cas 3958-60-9, 2-Nitrobenzyl bromide | Articles data

Articles about 3958-60-9Total 56 be found

Article title
Article abstract
Author
Journal number and time
Download

A photo-degradable injectable self-healing hydrogel based on star poly(ethylene glycol)-: B -polypeptide as a potential pharmaceuticals delivery carrier
As one of the most promising biomaterials, injectable self-healing hydrogels have found broad applications in a number of fields such as local drug delivery. However, controlled release of drugs in hydrogels is still difficult to realize up to now. Here, we report a novel photo-degradable injectable self-healing hydrogel based on the hydrophobic interaction of a biocompatible four-arms star polymer, poly(ethylene glycol)-b-poly(γ-o-nitrobenzyl-l-glutamate). The hydrophobic interaction between poly(γ-o-nitrobenzyl-l-glutamate) not only connects poly(ethylene glycol)-b-poly(γ-o-nitrobenzyl-l-glutamate) together with a crosslink but also provides a hydrophobic domain to encapsulate hydrophobic pharmaceuticals such as doxorubicin (DOX). Due to the dynamic character of the hydrophobic interaction, the hydrogel exhibits excellent injectable and self-healing ability. In particular, the photolabile o-nitribenzyl ester group is cleaved under UV irradiation. As a result, the hydrophobic domain transforms into the hydrophilic one and the embedded DOX is released effectively. An increasing release ratio of DOX dramatically enhances the apoptosis ratio of HeLa cells. We expect these attractive properties may be beneficial to practical applications of the hydrogel as an effective local drug delivery means in a truly physiological environment.
Zhao, Dinglei,Tang, Quan,Zhou, Qiang,Peng, Kang,Yang, Haiyang,Zhang, Xingyuan
p. 7420 - 7428
(2018)
Read Online

Design, synthesis, biological screening and molecular docking studies of novel multifunctional 1,4-di (aryl/heteroaryl) substituted piperazine derivatives as potential antitubercular and antimicrobial agents
In this paper, two series of novel multifunctional 1, 4-di (aryl/heteroaryl) substituted piperazine derivatives (6a-d & 7a-d) were synthesized, characterized, and evaluated for their antitubercular, antibacterial, and antifungal activities. A step-wise reduction, bromination and substitution reactions on various aldehydes resulted in alcohols (2a–d), bromides (3a–d), and titled novel compounds (6a–d & 7a–d) in moderate to good yields (48–85%). The novel compounds were evaluated for their antitubercular and antimicrobial activities. Compound 7a exhibited promising antitubercular activity (MIC: 0.65 μg/mL) almost equal to the Rifampicin, while the rest of the compounds were moderately active against MTB H37Rv except 6b. Compounds 7a and 6b showed good activity against tested fungal pathogens. Compounds 7a and 7b were proven as the best bacterial agents. Molecular docking studies were in agreement with the in-vitro results. Docking analyses show that all the synthesized molecules bind to the target protein Mtb RNAP (PDB ID: 5UHC) fairly strongly. All the compounds were evaluated for their in vitro cytotoxicity effect using the MTT assay method against human cancer cell line MCF-7. The compounds demonstrated growth inhibitory effect on the cell line with significant IC50 values ranging between 8.20 and 34.45 μM. Most importantly, compound 7a displayed good binding affinity towards the tested protein with binding energy ?7.30 kcal/mol and a stronger hydrogen bond distance of 2.2 ? with ASN-493 residue. Thus, the present research highlighted the potential role of novel piperazine derivatives as potential antitubercular, and antimicrobial candidates and further good research into optimization might result in the development of new antitubercular drug candidates.
Mekonnen Sanka, Bruktawit,Mamo Tadesse, Dereje,Teju Bedada, Endale,Mengesha, Ephriem T.,Babu G., Neelaiah
(2022/01/20)

NovelN-transfer reagent for converting α-amino acid derivatives to α-diazo compounds
A novel universalN-transfer reagent for direct and effective transformation of α-amino ketones, acetamides, and esters to the corresponding α-diazo products under mild basic conditions has been developed. This one-step synthetic approach not only allows for generation of α-substituted-α-diazo carbonyl compounds from α-amino acid derivatives but also permits preparation of α-diazo dipeptides fromN-terminal dipeptides (32 examples, up to 91%).
Lu, Guan-Han,Huang, Tzu-Chia,Hsueh, Hsiao-Chin,Yang, Shin-Cherng,Cho, Ting-Wei,Chou, Ho-Hsuan
supporting information
p. 4839 - 4842
(2021/05/25)

N-transfer reagent and method for preparing the same and its application
Provided are a novel N-transfer reagent and a method for preparing the same and its application. The N-transfer reagent is represented by the following Formula (I): The various novel N-transfer reagents of the present invention can be quickly prepared by employing different nitrobenzene precursors. The N-transfer reagents can directly convert a variety of amino compounds into diazo compounds under mild conditions. Particularly, the N-transfer reagents can facilitate the synthesis of the diazo compounds. The application of synthesizing diazo compounds of the present invention can greatly decrease the difficulty in operation, increase the safety during experiments, reduce the cost of production and the environmental pollution, and enhance the industrial value of diazo compounds.
-
Page/Page column 16-17

(2021/06/25)

Ethylene homo- and copolymerization catalyzed by vanadium, zirconium, and titanium complexes having potentially tridentate Schiff base ligands
New potentially tridentate Schiff base ligands, 2-[({4-[(3-N,N-dimethylamino)propyl] phenyl}imino)methyl]-4,6-di-tert-butylphenol (L1H) and 2-[{2-(N-phenyl-N-methylaminomethyl)-phenylimino}-methyl]-4,6-di-tert-butylophenol (L2H) were prepared and after deprotonation they were reacted with VOCl3 or MCl4 (where M = Zr or Ti) to produce corresponding complexes (L1-V, L2-V, L1-Zr, L2-Ti) with good yields. All new compounds were characterized by the 1H and 13C NMR as well as FTIR spectroscopic methods. Upon activation with Et2AlCl or EtAlCl2, both the vanadium complexes exhibited exceptionally high catalytic activities in the ethylene polymerization (up to 69,000 kg/(molV?h) for L1-V and 101,500 kg/(molV?h) for L2-V) and remarkable thermal stability, and they produced UHMWPE. The complexes of group 4 metals were tested in the ethylene polymerization in conjunction with MMAO and Al(iBu)3/Ph3CB(C6F5)4, and L1-Zr was highly active (11,300 kg/(molZr?h)) and L2-Ti was moderately active (750 kg/(molTi?h)) when activated with MMAO. Furthermore, L1-2-V/EtAlCl2 systems were found to be very efficient in 1-octene incorporation and they produced copolymers with narrow chemical composition distributions and very narrow molecular weight distributions (Mw/Mn ≈ 2). In contrast to them, the catalysts based on titanium and zirconium complexes in conjunction with Al(iBu)3/Ph3CB(C6F5)4 gave copolymers with very broad comonomer and molecular weight distributions as well as with high molecular weights (Mw = 440,000–690,000 g/mol). It was also found that the chain transfer mechanism involved in the copolymerization process in the presence of vanadium and group 4 metal complexes was different.
Bia?ek, Marzena,Fryga, Julia,Hajdasz, Natalia,Matsko, Mikhail A.,Spaleniak, Grzegorz
p. 184 - 194
(2021/07/09)

Thiourea-Mediated Halogenation of Alcohols
The halogenation of alcohols under mild conditions expedited by the presence of substoichiometric amounts of thiourea additives is presented. The amount of thiourea added dictates the pathway of the reaction, which may diverge from the desired halogenation reaction toward oxidation of the alcohol, in the absence of thiourea, or toward starting material recovery when excess thiourea is used. Both bromination and chlorination were highly efficient for primary, secondary, tertiary, and benzyl alcohols and tolerate a broad range of functional groups. Detailed electron paramagnetic resonance (EPR) studies, isotopic labeling, and other control experiments suggest a radical-based mechanism. The fact that the reaction is carried out at ambient conditions, uses ubiquitous and inexpensive reagents, boasts a wide scope, and can be made highly atom economic, makes this new methodology a very appealing option for this archetypical organic reaction.
Mohite, Amar R.,Phatake, Ravindra S.,Dubey, Pooja,Agbaria, Mohamed,Shames, Alexander I.,Lemcoff, N. Gabriel,Reany, Ofer
p. 12901 - 12911
(2020/11/26)

Method for preparing O-nitrobenzyl bromide by micro-channel reactor
The invention discloses a method for preparing o-nitrobenzyl bromide by a micro-channel reactor. According to the preparation method, o-nitrotoluene as a raw material and bromine as a bromine source react through a micro-channel reactor under the initiation of a catalyst to generate o-nitrobenzyl bromide. The method has the advantages of high production efficiency, high purity, simplicity and convenience in operation, safety and the like, and is suitable for industrial production.
-
Paragraph 0030-0051

(2020/06/16)

Preparation method of O-nitrobenzyl bromide
The invention discloses a preparation method of nitrobenzyl bromide. The preparation method comprises the following steps of: step 1, dissolving ortho-nitrotoluene in halohydrocarbon, sequentially adding a hydrogen bromide solution, an initiator and lewis acid, continuing stirring and heating for backflow reaction, and step 2, dropwise adding a hydrogen peroxide solution into a reaction system instep 1 at a speed of 1-2 drops per min, after the backflow reaction for 1-3h, performing natural cooling, stopping stirring, and performing separation to form an organic phase, namely nitrobenzyl bromide. The method takes ortho-nitrotoluene as a raw material and hydrogen bromide as a bromine source; the hydrogen peroxide solution is added as an oxidant; the initiator and lewis acid are added for ortho-nitrotoluene bromination reaction to generate nitrobenzyl bromide; the preparation method is easy and simple to operate and high in yield; and a content of a byproduct, namely o-nitrocyclite is low.
-
Paragraph 0018-0025

(2020/07/31)

Design, synthesis and biological evaluation of novel 3,4-dihydro-2(1H)-quinolinone derivatives as potential chitin synthase inhibitors and antifungal agents
A series of 3,4-dihydro-2(1H)-quinolinone derivatives contained butenediamide fragment were designed and synthesized. Their inhibition potency against chitin synthase and antimicrobial activities were screened in vitro. The enzymatic assays showed that all the synthesized compounds had inhibition potency against chitin synthase at concentration of 300 μg/mL. Compound 2d displayed excellent potency with inhibition percentage (IP) value of 82.3%, while IP value of the control polyoxin B was 87.5%. Compounds 2b, 2e and 2s whose IP values were above 70% showed good inhibition potency against chitin synthase. Moreover, the IC50 value of 2b was comparable with that of polyoxin B (0.09 mM). The Ki of compound 2b was 0.12 mM and the result from Lineweaver-Burk plot showed that 2b was non-competitive inhibitor to bind chitin synthase. The antifungal experiment showed that these compounds had excellent antifungal activity against fungal strains, especially for candida albicans. The antifungal activities against C .albicans of compounds 2b, 2d, 2e and 2l were comparable with that of fluconazole and were superior to that of polyoxin B. Meanwhile, the other compounds against C. albicans showed better antifungal activity (MIC 2 μg/mL) than polyoxin B except for compound 2n (MIC 4 μg/mL). The trial of drug combination use showed that these synthesized compounds had synergistic effects with fluconazole and polyoxin B. It indicated that these compounds were not competing with polyoxin B to bind with chitin synthase, which was also consistence with the result of enzymatic assays. The antibacterial experiment showed that these compounds had no activity against selected strains including three Gram-positive and three Gram-negative bacteria. These results showed that the designed compounds were chitin synthase inhibitors and had selective antifungal activity.
Ji, Qinggang,Li, Baihui,Shen, Yangli,Wu, Hu,Wu, Xiaobo,Yuan, Lvjiang
supporting information

(2020/04/15)

Preparation method of O-nitryl phenmethyl bromine (by machine translation)
The invention discloses a O-nitryl phenmethyl bromine of the preparation method, the preparation method is to O-nitro-toluene as the raw materials, to NaClO/HBr as the brominating agent, in the azo azobisisobutyronitrile as initiator of the initiation action through the brominating reaction to obtain O-nitryl phenmethyl bromine. Preparation method of this invention, to the O-nitryl phenmethyl bromine as a brominating NaClO/HBr, raw materials are easy, and the cost is low, and the process is simple, the operation is simple, mild reaction conditions, the higher selectivity of the reaction, the reaction yield>72% (in order to O-nitro-toluene idea), solid product after the purification processing in the content of the O-nitryl phenmethyl bromine>97%, suitable for industrialization to popularize. (by machine translation)
-
Paragraph 0028-0075; 0078

(2019/03/08)

Preparation method of benzyl bromide compound
The invention relates to a method for producing a benzyl bromide compound (I or II). The method has high reaction yield, high product purity, fewer produced three wastes and good environmental compatibility. The method has remarkable economic benefit, social benefit and environmental benefit. The formula is shown in the description.
-
(2019/02/04)

Preparation method for high-purity pyraclostrobin
The invention relates to the technical field of compound synthesis, in particular to a preparation method for high-purity pyraclostrobin. The pyraclostrobin is synthesized from p-chloroaniline and o-nitrosotoluene as initial raw materials through the steps of diazotizing, cyclizing, oxidizing, bromizing, condensating, reducing, acylating, methylating and the like. According to the preparation method, the problem that the purity of the pyraclostrobin in the prior art is low is solved; and the preparation method for the pyraclostrobin has the advantages of high yield, high purity and high material utilization rate.
-
Paragraph 0022; 0049; 0065-0066

(2019/04/02)

Preparation method of o-nitrobenzaldehyde
The invention relates to a preparation method of o-nitrobenzaldehyde, and is mainly applied to the field of medicine synthesis. According to the method disclosed by the invention, o-nitrotoluene is taken as a raw material, an initiator is added and subjected to a bromination reaction with liquid bromine in an oil-water two-phase solvent, hydrolyzed by sodium carbonate, and oxidized by dilute nitric acid to obtain crude o-nitrobenzaldehyde, and finally purification and discoloration are performed to obtain white o-nitrobenzaldehyde with the purity is 99.9%.
-
Paragraph 0008; 0010-0012

(2019/10/23)

Reversible modification of DNA by methyltransferase-catalyzed transfer and light-triggered removal of photo-caging groups
Methyltransferases are powerful tools for site-specific transfer of non-natural functional groups from synthetic analogs of their cosubstrate S-adenosyl-l-methionine (AdoMet). We present a new class of AdoMet analogs containing photo-caging (PC) groups in their side chain, enzymatic transfer of PC groups by a promiscuous DNA MTase as well as light-triggered removal from the target DNA. This strategy provides a new avenue to reversibly modulate the functionality of DNA at MTase target sites.
Anh?user, Lea,Muttach, Fabian,Rentmeister, Andrea
supporting information
p. 449 - 451
(2018/01/19)

Novel nitrobenzyl bromide synthesis process
The invention relates to a novel nitrobenzyl bromide synthesis process which comprises the following steps: in the presence of 40% hydrobromic acid, 30% hydrogen peroxide and an initiator, namely azodiisobutyronitrile, by taking ortho-nitrotoluene as a raw material, performing a free radical bromination reaction, thereby synthesizing the nitrobenzyl bromide. The 30% hydrogen peroxide is adopted asan oxidant in the process, bromine is provided by oxidizing the hydrobromic acid, the testing conditions are strictly regulated and controlled, then the free radical bromination reaction of the ortho-nitrotoluene has selectivity, the synthesis procedures are controllable, no dibromo-byproduct is generated, meanwhile the yield is far greater than that of the prior art, the production cost is low,the environment is protected, and the process is an ideal method applicable to large-scale industrial production at present.
-
Paragraph 0008; 0028; 0029

(2018/03/23)

Preparation method of 2-nitrobenzyl bromide
The invention discloses a preparation method of 2-nitrobenzyl bromide, and belongs to the technical field of chemical synthesis. According to the method, o-nitrotoluene, hydrobromic acid and hydrogenperoxide are taken as raw materials, under the initiation of catalysts, the 2-nitrobenzyl bromide is generated by conducting substitution reaction through a micro-channel reactor constantly; the 2-nitrobenzyl bromide is prepared through the micro-channel reactor, the operation is simple, the procedures are simple and the reaction time is greatly shortened.
-
Page/Page column 0038-0058

(2018/09/13)

Method used for preparing o-nitrobenzyl bromide
The invention discloses a novel preparation method of o-nitrobenzyl bromide. According to the preparation method, ortho-nitrotoluene is taken as a raw material, azodiisobutyronitrile is taken as a catalyst, at 20 to 100 DEG C, a bromination reagent is adopted for bromination to prepare the target product. Compared with the prior art, the preparation method possesses following advantages: 1, yieldis increased obviously from about 60% to about 90%; 2, the bromination reagent can be recycled, and bromine element utilization rate is relatively high, is 90% or higher; 3, reactants can be subjectedto direct mixing reaction, so that operation complexity is reduced; and 4, reaction conditions are convenient to control, the post-treatment is simple, less three waste is generated, and the industrial using value is relatively high.
-
Paragraph 0022; 0023; 0024; 0025; 0026; 0027

(2018/07/10)

Visible-Light-Driven Oxidative Mono- and Dibromination of Benzylic sp 3 C-H Bonds with Potassium Bromide/Oxone at Room Temperature
Benzylic sp 3 C-H bonds have been successfully brominated with potassium bromide by using Oxone as an oxidant in water/dichloromethane under visible light at room temperature. Toluene, ethylbenzene and other alkylbenzenes bearing an electron-withdrawing group, such as Br, Cl, COMe, CO 2 Et, CO 2 H, CN or NO 2, provide the corresponding benzylic monobromides in good to excellent yields in this reaction. Dibromides can also be produced in the presence of excess potassium bromide in a prolonged reaction time. Control of the illuminance of visible light (~500 lux) is crucial to achieving both high yield and high selectivity in these brominations. Mono- and difluorides can be conveniently prepared through nucleophilic substitutions of the benzylic bromides with potassium fluoride.
Zhao, Mengdi,Li, Meiqi,Lu, Wenjun
supporting information
p. 4933 - 4939
(2018/12/14)

Preparation method of benzyl halide and process for preparing pyraclostrobin
The invention relates to the field of pharmaceutical synthesis, in particular to a preparation method of benzyl halide and a technique for preparing pyraclostrobin. The preparation method of benzyl halide comprises the following steps: reaction taking place according to the synthetic route in the following formula (the formula is shown in the formula), wherein R is selected from any one of nitro,hydroxyl, amino or alkoxy, X is halogen; LED lamp is adopted for lighting. The operation process is simple, the technique process is environment-friendly, the cost is low, the impurities generated inthe synthesis process are less, and the requirements of green chemistry can be met.
-
Paragraph 0032-0052

(2018/10/11)

Not purification directly making 2 - {(N - 4 - chlorophenyl) -3 - [...] methyl} nitrobenzene
Without purification directly making 2 - {(N - 4 - chlorophenyl) - 3 - methyl pyrazole oxygen radical} nitrobenzene method, steps of the method are: in the reactor of the 1 - (4 - chlorophenyl) - 3 - after the end of the reaction the pyrazole is mellow, will be made before O-nitryl phenmethyl bromine a batch of all input to the 1 - (4 - chlorophenyl) - 3 - in the pyrazole is mellow solution, adding an amount of the sodium hydroxide solution, adjusting PH=13 above; and then to the reaction kettle is added 4 butyl ammonium bromide catalyst 0.2 kg, raising the temperature to 80 °C -82 °C, thermal insulation 2 hours, still 1 hours, layered, cooling to 0 - 5 °C; congeals the centrifugal separation, inlet dryer drying, to obtain the finished product 2 - {(N - 4 - chlorophenyl) - 3 - [...] methyl} nitrobenzene. This method avoids the acid neutralization, thermal insulation, the drying procedure, save the material repeatedly turnover, shorten the reaction time, the process is simple, easy to operate, the production efficiency is high; without the loss of the material in the production process, high yield; sewage and low emission, and protect the environment.
-
Paragraph 0011

(2018/07/30)

Novel D-amino acid oxidase (DAAO) inhibitor as well as preparation method and application thereof
The invention provides a novel D-amino acid oxidase (DAAO) inhibitor as well as a preparation method and application thereof, and in particular discloses 3-hydroxyl-3,4-dihydroquinazoline-2(1H)-one compounds as shown in a formula A, derivatives of the compounds, a preparation method of the compounds and the derivatives of the compounds, and use of the compounds and the derivatives of the compounds as the DAAO inhibitor. The compounds have good functions of easing pain and blocking tolerance to morphine analgesia, thus having the application value of analgesia, treatment for opium drug tolerance and schizophrenia resistance.
-
Paragraph 0200-0201

(2017/07/18)

Design, synthesis and biological evaluation of dual acetylcholinesterase and phosphodiesterase 5A inhibitors in treatment for Alzheimer's disease
With the recent research advances in molecular biology and technology, multiple credible hypotheses about the progress of Alzheimer's disease (AD) have been proposed; multi-target drugs have emerged as an innovative therapeutic approach for AD. Current clinical therapy for AD patients is mainly palliative treatment targeting acetylcholinesterase (AChE). Inhibition of phosphodiesterase 5A (PDE5A) has recently been validated as a potentially novel therapeutic approach for Alzheimer's disease (AD). In this work, series of new compounds were designed, synthesized and evaluated as dual cholinesterase and PDE5A inhibitor. Biological results revealed that some of these compounds display good biological activities against AChE with IC50 values about 44.67–169.80 nM (donepezil IC50 50.12 nM). Notably, compound 12 presented potent activities against PDE5A with IC50 values about 50 μM (sildenafil IC50 12.59 μM), and some of these compounds showed low cell toxicity to A549 cells in vitro.
Zhou, Li-yun,Zhu, Yao,Jiang, Yu-ren,Zhao, Xiong-jie,Guo, Dong
supporting information
p. 4180 - 4184
(2017/08/23)

2-Indolone derivatives and open-ring derivatives, and synthetic methods and use thereof
The invention discloses 2-indolone derivatives and open-ring derivatives thereof, and synthetic method and a use thereof, belongs to the technical field of medicines, and relates to 2-indolone derivatives with the structure represented by general formula (I), and open-ring derivatives (II) thereof. In the formula (I) and formula (II), X is CO(CH2)n-1 and n is 1 to 10, or X is CO(CH2)n-1NH2 and n is 1 to 10; Y is CO or CH2; and R1, R2, R3, R4, R5, R6, R7 and R8 are different substituent groups. The invention also discloses structures, the synthetic methods and an in-vitro acetylcholinesterase and phosphodiesterase 5 inhibition activity, and can be further developed into new medicines for treating the Alzheimer's disease.
-
Paragraph 0038-0042

(2017/08/31)

Dinuclear Spin-Crossover Complexes Based on Tetradentate and Bridging Cyanocarbanion Ligands
Spin-crossover (SCO) Fe(II) dinuclear complexes of formula [Fe2(tmpa)2(μ2-tcpd)2]·0.8(CH3OH) (1·MeOH) and [Fe2(andmpa)2(μ2-tcpd)2]·2CH3OH (2·MeOH) (tmpa = tris(2-pyridylmethyl)amine, andmpa = bis(2-pyridylmethyl)aminomethyl)aniline, (tcpd)2- = 2-dicyanomethylene-1,1,3,3-tetracyanopropanediide) have been synthesized and characterized by infrared spectroscopy, X-ray diffraction, and magnetic measurements. The crystal structure determinations of the two complexes (1·MeOH and 2·MeOH) and the desolvated complex 1 (from 1·MeOH) revealed a neutral centrosymmetrical dinuclear structure in which the (tcpd)2- cyanocarbanion acts as a double μ2-bridging ligand between two [FeL]2+ (L = tmpa (1), andmpa (2)) units involving two free coordination sites in the cis configuration. Examination of the shortest intermolecular contacts in 1·MeOH and 1 reveals no significant hydrogen bonding between the dinuclear units, while in 2·MeOH these units are held together by significant hydrogen bonds between one of the uncoordinated nitrile groups and the anilate function, giving rise to 1D supramolecular structure. The three dinuclear complexes 1, 2·MeOH, and 2 exhibit SCO behaviors which have been evidenced by the thermal evolutions of the χmT product and by the average values of the six Fe-N distances for 1 and 2·MeOH, that reveal a gradual conversion with transition temperatures (T1/2) at ca. 352 K (1), 196 K (2), and 180 K (2·MeOH). For the solvated 1·MeOH, the sharp SCO transition observed around 365 K was induced by the desolvatation process above 330 K during the magnetic measurements.
Milin, Eric,Bela?d, Sabrina,Patinec, Véronique,Triki, Smail,Chastanet, Guillaume,Marchivie, Mathieu
p. 9038 - 9046
(2016/10/31)

A preparing method of 2-nitrobenzaldehyde
The invention discloses a preparing method of 2-nitrobenzaldehyde. 2-nitrotoluene is adopted as a raw material and is brominated with bromine under catalytic function of azo-bis alkyl nitrile to generate 2-nitrobenzyl bromide and hydrogen bromide. The 2-nitrobenzyl bromide is hydrolyzed under catalytic function of an aqueous carbonate solution to generate 2-nitrobenzyl alcohol. The 2-nitrobenzyl alcohol is oxidized with hydrogen peroxide under catalytic function of sodium hydroxide to generate the objective compound, namely the 2-nitrobenzaldehyde. A hydrogen peroxide oxidation manner is adopted by the method, thus improving cleanliness of industrial preparation reactions, and reducing environment pollution. Oxidation is catalyzed by adopting the inorganic solid alkali catalyst and no metal organic complex catalyst is used, thus improving reaction stability and greatly reducing the cost of industrial preparation. An azo-bis alkyl nitrile solid catalyst in place of a peroxydicarbonate liquid catalyst is adopted to catalyze the bromination, thus improving reaction operation safety of industrial preparation. The method increases the product yield. The yield of the method is increased by about 5% than that of traditional industrial methods at present. The total yield can reach 77% and product purity is higher than 99%.
-
Paragraph 0021; 0030; 0031

(2016/10/31)

Design, synthesis, and pharmacological evaluation of fused β-homophenylalanine derivatives as potent DPP-4 inhibitors
Dipeptidyl peptidase-4 (DPP-4) inhibitors are accepted as a favorable class of agents for the treatment of type 2 diabetes. Herein, a series of fused β-homophenylalanine derivatives as novel DPP-4 inhibitors were designed, synthesized, and evaluated for their inhibitory activities against DPP-4. Most of them displayed excellent DPP-4 inhibitory activities and good selectivity. Among them, 9aa, 18a, and 18m also showed good efficacy in an oral glucose tolerance test (OGTT) in ICR mice. Moreover, when dosed 8 h prior to glucose challenge, 18m showed significantly greater potency than sitagliptin. It thus provides potential candidates for the further development into potent drugs targeting DPP-4.
Jiang, Tao,Zhou, Yuren,Chen, Zhuxi,Sun, Peng,Zhu, Jianming,Zhang, Qiang,Wang, Zhen,Shao, Qiang,Jiang, Xiangrui,Li, Bo,Chen, Kaixian,Jiang, Hualiang,Wang, Heyao,Zhu, Weiliang,Shen, Jingshan
supporting information
p. 602 - 606
(2015/05/27)

Development of a novel class of pyrrolo-[1,2,5]benzothiadiazepine derivatives as potential anti-schistosomal agents
Analogues of pyrrolo-[1,2,5]benzothiadiazepine were prepared and evaluated against Schistosoma japonica. The biological data revealed that most benzothiazepine derivatives show anti-schistosomal activity to some extent, while α-chloronation of the title compound and another bioisosteric derivative pyrrolo-[1,2,5]benzodiazepine displayed the most distinct worm killing activity. This study proved that benzodiazepine may serve as a novel structural skeleton for the development of anti-schistosomal agents.
Chen, Jinglei,Sun, Weizhen,Yang, Jingjing,Sun, Huan,Wang, Zhixia,Dong, Lanlan,Qiao, Chunhua,Xia, Chao-Ming
p. 3785 - 3787
(2013/07/25)

In situ generated Ph3P(OAc)2as a novel reagent for the efficient acetylation of alcohols and thiols at room temperature
Ph3P, Br2, and ammonium acetate are used for the in situ generation of Ph3P(OAc)2, which was characterized by different NMR techniques. The Ph3P(OAc)2generated was used as a novel and efficient reagent for the acetylation of alcohols and thiols in acetonitrile at room temperature under homogeneous conditions. This reaction was also performed under heterogeneous conditions using 1,3,2,4- diazadiphosphetidine as an easily prepared, stable, and heterogeneous P(III) compound.
Iranpoor, Nasser,Firouzabadi, Habib,Elham, Etemadi Davan
p. 1813 - 1816
(2013/04/24)

Synthesis and study of 2-(pyrrolesulfonylmethyl)- N -arylimines: A new class of inhibitors for human glutathione transferase A1-1
Overexpression of human GSTA1-1 in tumor cells is part of MDR mechanisms. We report on the synthesis of 11 pyrrole derivatives as hGSTA1-1 inhibitors starting from 1-methyl-2-[(2-nitrobenzylsulfanyl]-1H-pyrrole. Molecular modeling revealed two locations in the enzyme H binding site: the catalytic primary one accommodating shorter and longer derivatives and the secondary one, where shorter derivatives can occupy. Derivative 9, displaying the highest inhibition and bearing a p-nitroarylimino moiety, and derivative 4, lacking this moiety, were studied kinetically. Derivative 9 binds (Ki(9) = 71 ± 4 μM) at the primary site competitively vs CDNB. Derivative 4 binds (K i(4) = 135 ± 27 μM) at the primary and secondary sites, allowing the binding of a second molecule (4 or CDNB) leading to formation of unreactive and reactive complexes, respectively. The arylmethylsulfonylpyrrole core structure is a new pharmacophore for hGSTA1-1, whereas its derivative 9 may serve as a lead structure.
Koutsoumpli, Georgia E.,Dimaki, Virginia D.,Thireou, Trias N.,Eliopoulos, Elias E.,Labrou, Nikolaos E.,Varvounis, George I.,Clonis, Yannis D.
body text
p. 6802 - 6813
(2012/09/25)

Synthesis of benzyl bromides with hexabromoacetone: An alternative path to drug intermediates
A series of benzyl bromides were efficiently prepared from the corresponding alcohols with Br3CCOCBr3/PPh3 at low temperatures and under neutral conditions. The present protocol was applied to the heterocyclic analogues and to the successful synthesis of the precursor of the antiulcer drug omeprazole, thus furnishing an alternate, mild method for the preparation of these drug intermediates. A significant steric factor was observed throughout both series supporting a SN2 mechanism.
Joseph, Kara M.,Larraza-Sanchez, Isabel
experimental part
p. 13 - 16
(2011/02/25)

HISTONE DEACETYLASE INHIBITORS AND USES THEREOF
The present invention discloses a group of histone deacetylase inhibitors and use thereof. The histone deacetylase inhibitors are useful in the treatment of malignant tumors and the diseases associated with differentiation and proliferation. The histone deacetylase inhibitors are the compounds represented by the following formula or salts thereof
-
Page/Page column 18

(2011/04/25)

Histone deacetylase inhibitors and uses thereof
The present invention discloses a group of histone deacetylase inhibitors and use thereof. The histone deacetylase inhibitors are useful in the treatment of malignant tumors and the diseases associated with differentiation and proliferation. The histone deacetylase inhibitors are the compounds represented by the following formula or salts thereof:
-
Page/Page column 20

(2011/07/06)

Synthetic scope, computational chemistry and mechanism of a base induced 5-endo cyclization of benzyl alkynyl sulfides
We present an experimental and computational study of the reaction of aryl substituted benzyl 1-alkynyl sulfides with potassium alkoxide in acetonitrile, which produces 2-aryl 2,3-dihydrothiophenes in poor to good yields. The cyclization is most efficient with electron withdrawing groups on the aromatic ring. Evidence indicates there is rapid exchange of protons and tautomerism of the alkynyl unit prior to cyclization. Theoretical calculations were also conducted to help rationalize the base induced 5-endo cyclization of benzyl 1-propynyl sulfide (1a). The potential energy surface was calculated for the formation of 2,3-dihydrothiophene in a reaction of benzyl 1-propynyl sulfide (1a) with potassium methoxide. Geometries were optimized with CAM-B3LYP/6-311+G(d,p) in acetonitrile with the CPCM solvent model. It is significant that the benzyl propa-1,2-dien-1-yl sulfane (6) possessed a lower benzylic proton affinity than the benzyl prop-2-yn-1-yl sulfane (8) thus favoring the base induced reaction of the former. From benzyl(propa-1,2-dien-1- yl sulfane (6), 2,3-dihydrothiophene can be formed via a conjugate base that undergoes 5-endo-trig cyclization followed by a protonation step.
Motto, John M.,Castillo, álvaro,Greer, Alexander,Montemayer, Laura K.,Sheepwash, Erin E.,Schwan, Adrian L.
supporting information; experimental part
p. 1002 - 1010
(2011/03/19)

4- [HETEROCYCLYL-METHYL] -8-FLUORO-QUINOLIN-2-ONES USEFUL AS NITRIC OXIDE SYNTHASE INHIBITORS
Novel compounds of formulae (II, III) and pharmaceutical compositions have been found to inhibit inducible NOS synthase wherein: R4, R5, R6 and R7 are independently selected from the group consisting of hydrogen, lower alkyl, and halogen; and, R8 has the structure whrein X1, X2, X3, X4, X5, X6, R9, R13, R14 and n are as described herein.
-
Page/Page column 52-53

(2009/04/25)

Visible-light-promoted Wohl-Ziegler functionalization of organic molecules with N-bromosuccinimide under solvent-free reaction conditions
The visible-light-induced transformation of toluenes with N-bromosuccinimide (NBS) under solvent-free reaction conditions (SFRC) was studied. The reaction took place in spite of the very restricted molecular motion; toluenes could be regioselectively converted to benzyl bromides. Selective radical-chain reactions with NBS were carried out in liquid/liquid and in solid/solid systems; furthermore, reactions could be performed in the presence of air. The radical scavenger TEMPO (=2,2,6,6-tetramethylpiperidin-1- yloxy) completely suppressed the side-chain bromination of toluenes with NBS under SFRC. Electron-withdrawing groups decreased the reactivity of the toluenes, and the Hammett reaction constant ρ+ = -1.7 indicated involvement of polar radical intermediates with electrophilic character.
Jereb, Marjan,Zupan, Marko,Stavber, Stojan
experimental part
p. 555 - 566
(2009/09/06)

Amino acid-based enantiomerically pure 3-substituted 1,4-benzodiazepin-2-ones: A new class of anti-ischemic agents
A series of 3-substituted 1, 4-benzodiazepin-2-ones derived from S and R amino acids were evaluated for their anti-ischemic activity in vitro. Treatment with compounds 7h, 16, 9d, and 17 decreased the apoptotic neuronal number, however increased the neuronal viability. The compounds decreasing apoptosis could protect neurons from the ischemic injury. The difference in the activities of 1,4-benzodiazepin-2-ones derived from S- and R-amino acids is discussed and explained on the basis of molecular modeling studies.
Mishra, Jitendra Kumar,Garg, Puja,Dohare, Preeti,Kumar, Ashutosh,Siddiqi, Mohammad Imran,Ray, Madhur,Panda, Gautam
p. 1326 - 1331
(2007/10/03)

4-Aminophenyldiphenylphosphinite (APDPP), a new heterogeneous and acid scavenger phosphinite - Conversion of alcohols, trimethylsilyl, and tetrahydropyranyl ethers to alkyl halides with halogens or N-halosuccinimides
A new heterogeneous phosphinite, 4-aminophenyldiphenylphosphinite (APDPP), is prepared and used for the efficient conversion of alcohols, trimethylsilyl ethers, and tetrahydropyranyl ethers to their corresponding bromides, iodides, and chlorides in the presence of molecular halogens or N-halosuccinimides. The amino group in this phosphinite acts as an acid scavenger and removes the produced acid. A simple filtration easily removes the phosphinate by-product.
Iranpoor, Nasser,Firouzabadi, Habib,Gholinejad, Mohammad
p. 1006 - 1012
(2007/10/03)

Mechanistic studies of intramolecular CH insertion reaction of arylnitrenes: Isotope effect, configurational purity and radical clock studies
In order to reveal the mechanism of the intramolecular CH insertion of arylnitrenes, three experiments were carried out: measurement of isotope effects, determination of the extent of configurational retention and radical clock studies. Irradiation of the deuterium-substituted azide 4-d in an inert solvent exclusively afforded the indolines 5-h and 5-d, in which the kinetic isotope effect kH/kD on the intramolecular CH insertion of the nitrene was evaluated as 12.6-14.7 at room temperature. A chiral Chromatographic analysis of the indoline 11 obtained from the optically active azide (S)-6 revealed that the enantiomeric purity of the starting azide was almost completely lost during the intramolecular CH insertion of the photolytically generated nitrene (enantiomeric excess 10%). The thermolysis of the azide 7 at 180°C mainly gave a mixture of the cyclopropyl ring-opened products 20-22, together with the intramolecular CH insertion product with an intact cyclopropyl ring 19. On the basis of these observations, we concluded that the intramolecular CH insertion of the nitrene proceeds primarily by the hydrogen abstraction-recombination mechanism. We propose, however, a small contribution of the concerted mechanism to the intramolecular CH insertion, based on the solvent dependence of the isotope effect and the extent of the configurational retention. Copyright
Murata, Shigeru,Tsubone, Yasuhiro,Kawai, Reina,Eguchi, Daisuke,Tomioka, Hideo
p. 9 - 20
(2007/10/03)

Side chain bromination of mono and dimethyl heteroaromatic and aromatic compounds by solid phase N-bromosuccinimide reaction without radical initiator under microwave
A series of side chain mono and dibromo derivatives of mono and dimethyl heteroaromatic and aromatic compounds (1-17) were synthesized by one step solid phase N-bromosuccinimide (NBS) reaction without radical initiator by microwave irradiation. The benzylic mono and dibromo products were exclusively preferred except in the case of 6-methylpyridine amides (8 and 9) where nuclear and also side chain bromination resulted. Naphthyridine systems resulted improved yields. By this method, we also report the synthesis of 2-pivaloylaminopterin-6- carbaldehyde.
Goswami, Shyamaprosad,Dey, Swapan,Jana, Subrata,Adak, Avijit Kumar
p. 916 - 917
(2007/10/03)

De novo design and synthesis of HIV-1 integrase inhibitors
Existing AIDS therapies are out of reach for most HIV-infected people in developing countries and, where available, they are limited by their toxicity and their cost. New anti-HIV agents are needed urgently to combat emerging viral resistance and reduce the side effects associated with currently available drugs. Toward this end, LeapFrog, a de novo drug design program was used to design novel, potent, and selective inhibitors of HIV-1 integrase. The designed compounds were synthesized and tested for in vitro inhibition of HIV-1 integrase. Out of the 25 compounds that were designed, and synthesized, four molecules (compounds 23, 26, 43, and 59) showed moderate to low inhibition of HIV-1 integrase for 3′-processing and 3′- strand transfer activities. Nonetheless, these compounds possess structural features not seen in known HIV-1 integrase inhibitors and thus can serve as excellent leads for further optimization of anti-HIV-1 integrase activity.
Makhija, Mahindra T.,Kasliwal, Rajesh T.,Kulkarni, Vithal M.,Neamati, Nouri
p. 2317 - 2333
(2007/10/03)

The development of a manufacturing route for the GPIIb/IIIa receptor antagonist SB-214857-A. Part 1: Synthesis of the key intermediate 2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid methyl ester, SB-235349
The development of an efficient manufacturing route to 2,3,4,5-tetrahydro-4-methyl-3-Oxo-1H-1,4-benzodiazepine-2-acetic acid methyl ester SB-235349, a key intermediate in the synthesis of lotrafiban is described. The synthesis starts with 2-nitrobenzyl alcohol which is mesylated, reacted with methylamine and then dimethylacetylene dicarboxylate followed by reduction of the nitro group. Treatment of the resultant aniline with acid gives an intermediate quinazoline which rearranges on treatment with base to give a 1,4-benzodiazapine. Reduction of the exocyclic double bond affords SB-235349. The process can be run without isolation of any of the intermediates and has been used to prepare several tons of SB-235349.
Andrews, Ian P.,Atkins, Richard J.,Breen, Gary F.,Carey, John S.,Forth, Michael A.,Morgan, David O.,Shamji, Amin,Share, Andrew C.,Smith, Stephen A. C.,Walsgrove, Timothy C.,Wells, Andrew S.
p. 655 - 662
(2013/09/05)

Nonpeptide agonists and antagonists of vasopressin receptors
The disclosed invention is a composition agonists and/or antagonists of V2, V1a or both receptors, in a host, including animals, and especially humans, using a small molecule or its pharmaceutically acceptable salt or prodrug.
-
(2008/06/13)

Electrosynthesis of dibenzonaphthyridine derivatives from 2,2-(2-nitrobenzyl)-2-substituted-acetonitriles
An indirect electrochemical procedure involving an ex-cell two-phase process is proposed to produce dibenzonaphthyridine derivatives from 2,2-(2-nitrobenzyl)-2-substituted-acetonitriles in dichloromethane. The selective reduction of both nitro groups into amino groups using Cp2Ti+ in aqueous acidic medium avoids a cyclization of hydroxylamine intermediates as observed by direct electrolysis.
Jan, Thierry,Dupas, Béatrice,Floner, Didier,Moinet, Claude
p. 5949 - 5952
(2007/10/03)

Catalytic processes of oxidation by hydrogen peroxide in the presence of Br2 or HBr. Mechanism and synthetic applications
The mechanism and the synthetic applications for the oxidation of alcohols, ethers, and aldehydes by H2O2 catalyzed by Bf2 or Br- in a liquid two-phase system (aqueous and organic) are reported. Aliphatic and benzylic primary alcohols and ethers show an opposite behavior, which has been rationalized on the ground of the different electronic configurations of the intermediate alkyl (π-type) and acyl (σ-type) radicals and their influence on enthalpic and polar effects. A two-phase system is particularly useful also for an efficient benzylic bromination by Br2 or Br-; the substitution of the benzyl bromide by OH, OR, and OCOR regenerates Br-, which can be recycled. The evaluation of the relative reactivities of the involved substrates and intermediates has allowed to develop a variety of simple, facile, convenient, and selective syntheses of alcohols, aldehydes, ketones, esters, and benzyl bromides, which fulfill the conditions for practical applications.
Amati, Alessandro,Dosualdo, Gabriele,Zhao, Lihua,Bravo, Anna,Fontana, Francesca,Minisci, Francesco,Bjorsvik, Hans-Rene
p. 261 - 269
(2013/09/08)

Studies on pyrrolidinones. Synthesis of N-(2-nitrobenzyl)pyroglutamic acid
While methyl N-(4-nitrobenzyl)pyroglutamate can be obtained from methyl-N-trimethylsilylpyroglutamate, the best way to obtain methyl N-(2-nitrobenzyl)pyroglutamate is to react 4-nitro benzyl bromide with the iminoether derived from methyl pyroglutamate.
Rigo, Benoit,Dolaine, Regis,El Ghammarti, Samira,Couturier, Daniel
p. 1063 - 1066
(2007/10/03)

2-(aminobenzyl)-1,2,3,4-tetrahydroisoquinolines: A new class of α2-adrenergic receptor antagonists
A new class of α2-adrenergic receptor antagonists, the 2-(aminobenzyl)-1,2,3,4-tetrahydroisoquinolines 4 and their derivatives, is described. Two synthetic routes are reported. An investigation of the structure-activity relationships including various substitutions of the isoquinoline moiety and the benzyl group is discussed. The affinity and selectivity for both α1- and α2-adrenoceptors was defined by studying the displacement of [3H]-prazosin (α1-sites) and [3H]-yohimbine (α2-sites) from rat brain membranes. The 2-(2-amino-3,4-dimethoxybenzyl)-6-methoxy-1,2,3,4- tetrahydroisoquinoline 4a presented affinity and selectivity close to yohimbine. In functional experiments the α-adrenoceptor blocking properties of 4a have been evaluated on isolated rat aorta and on the twitch responses of the isolated rat vas deferens.
Stambach,Kanmacher,Jung,Schott,Heitz,Stoclet
p. 427 - 432
(2007/10/02)

Substitution Reactions toward 2-Nitrobenzyl Pseudohalides. The Crystal Structure of 2-Nitrobenzyl Tellurocyanate
The reactions between 2-nitrobenzyl pseudohalides, 2-NO2-PhCH2XCN, and pseudohalide ions, NCX- (X = S, Se or Te) have been studied kinetically in acetonitrile at 25.0 deg C.The reactions proceed through nucleophilic attack at the methylene carbon atom, forming exclusively the exchange products.The average nucleophilicity order, NCTe- >> NCSe- > NCS-, and the average leaving group order, NCTe- >/= NCSe- >/= NCS-, lead to a carbon basicity order NCTe- > NCSe- >/= NCS-, which is confirmed with equilibrium studies.A crystal structure determination of 2-nitrobenzyl tellurocyanate at ca. 135 deg C has revealed that the TeCN group is syn-clinal (gauche) to the C(CH2)-C(Ar) bond with a torsion angle of -48.5(5) deg.The TeCC plane forms an angle of 103.4(5) deg with the phenyl ring plane.In this conformation the steric influence of the 2-NO2 group in substitution reactions at the methylene carbon atom will be negligible except for bulky nucleophiles.The tellurium atom forms two fairly strong intermolecular bonds to nitrogen atoms from neighbouring tellurocyanate groups, viz. 2.889(6) Angstroem trans to the cyano group and 3.382(6) Angstroem trans to the methylene group.In the crystalline state the compound may be considered both as a tellurium(II) complex and as an organic pseudohalide.No intermolecular tellurium-oxygen contacts could be observed.
Grung, Knut Eric,Roemming, Christian,Songstad, Jon
p. 518 - 526
(2007/10/02)

Model synthetic studies for the construction of 5H-phenanthro[4,5-bcd]pyran and pyrone systems
-
Majumder,Sarkar
p. 673 - 680
(2007/10/02)

Synthesis of three isotopomers of L-tryptophan via a combination of organic synthesis and biotechnology
In this paper, we report the preparation of three isotopomers of L-tryptophan on a gram scale, specifically labelled with 99percent 15N (position 1) and 99percent 13C (position 2) in the indole ring; for position 3, the incorporation was 90percent 13C.The isotopically enriched indoles were synthesized from H(15)NO3, K(13)CN and (13)CH3CN and then converted, with L-serine, into the corresponding labelled L-tryptophans using genetic manipulated E. coli bacteria, which contain high amounts of the enzyme tryptophan synthetase.The 13C-13C, 13C-1H, 13C-15N and 15N-1H coupling constants of the indoles and the tryptophans were determined from the 1H NMR and 13C NMR spectra.
Berg, E. M. M. van den,Baldew, A. U.,Goede, A. T. J. W. de,Raap, J.,Lugtenburg, J.
p. 73 - 81
(2007/10/02)

TOTAL SYNTHESIS OF ANTITUMOR AGENT AT-125, (αS,5S)-α-AMINO-3-CHLORO-4,5-DIHYDRO-5-ISOXAZOLEACETIC ACID
A short and efficient total synthesis of racemic AT-125 and its racemic threo isomer proceeds via an intramolecular Michael cyclization of a protected α,β-dehydroglutamic acid γ-hydroxamate.Separation of diastereomers and deprotection to racemic AT-125 followed by enzymatic resolution of the N-chloroacetamide with hog-kidney acylase provides the natural αS,5S isomer.
Baldwin, Jack E.,Cha, Jin K.,Kruse, Lawrence I.
p. 5241 - 5260
(2007/10/02)