cas 4548-45-2, 2-Chloro-5-nitropyridine | Articles data

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Deaminative chlorination of aminoheterocycles
Selective modification of heteroatom-containing aromatic structures is in high demand as it permits rapid evaluation of molecular complexity in advanced intermediates. Inspired by the selectivity of deaminases in nature, herein we present a simple methodology that enables the NH2 groups in aminoheterocycles to be conceived as masked modification handles. With the aid of a simple pyrylium reagent and a cheap chloride source, C(sp2)?NH2 can be converted into C(sp2)?Cl bonds. The method is characterized by its wide functional group tolerance and substrate scope, allowing the modification of >20 different classes of heteroaromatic motifs (five- and six-membered heterocycles), bearing numerous sensitive motifs. The facile conversion of NH2 into Cl in a late-stage fashion enables practitioners to apply Sandmeyer- and Vilsmeier-type transforms without the burden of explosive and unsafe diazonium salts, stoichiometric transition metals or highly oxidizing and unselective chlorinating agents. [Figure not available: see fulltext.]
Cornella, Josep,Faber, Teresa,Gómez-Palomino, Alejandro,Ghiazza, Clément
(2021/12/23)

Preparation method of 2-chloro-5-nitropyridine
The invention provides a preparation method of 2-chloro-5-nitropyridine. The preparation method comprises the following steps: preparing 2-hydroxy-5-nitropyridine by taking 2-nitroacetaldehyde diethylacetal as an initial raw material through two methods; and then carrying out a chlorination reaction on the 2-hydroxy-5-nitropyridine and a chlorination reagent to prepare the 2-chloro-5-nitropyridine. The method has the advantages of cheap and accessible raw materials and low cost, does not use a diazotization hydrolysis reaction, is safe, simple and convenient to operate, does not use mixed acid, is less in wastewater yield and environmentally-friendly, does not use a nitration reaction, is high in reaction selectivity, few in side reactions, simple in post-treatment and high in product yield and product, and is suitable for industrial production.
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(2020/06/17)

Methnaridine is an orally bioavailable, fast-killing and long-acting antimalarial agent that cures Plasmodium infections in mice
Background and Purpose: Malaria is one of the deadliest diseases in the world. Novel chemotherapeutic agents are urgently required to combat the widespread Plasmodium resistance to frontline drugs. Here, we report the discovery of a novel benzonaphthyridine antimalarial, methnaridine, which was identified using a structural optimization strategy. Experimental Approach: An integrated pharmacological approach was used to evaluate the antimalarial profile of methnaridine. The pharmacokinetic properties of methnaridine were investigated along with the associated safety profile. Host immune response patterns were also analysed. Key Results: Methnaridine exhibited potent antimalarial activity against P. falciparum (3D7: IC50 = 0.0066 μM; Dd2: IC50 = 0.0056 μM). In P. berghei-infected mice, oral administration effectively suppressed parasitemia (ED50 = 0.52 mg·kg?1·day?1) and cured the established infection (CD50 = 10.13 mg·kg?1·day?1). These results are equivalent to or better than those of other antimalarial agents in clinical use. Notably, a four-dose oral regimen at a dosage of 25 mg·kg?1 achieved a complete cure of P. berghei infection in mice. Methnaridine exhibited a rapid parasiticidal profile (PCT99 = 36.0 h) and showed no cross-resistance to chloroquine. Pharmacokinetic studies revealed that methnaridine is readily absorbed, long-lasting and slowly cleared. The safety profile of methnaridine is also satisfactory (maximum tolerated dose = 1,125 mg·kg?1). In addition, following methnaridine treatment, infection-induced Th1 immune response was almost fully alleviated in mice. Conclusion and Implications: Methnaridine is an orally bioavailable, fast-acting and long-lasting agent with excellent antimalarial properties. Our study highlights the potential of methnaridine for clinical development as a promising antimalarial candidate.
Wang, Weisi,Yao, Junmin,Chen, Zhuo,Sun, Yiming,Shi, Yuqing,Wei, Yufen,Zhou, Hejun,Yu, Yingfang,Li, Shizhu,Duan, Liping
p. 5569 - 5579
(2020/11/03)

Efficient Phosphorus-Free Chlorination of Hydroxy Aza-Arenes and Their Application in One-Pot Pharmaceutical Synthesis
The chlorination of hydroxy aza-arenes with bis(trichloromethyl) carbonate (BTC) and SOCl2 has been effectively performed by refluxing with 5 wt % 4-dimethylaminopyridine (DMAP) as a catalyst. Various substrates are chlorinated with high yields. The obtained chlorinated aza-arenes can be used directly with simple workup for succedent one-pot synthesis on a large scale.
Wang, Jian,Li, Yan-Hui,Pan, Song-Cheng,Li, Ming-Fang,Du, Wenting,Yin, Hong,Li, Jing-Hua
supporting information
p. 146 - 153
(2020/03/10)

Preparation method of high-yield 2-chloro-5-nitropyridine
The invention relates to a preparation method of high-yield 2-chloro-5-nitropyridine. According to the method, 2-halogenated acrylate serves as an initial raw material and is sequentially condensed with nitromethane and triethyl orthoformate and cyclized with pyridine to obtain 2-hydroxy-5-nitropyridine, and then the 2-chloro-5-nitropyridine is prepared by chlorination. Used raw materials are lowin cost and easy to obtain, operation is simple and convenient, conditions are mild, nitration reaction is omitted, wastewater quantity is small, operation safety is high, product yield and purity arehigh, and the cost is low.
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Paragraph 0052-0057

(2019/04/02)

Preparation method for preparing 2-chloro-5-nitropyridine from dichlorine monoxide
The invention aims at providing a preparation method for preparing 2-chloro-5-nitropyridine from dichlorine monoxide. The problems can be solved for realizing easy production, high yield, low cost andlow pollution of 2-chloro-5-nitropyridine. The preparation method comprises the following steps of uniformly mixing 3-nitropyridine, alkali, chlorate and solvents; performing low-temperature coolingto -15 to -10 DEG C; under the sufficient stirring, dissolving dichlorine monoxide into the solvents; dripping the materials into a reaction mixed solution; maintaining the temperature at -10 DEG C to0 DEG C; completing the dripping in 2 hours; raising the temperature to the room temperature; continuously stirring the materials for 2 hours until 3- nitropyridine completely reacts; pouring reactants into ice water; separating an organic layer; collecting the organic layer; washing the organic layer by hydrochloric acid with the mass concentration being 5 percent; performing water washing once;performing drying by anhydrous magnesium sulfate; performing reduced pressure distillation to remove organic solvents to obtain 2-chloro-5-nitropyridine. The preparation method has the advantages that the raw materials are rich; the preparation method is simple; the cost is low; the production and the preparation are easy; the yield is high; the energy is saved; the environment is protected; theeconomic and social benefits are huge.
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Paragraph 0014; 0017-0024

(2018/11/04)

One-Pot C?H Functionalization of Arenes by Diaryliodonium Salts
A transition-metal-free, mild, and highly regioselective synthesis of nitroarenes from arenes has been developed. The products are obtained in a sequential one-pot reaction by nitration of iodine(III) reagents with two carbon ligands, which are formed in situ from iodine(I). This novel concept has been extended to formation of aryl azides, and constitutes an important step towards catalytic reactions with these hypervalent iodine reagents. An efficient nitration of isolated diaryliodonium salts has also been developed, and the mechanism is proposed to proceed by a [2,2] ligand coupling pathway.
Reitti, Marcus,Villo, Piret,Olofsson, Berit
p. 8928 - 8932
(2016/07/26)

Preparation method for malaridine intermediate 2-methoxy-5-aminopyridine
The invention provides a green environment-friendly preparation method for a malaridine intermediate 2-methoxy-5-aminopyridine. The preparation method comprises the specific method: with 2-aminopyridine as a raw material, nitrating 2-aminopyridine with a mixed acid in the presence of a solvent to obtain 2-amino-5-nitropyridine; and carrying out hydrolysis, chlorination, methoxylation and reduction to obtain the intermediate 2-methoxy-5-aminopyridine. The preparation method has the advantages of simple process, short production cycle, mild reaction conditions, fewer three wastes, high product purity and yield, cheap and easily obtained raw materials, and higher economic property and environmental protection, and is suitable for industrialized production.
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(2016/10/10)

A novel transition metal free [bis-(trifluoroacetoxy)iodo]benzene (PIFA) mediated oxidative ipso nitration of organoboronic acids
A mild, convenient and transition metal free methodology for oxidative ipso nitration of diversely functionalized organoboronic acids, including heteroaryl- and alkylboronic acids, has been developed at ambient temperature using a combination of [bis-(trifluoroacetoxy)]iodobenzene (PIFA) - N-bromosuccinimide (NBS) and sodium nitrite as the nitro source. It is anticipated that the reaction proceeds through in situ generation of NO2 and O-centred organoboronic acid radicals followed by the formation of an O-N bond via combination of the said radicals. Finally transfer of the NO2 group to the aryl moiety occurs through 1,3-aryl migration to provide the nitroarenes.
Chatterjee, Nachiketa,Bhatt, Divya,Goswami, Avijit
supporting information
p. 4828 - 4832
(2015/05/05)

SUBSTITUTED HETEROAROMATIC PYRAZOLE-CONTAINING CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
The invention relates to substituted heteroaromatic pyrazole-containing carboxamide and urea derivatives as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Page/Page column 129

(2013/03/26)

Substituted Heteroaromatic Pyrazole-Containing Carboxamide and Urea Compounds as Vanilloid Receptor Ligands
Substituted heteroaromatic pyrazole-containing carboxamide and urea compounds as vanilloid receptor ligands, pharmaceutical compositions containing these compounds and also to a method of using these compounds for treating and/or inhibiting pain and further diseases and/or disorders.
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Paragraph 0754

(2013/03/26)

Copper-catalyzed conversion of aryl and heteroaryl bromides into the corresponding chlorides
An efficient method for the synthesis of aryl and heteroaryl chlorides is described. The reactions of aryl and heteroaryl bromides with tetramethylammonium chloride proceeded smoothly in the presence of a copper catalyst under mild reaction conditions to produce the corresponding chlorides in satisfactory to excellent yields.
Feng, Xiujuan,Qu, Yiping,Han, Yanlei,Yu, Xiaoqiang,Bao, Ming,Yamamoto, Yoshinori
supporting information
p. 9468 - 9470
(2012/10/29)

Large-scale solvent-free chlorination of hydroxy-pyrimidines,-pyridines,- pyrazines and-amides using equimolar POCl3
Chlorination with equimolar POCl3 can be efficiently achieved not only for hydroxypyrimidines, but also for many other substrates such as 2-hydroxy-pyridines,-quinoxalines, or even-amides. The procedure is solvent-free and involves heating in a sealed reactor at high temperatures using one equivalent of pyridine as base. It is suitable for large scale (multigram) batch preparations.
Wang, Han,Wen, Kun,Wang, Le,Xiang, Ye,Xu, Xiaocheng,Shen, Yongjia,Sun, Zhihua
experimental part
p. 4533 - 4544
(2012/06/30)

Structure-based ligand design of novel bacterial RNA polymerase inhibitors
Bacterial RNA polymerase (RNAP) is essential for transcription and is an antibacterial target for small molecule inhibitors. The binding region of myxopyronin B (MyxB), a bacterial RNAP inhibitor, offers the possibility of new inhibitor design. The molecular design program SPROUT has been used in conjunction with the X-ray cocrystal structure of Thermus thermophilus RNAP with MyxB to design novel inhibitors based on a substituted pyridyl-benzamide scaffold. A series of molecules, with molecular masses 350 Da, have been prepared using a simple synthetic approach. A number of these compounds inhibited Escherichia coli RNAP.
McPhillie, Martin J.,Trowbridge, Rachel,Mariner, Katherine R.,O'Neill, Alex J.,Johnson, A. Peter,Chopra, Ian,Fishwick, Colin W. G.
supporting information; experimental part
p. 729 - 734
(2011/11/30)

Substitution reactions of 5-nitropyridine-2-sulfonic acid. A new pathway to 2,5-disubstituted pyridines
We have investigated reactions of 5-nitropyridine-2-sulfonic acid and its potassium salt in which substitution of the sulfonate group by oxygen, nitrogen and halogen nucleophiles has been attempted. By this approach, 2-methoxy-(95% yield), 2-ethoxy- (97%), 2-isopropoxy- (65%), 2-amino- (92%), 2- butylamino- (76%), 2-diethylamino- (62%), 2-ethylamino- (32%), 2-benzylamino- (77%), 2-(R-1-phenylethylamino)- (71%) and 2-chloro-5-nitropyridine (87%) have been obtained. No reactions were observed with phenols or anilines. With t-BuOH, 2-hydroxy-5-nitropyridine was formed together with 2-methylpropene.
Bakke, Jan M.,Sletvold, Ingrid
p. 2710 - 2715
(2007/10/03)

Synthesis of 2-azastilbene derivatives with intramolecular charge transfer
The condensation reaction of 2-cyanomethyl-5-nitropyridine with aromatic aldehydes has been carried out with the aim of preparing 2-azastilbene derivatives having intramolecular charge transfer. The yield of the condensation products can be increased if the reaction is carried out in the medium used for obtaining the starting 2-cyanomethyl-5-nitropyridine without separating or purifying it. The electronic absorption spectra of the compounds show a charge-transfer band, the energy of which increases and the intensity falls with lowering of the electron-donor properties of the substituent in the 4-position. Introduction of the heteroatom into the acceptor part when changing from the stilbene to the 2-azastilbene system is accompanied by a decrease in the energy and increase in the intensity of the charge-transfer electronic transition.
Kokars,Yanishevskii,Kampars
p. 805 - 809
(2007/10/03)

Substituent Effect on the Chlorination of 2-Alkoxypyridines to give 2-Chloropyridines under Vilsmeier-Haack Conditions
Various substituted 2-alkoxypyridines were converted into the corresponding 2-chloropyridines in 28-91% yields by use of POCl3 and DMF, in which the methyl, halogen, ester and nitro groups displayed an activating effect; in contrast, an amino group exhibited a deactivating effect.
Lai, Long-Li,Lin, Pen-Yuan,Wang, Jy-Shih,Hwu, Jih Ru,Shiao, Min-Jen,Tsay, Shwu-Chen
p. 194 - 195
(2007/10/03)

Oxidative Transformations of Minor Components of Nucleic Acids. An Anomalous Reaction Course of Oxidation of N6,N6-Dialkyladenosines and Related Compounds with m-Chloroperoxybenzoic Acid
Oxidation of N6-methyladenosine (1a) or the corresponding tribenzoate 1b with m-chloroperoxybenzoic acid gave N1-oxides 2a and 2b whereas N6,N6-dimethyladenosine tribenzoate (3a) afforded 2',3',5'-tri-O-benzoylinosine (4a) and N6-methyl-N6-formyl derivative 5.The N6,N6-diethyladenosine 3b and piperidine derivative 3c yielded only 4a, but N6,N6-dibenzyl compound 3d was not oxidized.N,N-Dimethyl-2,4-dinitroaniline (6a) was oxidized with m-chloroperoxybenzoic acid to give N-methyl-N-formyl derivative 7a, N-methyl-2,4-dinitroaniline (8a), N-oxide 10a, and only traces of 2,4-dinitrophenol (9a).By contrast, 2-(dimethylamino)-5-nitropyridine (6b) afforded 5-nitro-2-pyridone (9b) and N-demethylated N1-oxide 11. 2-(Dimethylamino)pyridine (6c) and 2-(methylamino)-5-nitropyridine (8b) gave the respective N2- and N1-oxides 10c and 11.The reaction of 6-chloropurine nucleosides 15a and 15b with N,N-dimethylhydroxylamine gave inosine 4a or 4b accompanied by a smaller amount of 3a or 3e. 2,4-Dinitrofluorobenzene (16) afforded O-(2,4-dinitrophenyl)-N,N-dimethylhydroxylamine (17).Mass spectra of compounds 10a, 10c, and 17 provided evidence for Meisenheimer rearrangement and subsequent cyclic transformation.The N-oxide 10a and hydroxylamino derivative 17 gave 2,4-dinitrophenol (9a), and N2-oxide 10c afforded fragments belonging to 2-pyridone (9c).Compound 17 is thermally stable whereas N-oxide 10a yielded at 100 deg C a mixture of 8a, 8b, 9a, and 17.
Endo, Takeshi,Zemlicka, Jiri
p. 1887 - 1894
(2007/10/02)

Site-Selectivity in the Reaction of 3-Substituted Pyridine 1-Oxides with Phosphoryl Chloride
Site-selectivity in the reaction of 3-substituted pyridine 1-oxide with phosphoryl chloride was investigated.When a strongly electron-withdrawing group (e.g.CN, CONRR', COOR, or NO2) was substituted at the 3-position, the reaction of 3-substituted pyridine 1-oxides with phosphoryl chloride yielded 3-substituted 2-chloropyridines as the main products.Keywords- site-selectivity; 3-substituted pyridine 1-oxide; phosphoryl chloride; 3-substituted 2-chloropyridine; chlorination
Yamanaka, Hiroshi,Araki, Tomio,Sakamoto, Takao
p. 2244 - 2247
(2007/10/02)

Alkaline Hydrolysis of N-Methyl-2,4-dinitroacetanilide and N-Alkyl-N-(5-nitro-2-pyridyl)acetamides
The kinetics of the alkaline hydrolysis of N-methyl-2,4-dinitroacetanilide (2), N-ethyl- (3), and N-methyl-N-(5-nitro-2-pyridyl)acetamide (4) was carried out.The reaction path consists of two stages: the first one is the rate-limiting formation of the first tetrahedral intermediate (monoanionic) and the second one the fast decomposition of the intermediate.The latter fast decomposition of the intermediate (monoanionic) involves two processes: one is the direct decomposition of the intermediate to the products and the other is a proton abstraction of the hydroxyl group of the intermediate by -OH giving the second tetrahedral intermediate (dianionic), followed by its deconposition to the products.For the alkaline hydrolysis of 2-4, the decomposition of the first intermediate occurred predominantly via the latter process.
Kijima, Atsushi,Sekiguchi, Shizen
p. 3597 - 3602
(2007/10/02)

On the Amination of Halogenonitropyridines
Evidence is presented, based on 15N-labeling experiments and 1H NMR spectroscopy, that the conversion of 2-chloro-5-nitropyridine (1) into 2-amino-5-nitropyridine by treatment with potassium amide/liquid ammonia proceeds to about 75percent according to a sequence of reactions involving addition of the amide ion to C-6, ring-opening, and ring-closure N(ANRORC) mechanism>.On the contrary, 2-chloro-3,5-dinitropyridine (11) is nearly quantitatively aminated by liquid ammonia (containing no potassium amide) into 2-amino-3,5-dinitropyridine according to an SN(AE) process, thus no ring-opening being involved.As shown by NMR spectroscopy, the position of addition of liquid ammonia to 11 is temperature dependent.At -60 deg C the addition takes place at C-4, while at -40 deg C the addition at C-6 is strongly favored.Apparently the addition at C-4 is kinetically controlled; the addition at C-6 leads to the thermodynamically more stable adduct.Amination of 11 with liquid ammonia in the presence of potassium permanganate yields mainly 2,6-diamino-3,5-dinitropyridine.
Bie, Dick A. de,Geursten, Bart,Plas, Henk C. van der
p. 484 - 487
(2007/10/02)