- One-pot synthesis method for synthesizing 2-hydroxy-5-nitropyridine
-
The invention discloses a one-pot synthesis method for synthesizing 2-hydroxy-5-nitropyridine. The method comprises the following specific reaction steps: adding 2-aminopyridine into concentrated sulfuric acid in batches, controlling the temperature at 10-20 DEG C, adding concentrated nitric acid, keeping the temperature at 40-50 DEG C, and stirring; after nitration is completed, adding reaction liquid into water for quenching, controlling the temperature to be 0-10 DEG C, dropwise adding a sodium nitrite aqueous solution, and carrying out diazo reaction; adding a proper amount of ammonia water to adjust the acid concentration; and filtering the solution after the acid concentration is adjusted, and drying a filter cake to obtain the product. The invention provides a novel preparation method of 2-hydroxy-5-nitropyridine. The method has the advantages that the post-treatment is simple, isomers are separated by utilizing the concentration of acid, and the isomers generated by nitration reaction do not need to be independently purified, the nitration reaction and the diazotization reaction are continuously operated, and thus the waste water generated in the amplified production is greatly reduced, and the production cost is saved; the preparation method is never reported in literatures, is a brand-new preparation method of the 2-hydroxy-5-nitropyridine, and provides a new synthesis thought for similar compounds of the 2-hydroxy-5-nitropyridine.
- -
-
Paragraph 0027-0031
(2021/05/05)
-
- 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.
- -
-
Paragraph 0073-0074; 0092-0093
(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)
-
- 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.
- -
-
Paragraph 0046; 0047
(2019/04/02)
-
- Synthesis of Amides by Nucleophilic Substitution of Hydrogen in 3-Nitropyridine
-
3-Nitropyridine reacted with nitrogen-centered carboxylic acid amide anions in anhydrous DMSO in the presence of K3Fe(CN)6 via oxidative nucleophilic substitution of hydrogen to give previously unknown N-(5-nitropyridin-2-yl) carboxa
- Amangasieva,Borovlev,Demidov,Avakyan,Borovleva
-
p. 867 - 872
(2018/07/31)
-
- 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.
- -
-
-
- 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)
-
- Catalytic hydrolysis of phosphate esters by metallocomplexes of 1,10-phenanthroline derivatives in micellar solution
-
Divalent metal-ion complexes of 2,9-bis-1,10-phenanthroline (C12Phen-MII) in neutral Brij 35 micelles catalyse the hydrolysis of various phosphate triesters, diesters and monoesters.The catalytic activity of C12Phen-MII has been compared with that of the metal-ion complexes of its water-soluble counterpart 2,9-bis-1,10-phenanthroline (C1Phen-MII).Saturation kinetics provide evidence for preliminary formation of ligand-MII-phosphate ester complexes, which decay to products.The hydroysis of diphenyl 4-nitrophenyl phosphate (1b) coordinated to C12Phen-ZnII proceeds 8700 times faster than the hydrolysis of 1b in the absence of metallocatalyst.Kinetic studies indicate that phosphate triesters containing a metal-ion-binding site in close proximity to the phosphoryl bond, i.e., diphenyl 5-nitro-2-pyridyl phosphate (2b) and diphenyl 5-nitro-8-quinolyl phosphate (3), are hydrolysed by the same mechanism as 1b.
- Weijnen, John G. J.,Engbersen, Johan F. J.
-
p. 351 - 357
(2007/10/02)
-
- Study of the Reaction of Sodium Cumyl Peroxide with Haloaromatic Compounds under PTC Conditions
-
The SNAr reaction of sodium cumyl peroxide with selected haloaromatic compounds under phase transfer catalysis conditions has been studied. Corresponding phenols have been obtained. The mechanism of the reaction has been proposed. Key words: SNAr, nucleophilic aromatic substitution, PTC, phenols, peroxides
- Baj, S.
-
p. 1967 - 1972
(2007/10/02)
-
- 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)
-
- 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)
-
- Reaction of 2-Halo-5-nitropyridines with Hydroxide Ion in Dimethyl Sulfoxide
-
Addition of aqueous base to sulutions of 2-halo-5-nitropyridines in dimethyl sulfoxide produces a stable substance which forms 2-hydroxy-5-nitropyridine if the molar ratio of hydroxide to pyridine is greater than 2:1.IR and 1H and 13C NMR spectra of the intermediate stable substance indicate that the pyridine ring is cleaved to form this material.An SN(ANRORC) mechanism is proposed for the reaction.
- Reinheimer, J. D.,Mayle, L. L.,Dolnikowski, G. G.,Gerig, J. T.
-
p. 3097 - 3100
(2007/10/02)
-
- N-pyridinyl urea and cyclopropanecarboxamide herbicides
-
Compounds of the formula STR1 wherein A is STR2 in which R1 is alkyl and n is 0-1, or STR3 in which R2 is hydrogen, alkyl or halogen; Y is halogen or alkyl; and X is halogen, --NR3 R4 in which R3 and R4 each independently is hydrogen or alkyl; OR5 ; SR5 ; S(O)R5 or S(O)2 R5, in which R5 is alkyl, are useful as herbicides.
- -
-
-
