Zur Molekülverknüpfung mit Schwefelchloriden. V. Die Reaktion von Dichlorsulfan mit Allyl-phenyl-äthern. Eine Synthese für 3-Chlormethyl-2,3-dihydro-1,4-benzoxathiine durch intramolekulare Sulfenylierung

Molecule Linkage by Sulfur Chlorides. V. The Addition Reaction of Dichlorosulfane with Allyl-phenyl-ethers. A Synthesis for 3-Chloromethyl-2,3-dihydro-benz-1,4-oxathiines via Intramolecular Sulfenylation Intermediates in the reaction of dichlorosulfane (sulfur dichloride) with allylphenyl-ethers are sulfenyl chlorides (1:1 adducts). The sulfenyl chlorides with anti-Markovnikov-structure cyclize at the activated aromatic nucleus via intramolecular sulfenylation to 3-chloromethyl-2,3-dihydro-benz-1,4-oxathiines.     

8种新型7胺-基取代的1,4二-氢-3H-2,3苯-并噁嗪-3甲-酸乙酯衍生物的合成

1,4二-氢-3H-2,3苯-并口恶嗪-3甲-酸乙酯经过硝化、还原和重氮化溴代得到了7溴--1,4二-氢-3H-2,3苯-并口恶嗪-3甲-酸乙酯(C)。以Pd(OAc)2/R(+)B INAP(2,2′-二苯膦-1,1′-联萘)为催化体系,C与苯胺、N-甲基苯胺、对氟苯胺、对乙氧基苯胺、环己胺、吗啡、四氢吡咯及六氢吡啶等8种有机胺类化合物(Am ine1~8),在氮气保护下,以碳酸铯为碱于干燥的甲苯中100℃反应16~24 h,生成了相应的8种新的7胺-基取代的1,4二-氢-3H-2,3苯-并口恶嗪-3甲-酸乙酯类化合物(D1~8),反应收率分别为83%、85%、71%、90%、72%、63%、75%和83%。通过1HNMR、质谱和元素分析对这些化合物的结构进行了表征。     

Zur Molekülverknüpfung mit Schwefelchloriden. IX. Reaktion von Schwefeldichlorid mit N-Allyl-anilinen. Eine Synthese für 2-Chlormethyl-2,3-dihydro-1,4-benzothiazine

Molecule Linkage by Sulfur Chlorides. IX. The Addition Reaction of Sulfur Dichlorides with N-Allyl-anilines. A Synthesis for 2-Chloromethyl-2,3-dihydrobenzo-1,4-thiazines Reactions of different substituted N-allyl-anilines 1 with sulfur dichloride yield 2-chloromethyl-2,3-dihydrobenzo-1,4-thiazines 3a – i . The identification of the products was carried out by mass spectroscopy and ¹H-n.m.r.-spectroscopy. The seven-membered cyclic isomers of the S, N-heterocycles 3 , dihydro-benzo-1,5-thiazepanes 5 were not obtained.     

Cyclisierungsreaktionen β,γ-ungesättigter Kohlensäurederivate. V . Reaktionen β,γ-ungesättigter Carbamidsäureester mit Sulfenylchloriden - Synthese von 3,5,5-trisubstituierten Oxazolidin-2-onen

Cyclization Reactions of β,γ-Unsaturated Derivatives of Carbonic Acid. V. Reactions of β,γ-Unsaturated Carbamic Acid Esters with Sulfenyl Chlorides — Synthesis of 3,5,5-Trisubstituted Oxazolidine-2-ones N,N-Disubstituted β,γ-Unsaturated urethanes 1 have been cyclized to 3,5,5-trisubstituted oxazolidine-2-ones 3 by aromatic sulfenyl chlorides in methylene chloride. The same oxazolidine-2-ones 3 were obtained by reaction of 5-bromomethyloxazolidine-2-ones 8 with thiophenols.     

Cyclisierungsreaktionen β,γ-ungesättigter Kohlensäurederivate. XI [1] Untersuchungen zur Stereochemie der Cyclofunktionalisierung β,γ-ungesättigter Carbamidsäureester

Cyclization Reactions of β,γ-Unsaturated Derivatives of Carbonic Acid. XI. Investigation of Stereochemistry of the Cyclofunctionalization of β,γ-Unsaturated Carbamic Acid Esters N, N-Disubstituted β,γ-unsaturated urethanes 1 have been cyclized to 3,5-disubstituted oxazolidine-2-ones 3 by aromatic sulfenyl chlorides 2 . The stereochemistry of the products and the cyclofunctionalization reaction were investigated.     

Synthesis and derivatization of angular 3-chloro-3-chlorosulfenyl naphtho[1,2-b]pyran(4H)-4-ones with evaluation of antiviral activity

Angular 2,3-dihydronaphtho[1,2-b]pyran(4H)-4-ones 1a,b react with an excess of thionyl chloride to give the α-chlorosulfenyl chlorides 2a,b, which are reduced by iodide ion to give the corresponding 1,3,4-oxadithiino derivatives 3a,b. However, the aducts 4a,b and 5a,b were obtained by reduced 2a,b with iodide ion in the presence of 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene, respectively. Direct oxidation of 2a,b afford 3,3-dichloronaphthopyran-4-ones 6a,b, whilst conversion to the sulfenamides 7a,b prior to oxidation provides 3-chloronaphthopyranones 8a,b. While α-chloro β-oxo sulfenyl chlorides 2a,b undergo straight forward substitution with 1-methylpiperazine and with potassium cyanide to give 9a,b and 10a,b, respectively. Some of the prepared products were selected and tested for their antiviral activity against herpes simplex virus type-1 (HSV-1). Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with test compounds. Compound 5a showed moderate effect against HSV-1.     

Stereospecific synthesis of chiral 2,3-dihydro-1,4-benzodithiine and methyl-2,3-dihydro-1,4-benzodithiine derivatives and their toxic effects on Trypanosoma brucei

Preparation of chiral 2,3-dihydro-1,4-benzodithiine and methyl-2,3-dihydro-1,4-benzodithiine derivatives with known absolute configurations from the easily accessible chiral synthons benzyl 4-O-trifloxy-2,3-anhydro-beta-L-ribopyranoside and benzyl 4-O-trifloxy-2,3-anhydro-alpha-D-ribopyranoside is described. These compounds showed significant in vitro toxicity of the bloodstream form of Trypanosoma brucei with an IC50 of 11 microM. The parasites' energy metabolism and consumption of oxygen were found to be affected during incubation.     

Synthesis of Condensed 4H-Pyrans: The reaction of 1,1-dimethyl-3,5-diketocyclohexane with cinnamonitriles

Cyclohexano-4H-pyrans could be prepared by reaction of 1,1-dimethyl-3,5-diketo-cyclohexane 2 with cinnamonitriles 1 and converted into 2-amino-4-aryl-1,4-dihydro-7,7-dimethyl-5-oxocyclohexanopyridin-3-carbonitrile 7a, b ; 7,7-dimethyl-2,5-dioxo-4-phenyl-1,2,3,4-tetrahydro-cyclohexanopyridin-3-carbonitrile 8 , 5-aryl-1,1-dicyano-2-phenyl-8,8-dimethyl-1,2,3,4,6,7,8,9-octahydro-3-azaacridin-4,6-dione 12a, b and 2-thioxo-4-amino-5-aryl-3-benzoyl-2,3-dihydro-9,9-dimethylcyclohexano-[g]-4H-pyrano[2,3-d]pyrimidin-7-one 14a, b .     

甲磺酸帕珠沙星的合成

研究了甲磺酸帕珠沙星的合成路线及工艺。以左旋氧氟沙星的中间体（S）-9,10-二氟-3-甲基-2,3-二氢-7-氧代-7H-吡啶[1,2,3-de][1,4]苯并噁嗪-6-羧酸乙酯为起始原料,经亲核取代反应、酯水解并选择性脱羧、环合、水解、Hofmann降解、成盐,制得甲磺酸帕珠沙星,总收率49．4％。其化学结构经元素分析、^1H NMR、^13C NMR、MS得以确证。该合成路线及工艺适合工业化大生产。     

Synthesis and anticancer activity of (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purines

A series of eleven 2- and 6-substituted (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purine derivatives was obtained by applying a standard Mitsunobu protocol that led to a six-membered ring contraction from (R,S)-3,4-dihydro-2H-1,5-benzoxathiepin-3-ol via an episulfonium intermediate. The signal approximately delta=151 ppm, which corresponds to the C4' carbon atom, is unequivocal proof of the N9' regioisomer. The potential of the target molecules as anticancer agents is reflected in their activity against the MCF-7 cancer cell line. The most active compounds have IC(50) values of (6.18+/-1.70) and (8.97+/-0.83) microM. The results indicate that the anticancer activity for the most active compounds is correlated with their capacity to induce apoptosis.     

Synthesis and characterization of Cu(I) and Zn(II) complexes with new sulfur-bearing isoxazole- or pyrazole-based ligands

The synthesis of the new ligands 6-(5-methyl-1,2-oxazol-3-yl)-2,3-dihydro-5H-[1,4] dithiino[2,3-c]pyrrole-5,7(6H)-dione (isox′) and 6-(3-methyl-1H-pyrazol-5-yl)-2,3-dihydro-5H-[1,4]dithiino[2,3-c]pyrrole-5,7(6H)-dione (pyraz′) and their coordination chemistry toward Cu(I) and Zn(II), was studied. The ligands and their complexes were characterized using a combination of either multinuclear NMR (¹H and ¹³C{¹H}), HRMS, FTIR or Uv–Vis spectroscopy. The solid state structures of ligand isox′ and complexes [Cu(pyraz′)₂]OTf and [Zn(OOCCF₃)₂(pyraz′)₂] were determined. Interestingly, isox′ presents a yellow luminescence in its free form. Additionally, the ability of isox′ to coordinate as an N–O bidentate ligand or as an N–S bridge between two copper centers, forming a coordination polymer, is studied. The solid state structure of this Cu(I)-isox′ 1D coordination polymer is also reported.     

6-(4-甲基-3-戊烯基)-2,3-环氧基-2,3-二氢萘-1,4-二醌的合成

6-(4-甲基-3-戊烯基)-2,3-环氧基-2,3-二氢萘-1,4-二醌对肿瘤细胞有一定的抑制作用,研究其新的合成方法具有较重要的理论和实践意义。本文以6-(4-甲基-3-戊烯基)萘-1,4-二醌为原料,过氧化氢为氧化剂,通过环氧化反应制备了目标产物6-(4-甲基-3-戊烯基)-2,3-环氧基-2,3-二氢萘-1,4-二醌。采用FT-IR、GC-MS和¹H NMR等手段对产物进行了表征,确定了产物结构。探讨了氧化剂用量、反应时间、溶剂种类和无水碳酸钠用量对反应转化率和得率的影响,得到适宜的工艺条件为:以过氧化氢为氧化剂,n(萘二醌):n(过氧化氢):n(无水碳酸钠)=1:8:0.5,溶剂为乙醇,反应温度为30℃,反应时间为2h。在上述条件下,产物得率为83.9%。     

Synthesis of 2,3-trans-3,4-cis- and 2,3-trans-3,4-trans-2,3,4-triphenyltetrahydrofurans

The synthesis of 2,3-trans-3,4-cis- and 2,3-trans-3,4-trans-2,3,4-triphenyltetrahydrofurans was undertaken because these compounds incorportae the essential structural features of certain 2,3-diphenyl-benzofurans and 1,2,3-triphenylalkanones reported earlier to have marked antifertility activity. The synthesis of the 2 tetrahydrofurans was achieved by the cyclization of corresponding 2,3,4-triphenylbutane-1,4-diols upon heating with dimethyl sulfoxide (DMSO). The butane 1,4-diols were in turn prepared either by direct litium aluminum hydride (LAH) reduction of methyl 3-benzoyl-2,3-diphenylpropionates or by conversion of these propionates to delta-3,4-butryrolactones followed by LAH reduction. The propionates were prepared from the Fiedel-Crafts reaction of 2,3-diphenylsuccinic anhydride with benzene. Tetrahydrofurans were tested for their antiimplantation activity in rats. 2,3-trans-3,4-cis-2,4-diphenyl-3-p -(beta-pyrrolidinoethoxy) phenyltetrahydrofuran oxalate was found to inhibit implantation completely at 50 mg/kg, but was inefective at a lower dose.     

A 3-D silver(I) polymer with 5,6-dihydro-1,4-dithiin-2,3-dicarboxylate ligand,showing an unusual 6-connected (412.63)2(49.66) topology

The in situ reaction of AgClO₄·6H₂O with 5,6-dihydro-1,4-dithiin-2,3-dicarboxylic anhydride in the presence of lithium hydroxide afforded a photoluminescent three-dimensional (3-D) Ag^I coordination polymer, [Ag₂(L)]_∞ (1), which exhibited an unusual trinodal 6-connected (4¹².6³)₂(4⁹.6⁶) topological net (L = 5,6-dihydro-1,4-dithiin-2,3-dicarboxylate). Moreover, the luminescent/thermal properties of 1 have also been briefly investigated.     

Synthesis of Thiazolo(4,5-b)-quinoxalines and related compounds

The reaction of 2,3,7-trichloroquinoxaline ( 1 ) or 2,3-dichloro-7-bromoquinoxaline ( 2 ) with thiourea in DMSO gave 6,6′-dichloro- or 6,6′-dibromodiquinoxalino[2,3-b:2′:3′-e]1,4-dithiien ( 3 or 4 ). However, 1 or 2 reacts with thiourea in ethanol to give ( 3 or 4 ) beside 7-chloro- or 7-bromo-2-imino-2,3-dihydrothiazolo[4,5-b] quinoxaline ( 5 or 6 ) respectively. Interaction of 1 or 2 with acetone thiosemicarbazone gave 7-chloro- or 7-bromo-3-amino-2-imino-2,3-dihydro-thiazolo[4,5-b] quinoxaline hydrochloride ( 13 or 14 ) respectively. Cyclization of 7-chloro- or 7-bromo-3-amino-2-imino-2,3-dihydrothiazolo[4,5-b]quinoxaline ( 15 or 16 ) on treatment with aromatic acid chlorides or isothiocyanates succeeded to give 19—21 or 28 and 29 .     

硝基-3-氧-3，4-二氢-2H-[1，4]苯并噁嗪-6-羧酸的合成

以4-羟基-3-硝基苯甲酸为原料,经酯化、醚化、还原合环、硝化、水解等5步反应,合成了两个未见文献报导的化合物7-硝基-3-氧-3,4-二氢-2H-[1,4]苯并噁嗪-6-羧酸和8-硝基-3-氧-3,4-二氢-2H-[1,4]苯并嗪-6-羧酸,其结构经IR、LC/MS、1HNMR和元素分析确证。     

A novel synthesis of indeno[2',1': 5,6] pyrido[2,3- d ][1,2,4]triazolo[4,3- a ]pyrimidines

Reaction of 5-(4-chlorophenyl)-2-thioxo-2,3-dihydro-1H-indeno[2',1':5,6] pyrido[2,3-d]pyrimidine-4,6-dione with hydrazonoyl chlorides gave 1,2,4-triazolo[4,3-a]pyrimidine derivatives regioselectively in good yields. The structures of the newly synthesized compounds are established on the basis of chemical and spectroscopic evidence as well as their synthesis by alternative methods.     

Reactions of 2-arylhydrazones of 1,2,3-triketones with 1,2-diaminoethane. I. Synthesis and spectral characterization of 6-arylazo-2,3-dihydro-1H-1,4-diazepines and 3,10-diarylazo-4,9-dimethyl-5,8-diaza-3,9-dodecadiene-2,11-diones

Reactions of 3-arylhydrazones of 2,3,4-pentanetrione ( 1a–1e ) and 2-arylhydrazones of 1,3-diphenyl-1,2,3-propanetrione ( 1f–1l ) with 1,2-diaminoethane have been studied. It was found, that 3-arylhydrazones of 2,3,4-pentanetrione react with 1,2-diaminoethane with formation of 6-arylazo-2,3-dihydro-1,4-diazepines ( 2a–2e ) or the diarylazo derivatives of 4,9-dimethyl-5,8-diaza-3,9-dodecadiene-2,11-dione ( 3a–3e ). Analogous reactions of 2-arylhydrazones of 1,3-diphenyl-1,2,3-propanetrione yielded exclusively the derivatives of dihydrodiazepine. The structure of obtained products has been elucidated on the basis of i.r., m.s. and ¹H-n.m.r. spectra.     

甲磺酸帕珠沙星的合成

以左氧氟沙星中间体(S)-9,10-二氟-3-甲基-7-氧代-2,3-二氢-7-H吡啶[1,2,3-de][1,4]苯并噁嗪-6-羧酸乙酯为起始原料,经与氰乙酸乙酯进行亲核取代反应、水解脱羧、环合、水解、Hoffman降解,与甲磺酸成盐得甲磺酸帕珠沙星,总收率为38%,产品纯度符合药用标准。     

6-甲基-4-羟基-噻嗯并[2,3-b]噻喃-2-磺酰胺的合成

以2-巯基噻吩和巴豆酸为起始原料,经加成缩合制得3-(2-噻吩巯基)丁酸;在P2O5催化下环合制得6-甲基-4-氧-噻嗯并[2,3-b]噻喃;再用氯磺酸进行氯磺化、氨水氨解制得6-甲基-4-氧-噻嗯并[2,3-b]噻喃-2-磺酰胺;最后用硼氢化钠还原得到盐酸杜塞酰胺的中间体6-甲基-4-羟基-噻嗯并[2,3-b]噻喃-2-磺酰胺,合成总收率为16.0%。其化学结构经IR,1H NMR,MS得以确证。