1-苯基-3-甲基-2-吡唑啉-5-酮衍生物的合成

合成了1-苯基-3-甲基-2-吡唑啉-5-酮的两种衍生物:具有β-双酮结构的1-苯基-3-甲基-4-甲醛基-2-吡唑啉-5-酮和1-苯基-3-甲基-4-甲醛基-5-氯吡唑,收率分别为87.5%和61.5%,通过IR、1HNMR、MS对产物进行了表征.     

克卓替尼中间体4-(4-碘-1H-吡唑-1-基)哌啶的合成

以4-氯吡啶盐酸盐为起始原料,与1H-吡唑发生芳香亲核取代得到4-(1H-吡唑-1-基)吡啶盐酸盐,在Rh/C-20A的催化下对4-(1H-吡唑-1-基)吡啶盐酸盐中的吡啶环选择性氢化得到4-(1H-吡唑-1-基)哌啶盐酸盐,最后用碘/过氧化氢(I2/H2O2)对4-(1H-吡唑-1-基)哌啶盐酸盐中的吡唑环4-位选择性碘代合成克卓替尼重要中间体4-(4-碘-1H-吡唑-1-基)哌啶,总收率为67.2%。     

1-(3-氯吡啶-2-基)-3-吡唑烷酮-5-羧酸乙酯合成方法的改进

以3-氯-2肼基吡啶和马来酸二乙酯为原料,在适宜催化剂的作用下,合成氯虫苯甲酰胺中间体1-(3-氯吡啶-2-基)-3-吡唑烷酮-5-羧酸乙酯,使其收率提高到70%,降低了最终产品的生产成本,使其在推广上具有更大的优势。     

氯虫酰胺的合成与杀虫活性

以2,3-二氯吡啶和2-甲基-4-氯苯胺为起始原料,经过多步反应得到6-氯-2-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-8-甲基-4H-3,1-苯并嗪-4-酮,再与甲胺反应得到目标产物氯虫酰胺,经核磁验证其结构,生物活性测定结果表明该化合物对鳞翅目害虫如小菜蛾、甜菜夜蛾、稻纵卷叶螟等具有优异的杀虫活性。     

3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酸的合成研究

3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酸是合成新型鱼尼丁受体杀虫剂氯虫酰胺(chlorantraniliprole)的关键中间体.以2,3-二氯吡啶为原料通过肼基取代、马来酸二乙酯环合、对甲基苯磺酰氯酯化、溴化氢溴化、浓硫酸氧化脱氢以及水解6步反应制得3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-...     

TRFIA螯合剂中间体2,6-二（3＇-溴甲基-1＇-吡唑基）-4-溴吡啶的合成、分离与表征

以2,6-二（3-甲基-1-H-吡唑基）-4-溴吡啶为原料,经重氮化、溴化合成了新型时间分辨荧光免疫分析（TR-FIA）双功能螯合剂中间体2,6-二（3＇-溴甲基-1＇-吡唑基）-4-溴吡啶,通过IR、GC-MS1、HNMR和元素分析等对其结构进行了确认,探讨了合成条件及反应机理。同时,通过GC-MS1、HNMR和元素分析等对第一副产物4-溴-2-（3＇-溴甲基-1＇-吡唑基）-6-（3＇-甲基-1＇-吡唑基）吡啶的结构也进行了确认,以其为原料可继续合成目标化合物,大幅提高总产率。     

TRFIA螯合剂中间体2,6-二(3′-溴甲基-1′-吡唑基)-4-溴吡啶的合成、分离与表征

以2,6-二（3-甲基-1-H-吡唑基）-4-溴吡啶为原料,经重氮化、溴化合成了新型时间分辨荧光免疫分析（TR-FIA）双功能螯合剂中间体2,6-二（3＇-溴甲基-1＇-吡唑基）-4-溴吡啶,通过IR、GC-MS1、HNMR和元素分析等对其结构进行了确认,探讨了合成条件及反应机理。同时,通过GC-MS1、HNMR和元素分析等对第一副产物4-溴-2-（3＇-溴甲基-1＇-吡唑基）-6-（3＇-甲基-1＇-吡唑基）吡啶的结构也进行了确认,以其为原料可继续合成目标化合物,大幅提高总产率。     

（叔丁氧基羰基亚氨基吡唑—1—基—甲基）氨基甲酸酯类的制备

(叔丁氧基羰基亚氨基吡唑-1-基-甲基)氨基甲酸酯类如(叔丁氧基羰基亚氨基吡唑-1-基-甲基)-氨基甲酸叔丁基酯、双叔丁氧基羰基-1H-吡唑-1-甲脒(carboxamidine)是重要的胺基保护剂,用于合成复杂胍类化合物,也可用于精氨酸等的制备,特别是用于zanamivir和BCX-1812的制备.     

柠檬黄合成新工艺

以苯肼-4-磺酸和顺丁烯二酸二甲酯为原料,经缩合、水解和空气氧化得到中间体1-(4′-磺酸基苯基)-3-羧基-5-吡唑啉酮,然后与对氨基苯磺酸的重氮盐偶合而得柠檬黄.对合成的1-(4 ′-磺酸基苯基)-3-羧基-5-吡唑啉酮结构进行了表征,对反应机理进行了讨论.产品柠檬黄经检测符合GB 4481.1-2010要求.     

新方法合成溴氰虫酰胺

3-溴-1-(3-氯-2-吡啶基)-4,5-二氢-1H-吡唑-5-甲酸(M-4)与酰卤化试剂反应可同时将吡唑啉环氧化为吡唑环制得3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酰氯中间体(M-5),该酰氯与取代苯胺无缚酸剂存在下制得溴氰虫酰胺。该路线缩短了反应步骤,减少了氧化剂的使用。     

Direct Synthesis of Pyrazoles via reaction of C-ethoxycarbonyl-N-arylnitrilimines with benzalmalononitriles and some α-cyanocinnamic acid derivatives

Reaction of C-ethoxycarbonyl-N-arylnitrilimines ( 2a–d ) with α, β-disubstituted acrylonitriles ( 3a–f ) in refluxing benzene affords the corresponding substituted pyrazoles 5a–f and 6a–c respectively in good yield. However, reaction of 2a–e with 3g gives the 2-pyrazoline derivatives 7a–d . The assigned structures for the products 5–7 were confirmed by their spectra (i.r., ¹H-n.m.r.) and elemental analyses. Also the structures of the pyrazoles 5 were substantiated by comparison with their regioisomeres 8 .     

Ableitung und Diskussion rationeller 1H-NMR-Struktur-parameter für 1,3-bzw. 1,5-disubstituierte Pyrazolderivate

Discussion and Rationalization of ¹H-n.m.r. Parameters for the Structural Assignment of 1,3- or 1,5- Disubstituted Pyrazoles For 44 1,3-disubstituted ( 1 ) or 1,5-disubstituted pyrazoles ( 2 ) with growing polarity μ of solvent the ¹H-chemical shift δ (HC-5) (for 1 ) increases considerably more than δ (HC-3) (for 2 ), and, depending on the 5-substituent, δ (HC-3) often even decreases. This is interpreted in terms of nucleophilic interaction between polar solvent and “pyridine-like” pyrazole-(N-2), in enhancement of the contributions of polar canonical structures, in substituent effects, and in influences of the pyrazole dipole moments μ_r. Resultant dipole moments μ_r of disubstituted pyrazoles with the 3-resp. 5-substituents Me, Cl, NH₂, and OMe, and their projections μ′_r on the H-(C-5)-resp. H-(C-3)- bond axes are calculated. The chloro-pyrazoles 1h, 1i, 2h and 2i , 3-methoxy-, and 5-methoxy-1-benzyl-pyrazole are synthesized unambiguously. is recommended as significant parameter for the structural assignment of 1,3-disubstituted pyrazoles 1 and 1,5-disubstituted pyrazoles 2 .     

Direct Synthesis of 4‐Organylselanylpyrazoles by Copper‐ Catalyzed One‐Pot Cyclocondensation and C?H Bond Selenylation Reactions

We describe herein an efficient protocol to synthesize selanyl‐substituted pyrazoles by cyclocondensation and copper‐catalyzed direct C H bond selenation reactions. The products were obtained in moderate to excellent yields by the one‐pot multicomponent reactions of hydrazines, 1,3‐diketones and diorganyl diselenides, using catalytic amounts of copper bromide and bipyridine. These reactions tolerated a range of substituents in the starting materials and proved to be an efficient methodology for combinatorial synthesis of new selenium‐containing pyrazoles with potential applications in biological studies.

     

4-(1-Methyl-2-sulfamoylvinyl)pyrazoles by Ring Transformation of 1,1-dioxo-2H-1,2-thiazine-4-carbaldehydes with hydrazines

As masked 1,3-dicarbonyl compounds, 1,1-dioxo-2H-1,2-thiazine-4-carbaldehydes ( 2a–e, 7 ) undergo ring transformations with nucleophilic hydrazines to produce 4-[1-methyl-2-(arylsulfamoyl)vinyl]pyrazoles ( 9a–i ). For 9h , an X-ray structural analysis is reported. With less nucleophilic semicarbazide and p-nitrophenylhydrazine the hydrazones ( 11a, b ) were isolated. The carbaldehydes 2a–e , 7 and 8a, b were synthesized by formylation of the 1,1-dioxo-2H-1,2-thiazines 1a–e, 5 and 6a, b with dichloromethyl methyl ether/TiCl₄. In the case of 1a–e mixtures of 4- and 6-carbaldehydes ( 2a–e/3a–e ) were obtained, which, however, could be used for the synthesis of pyrazoles.     

Curcumin‐Derived Pyrazoles and Isoxazoles: Swiss Army Knives or Blunt Tools for Alzheimer's Disease?

Curcumin binds to the amyloid beta peptide (Abeta) and inhibits or modulates amyloid precursor protein (APP) metabolism. Therefore, curcumin-derived isoxazoles and pyrazoles were synthesized to minimize the metal chelation properties of curcumin. The decreased rotational freedom and absence of stereoisomers was predicted to enhance affinity toward Abeta(42) aggregates. Accordingly, replacement of the 1,3-dicarbonyl moiety with isosteric heterocycles turned curcumin analogue isoxazoles and pyrazoles into potent ligands of fibrillar Abeta(42) aggregates. Additionally, several compounds are potent inhibitors of tau protein aggregation and depolymerized tau protein aggregates at low micromolar concentrations.     

Amino-thieno[2,3–c]pyrazole und Amino-thieno[2,3–b]pyrrole

Amino-thieno[2,3–c]pyrazoles and Amino-thieno[2,3–b]pyrroles The synthesis of thieno[2,3–c]pyrazoles and thieno[2,3–b]pyrroles is described. From the dithioliumsalt ( 1 ) and potassium hydroxide the potassium-(2,2-dicyan-1-methylthio-ethen-1-yl)-thiolate ( 2 ) is formed. This reacts with hydrazine hydrate to form the 3-amino-5-thioxo-pyrazol-4-carbonitrile ( 3 ) S-Alkylation with α-chlorocarbonyl compounds yielding ( 6a–c ) leads via Thorpe-Ziegler-cyclization to 3,4-diamino-thieno[2,3–c]pyrazoles ( 9 ) if the position 1 is alkylated ( 8 ). Acetyl acetone yields 2-mercapto-pyrazolo[1,5–a]pyrimidine ( 5 ). After S-alkylation ( 10a–d ) are immediately cyclized to thieno [2′,3′:3,4]pyrazolo[1,5-a]pyrimidine ( 11a–d ). The ketone ( 6a ) can be cyclized to the pyrazolo [5,1–b]thiazole ( 12 ). 3 reacts with oxalyl chloride to form the 2,3-dioxo-6-thioxo-imidazo[1,2-b]pyrazole ( 13 ) of which S-phenacyl derivative ( 14 ) because the NH-proton cannot be cyclized. The 5-amino-3,4-dicyano-pyrrol-2-thiolate ( 16 ) shows the analogous behaviour. The S-alkylation is followed by cyclization, and 3,5-diamino-thieno[2,3–b]pyrroles ( 18a–b ) arise. Reaction of 5-amino-2-alkylthio-pyrrol-3,5-dicarbonitrile ( 17 ) with acetyl acetone provides pyrrolo[1,2-a]pyrimidine ( 20a–c ) which can be cyclized to form thieno[3′,2′:4,6]pyrimidines ( 21a–c ) very easily.     

β-Thiocyanatovinylcarbonylverbindungen. IV. Darstellung und Reaktionen der 2-Thiocyanatomethylen-cycloalkanone-(1)

β-Thiocyanato-Vinylcarbonyl Compounds. IV. Preparation and Reactions of 2-Thiocyanatomethylene-cycloalkanones-(1) 2-Thiocyanatomethylene-cycloalkanones-(1) 2 were obtained from the corresponding 2-chlormethylene-cycloalkanones-(1) 1 . On reaction with substituted phenylhydrazines, the 2,4-dinitrophenylhydrazones 4b, 4c and 4e , 1,2,3-thiadiaziniumperchlorates 5a and 5a ′, and the substituted pyrazoles 7e and 7f , were isolated, respectively. From reaction of 2 with liquid ammonia, the isothiazoles 8a and 8b as well as the bis-(2-acyl-vinyl)-sulfides 9c and 9f were obtained.     

Reaction of Tetracyanoethylene with Arylazoaminopyrazoles via charge-transfer complexation

Arylazoaminopyrazoles ( 1a – d ) reacts with tetracyanoethylene (TCNE) to yield pyrazolo[1,5-a]pyrimidines (9) via charge-transfer (CT) complex formation. The effect of the substituents on the basicity of the pyrazole nucleus as well as the complexation centre in different types of pyrazoles is discussed.     

Über die Ringtransformation am 5-Acetonyl-2-amino-1,3,4-oxadiazol

About Ringtransformation of 5-Acetonyl-2-amino-1,3,4-oxadiazoles Treatment of 1 with hydrazine derivatives gives first of all the 5-acetonyl-2-amino-1,3,4-oxadiazole-hydrazones 2 which can be isolated partially. In the second reaction step ringtransformation to the pyrazoles 3 takes place. Hydroxylamine reacts in the same manner to the 3-methyl-5-semicarbazido-isoxazol 4 . The pyrazoles 3b and 3h can be dehydrogenated to the carboamoylazo-pyrazoles 5a and 5b .     

Adamantyl Arotinoids That Inhibit IκB Kinase α and IκB Kinase β

A series of analogues of the adamantyl arotinoid (AdAr) chalcone MX781 with halogenated benzyloxy substituents at C2′ and heterocyclic derivatives replacing the chalcone group were found to inhibit IκBα kinase α (IKKα) and IκBα kinase β (IKKβ) activities. The growth inhibitory capacity of some analogues against Jurkat T cells as well as prostate carcinoma (PC‐3) and chronic myelogenous leukemia (K562) cells, which contain elevated basal IKK activity, correlates with the induction of apoptosis and increased inhibition of recombinant IKKα and IKKβ in vitro, pointing toward inhibition of IKK/NFκB signaling as the most likely target of the anticancer activities of these AdArs. While the chalcone functional group present in many dietary compounds has been shown to mediate interactions with IKKβ via Michael addition with cysteine residues, AdArs containing a five‐membered heterocyclic ring (isoxazoles and pyrazoles) in place of the chalcone of the parent system are potent inhibitors of IKKs as well, which suggests that other mechanisms for inhibition exist that do not depend on the presence of a reactive α,β‐unsaturated ketone.