N,N-bis (2-chloroethyl) amides and N,N-bis(2-chloroethyl) hydrazides of carboxylic acids of the furan series

Reaction of N, N-bis(2-chloroethyl)amine hydrochloride with chloroanhydrides of carboxylic acids of the furan series, in chloroform in the presence of pyridine gives N, N-bis(2-chloroethyl)amides of furan carboxylic acid, furylacrylic acid, 5-nitrofuran carboxylic acid, and 5-nitrofurylacrylic acid.N, N-bis(2-chloroethyl)hydrazides of furan carboxylic acid, furyl carboxylic acid, 5-nitrofuran carboxylic acid, and 5-nitrofurylacrylic acid were obtained in 78–88% yields by reacting N, N-bis(2-chloroethyl)hydrazine hydrochloride with the chloroanhydrides of the appropriate acids in chloroform in the presence of pyridine. The last two hydrazides were prepared in 31 % and 56 % yield, respectively, using anhydrous sodium acetate in place of pyridine.     

2-Halogenoethyl and 2-halogenoethylthiol esters of furan series carboxylic acids

The corresponding 2-chloroethyl (2-chloroethylthiol) esters are synthesized by the action of ethylene chlorohydrin (chloroethylmercaptan) on the acid chlorides of 5-nitrofuran carboxylic acid and 3-(5-nitrofuryl-2)acrylic acid. The acid chlorides of benzoic, furan carboxylic, and 3-(furyl-2)-acryllc acids react with ethylene sulfide, to give 2-chloroethyl esters of those acids. Ethylene oxide does not react with the acid chlorides of benzoic acid and furan series carboxylic acids either at room temperature or on heating at 50° for 1 hour.     

The birch reduction of heterocyclic compounds V Birch reduction of 2‐ and 5‐acylfuran‐3‐carboxylic acids and reductive elimination of 2‐(arylmethoxymethyl)furan‐3‐carboxylic acids

The Birch reduction of 2‐ and 5‐acylfuran‐3‐carboxylic acid 1 and 4 gave 2‐acyl‐2,3‐dihydrofuran‐3‐carboxylic acid 2 and 5‐acyltetrahydrofuran‐3‐carboxylic acid 5 , respectively. Further examination of the reductive elimination was also studied on 2‐(arylmethoxymethyl)furan‐3‐carboxylic acids 7.     

Synthesis and properties of furan derivatives. 4. Synthesis of 2,5-disubstituted 1,3,4-oxadiazoles containing furan fragments

The condensation of hydrochloride sats of iminoesters of furan acids with hydrazides of carboxylic acids gives 2,5-disubstituted 1,3,4-oxadiazoles containing furan fragments. Such compounds are also formed in the condensation of hydrazides of 5-R-furan-2-carboxylic acids with hydrocloride salts of carboxylic acid iminoesters. The reaction of furan acids with hydrazine dihydrochloride in polyphosphoric acid gave symmetrically disubstituted 1,3,4-oxadiazoles containing furan fragments.Communication 3, see ref. [1].I. M. Gubkin State Petroleum and Natural Gas Institute, 117917, Moscow. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 238–249, February, 1995. Original article submitted January 24, 1995.     

Dynamic Kinetic Resolution of 2,3‐Dihydrobenzo[b]furans: Chemoenzymatic Synthesis of Analgesic Agent BRL 37959

An efficient asymmetric synthesis of (S)‐2,3‐dihydrobenzo[b]furan‐3‐carboxylic acid ( 8 a ) and (S)‐5‐chloro‐2,3‐dihydrobenzo[b]furan‐3‐carboxylic acid ( 8 b ) was established. Key to the success was the highly stereoselective enzymatic kinetic resolution of the corresponding methyl or ethyl esters that was further developed into a dynamic process. As a reliable and fast tool for analysing the enantiomeric excess, HPLC coupled with a CD detector was utilized. The route was completed by a Friedel–Crafts acylation of ethyl (S)‐5‐chloro‐2,3‐dihydrobenzo[b]furan‐3‐carboxylate ( 7 c ) followed by saponification leading to (S)‐5‐chloro‐2,3‐dihydrobenzo[b]furan‐3‐carboxylic acid ( 2 ), an analgesic agent.     

A novel pathway for the synthesis of a carboxylic acid-functionalised Ru(II) terpyridine complex

A new terpyridinyl ruthenium(II) complex functionalised with a carboxylic acid moiety was synthesised. This complex was prepared according to two different pathways. The first one successively involves protection of the carboxylic group on the ligand before formation of the complex followed by hydrolysis. The second one is a new route based on oxidation of a furan ring directly on the complex.     

New Method for the Synthesis and Reactivity of (5‐R‐1,3,4‐Oxadiazol‐2‐yl)furoxans

A new, simple and general one‐pot method for the preparation of (5‐R‐1,3,4‐oxadiazol‐2‐yl)furoxans has been developed on the basis of the interaction between accessible 3‐methylfuroxan‐4‐carboxylic acid hydrazide and aliphatic, aromatic and heterocyclic carboxylic acids or their chlorides in the presence of POCl₃. The synthesis and study of (5‐R‐1,3,4‐oxadiazol‐2‐yl)furoxans reactivity resulted in new polyheterocyclic ensembles incorporating furoxan, 1,3,4‐oxadiazole, pyrrole, triazole, furan, thiophene, pyrimidine, and other heterocycles in different combinations.     

Sesquiterpenoids‐Related Metabolites from the Soft Coral Sinularia sp.

Two new sesquiterpenoids, sinularioperoxide E ( 1 ), ethyl 5‐[(2′S,5′E)‐2′, 6′‐dimethylocta‐5′,7′‐dienyl]furan‐3‐carboxylate ( 3 ), and a new C₁₁ terpenoid‐related carboxylic acid, (3S,6E)‐3,7‐dimethyl‐nona‐6,8‐dienoic acid ( 2 ) were isolated from a Formosan soft coral Sinularia sp. The structures of 1‐3 were elucidated on the basis of extensive spectroscopic analyses and by comparison of the spectral data with those of the related metabolites.     

Influence of ozonized kraft lignin on the crystallization of CaCO3

Results are reviewed from a study examining how structural modifications introduced by ozonization enhance the influence of kraft lignin on the crystallization of CaCO(3). Ozone treatment of kraft lignin in an aqueous environment is shown to increase its carboxylic acid and overall oxygen content and reduce its molecular weight. Calcium concentration and temperature were monitored in heated supersaturated solutions containing ozonized kraft lignins to gauge their influence on CaCO(3) crystallization processes. The presence of kraft lignin raises the temperature necessary to induce crystallization. This effect is shown to level off at relatively low lignin concentrations and be dependent on the extent of ozone treatment the kraft lignin has undergone. A linear correlation is found between crystallization temperatures and the carboxylic acid content of ozonized lignin samples indicating the introduction of these functional groups plays an important role in enhancing its inhibitory effect. Scanning electron microscopy images of crystals grown in the presence of kraft lignins show significant morphological modifications. These are consistent with specific or pseudo specific interactions between the lignin and crystal faces of calcite to inhibit growth parallel to its c axis. The influence over crystal morphology demonstrated by modified kraft lignin increases with increasing ozonization. Also presented here are crystallization temperature data for a range of kraft lignin ultrafiltration fractions, which indicate that the optimal (nominal) molecular weight of kraft lignin for inhibiting the crystallization of CaCO(3) lies between 5000 and 10000.     

LC method for the direct and simultaneous determination of four major furan derivatives in coffee grounds and brews

The simultaneous quantification of two potential genotoxic hydroxymethyl furan derivatives in coffee (furfuryl alcohol and 5‐hydroxymethylfurfural) alongside their carboxylic acid derivatives (2‐furoic acid and 5‐hydroxymethyl furoic acid, respectively) was carried out. Their extraction from ground roasted coffee using sonication, simple shaking or heat‐assisted shaking lead to similar results. A minimum of 97.3% of the four furan derivatives were extracted during the first extraction cycle using water, whereas methanol showed considerably lower extraction efficiency. A simple high‐performance liquid chromatography method coupled with diode array detection was developed for the simultaneous determination and was applied to roasted coffee extracts or brews. No sample pre‐treatment except for centrifugation was needed. The diode array detector was used to assess the purity of the peaks of interest in analyzed samples against authentic standards. The linearity according to Mandel, accuracy (recovery ≥ 89.9%) and precision (inter‐ and intraday relative standard deviation ≤ 4.5%) were checked. The values for the limit of detection and quantification ranged within 0.11–0.76 and 0.35–2.55 μg/mL, respectively. Filtered and espresso brews were analyzed for the four furan derivatives where furfuryl alcohol showed double the concentration of 5‐hydroxymethylfurfural and about ten times the concentrations of 2‐furoic acid or 5‐hydroxymethyl furoic acid.     

Four New Alkaloids from the Fermentation Broth of Armillaria mellea

Four compounds with similar structures and UV spectra were isolated from the fermentation broth of Armillaria mellea by means of preparative HPLC. Their structures were established as methyl (2S)‐1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]‐5‐oxopyrrolidine‐2‐carboxylate ( 1 ), (2S)‐1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]‐5‐oxopyrrolidine‐2‐carboxylic acid ( 2 ), 1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]pyrrolidin‐2‐one ( 3 ) and 1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]piperidin‐2‐one ( 4 ) on the basis of their 1D‐ and 2D‐NMR, and HR‐MS data. The absolute configurations of compounds 1 and 2 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) data. Additionally, four known compounds, 5 – 8 , were also isolated.     

Synthesis and photolysis studies of carboxylic esters of 2-hydroxy-1,2,2-triphenylethanone: a novel tandem photocyclisation

Carboxylic esters of 2-hydroxy-1,2,2-triphenylethanone can be prepared in good yield by reaction between 2-chloro-1,2,2-triphenylethanone and a carboxylic acid in the presence of silver carbonate and silver tetrafluoroborate. Irradiation of the ester with a medium pressure mercury lamp results in a rapid and quantitative photolysis to afford the carboxylic acid and benzo[b]phenanthro[9,10-d]furan.     

Die Herstellung von 3, 5-disubstituierten Cyclopentenen durch Ozonolyse von Norbornadien

The ozonization of norbornadiene is described. Oxidation of the intermediate with silver oxide furnishes 4-cyclopentene-cis-1, 3-dicarboxylic acid, reduction with sodium borohydride cis-1, 3-bis-hydroxymethylcyclopent-4-ene. The latter was converted to cis-3, 5-dimethylcyclopentene by reduction of the corresponding bis-tosylate with LiAlH₄. Hydrogenation of the ozonization intermediate over palladium-lead carbonate (Lindlar's catalyst) afforded 4-cyclopentene-cis-1, 3-dialdehyde. This reaction represents a new and selective method for the reduction of unsaturated ozonization intermediates.     

2-Hydroxy-1,2,2-triphenylethanone as an efficient photolabile protecting group for carboxylic acids

The synthesis is reported of 2-hydroxy-1,2,2-triphenylethanone esters of carboxylic acids by the reaction between 2-chloro-1,2,2-triphenylethanone and a carboxylic acid in the presence of silver carbonate and silver tetrafluoroborate. Photolysis of the esters occurs rapidly on irradiation with a medium-pressure mercury lamp through quartz or Pyrex to return the carboxylic acid. The side product of the photolysis is benzo[b]phenanthro[9,10-d]furan, formed through a tandem process involving initial generation of 2,3-diphenylbenzofuran, photochemical cyclisation and re-aromatisation by aerial oxidation.     

Modular Synthesis of Multisubstituted Furans through Palladium‐Catalyzed Three‐Component Condensation of Alkynylbenziodoxoles,Carboxylic Acids,and Imines

Mild and regiocontrolled synthesis of a multisubstituted furan is achieved through Pd(OAc)₂‐catalyzed room‐temperature condensation of an alkynylbenziodoxole, a carboxylic acid, and an enolizable ketimine, which contribute to C1, CO, and C2 fragments, respectively, to the furan skeleton. The reaction tolerates a broad range of functional groups in each of the reaction components, and enables highly modular and flexible synthesis of variously substituted furans. The reaction is particularly effective for the rapid generation of tri‐ and tetraarylfurans and furan‐containing oligoarylenes without relying on conventional cross‐coupling chemistry.     

Modular Synthesis of Multisubstituted Furans through Palladium‐Catalyzed Three‐Component Condensation of Alkynylbenziodoxoles,Carboxylic Acids,and Imines

Mild and regiocontrolled synthesis of a multisubstituted furan is achieved through Pd(OAc)₂‐catalyzed room‐temperature condensation of an alkynylbenziodoxole, a carboxylic acid, and an enolizable ketimine, which contribute to C1, CO, and C2 fragments, respectively, to the furan skeleton. The reaction tolerates a broad range of functional groups in each of the reaction components, and enables highly modular and flexible synthesis of variously substituted furans. The reaction is particularly effective for the rapid generation of tri‐ and tetraarylfurans and furan‐containing oligoarylenes without relying on conventional cross‐coupling chemistry.     

Reactions of aldehydes of the furan series. 3. Oxidative-reductive conversions on the surface of alkali granules

Furan aldehydes undergo an oxidative-reductive disproportionation over solid alkali in a solvent inert to alkali. Molecular oxygen increases the yield of the furan carboxylic acid. A reaction scheme is proposed that takes into account the important role of alcoholates of gem-polyols.For Communication 2, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 741–744, June, 1990.     

Synthesis of 1-functionalyzed 3-(diethoxyphosphorylmethyl)-4,5,6,7-tetrahydrobenzo[<Emphasis Type="Italic">c</Emphasis>]furans

A series of 3-(diethoxyphosphorylmethyl)-4,5,6,7-tetrahydrobenzo[c]furans functionalized in the position 1 including the unsubstituted phosphonate, diethylaminomethyl derivative, carboxylic acid, its ester, chloride, amide, and nitrile was synthesized. For the first time in the furan series decarboxylation of PO-ester of phosphonocarboxylic acid was carried out. Some specific features of behavior of the derivatives of 4,5,6,7-tetrahydrobenzo[c]furan in the reactions with thionyl chloride, phosphorus pentachloride, ammonia, and N-bromosuccinimide unusual for common alkylfurans were found.     

Evaluating the use of chiral anthracene templates to access pyroglutamic acids

An approach for the asymmetric synthesis of pyroglutamic acid derivatives is described based on an anthracene chiral auxiliary. The introduction of a furan ring as a masked carboxylic acid moiety proceeded with excellent levels of diastereo-selectivity, followed by conversion into a carboxylate ester. The ensuing retro-Diels–Alder procedure using flash vacuum pyrolysis (FVP) followed by reduction gave pyroglutamate esters in good yield but poor enantioselectivity, the latter of which was found to be dependant on the electronic nature of the N-protecting group.     

The catalytic ozonization of model lignin compounds in the presence of Fe(III) ions

The ozonization of several model lignin compounds (guaiacol, 2,6-dimethoxyphenol, phenol, and vanillin) was studied in acid media in the presence of iron(III) ions. It was found that Fe³⁺ did not influence the initial rate of the reactions between model phenols and ozone but accelerated the oxidation of intermediate ozonolysis products. The metal concentration dependences of the total ozone consumption and effective rate constants of catalytic reaction stages were determined. Data on reactions in the presence of oxalic acid as a competing chelate ligand showed that complex formation with Fe³⁺ was the principal factor that accelerated the ozonolysis of model phenols at the stage of the oxidation of carboxylic dibasic acids and C₂ aldehydes formed as intermediate products.