A Novel Route to Acyl Ureas: Syntheses of N-[5-(2-Chlorophenyl)-2-Furoyl]-N'-Arylthioureas and Ureas

A novel route to acyl ureas is described. Reaction of 5-(2-chlorophenyl)-2-furoyl chloride with ammonium thiocyanate first, then arylamine under phase transfer catalysis gives N-[5-(2-chlorophenyl)-2-furoyl]-N'-arylthioureas (1a-o). Compounds 1a-o on oxidation with potassium iodate respectively under reflux result in the formation of N-[5-(2-chlorophenyl)-2-furoyl]-N'-arylureas (2a-o).     

Synthesis and Transformations of 5-Substituted 2-Furoyl Phosphonates

5-Chloromethyl-2-furoyl chloride when treated with triethyl phosphite has given 5-chloromethyl-2-furoyl phosphonate. This compound has reacted with sodium azide in the presence of potassium iodide to give 5-azidomethyl-2-furoyl phosphonate. Treatment of 5-chloromethyl-2-furoyl phosphonate with secondary amines even under mild conditions has caused cleavage of P–C bond with liberation of diethyl hydrogen phosphite and formation of 5-chloromethyl-2-furancarboxamide. Butanthiol in the presence of potassium carbonate in acetonitrile has converted the chloromethyl group into the butylthiomethyl one and simultaneously split the P–C bond with the formation of the corresponding thioester. Under the action of S-methylthiuronium iodide and triethylamine, 5-chloromethyl-2-furoyl phosphonate has been unexpectedly reduced into the 5-methyl derivative. 5-Butylthiomethyl- and 4-(N-morpholinomethyl)-2-furoul chlorides have been phosphorylated with triethyl phosphite into the corresponding 5-functionalized 2-furoyl phosphonates. The prepared furoyl phosphonates have reacted with resonance-stabilized phosphoranes to give phosphorylated derivatives of 3-(furyl)acrylates and 4-(furyl)but-3-en-2-one with trans-location of phosphoryl and carbonyl groups with respect to the double bond.

     

Diethoxyphosphorylmethylfurans in Curtius reaction

Methyl (diethoxyphosphorylmethyl)furoates are selectively hydrolyzed at the carboxy group with the equimolar amount of potassium hydroxide in ethanol. The carboxylic acids obtained by means of the consecutive treatment with ethyl chloroformate in the presence of triethylamine and sodium azide are converted into furoyl azides. 3-Furoylazides and 5-(diethoxyphosphorylmethyl)-2-furoyl azide while heating to 110°C undergo Curtius rearrangement in the corresponding isocyanates which add methanol to form stable methyl urethanes. 4-(Diethoxyphosphorylmethyl)-5-methyl-2-furoyl azide also forms stable isocyanate, but while treating this substance with methanol the process does not stop on the formation of methyl urethane. Addition of the second methanol molecule takes place, and the subsequent nucleophilic substitution and elimination of ammonia lead to O-[4-(diethoxyphosphorylmethyl)furyl-2](methyl)carbonate. 3-(Diethoxyphosphorylmethyl)-2-furoyl azide forms polymer at 100°C in toluene, but while boiling it in the 1:1 toluene-methanol mixture formation of urethane is observed spectroscopically. The latter compound also undergoes conversion to phosphorylated furyl carbonate. By means of the ¹H and ³¹P NMR spectroscopy the intermediate products formed in the course of transformations described were traced, and on this basis probable mechanisms of addition of methanol to isocyanate and rearrangement of urethane to carbonate were suggested.     

Syntheses in the methyl-2-furylketone series

5-Nitro-2-furylglyoxylic acid is prepared from 5-nitro-2-furacylpyridinium bromide via 4-dimethylaminophenylirnino (5-nitro-2-furoyl) acetonitrile, and also by the action of N -bromosuccinimide on 5-nitro-2-furylglyoxal. The following derivatives are prepared: semicarbazone, thiosemicarbazone, guanylhydrazonef 2, 4-dinitrophenylhydrazone, 4-dimethylaminoanilide and 3- (5-nitro-2-furyl) quinoxalin-2-ol.For Part IX see [1].     

4-(对取代苯基)-2-[2-(取代苯基)呋喃-4-甲酰胺]-1',3',4'-均三唑[1,2-d]-1,3,4-噻二唑类衍生物的合成和生物活性

以1-氨基-5-巯基-2-(对取代苯基)-1,3,4-均三唑和5-取代苯基-2-呋喃甲酰异硫氰酸酯为原料, 合成了10个未见文献报道的含苯环连呋喃的均三唑并噻二唑类衍生物, 通过元素分析, ¹H NMR, IR和MS确定化合物的结构, 初步生物活性测试表明标题化合物具有一定的除草活性.     

膦、胂叶立德的化学与应用26: 含全氟烷基胂叶立德的合成及 水解反应研究

报道溴化α-呋喃甲酰基)甲基三苯基申(1)在无水碳酸钾存在下,以无水二氯甲烷作溶剂,保持0-5℃下与2-全氟炔酸甲酯(2)反应,高产率地得到加合产物4-(α-呋喃甲酰基)-2-三苯基胂基-3-全氟烷基-3-丁烯酸甲酯(3)。加合产物3在V(甲醇):V(水)=9:1溶液中分别于室温、回流和封管120℃三种条件下反应,高产率地得到4-全氟烷基-6-(α-呋喃基)-2-吡喃酮(4)和4-(α-呋喃甲酰基)-3-全氟烷基-3-丁烯酸甲酯(5)。化合物4和5可以通过柱层析分离;化合物5为一对Z,E异构体,它们不能通过柱层析分离,但其比例可以由^1HNMR估算得到。研究还发现硅胶对该反应具有催化作用,提出并讨论了反应机理。     

Furannes et pyrroles disubstitues en 2,3—XV : Synthese de benzo(f)furo(2,3-c)(10H)-oxepinones-4 et leur transformation en furonaphtoquinones

2-Aryloxymethyl 3-furoyl chlorides are cyclised by stannic chloride to give benzo(f)furo(2,3-c)(10H)oxepin-4-ones. These compounds are rearranged through the action of potassium hydroxide into furo[2,3-b]naphthoquinones. The same typical transformations were obtained with 2-(β-naphthyloxymethyl) 3-furoyl chloride.     

Synthesis of Furo[2,3-c]isoquinoline Derivatives

2-Methylfuro [2,3-c] isoquinolin-5(4H)one (X) and 1-phenylfuro[2,3-c] isoquinolin-5(4H)one (XI) were prepared from thermal cyelization via the Curtius rearrangement of 5-methyl-3-phenyl-2-furoyl azide (VI) and 3,4-diphenyl-2-furoyl azide (VII), respectively. Stability against acid, alkylation and conversion of the NHCO group to a C=N double bond of X and XI, which were synthesized, are described. Also, 5-substituted furo[2,3-c] isoquinolines (XVIIIa-c) and (XIXa-c) were prepared.     

The chemistry of heterocycles. IV. 2H-pyrido[4,3-e]-1,3-oxazine-2,4(3H)-dione,its precursors and some 3-substituted derivatives.

The preparation of 2H-pyrido[4, 3-e]-1, 3-oxazine-2, 4(3H)-dione (II) and the anisoyl, benzoyl, 4-chlorobenzoyl, trans-cinnamoyl, 3, 5-dinitrobenzoyl, 2-furoyl, and 2-naphthoyl derivatives substituted at position 3 of II together with their infrared and ultraviolet spectra are described. The 3-substituted 2 and 4-(2-pyridylethyl) and hydroxymethyl derivatives of quinolinimide and cinchomeronimide were also prepared and their spectra recorded.     

N-(5-邻氯苯基-2-呋喃甲酰氨基)丙氨酰胺衍生物的合成和 生物活性测定

以5-邻氯苯基-2-呋喃甲酰氯和丙氨酸为起始原料, 通过非均相法得到N-(5-邻氯苯基-2-呋喃甲酰氨基)丙氨酸, 再与10种不同取代苯胺反应, 通过N,N’-二环己基碳二亚胺和4-二甲氨基吡啶(DCC/DMAP)偶合法设计合成了10个未见文献报道的N-(5-邻氯苯基-2-呋喃甲酰氨基)丙氨酰胺类衍生物4a～4j. 通过元素分析, 1H NMR, IR 和MS确定化合物的结构, 初步生物活性测试表明标题化合物具有一定的除草活性.     

Improved synthesis of proline-derived Ni(II) complexes of glycine: versatile chiral equivalents of nucleophilic glycine for general asymmetric synthesis of alpha-amino acids

A synthetically practical and operationally convenient method for preparing (S)-2-[N-(N'-benzylprolyl)amino]benzophenone (BPBP) and hitherto unknown (S)-2-[N-(N'-benzylprolyl)amino]-4-methylbenzophenone (4-Me-BPBP), (S)-2-[N-(N'-benzylprolyl)amino]-5-nitrobenzophenone (5-NO(2)-BPBP), and their corresponding Ni(II) complexes with glycine [GlyNi(II)BPBP], a widely used chiral equivalent of nucleophilic glycine, and new analogues [GlyNi(II)-4-Me-BPBP] and [GlyNi(II)-5- NO(2)-BPBP] is described. The key step of the method is the synthetically efficient amid bond formation between the corresponding o-aminobenzophenones, featuring significant steric shielding and low nucleophilicity of the amino functionality as well as sterically constrained (S)-N-benzylproline (BP).     

New practical synthesis of prazosin

A new four step synthesis of prazosin, 2-[4-(2-furoyl)piperazin-l-yl]-4-amino-6,7-dimethoxyquinazoline, has been described. The method is also adaptable for the preparation of other substituted 4-aminoquinazolines. The yields are good in every step and the reactions are performed with ease. Prazosin hydrochloride of high purity is obtained directly in the last step.     

Thermodynamic functions of Ni(II) complexes with 5-(2-hydroxyphenyl)-pyrazole derivatives. A potentiometric study

Proton-ligand dissociation constants of five biologically important pyrazole derivatives, viz. [5-(2-hydroxyphenyl)-3-(pyridin-3-yl)-4-benzoyl]-pyrazol (HPPBP), [5-(2-hydroxyphenyl)-3-(3-nitrophenyl)-4-(3-pyridinoyl)]-pyrazol (HPNPPP), [5-(2-hydroxyphenyl)-3-(3-nitrophenyl)-4-benzoyl]-pyrazol (HPNPBP), [5-(2-hydroxyphenyl)-3-phenyl-4-(3-pyridinoyl)]-pyrazol (HPPPP), and [5-(2-hydroxyphenyl)-3-(3-nitrophenyl)-4-(2-furoyl) pyrazol (HPNPFP) and metal ligand stability constants of their Ni(II) complexes in 70% (v/v) dioxane-water and 0.1 M KNO₃ were determined at 298.15, 303.15, and 308.15 K by potentiometric method. Thermodynamic functions, such as, free energy change (ΔG ^○), enthalpy change (ΔH ^○) and entropy (ΔS ^○) change for dissociation and complex formation have been estimated form temperature dependence of proton-ligand and metal-ligand stability constants and interpreted in terms of feasibility of these processes.     

Reaction of chloromethyl derivatives of ethyl 3-(furyl)-3-(diethoxyphosphoryl)acrylates with sodium azide and potassium thiocyanate

Reaction of chloromethyl derivatives of ethyl 3-furyl-3(diethoxyphosphoryl)acrylates with sodium azide in acetonitrile in the presence of catalytic amount of potassium iodide proceeds with substitution of halogen with the azido group. The same chloromethyl derivatives react with potassium thiocyanate under analogous conditions to give a mixture of thiocyanates and isothiocyanates in (0.6–0.8) : 1 ratio save the case of ethyl 3-(3-chloromethylfur-2-yl)- and 3-(4-chloromethylfur-3-yl)acrylates when only thiocyanates are formed. Bromination of diethyl 5-methyl-2-furoyl phosphonate with N-bromosuccinimide afforded 5-bromomethyl-2-furoyl phosphonate. In the reaction with potassium thiocyanate it forms only thiocyanate.     

Synthesis of enantiopure 7-[3-azidopyl]indolizidin-2-one amino acid. A constrained mimic of the peptide backbone geometry and heteroatomic side-chain functionality of the ala-lys dipeptide

Enantiopure N-(BOC)amino-7-[3-azidopropyl]indolizidin-2-one acid 1 has been synthesized by displacement of the methanesulfonate of its 7-hydroxypropyl counterpart 11 with sodium azide and subsequent ester hydrolysis. N-(BOC)Amino-7-[3-hydroxypropyl]indolizidin-2-one ester 11 was obtained from a sequence commencing with the alkylation of (2S,8S)-di-tert-butyl 5-oxo-2,8-di-[N-(PhF)amino]azelate 5 (PhF = 9-(9-phenylfluorenyl)). Stereoselective allylation of 5, regioselective olefin hydroboration, selective primary alcohol protection as a silyl ether, and oxidation of the secondary alcohol gave (2S,4R,8S)-di-tert-butyl 4-[3-tert-butyldimethylsiloxypropyl]-5-oxo-2,8-di-[N-(PhF)amino]azelate 9 as a pure diastereomer in 33% overall yield. Linear ketone 9 was then converted into the indolizidinone heterocycle by a route featuring reductive amination, lactam cyclization, and isolation by way of a silyl ether which provided the (6S,7R)-isomer of 11.     

Promising Ultraviolet Absorbers—Novel Guanine Analogs Having Significantly Improved Ultraviolet Absorption Capacity and Dissipating the Energy of Absorbed Photons by Nonradiative Decay Mechanism

Structural properties of nucleobase underlie their ultrafast excited-state dynamics and low fluorescence quantum yields, which cause effectively nonradiative decay process and render them like sunscreens. Thus, eight guanine analogs[N-2-(2'-nitrobenzoyl)-guanine, N-2-(3'-nitrobenzoyl)-guanine, N-2-(4'-nitrobenzoyl)-guanine, N-2-(2'-hydroxybenzoyl)-guanine, N-2-(4'-methoxylbenzoyl)-guanine, N-2-(4'-chloricbenzoyl)-guanine, N-2-(4'- methylicbenzoyl)- guanine and N-2-(3',5'-dinitrobenzoyl)-guanine] with different substituted benzoyls, except N-2-(4'-chloricbenzoyl)-guanine, were newly synthesized. In contrast with guanine, they exhibit wider ultraviolet absorbent range, higher molar extinction coefficient and lower fluorescence intensity.     

Synthesis of 3-dialkylaminochromans via thallium(III)-induced cyclization of allyl aryl ethers

The sulfur-containing 3-alkylaminochromans, 5-methoxy-3-[N-(2- methylthioethyl)-propylamino]chroman (15), 5-hydroxy-3-[N-(2-methylthioethyl)propylamino]chroman (5) and 5-methoxy-8-methylthio-3-(dipropylamino)chroman (6), have been prepared from 8-bromo-5-methoxy-3-chromanol (11). This precursor was synthesized from 3-allyloxy-4-bromoanisole (8), by a thallium(III)-mediated ring-closure reaction. Compound 11 also served as starting material for the synthesis of 8-bromo-3-(dipropylamino)-5-methoxychroman (7).     

Synthesis of N-[2-(2,4-Difluorophenoxy)trifluoromethyl-3-pyridyl]sulfonamides and their inhibitory activities against secretory phospholipase A₂

N-[2-(2,4-Difluorophenoxy)trifluoromethyl-3-pyridyl]sulfonamide derivatives 3-6 were prepared by the reaction of 3-pyridylamines and sulfonyl chlorides. Inhibitory activities of these compounds toward secretory phospholipase A? (sPLA?) were examined and N-[2-(2,4-difluorophenoxy)-5-trifluoromethyl-3-pyridyl]-2-naphthalenesulfonamide (5c) was found to be the most potent against sPLA? with an IC?? value of 90 μM.     

呋喃西林,呋喃西林类似物及其铜(Ⅱ)、锌(Ⅱ)、镍(Ⅱ)络合物的合成和抑菌作用

近年来,文献上报导了许多缩氨基脲、缩氨基硫脲及其金属配合物的抗癌、抗微生物活性,发现金属配合物往往比配体表现出更高和更广泛的生物活性。呋喃西林(O₂N-C₄H₂O-CH=NNHCONH₂)是一种曾用于临床的硝基呋喃类广谱抗菌药物。但由于副作用大不再用于体内。近年来耐药菌株不断增加以及交叉耐药性的出现,使得治疗耐药菌株感染成为医学上的一大难题。     

3-（2-呋喃基）-4-芳基-1，2，4-三唑啉-5-硫酮的合成及生物活性

1-（2-呋喃甲酰基）-4-芳基氨基硫脲经过环化反应，制备了一系列新的化合 物3-（2-呋喃基）-4-芳基-1，2，4-三唑啉-5-硫酮类化合物，并通过元素分析和 IR，^1H NMR等波谱数据确证了上述化合物的结构。初步的生物活性实验表明其中 有些化合物的具有非常好的植物生长调节活性。