17972-13-3

We herein report a general, practical, and highly efficient method for asymmetric synthesis of a wide range of chiral vicinal diamines via reductive coupling of imines templated by chiral diboron. The protocol features high enantioselectivity and stereospecificity, mild reaction conditions, simple operating procedures, use of readily available starting materials, and a broad substrate scope. The method signifies the generality of diboron-enabled [3,3]-sigmatropic rearrangement.

1,1′-(1,4-Butanediyl)bis(imidazole) was prepared by a modified method and its application as an efficient promoter was demonstrated for the mechanosynthesis of N-methyl imines using ball milling as a non-conventional process under solvent-free conditions. In this new protocol design, the bis-imidazole acted as a recyclable acid-scavenging agent. This efficient approach to the N-methyl imines displays a combination of the synthetic virtues of a non-conventional condensation reaction with ecological benefits and convenience of a facile mechanosynthetic process. The current method has advantages such as reduced waste by avoiding solvent, exclusion of hazardous materials during the reaction, elimination of handling an anhydrous gas in an evacuated container or a solution of methylamine in ethanol, good yields for relatively unreactive benzaldehydes containing electron-donating substituents, short reaction times, and metal- and acid-free conditions. Furthermore, the promoter was easily regenerated and reused several times with no significant loss of activity.

The invention belongs to the technical field of chemical engineering and pharmaceutical industry, and particularly relates to a method for synthesizing imine by catalytic oxidation of asymmetric secondary amine in the presence of visible light. With aza-metalloporphyrin containing sulfur as a visible light catalyst, 1,8-diazabicycloundecene-7-alkene as an auxiliary agent, and oxygen as an oxidant,asymmetric secondary amine is subjected to catalytic oxidation under irradiation of visible light of lambda being larger than or equal to 420nm, so as to obtain the oxidation product imine. A new andefficient imine production way is provided.

Nitrones are key intermediates in organic synthesis and the pharmaceutical industry. The heterogeneous synthesis of nitrones with multifunctional catalysts is extremely attractive but rarely explored. Herein, we report ultrasmall platinum nanoclusters (PtNCs) encapsulated in amine-functionalized Zr metal–organic framework (MOF), UiO-66-NH2 (Pt@UiO-66-NH2) as a multifunctional catalyst in the one-pot tandem synthesis of nitrones. By virtue of the cooperative interplay among the selective hydrogenation activity provided by the ultrasmall PtNCs and Lewis acidity/basicity/nanoconfinement endowed by UiO-66-NH2, Pt@UiO-66-NH2 exhibits remarkable activity and selectivity, in comparison to Pt/carbon, Pt@UiO-66, and Pd@UiO-66-NH2. Pt@UiO-66-NH2 also outperforms Pt nanoparticles supported on the external surface of the same MOF (Pt/UiO-66-NH2). To our knowledge, this work demonstrates the first examples of one-pot synthesis of nitrones using recyclable multifunctional heterogeneous catalysts.

The synthesis of N-methyl imines was performed in the presence of catalytic amounts of poly(4-vinylpyridine) in high yields and rapidly at room temperature by a ball milling process. This new method has some advantages including good yields for relatively unreactive carbonyl compounds and short reaction times as well as being green in terms of avoiding the use of toxic reagents and solvents. The major advantage of this process is that the catalyst can be easily regenerated and reused several times without any significant loss of activity.

A four-electron electrocyclic ring-opening/intermolecular [4+2] cycloaddition of α-hydroxycyclobutenones is reported. The reaction represents the first example for the intermolecular cycloaddition of the extensively studied enol-ketene intermediate, and provides a new synthetic route to multiply substituted δ-lactams in high stereoselectivity.

A low loading of a quinine-derived squaramide efficiently catalyzes the triple-domino Michael/aza-Henry/cyclization reaction between 1,3-dicarbonyl compounds, β-nitroolefins, and aldimines to provide tetrahydropyridines bearing three contiguous stereogeni

Cobalt-catalyzed cyclization of CO, imine, and epoxide has been developed. A convenient catalyst system composed of Co2(CO)8 and LiCl is identified, and the substrate scope has been explored. The reaction provides an efficient method for the synthesis of substituted 1,3-oxazinan-4-ones.

A one-pot solvent-free synthesis of N-methyl imines in good to excellent yields was performed by grinding together aromatic aldehydes and methylamine hydrochloride in the presence of a base. The best yields were achieved when an excess of methylamine hydrochloride and inexpensive sodium hydrogen carbonate was used (usually in a molar ratio ArCHO/CH3NH2· HCl/NaHCO3 = 1:5:5), allowing the reaction to proceed for 1 h (in the case of aromatic aldehydes containing electron-withdrawing substituents) or overnight (in the case of electron-rich aldehydes). After a simple work-up (extraction with diethyl ether) the obtained products were mostly pure enough for spectral characterization. In this way, 31 N-methyl imines were prepared, among which eight were synthesized for the first time. Their structures were elucidated by spectral means (1H- and 13C-NMR, IR, MS) whenever it was possible. In the case of salicylaldehyde and 4-chlorobenzaldehyde, the synthesis of the corresponding imines was also conducted on a gram-scale with a 72% and 84% isolated yield, respectively. The present approach not only provides good to high yields, but also eliminates the disadvantages of the traditional synthesis of N-methyl imines, such as the use of hazardous solvents and more or less expensive catalysts and the necessity of work/handling with an anhydrous gas in pressurized containers.

Novel 4-phenyl tetrahydroisoquinolines that inhibit both dopamine and norepinephrine transporters were designed and prepared. In this Letter, we describe the synthesis, in vitro activity and associated structure-activity relationships of this series. We also report the ex vivo NET occupancy of a representative compound, 41.

A chiral catalyst prepared from N,N′-dioxide and Co(BF 4)2·6H2O was applied in the asymmetric hydride transfer initiated cyclization reaction, giving optically active tetrahydroquinolines in good yields with high enantioselectivities under mild reaction conditions. Meanwhile, in light of the absolute configuration of the product, a possible working model was proposed to explain the origin of the activation and asymmetric induction.

Parallel solution-phase synthesis of combinatorial libraries of dihydroindenoisoquinolines employing a sequential Cu(I)/Pd(0)-catalyzed multicomponent coupling and annulation protocol was realized. The scope and limitations of the protocol with respect to the substitution pattern in the aryl ring of the indene core, as well as the N-substituent have been defined, revealing that the methodology is compatible with a wide-range of aliphatic linear, branched, and ester functionalized N-substituents. Unexpectedly, the formation of regioisomers featuring a 1,2,3-contiguous substitution pattern in the aromatic ring of the indene core was observed. Three distinct combinatorial libraries with a total of 111 of members were synthesized, and 80 highly substituted dihydroindenoisoquinolines structurally related to known medicinal agents including some consisting of mixtures of two regioisomers were made available for biological activity testing.

A novel catalyzed intermolecular heterodehydro-Diels-Alder reaction between push-pull 1,3-dien-5-ynes and aldimines or silylaldimines is reported. The sequence is promoted both by gold(I) or silver(I) catalysts and leads to the diastereo- and regioselective formation of 5,6- dihydropyridin-2-ones.

A 2+3 condensation of a wide assortment of Schiff bases, prepared from aromatic aldehydes and primary amines, with methyl (1-ethoxyethylideneamino) acetate allows convenient access to an extensive family of substituted 4-arylideneimidazolin-5-one analogues of the green fluorescent protein (GFP) chromophore. Georg Thieme Verlag Stuttgart · New York.

(Figure Presented) Chromophores related to fluorescent proteins, when sequestered into the "octaacid" capsule, recover their fluorescence. The fluorescence recovery is related to the inhibition of torsional motions within the cavity, implicating the single-bond torsion as an important contributor to internal conversion within this important class of chromophores.

A novel class of α7 nicotinic acetylcholine receptor (nAChR) agonists has been discovered through high-throughput screening. The cis γ-lactam scaffold has been optimized to reveal highly potent and selective α7 nAChR agonists with in vitro activity and selectivity and with good brain penetration in mice.

Monocyte infiltration is implicated in a variety of diseases including multiple myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1 (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage inflammatory protein 1a (MIP-1a) and regulated on normal T-cell expressed and secreted (RANTES), mediates monocyte trafficking to sites of inflammation. High throughput screening of our combinatorial collection identified a novel, moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of monocytes with an IC50 of 20 nM. In addition, the compound was highly selective over other chemokine receptors. It had good microsomal stability when incubated with rat and human liver microsomes and showed no significant cytochrome P450 (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed good oral bioavailability.

A preparative procedure for the synthesis of 2-alkyl-1-aryl-1,2- dihydrochromeno[2,3-c]pyrrole-3,9-diones from methyl 4-(o-hydroxyphenyl)-2,4- dioxobutanoate, aromatic aldehyde, and aliphatic amine is described.

Neat non-volatile amines react with various aromatic aldehydes in the absence of any catalyst, solid support, or solvent, to give imines after a reaction time of eight minutes under microwave irradiation by a clean and very efficient process (yields: 75-100%). In the case of volatile amine, methylamine, 1,3-dimethylurea dispersed on montmorillonite K10 is used as an amine precursor to prepare the corresponding imines. Georg Thieme Verlag Stuttgart.

Cyclohexanone monooxygenase from Acinetobacter calcoaceticus catalyzed the oxidation of tertiary and secondary amines to N-oxides and nitrones, respectively. The formation of a hydroxylamine intermediate was involved with secondary amines as starting substrates.

(Matrix presented) A new method of synthesis of 3-amino-1-alkenylphosphonates is described. It involves the addition of imines to the alkynylphosphonate titanium(II) complexes 2, which are prepared in situ from 1-alkynylphosphonates and Ti(O-i-Pr)4/2 equiv of i-PrMgCl. Compounds 4a-i were obtained regio- and stereoselectivily in high yields.

N-Methylbenzylamines react with bromine in acetonitrile to form N-benzylidenemethylamines.Under similar conditions 2-benzylaminoethanols and 3-benzylaminopropan-1-ols afford 3-benzyl-2-phenyl-1,3-oxazolidines and 3-benzyl-2-phenyl-1,3-oxazinanes, respectively. 2-Benzylidineaminoethanols and 3-benzylideneaminopropan-1-ols likewise give 2-aryl-4,5-dihydro-1,3-oxazoles and 2-aryl-5,6-dihydro-4H-1,3-oxazines, respectively.When N-benzylidenemethylamine is treated with bromine in the presence of alcohols, benzaldehyde acetals are obtained.

Elimination reactions of N-(arylsulfonoxy)-N-alkylbenzylamines 1-5 with MeONa-MeOH have been studied kinetically. The elimination reactions are regiospecific, producing only corresponding benzylidenalkylamines. The rate equation for the reactions is kobs = k0 + k2[MeONa], indicating that the reactions proceed by competing solvolytic- and base-promoted pathways. The relative rates of elimination for the k2 and k0 pathways are 1, 0.67, 0.53, 0.35, and 0.27 for R = Me, Et, i-Pr, s-Bu, and t-Bu and 1, 4.1, 5.1, and 8.7 for R = Et, i-Pr, s-Bu, and t-Bu, respectively. For MeONa-promoted elimination from 1-5, Hammett ρ and kH/kD decrease but ρ1g and |β1g| increase with a bulkier alkyl substituent. However, the values for the solvolytic eliminations are nearly the same for all substrates and are similar to those for the base-promoted pathway, except for the ρ values, which have opposite signs. From these results, the changes in transition-state structure wrought by variation of N-alkyl substituents are assessed.

A series of imine radical cations has been studied by EPR spectroscopy, generated in low-temperature halogenocarbon matrices by γ-radiolysis.Radicals of the type ArCH=NR.+ tend to be formed in the 2A'state, corresponding to ionisation of the in-plane (mainly the nitrogen lone-pair) a' orbital (I).These are isostructural with the corresponding vinyl radicals and show angular geometries at the radical centres and large couplings (ca. 85 G) to the proton trans to the nominally nitrogen-localised SOMO (I).When R = But, a 12 G long-range coupling is observed to a single proton from the But group, arising via the W-configuration (II).This coupling was found to persist in the CFCl3 matrix up to its melting point (ca. 160 K), but was lost reversibly in the higher melting CCl4 matrix at ca. 200 K. When R = phenyl, the radical centre is rendered linear, because of the partial ?-bonding between the aromatic ring and the nitrogen atom due to delocalisation of the unpaired electron, as shown by a fall in the parallel (14N) coupling with a concomitant increase in the nitrogen 2p/2s ratio, and by the observation of couplings to the ortho and para phenyl protons. For imines derived from benzophenone (Ph2C=NR) the tendency is for ionisation to occur from the ?-orbital (III) which has large spin densities on the para carbon atoms. Benzophenone imine (Ph2C=NH), in addition to forming the ?-state (III), was found to deprotonate, giving rise to the Ph2C=N. radical.Similar behaviour was shown by benzophenone oxime, which gave only the corresponding iminoxyl radical (Ph2C=N-O.), and we propose that this is due to the dissolution of the latter two materials in the form of hydrogen-bonded molecular clusters in the non-polar freon solvent, thus facilitating deprotonation of the primary cations.

Reactions of N-(arylsulfonoxy)-N-benzylmethylamines (1) with MeONa in MeOH have been investigated.The eliminations are quantitative, producing only benzylidenemethylamines.The reactions are first order in substrate and first order in base, and an E2 mechanism is evident.Comparison of the rate data reveals that the arenesulfonates are better leaving groups than halogens in imine-forming elimination.For elimination from 1, ρ = 1.14, kH?kD = 3.6, ρlg = 1.30, and β1g = -0.43 have been calculated.Differences in the transition-sate characters for imine-forming eliminations from ArCH2N(Cl)CH3 and 1 have been intepreted in terms of changes in the leaving-group properties and base strength.

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The preparation of ylides of the general structure RC(=NR')N-N+(CH3)2CH2Ar (14) is described.Thermolysis of 14a (R = CH3, R' = H, Ar = C6H5) gave dimethylamine and 2,4-dimethyl-6-phenyl-s-triazine.Thermolysis of ylides 14b (R = C6H5; R' = CH3, Ar = C6H5) and 14c (R = C6H5, R' = CH3, Ar = p-tolyl) gave dimethylamine, ArCH=NCH3 and 1-methyl-2-Ar-4,6-diphenyl-1,2-dihydro-s-triazines (19a,b).Triazines 19a and 19b were also prepared by condensation of N-methylbenzamidine with benzaldehyde and p-tolualdehyde, respectively.Thermolysis of 14d (R = C6H5, R' = CH2C6H5, Ar = C6H5) gave 1-benzyl-2,4,6-triphenyl-1,2-dihydro-s-triazine (19c) and N-benzylidenebenzylamine.Mechanistic aspects of these reactions are discussed.