- The cleavage of heterocyclic compounds in organic synthesis II [1] use of 5-nitroisatine for synthesis of various nitrogenous heterocycles
-
The reactions of 5-nitroisatine were studied with nucleophiles like heterocyclic amines and alkaline hydroxide. With the use of alkaline hydroxide it was converted into 2-amino-5-nitrophenylglyoxylic acid 2, with piperidine, morpholine and carbethoxypiperazine to its amides 4a-4c or by oxidation to 5-nitroanthranilic acid 7. This acid was used for synthesis of 3-hydroxy-6-nitro-2-phenyl-1H-quinolin-4-one 10. Semicarbazone of 5-nitroisatine 11 was converted to 5-(2-amino-5-nitrophenyl)-2,3,4,5-tetrahydro-1,2,4- triazine-3,5-dione 12. Cyclocondensation of this compound to afford 8-nitro-2,3-dihydro-5H-[1,2,4]triazino-[5,6-b]indol-3-one 13 was unsuccessful.
- Hlavac, Jan,Soural, Miroslav,Hradil, Pavel,Frysova, Iveta,Slouka, Jan
-
-
Read Online
- Isoxazole formamido-4 (3H)-quinazolinone derivative as well as synthesis method and application thereof
-
The invention relates to a 6-(isoxazolyl-3-formamido)-4 (3H)-quinazolinone derivative as well as a synthesis method and application thereof, belongs to the technical field of medicines, and relates to a general formula (I) in which R1, R2 and R3 are different substituent groups. The invention discloses structures and synthesis methods of the compounds, inhibitory activity of acetylcholin esterase and inhibitory activity of protein tyrosine phosphatase, and the compounds can be further developed into drugs for treating Alzheimer's disease.
- -
-
-
- Synthesis and Cytotoxicity of Quinazolin-4(3H)-one Based Peptides
-
Abstract: A novel series of quinazolin-4(3H)-one derivatives has been synthesized in high yields using the multicomponent Ugi reaction and characterized by IR, NMR and mass spectral data. The products have been tested for their cytotoxic activity against HeLa cells. Two tested compounds have shown potent activity compared to standard drug Doxorubicin. The in silico docking studies of the compounds against quinone reductase-2 (4ZVM) enzyme have also supported their activity.
- Bhavani, A. K. D.,Kumar, A. Kishore,Ramakrishna, K.,Shankaraiah, P.
-
p. 720 - 724
(2020/07/02)
-
- A green and recyclable ligand-free copper (I) catalysis system for amination of halonitrobenzenes in aqueous ammonia solution
-
The amination of halonitrobenzenes is an important reaction to produce the corresponding nitroanilines. Direct amination of p-chloronitrobenzene (p-CNB) to p-nitroaniline (p-NAN) with aqueous NH3 solution was investigated over various transition metal salts in the absence of ligand, inorganic base and organic solvent. It was found that CuI is the most effective catalyst with respect to p-CNB conversion, p-NAN selectivity (≈ 100%) and the post-reaction separation and recycling. A high p-NAN yield of 97% could be obtained at 200 °C in 6.5 h with molar ratios of NH3/p-CNB and CuI/p-CNB of 21 and 0.1, respectively. A possible reaction mechanism was proposed, in which NH3 was not only a substrate but also a ligand to coordinate with CuI and formed a water-soluble Cu complex, and then it started the catalytic cycle. The influence of reaction variables such as NH3 concentration, CuI concentration, temperature and time on the p-CNB conversion and the p-NAN selectivity was examined. At room temperature the desired product of p-NAN is insoluble in water but the Cu complex catalyst is water-soluble and so the aqueous phase including the catalyst and NH3 can be easily separated and reused for the subsequent reaction runs. The green and sustainable system is effective for the conversion of diverse halonitrobenzenes to nitroanilines.
- Li, Yan,Shi, Ruhui,Lin, Weiwei,Cheng, Haiyang,Zhang, Chao,Arai, Masahiko,Zhao, Fengyu
-
-
- Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles
-
Molecular hybridization is a powerful strategy in drug discovery. A series of novel diarylbenzopyrimidine (DABP) analogues were developed by the hybridization of FDA-approved drugs etravirine (ETR) and efavirenz (EFV) as potential HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). Substituent modifications resulted in the identification of new DABPs with the combination of the strengths of the two drugs, especially compound 12d, which showed promising activity toward the EFV-resistant K103N mutant. 12d also had a favorable pharmacokinetic (PK) profile with liver microsome clearances of 14.4 μL/min/mg (human) and 33.2 μL/min/mg (rat) and an oral bioavailability of 15.5% in rat. However, its activity against the E138K mutant was still unsatisfactory; E138K is the most prevalent NNRTI resistance-associated mutant in ETR treatment. Further optimizations resulted in a highly potent compound (12z) with no substituents on the phenyl ring and a 2-methyl-6-nitro substitution pattern on the 4-cyanovinyl-2,6-disubstitued phenyl motif. The antiviral activity of this compound was much higher than those of ETR and EFV against the WT, E138K, and K103N variants (EC50 = 3.4, 4.3, and 3.6 nM, respectively), and the cytotoxicity was decreased while the selectivity index (SI) was increased. In particular, this compound exhibited acceptable intrinsic liver microsome stability (human, 34.5 μL/min/mg; rat, 33.2 μL/min/mg) and maintained the good PK profile of its parent compound EFV and showed an oral bioavailability of 16.5% in rat. Molecular docking and structure-activity relationship (SAR) analysis provided further insights into the binding of the DABPs with HIV-1 reverse transcriptase and provided a deeper understanding of the key structural features responsible for their interactions.
- Han, Sheng,Sang, Yali,Wu, Yan,Tao, Yuan,Pannecouque, Christophe,De Clercq, Erik,Zhuang, Chunlin,Chen, Fen-Er
-
-
- Nickel-Catalyzed Regioselective C–H Bond Mono- and Bis-Nitration of Aryloxazolines with tert-Butyl Nitrite as Nitro Source
-
An efficient and regioselective nickel-catalyzed remote C–H nitration of 2-aryloxazoline amides using the non-corrosive tert-butyl nitrite (TBN) as nitro source has been developed. The protocol makes use of inexpensive nickel salts as catalysts and delivers the corresponding products in excellent yields. Notably, bis-nitration products were obtained by simply increasing the amount of tert-butyl nitrite. This reaction proceeds in air and features excellent functional group compatibility, broad substrate scope and is suitable for gram-scale synthesis. (Figure presented.).
- Wan, Li,Qiao, Kai,Yuan, Xin,Zheng, Ming-Wei,Fan, Bing-Bing,Di, Zhe Chen,Zhang, Dong,Fang, Zheng,Guo, Kai
-
p. 2596 - 2604
(2017/08/16)
-
- 6-amino-4(3H)-quinazolinone derivatives and their synthesis method and use
-
The invention discloses 6-amino-4(3H)-quinazolinone derivatives and their synthesis method and use and belongs to the technical field of drug synthesis. The invention also relates to a use of the 6-amino-4(3H)-quinazolinone derivatives with a general formula (I) and its synthesis method in medical science, wherein in the general formula (I), X represents (CH2)n-1, n=1 to 10 and R1, R2 and R3 represent different substituents. The invention discloses the compound structures and their synthesis method and external acetylcholinesterase inhibition activity. The 6-amino-4(3H)-quinazolinone derivatives can be further studied and developed to form novel drugs for treating Alzheimer disease.
- -
-
-
- Copper-catalyzed direct amination of ortho-functionalized haloarenes with sodium azide as the amino source
-
A simple copper-catalyzed direct amination of ortho-functionalized haloarenes (2-halobenzoic acid, 2-halobenzamide, and N-(2-bromophenyl)acetamide derivatives) has been developed with use of NaN3 as the amino source in ethanol, and the corresponding ortho-functionalized aromatic amines were synthesized in good to excellent yields. The protocol undergoes one-pot Ullmann-type coupling of ortho-functionalized haloarenes with NaN3 to lead to ortho-functionalized azidoarenes, followed by reduction with ethanol.
- Zhao, Haibo,Fu, Hua,Qiao, Renzhong
-
experimental part
p. 3311 - 3316
(2010/08/05)
-
- A convenient copper-catalyzed direct animation of nitroarenes with 9-alkylhydroxylamines
-
O-Alkylhydroxylamines, particularly O-methylhydroxylamine, aminate nitroarenes in the presence of a strong base and a copper catalyst to give aminonitroarenes in good yields, ortho- or para-Animation with respect to the nitro group takes place, and in some cases the ortho-aminated product is preferentially obtained. With 3-substituted nitrobenzenes where the substituent has a lone pair of electrons, preferential amination occurs at the 2-position to give the sterically most congested 3c-f, 14 and 22g.
- Seko, Shinzo,Miyake, Kunihito,Kavvamura, Norio
-
p. 1437 - 1444
(2007/10/03)
-
- Nitroarylamines via the Vicarious Nucleophilic Substitution of Hydrogen: Amination, Alkylamination, and Arylamination of Nitroarenes with Sulfenamides
-
A new reaction of sulfenamides with electrophilic arenes under basic conditions is described. The σ adducts formed from nitroarenes and the anions of sulfenamides undergo elimination of thiol to produce the corresponding o- and/or p-nitroanilines. This reaction is analogous to the known alkylation and hydroxylation of nitroarenes via the vicarious nucleophilic substitution of hydrogen (VNS). The reaction gives access to a wide range of substituted nitroanilines, nitronaphthylamines, and aminoheterocycles. By means of the reaction with N-alkyl- and N-arylsulfenamides, it is possible to obtain N-alkylnitroanilines and nitrodiarylamines. By varying the structure of sulfenamide and the reaction conditions, particularly the nature and concentration of the base, it is possible to control the orientation of animation.
- Makosza, Mieczyslaw,Bialecki, Maciej
-
p. 4878 - 4888
(2007/10/03)
-
- Micellar catalysis of organic reactions. Part 37. A comparison of the catalysis of ester and amide hydrolysis by copper-containing micelles
-
The hydrolysis of a number of nitroactivated esters and amides has been studied in the presence of copper-containing metallomicelles at neutral pH. The relative rates of hydrolysis in the pure metallomicelle and in co-micelles with either cetyltrimethylammonium bromide (ctab) or Triton X-100 depends on the hydrophobicity of the substrate and whether it is completely solubilized by the copper micelle. Thus it depends on the concentration of the copper micelle. At low concentrations of copper micelle (0.2 mM) where the substrate is incompletely solubilized, the reaction is faster when 2 mM crab is added. At higher concentrations (>0.6 mM) where the substrate may be almost completely solubilized by the copper micelle, the reaction is slower when 2 mM crab is added. For ester hydrolysis the presence of either a carboxylic acid group or a heterocyclic nitrogen atom close to the reaction centre resulted in much larger catalysis by the metallomicelle than for model compounds without these additional groups. It is postulated that these groups coordinate with the metal ion and thus present the reaction centre close to a metal-bound hydroxyl resulting in a significant increase in the rate of bond formation, which is the rate-determining step for ester hydrolysis. For amide hydrolysis the presence of a carboxyl group ortho to the reaction centre did not lead to larger catalysis by the copper micelle than for the compound without this group. This difference is attributed to the different rate-determining steps for amide and for ester hydrolysis.
- Broxton,Nasser
-
p. 202 - 206
(2007/10/03)
-
- An efficient solid phase synthetic route to 1,3-disubstituted 2,4(1H,3H)-quinazolinediones suitable for combinatorial synthesis
-
Novel, efficient solid phase chemistry has been developed for the synthesis of 1,3-disubstituted quinazolinediones. Anthranilic acids are linked to a chloroformate resin through the nitrogen, amines are coupled to the flee carboxylic acid, and thermal cyclization leads to heterocycle formation and concommitant resin release resulting in traceless linkage.
- Smith, Adrian L.,Thomson, Christopher G.,Leeson, Paul D.
-
p. 1483 - 1486
(2007/10/03)
-
- Micellar catalysis of organic reactions. Part 33. Amide hydrolysis in neutral solution in the presence of a copper-containing micelle
-
The hydrolysis of 5-nitro-2-(trifluoroacetylamino)benzoic acid (1) has been studied at pH 7 in water and in the presence of micelles of cetyltrimethylammonium bromide (ctab) and of copper-containing micelles formed from the reaction of N,N,N'-trimethyl-N'-hexadecylethylenediamine and cupric chloride.It has been found that the hydrolysis of 1 is inhibited by micelles of ctab but strongly catalysed by the copper-containing micelle at this pH.At a higher pH where the hydroxide ion reaction becomes important the reaction is catalysed by micelles of ctab as well, but the catalysis is stronger by the copper-containing micelle.The effect of added sodium chloride on the rate of reaction is shown to be larger for reaction in the presence of ctab than for reaction in the presence of the copper micelles.Also reported are the effects of the buffer concentration on the rate of reaction at various pH for both micelles.It is concluded that the mechanism of reaction in the copper-containing micelle involves a metal-bound hydroxyl rather than a free hydroxide ion loosely associated with the cationic micelle surface.It is interesting that the catalysis of this reaction by the copper-containing micelle is large enough to allow amide hydrolysis at a reasonable rate at neutral pH at ambient temperature.
- Broxton, Trevor J.,Cox, Robin A.
-
p. 670 - 673
(2007/10/02)
-
- Metal ion promoted hydroxide ion and water catalyzed hydrolysis of amides. Effects of the acyl group and the leaving group
-
The hydrolysis of anilide derivatives of N-methyl-4-nitroaniline in H2O is hydroxide ion catalyzed; plots of log kobsd vs pH are linear with slopes of 1.0 at pH > 8. When there is a chelating functional group in the acyl portion of the molecule (1,10-phenanthrolinyl or 6-carboxypicolinoyl) and in the presence of saturating concentrations of Cu2+, Co2+, or Zn2+, hydroxide ion catalyzed reactions are observed at pH > 4 (rate enhancements range from 104- to 105-fold), and pH-independent reactions occur from pH 1 to 4. Rate constants are very nearly the same in the metal ion promoted hydrolysis reactions for the anilides with these acyl groups. Thus, the negatively charged carboxylate ligand of N-(6-carboxypicolinoyl)-N-methyl-4-nitroaniline is equally good in facilitating the metal ion promoted hydrolysis reactions as the neutral ligands of the 1,10-phenanthroline derivative. A trifluoroacetyl acyl group produces the same general effect as a chelated metal ion, i.e., a facile OH--catalyzed reaction and a pH-independent reaction at pH 6 is favorable (kOH' = 1.0 × 104 M-1 s-1 at 50 °C), even though the pKa of the anilide N-H function is 5.5 and the second-order rate constant (kOH') is tnat for attack of OH- on the ionized species. Amide deprotonation does not have a large effect on the rate of hydrolysis; ionization of the amide N-H function of N-(trifluoroacetyl)-2-carboxy-4-nitroaniline produces only a 7-fold decrease in kOH. An N-methyl group accelerates the rate of hydrolysis of the (trifluoroacetyl)-2,4-dinitroanilide. N-(Trifluoroacetyl)-N-methyl-2,4-dinitroaniline hydrolyzes very rapidly at 50 °C, kOH = 5 × 106 M-1 s-1 and k0 = 10-2 s-1. The pH-independent reaction governed by k0 proceeds 2.1-fold more slowly in D2O than in H2O. General base catalysis occurs, and the Bronsted coefficient β is 0.3.
- Fife, Thomas H.,Bembi, Ramesh
-
p. 11358 - 11363
(2007/10/02)
-
- 13C NMR Study of 2-Iodoso- and 2-Iodoxy-benzoic Acids and Their Sodium Salts
-
The 13C NMR spectra for selected 2-iodosobenzoic acids, their sodium salts and the sodium salts of the corresponding iodoxybenzoic acids were measured and carbon assignments made using 2D and NOE experiments and relaxation times.Iodoso and iodoxy groups deshielded the ipso-carbon in these compounds by approximately 25 and 55 ppm, repectively, relative to the corresponding iodo compounds.The 13C NMR spectrs of the 2-iodosobenzoate anions were almost identical with those of the corresponding free acids, both possessing cyclic structures.The iodoxybenzoic acids are either insoluble in, or oxidize, suitable NMR solvents (i.e.DMSO-d6, DMF-d7).The cyclic structure postulated for iodoxybenzoate anions is supported by their 13C chemical shifts.----Key words 13C NMR 2-Iodosobenzoic acids 2-Iodoxybenzoic acids Sodium 2-iodosobenzoates Sodium 2-iodoxybenzoates
- Katritzky, Alan R.,Duell, Bradley L.,Gallos, John K.
-
p. 1007 - 1011
(2007/10/02)
-
- Bisazo brown reactive dye
-
A brown reactive dye represented by a free acid of the formula, STR1 wherein R is a hydrogen atom or a C1 to C4 alkyl group, X is --SO2 CH2 CH2 Cl, --SO2 CH=CH2, --SO2 CH2 CH2 OSO3 H or --SO2 CH2 CH2 OPO3 H2, rings A, B and C are each a benzene or naphthalene ring which may have other substituent, m is 0 to 3 and n is 0 to 1. This dye is suitable for dyeing cellulose fibers brown to afford dyeings superior in fastnesses, acid stability, build-up property and level dyeing property.
- -
-
-
- Direct Amination of Nitrobenzenes by Vicarious Nucleophilic Substitution
-
4-Amino-1,2,4-triazole reacts at 25 deg C with nitrobenzene and some substituted nitrobenzenes in the presence of potassium tert-butoxide in Me2SO to give 4-nitroanilines in good yields.The reaction represents an extension of Makosza's vicarious substitution to a convenient nitrogen nucleophile.
- Katritzky, Alan R.,Laurenzo, Kathleen S.
-
p. 5039 - 5040
(2007/10/02)
-
- Intramolecular Catalysis of Organic Reactions. III. Hydrolysis of 5-nitro-2-(trifluoroacetylamino)benzoic Acid
-
The hydrolysis of 5-nitro-2-(trifluoroacetylamino)benzoic acid (2) has been studied over the pH range 0-12.In acidic solution (pH 0-3.5), the hydrolysis occurs with intramolecular general acid catalysis by the adjacent CO2H group.Between pH 3.5 and 8, a plateau is observed in the pH-rate profile, and this is interpreted as acid catalysis by a water molecule of the breakdown of the tetrahedral intermediate formed between (2) and another water molecule.In alkaline solution (pH above 8), hydrolysis occurs with general acid-catalysed C-N bond breaking.Catalysis by phosphate and borate buffers was observed in the pH range 6-10.Phthalate buffers did not catalyse the reaction.For phosphate and borate buffers, plots of buffer concentration against rate showed a saturation phenomenon which was interpreted as indicating a change from rate-limiting decomposition of the tetrahedral intermediate to rate-limiting formation of the tetrahedral intermediate as the buffer concentration was increased.The pKa of the acid group was found to be about 2.5 as expected, but the pKa of the NH group is 10.4, higher than expected.The reduced acidity of the NH group is attributed to electrostatic effects of the adjacent ionized carboxy group.Unlike for aspirin, intramolecular catalysis by the ionized carboxy group was not observed, a result, perhaps, of intramolecular hydrogen bonding between the carboxylate ion and the adjacent NH group.Such an interaction would be geometrically unfavourable for either intramolecular general base or nucleophilic participation by the carboxylate ion.
- Broxton, Trevor J.
-
p. 1885 - 1893
(2007/10/02)
-
- Azo dyestuffs
-
Azo dyestuffs, which in the acid form, are represented by the formula: wherein A is an aromatic radical, M is a 1,4-benzene radical which may be substituted, E is the residue of a coupling component which is free from azo groups, At least one of A and M containing a phosphonic acid group, and the metal complexes of those having a metallisable group are reactive dyes suitable for use in the process of German OLS No. 2324809.
- -
-
-
