliminarily studied. The enantiomeric excess of the reduction product was up to 83.2% with cyclohexane as the solvent, the molar ratio of ligand: reductive agent: β-acetonaphthalene is 0.04:1.6:1, and 72-hours reaction time at 0°C. Furancontaining bisoxazoline with 4-benzyl on oxazoline rings exhibited higher enatioselectivity than congeneric bisoxazolines with 4-ethyl on oxazoline rings. __________ Translated from Chinese Journal of Applied Chemistry, 2005, 22(12) (in Chinese)     

Synthesis of 5-endo-, 5-exo-, 6-endo- and 6-exo-hydroxylated analogues of epibatidine

A convenient, high-yield synthesis of N-Boc-7-azabicyclo[2.2.1]hept-5-en-2-one (7) was developed by SmI₂-mediated desulfonylation of 6. Thus, 5-endo-, 5-exo-, 6-endo-, and 6-exo-hydroxylated epibatidine analogues 2a,b and 3a,b were synthesized from 7 by using a Pd(PPh₃)₄-catalyzed reductive Heck coupling reaction and SmI₂-mediated reduction of the carbonyl group as the key steps. Other reaction conditions for the reductive Heck procedure and the reduction step were also investigated.     

Microwave-assisted solid-phase synthesis of pseudopeptides containing reduced amide bond

Procedures were developed for reducing the reaction time and improving the yield of reductive alkylation in solid phase pseudopeptide synthesis by utilizing microwave irradiation. We chose dipeptides containing the reduced amide bond ψ[CH₂NH] as a model system and optimized the microwave assisted reductive alkylation reaction in solid phase pseudopeptide synthesis using Fmoc chemistry. Under the optimized condition, the reductive alkylation reaction used for incorporating the reduced amide bond into the dipeptides was completed in only 8.5 min, whereas the normal reductive alkylation reaction required a total of 300 min. The purity and yield of the various dipeptides containing the reduced amide bond synthesized in this way are better than those achieved using the reductive alkylation method without microwave irradiation. We chose α helical peptides, which are known as a difficult sequence to synthesize, and incorporated the reduced amide bond by the microwave-assisted reductive alkylation reaction. We successfully synthesized pseudopeptides containing the reduced amide bond as a major product by using the novel microwave-assisted method, whereas the same products were obtained as a minor product when using the reductive alkylation method without microwave irradiation.     

The synthesis of facial amphiphile 3α,7α-diaminocholestane

The facial amphiphile 3α,7α-diaminocholestane 3 was synthesized from 3β-acetoxy-7-ketocholestane 1 through a stepwise reductive amination. The reductive amination of 1 with NH₄OAc in the presence of NaBH₃CN, and protection with Boc₂O yielded 7α-(tert-butyloxycarbonyl)-aminocholestane 4 in 86% yield. The reductive amination of 6, which was obtained from 4 after hydrolysis and subsequent oxidation, with NH₄OT_f in the presence of NaBH(OEh)₃ provided 3 in 75% yield after protection with Boc₂O.     

二茂铁-肽Fc-Gly-Pro-Arg(NO_2)-OMe的合成及其与Cu(Ⅱ)作用

以二茂铁甲酸、甘氨酸(H-Gly-OMe)、脯氨酸(Boc-Pro-OH)、精氨酸(H-Arg(NO2)-OMe)等为原料,苯并三唑-1-四甲基六磷酸酯(HBTU)和1-羟基苯并三唑(HOBT)为缩合剂,采用液相法合成了二茂铁-肽Fc-Gly-Pro-Arg(NO2)-OMe(简称Fc-GPR),其总收率为48.1%.并对目标产物进行了红外(IR)光谱、核磁共振氢谱(1H-NMR)、质谱(ESI-MS)等表征.通过电化学方法研究了目标产物与Cu(Ⅱ)之间的相互作用.结果表明:目标产物在溶液中的电化学行为表现为可逆氧化还原反应,氧化和还原峰电位分别为0.624和0.552V(vsAg/AgCl),氧化和还原峰电流之比Ipa/Ipc为1.13,电极反应过程为扩散控制.目标产物与Cu(Ⅱ)形成配位比为2∶1的配合物.Fc-GPR与Cu(Ⅱ)的电极反应过程符合电化学-化学-电化学(ECE)历程.     

Selective ruthenium-catalyzed double reductive aminations using hydrosilane to access tertiary amines and piperidine derivatives

A highly selective double reductive aminations of aldehydes with anilines to give tertiary amines, in the presence of [RuCl₂(p-cymene)]₂ catalyst and PhSiH₃, was performed under neat conditions. Piperidine derivatives were successfully synthesized by a double reductive amination followed by cyclisation from glutaric dialdehyde with anilines.     

Convenient synthesis of optically active deuterated primary alcohols via deuteride reduction of acetals derived from homochiral (1R1,2R1)-3,3,3-trifluoro-1-phenylpropane-1,2-diols

(1R)-1-Deuterated alcohols with high enantiomeric excess were prepared via TiCl₄/Et₃SiD reduction of acetals arising from the reaction of aldehydes with (1S,2S)-3,3,3-trifluoro-1-phenylpropane-1,2-diol 9. Such a chiral auxiliary was synthesized in an enantiomerically pure form starting from l-mandelic acid. Due to its benzylic nature, it was easily removed from the reaction product of the reductive 1,3-dioxolane ring-cleavage to afford the desired α-deuterated alcohol.     

Direct reductive amination and selective 1,2-reduction of α,β-unsaturated aldehydes and ketones by NaBH4 using H3PW12O40 as catalyst

A simple and convenient procedure for direct reductive amination of aldehydes and ketones with sodium borohydride is described. The reaction has been carried out in methanol in the presence of a catalytic amount of H₃PW₁₂O₄₀ (0.5 mol %). α,β-Unsaturated aldehydes and ketones can be easily converted into the corresponding allyl alcohols by reaction with H₃PW₁₂O₄₀ (0.5 mol %)/NaBH₄.     

Degradation of Carbon Tetrachloride by nanoscale Zero‐Valent Iron @ magnetic Fe3O4: Impact of reaction condition,Kinetics, Thermodynamics and Mechanism

Nano‐scale zero‐valent Iron (nZVI) attached on the Fe₃O₄ nanoparticles were prepared and creatively applied in the reductive dechlorination of Carbon Tetrachloride (CT). The characterization results of the synthesized composite indicated a main component of nZVI particles assembled on the surface of Fe₃O₄ with a layer of iron‐oxide film on the periphery, of which the dispersibility was better and the specific surface area was larger. The effects of different reaction conditions like temperature, initial pH values, Fe⁰@Fe₃O₄ dosage and initial CT concentrations on the removal of CT were evaluated. Under the optimum conditions, the Fe⁰@Fe₃O₄ composites showed a CT removal efficiency of 89.1% in 60 min, which was much greater than that of nZVI (61.7%) and Fe₃O₄ particles (14.3%). The removal process obeyed the pseudo‐first‐order kinetic model. Synergy effects of the constituents in the composite which can promote the relative rates of mass transfer to reactive sites were proposed to be existed and the magnetism of Fe₃O₄ could help to overcome the aggregation and surface passivation problem of nZVI. Thus, Fe⁰@Fe₃O₄ nanoparticles in our study can effectively complete the reductive dechlorination of CT and an improved nZVI catalyst is provided for the remediation of chlorinated organic compounds.     

Synthesis of Isoindolo[2,1‐a]quinazoline‐5,11‐dione Derivatives via the Reductive One‐Pot Reaction of N‐Substituted 2‐Nitrobenzamides and 2‐Formylbenzoic Acids

Various isoindolo[2,1‐a]quinazoline‐5,11‐dione derivatives 3 were synthesized in good yields by means of the reductive reaction of N‐substituted 2‐nitrobenzamides 1 and 2‐formylbenzoic acids 2 in the presence of SnCl₂?2 H₂O under reflux in EtOH (Scheme, Table). The procedure needed two steps, the reduction of the nitro group of the 2‐nitrobenzamide and ring closure by nucleophilic addition of the NH₂ group to both the formyl and carboxylic acid C?O groups.     

Preparation and reductive lithiation of 2-deoxy-D-glucopyranosyl phenylsulfones: A highly stereoselective route to C-glycosides

2-Deoxy-D-glucopyranosyl phenylsulfones 3a–c have been synthesized in 75–83% yield from commercial tri-O-acetyl-D-glucal 1. Their reductive desulfonylation by lithium naphthalenide and reaction of the intermediate glycosyl-lithium 5 with aldehydes leads to α-D-C-glucopyranosides with high stereoselectivity.     

Reductive amination agents: comparison of Na(CN)BH3 and Si-CBH

Reductive amination is a chemical reaction commonly employed by organic chemists in academics and the pharmaceutical industry. In this reaction a carbonyl group is converted to an amine via an imine intermediate, the formation of which is rate limiting. A major reagent necessary for the completion of this reaction is a hydride source, commonly sodium cyanoborohydride (Na(CN)BH₃). The objective of this research was to compare the efficacy of Na(CN)BH₃ with silica-bound cyanoborohydride (Si-CBH) as hydride sources in reductive amination reactions. Work has shown that reactions employing Si-CBH as a hydride source showed significant improvement, exhibiting an average percent conversion 25% greater than reactions using Na(CN)BH₃.