Presence Of Triethylamine In Dichloromethane Research Articles

(E)-6-Hydroxy-2-oxo-2H-chromen-7-yl 3-(4-hydroxy-3-methoxyphenyl)acrylate

A hybrid compound 5: (E)-6-hydroxy-2-oxo-2H-chromen-7-yl 3-(4-hydroxy-3-methoxyphenyl)acrylate composed of (E)-3-(4-hydroxy-3-methoxyphenyl)acrylic acid (ferulic acid) 1 and 6,7-hydroxycoumarin (esculetin) 3 was prepared in a 61% yield by the esterification reaction of protected ferulic acid 2a with esculetin 3 in the presence of triethylamine in dichloromethane for 3 h, followed by deprotection using 3M HCl. The structure of compound 5 was confirmed by 1H, 13C NMR spectroscopy, mass-spectrometry and elemental analysis.

РОЗРОБКА ЕФЕКТИВНОГО МЕТОДУ СИНТЕЗУ 2-(5-ОКСО-4,5-ДИГІДРО-1,2,4-ОКСАДІАЗОЛ-3-ІЛ)БЕНЗОЙНОЇ КИСЛОТИ

2-(5-Oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)benzoic acid was synthesized using a new effective method – thermal heterocyclization of 3-(hydroxyimino)isoindolin-1-one, which occurs as a result of its interaction with 1,1'-carbonyldiimidazole (CDI) and subsequent base-promoted cycleopening of the obtained intermediate 3H,5H-[1,2,4]oxadiazolo[3,4-a]isoindole-3,5-dione. Direct cyclization of 3-(hydroxyimino)isoindolin-1-one by the reaction with diethyl carbonate in the presence of sodium ethylate in ethanol at room temperature and under heating was unsuccessful. The same result was observed when using triphosgene in the presence of triethylamine in dichloromethane. Treating 3-(hydroxyimino)isoindolin-1-one with methyl chloroformate gave 3-(((methoxycarbonyl)oxy)-imino)isoindolin-1-one which was thermally stable and was not cyclized into the desired acid by boiling in toluene and o-xylene for 24 hours. The reflux of the excess of CDI with 3-(hydroxyimino)isoindolin-1-one in anhydrous ethyl acetate and subsequent alkaline hydrolysis gave the desired 2-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)benzoic acid in a total yield of 90%. An attempt to stop the process at the stage of formation of the intermediate 3H,5H-[1,2,4]oxadiazolo[3,4-a]isoindole-3,5-dione by carrying out the reaction in the absence of a base failed. Its partial hydrolysis took place during the reaction, and especially at the stage of isolation, and as a result a mixture of 3H,5H-[1,2,4]oxadiazolo[3,4-a]isoindole-3,5-dione and 2-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)benzoic acid was formed in a ratio of about 2:3. The obtained substance after mixing with aqueousmethanolic NaOH solution and subsequent acidification with 1M HCl was quantitatively converted into the pure desired acid. The developed method allows the use of 3-(hydroxyimino)isoindolin-1-ones as convenient starting materials for the preparation of vic-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)aromatic acids and subsequently related compounds, in particular isomeric vic-carbamimidoyl(hetero)aromatic carboxylic acids, which cannot be obtained by other currently known methods. All the compounds obtained during the development of the method were studied by means of NMR spectroscopy.

ChemInform Abstract: One‐Pot Domino Synthesis of Polyfunctionalized Benzophenones, Dihydroxanthones, and m‐Terphenyls from 2‐(Polyfluoroalkyl)chromones.

Whereas 2-(polyfluoroalkyl)chromones activated by electron-withdrawing substituents in the benzene ring react with 2-(1-phenylalkylidene)malononitriles in the presence of triethylamine in dichloromethane to produce a wide range of polyfunctionalized benzophenones and dihydroxanthones, their reactions with ethyl α-cyano-β-methylcinnamate under the same conditions took an entirely different course and gave mainly m-terphenyl derivatives. The difference in behavior between the ylidene derivatives of malononitrile and those of ethyl cyanoacetate is remarkable.

One‐Pot Domino Synthesis of Polyfunctionalized Benzophenones, Dihydroxanthones, and m‐Terphenyls from 2‐(Polyfluoroalkyl)chromones

AbstractWhereas 2‐(polyfluoroalkyl)chromones activated by electron‐withdrawing substituents in the benzene ring react with 2‐(1‐phenylalkylidene)malononitriles in the presence of triethylamine in dichloromethane to produce a wide range of polyfunctionalized benzophenones and dihydroxanthones, their reactions with ethyl α‐cyano‐β‐methylcinnamate under the same conditions took an entirely different course and gave mainly m‐terphenyl derivatives. The difference in behavior between the ylidene derivatives of malononitrile and those of ethyl cyanoacetate is remarkable.

ChemInform Abstract: Synthesis of Electron‐Deficient Dienes Bearing a Chromonyl Moiety via the Reaction of 3‐Formylchromones with Ylidenemalononitriles and Ethyl α‐Cyano‐β‐methylcinnamate.

Abstract 3-Formylchromones react with ylidenemalononitriles in the presence of triethylamine in dichloromethane to produce the target electron-deficient dienes connected to the chromone system with excellent E-selectivity and in good yields. In a similar manner, their reaction with ethyl α-cyano-β-methylcinnamate gave a mixture of E,Z- and E,E-isomeric chromonyl dienes, from which the former could be isolated in a pure state by crystallization.

ChemInform Abstract: Cycloaddition Reactions of N‐Benzotriazolylketene as a Heteroarylketene: A Practical Approach to the Synthesis of Novel Azetidinones.

A series of novel functionalized azetidinones containing the benzotriazole moiety were synthesized stereoselectively by a ­reaction of benzotriazolylacetic acid, aromatic amines, and ­Mukaiyama’s reagent in the presence of triethylamine in dichloromethane at ambient temperature. This transformation generates a four-membered lactam and presumably proceeds via in situ generation of benzotriazolylketene as a heteroarylketene. In contrast to the products obtained from the reaction of pyrrolylketene with imines in which cis -azetidinones were formed as major products, the generated benzotriazolylyketene reacted with imines forming the trans -lactams as major products.

Synthesis of electron-deficient dienes bearing a chromonyl moiety via the reaction of 3-formylchromones with ylidenemalononitriles and ethyl α-cyano-β-methylcinnamate

3-Formylchromones react with ylidenemalononitriles in the presence of triethylamine in dichloromethane to produce the target electron-deficient dienes connected to the chromone system with excellent E-selectivity and in good yields. In a similar manner, their reaction with ethyl α-cyano-β-methylcinnamate gave a mixture of E,Z- and E,E-isomeric chromonyl dienes, from which the former could be isolated in a pure state by crystallization.

Cycloaddition Reactions of N-Benzotriazolylketene as a Heteroarylketene: A Practical Approach to the Synthesis of Novel Azetidinones

A series of novel functionalized azetidinones containing the benzotriazole moiety were synthesized stereoselectively by a ­reaction of benzotriazolylacetic acid, aromatic amines, and ­Mukaiyama’s reagent in the presence of triethylamine in dichloromethane at ambient temperature. This transformation generates a four-membered lactam and presumably proceeds via in situ generation of benzotriazolylketene as a heteroarylketene. In contrast to the products obtained from the reaction of pyrrolylketene with imines in which cis -azetidinones were formed as major products, the generated benzotriazolylyketene reacted with imines forming the trans -lactams as major products.

Solution-Phase Parallel Syntheses of Herbicidal 1-Phenyl-2,4,5- Imidazolidinetriones and 2-Thioxo-4,5-Imidazolidinediones

In order to find new herbicidally active compounds, a fifteen-member library, focusing on the variation of 3- position substituents of 2,4,5-imidazolidine-trione or 2-thioxo-4,5-imidazolidinedione, was designed and prepared in parallel by the reaction of various ureas or thioureas with oxalyl chloride using solution-phase technology. An interesting and, to the best of our knowledge, unprecedented finding is that a by-product of 1-phenyl-3-propylcarbodiimide was formed during the addition of oxalyl chloride into the solution of 1-phenyl-3-propylthiourea in the presence of triethylamine in dichloromethane. It has been shown that the herbicidal activity of 2,4,5-imidazolidinetriones is about the same as that of their analogous 2-thioxo-4,5-imidazolidinediones. Compound with propyl or isopropyl group at the 3- position of 2,4,5-imidazolidinetrione ring demonstrated good herbicidal activity. The most active compound, 1-(2-fluoro- 4-chloro-5-propargyloxy)-phenyl-3-propyl-2-thioxo-4,5-imidazolidinedione, gave 95% control of the growth of velvetleaf at 200 g/ha in the post-emergence test.

Efficient Swern oxidation and Corey–Kim oxidation with ion-supported methyl sulfoxides and methyl sulfides

The Swern oxidation of various benzylic and allylic alcohols, primary alcohols, and secondary alcohols with two ion-supported methyl sulfoxides A-1 (C6) and B-1 (C10), and oxalyl chloride in the presence of triethylamine in dichloromethane, followed by simple diethyl ether extraction of the reaction mixture, gave the corresponding aldehydes and ketones, respectively, in good yields with high purity. Similarly, the Corey–Kim oxidation of various benzylic and allylic alcohols, primary alcohols, and secondary alcohols with two ion-supported methyl sulfides A-2 (C6) and B-2 (C10), and N-chlorosuccinimide in the presence of triethylamine in dichloromethane, followed by simple diethyl ether extraction of the reaction mixture, furnished the corresponding aldehydes and ketones, respectively, in good yields with high purity. Both reactions did not produce any unpleasant odor at all. In the Swern oxidation, ion-supported methyl sulfides were recovered in high yields and could be re-oxidized to produce ion-supported methyl sulfoxides A-1 (C6) and B-1 (C10), for reuse in the same oxidation. In the Corey–Kim oxidation, ion-supported methyl sulfides A-2 (C6) and B-2 (C10) were recovered in high yields and could be also reused for the same oxidation.

Synthesis and Pseudomonas Lipase Inhibition Study of Stereoisomers of Decahydro-2-naphthyl-N-n-butylcarbamate

(2S,4aR,8aS)-Cis,cis-, (2R,4aS,8aR)-cis,cis-, rac-cis,cis-, and rac-trans,cis-decahydro-2-naphthyl-N-n-butylcarbamates are synthesized from condensation of (2S,4aR,8aS)-cis,cis-, (2R,4aS,8aR)-cis,cis-, rac-cis,cis-, and rac-trans,cisdecahydro- 2-naphthols, respectively, with n-butyl isocyanate in the presence of triethylamine in dichloromethane. Optically pure (2S,4aR,8aS)-(-)- and (2R,4aS,8aR)-(+)-cis,cis-decahydro-2-naphthols are resolved by the porcine pancreatic lipase- catalyzed acetylation of decahydro-2-naphthols with vinyl acetate in t-butyl methyl ether. Absolute configurations of (2S,4aR,8aS)-(-)- and (2R,4aS,8aR)-(+)- cis,cis-decahydro-2-naphthols are determined from the ¹⁹F NMR spectra of their Mosher's ester derivatives. (2S,4aR,8aR)-Trans,cis- and (2R,4aS,8aS)-trans,cis-decahydro-2-naphthols can't be resolved from the porcine pancreatic lipase-catalyzed acetylation of decahydro-2-naphthols with vinyl acetate in t-butyl methyl ether. For the inhibitory potency of Pseudomonas lipase, (2S,4aR,8aS)-cis,cis-decahydro-2-naphthyl-N-n-butylcarbamate is 3.5 times more potent than (2R,4aS,8aR)-cis,cis-decahydro-2-naphthyl-N-n-butylcarbamate; racemic cis,cis-decahydro- 2-naphthyl-N-n-butylcarbamate is about the same with trans,cis-decahydro-2-naphthyl-N-n-butylcarbamate. These inhibitors also show similar effects on porcine pancreatic lipase.

Swern Oxidation of Alcohols with Ion-Supported Methyl Sulfoxide and Oxalyl Chloride

The oxidation of primary and secondary alcohols with ion-supported methyl sulfoxide and oxalyl chloride in the presence of triethylamine in dichloromethane efficiently proceeded to give the corresponding aldehydes and ketones, respectively, in good yields with high purity. Isolation of the product was achieved very easily by simple diethyl ether extraction of the reaction mixture and subsequent removal of solvent from the extract. The reaction did not produce any unpleasant odor. Furthermore, ion-supported methyl sulfide was recovered in good yield and could be re-oxidized to ion-supported methyl sulfoxide for reuse in the same oxidation.

Selenium‐Containing Heterocycles From Isoselenocyanates: Synthesis of1,3‐Selenazolidine and Perhydro‐1,3‐selenazine Derivatives

AbstractTreatment of ω‐halo alkylamines 9 and 10 with aryl and alkyl isoselenocyanates 6a–g in the presence of triethylamine in dichloromethane gave the corresponding 1,3‐selenazolidines 11a–g and perhydro‐1,3‐selenazines 12a–g, respectively, in good to excellent yields. Chemical and spectroscopic evidence for the structures of all new compounds are presented, and in selected examples the molecular structures have been established by X‐ray crystallography. The analogous reactions with isothiocyanates have been used for the preparation of 1,3‐thiazolidines and perhydro‐1,3‐thiazines. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Regioselective sulfonylation of 6,1′,6′-tri- O-tritylsucrose through dibutylstannylation: synthesis of 4′- O-sulfonyl derivatives of sucrose

3- O-Mesyl-1,6-di- O-trityl-β- d-fructofuranosyl-(2→1)-6- O-trityl-α- d-glucopyranoside ( 3) was synthesized via stannylation of 6,1′,6′-tri- O-tritylsucrose with dibutyltin oxide in benzene, followed by treatment of the crude product with methanesulfonyl chloride in the presence of triethylamine in dichloromethane at 0 °C. A similar treatment of the tri-tritylsucrose in toluene, instead of benzene, yielded 4- O-mesyl-1,6-di- O-trityl-β- d-fructofuranosyl-(2→1)-6- O-trityl-α- d-glucopyranoside ( 4) as the major product. The X-ray crystal structure of the corresponding acetyl derivative, 3- O-acetyl-4- O-mesyl-1,6-di- O-trityl-β- d-fructofuranosyl-(2→1)-2,3,4-tri- O-acetyl-6- O-trityl-α- d-glucopyranoside ( 5), confirms the position and stereochemistry of the methanesulfonyl group at C-4 of the fructofuranosyl ring.

Determination of alcohols using condensation agent carbazole-9-acetyl-benzene-disulfonate by high performance liquid chromatography with pre-column fluorescence derivatization

A sensitive LC method for the determination of alcohols, using fluorescent condensation agent carbazole-9-N-acetylbenzne-disulfonate(CABS), has been developed. A mixture of alcohols and triethylamine catalyst in dichloromethane or chloroform is treated with CABS to give quantitative yields of esters. Emission maximum for the derivatized alcohols is 365 nm (λex 335 nm). The labeled derivatives are very stable, no significant decomposition is observed after heating in 40% at 40°C for 24 h. The method, in conjunction with a multigradient program, offers baseline resolution of common alcohol derivatives on a reversed-phase C18 column. Studies on derivatization conditions indicate that primary and secondary alcohols react very fast with CABS in the presence of triethylamine in dichloromethane or chloroform to give the corresponding fluorescent derivatives. This method is more convenient and more efficient than previous methods which require prior conversion of carboxylic acids to acyl chlorides. The separation of alcohol derivatives has good reproducibility and the rsd's (n=5) for 50 pmol of each alcohol are 4%. Detection limits are at the fmol level.

Derivatization of alcohols using acridone-9- N-acetyl-benzene-disulfonate as a condensation agent and its application for the determination of volatile alcohols in human plasma by liquid chromatography with fluorescence detection

A sensitive liquid chromatographic (LC) method for the determination of alcohols including the volatile alcohols from spiked plasma, using the fluorescent condensation agent, acridone-9- N-acetyl-benzene-disulfonate (AABS), has been developed. A mixture of alcohols and triethylamine in dichloromethane or chloroform is treated with AABS to give a quantitative yield of esters. Emission maxima for the derivatized alcohols are at 435 nm ( λ ex 404 nm). The labeled derivatives are very stable, no remarkable decomposition is observed after heating in 15% acetonitrile solution (pH 6.5) at 40°C for 24 h. The method, in conjunction with a multi-gradient program, offers a baseline resolution of the common alcohol derivatives on a reversed-phase C 18 column. Studies on derivatization conditions indicate that alcohols react very fast with AABS in the presence of triethylamine in dichloromethane or chloroform to give the corresponding fluorescent derivatives. The established method for the analysis of alcohol derivatives is more convenient and more efficient than previous methods which require the prior conversion of the carboxylic acids to the acyl chlorides. The application for the analysis of volatile alcohols in spiked human plasma is also investigated. The LC system shows good selectivity and reproducibility for volatile alcohols from spiked plasma. The relative standard deviations ( n=5) for 50 pmol of each alcohol are <4%. The detection limits are at the fmol level. The method is also suitable for the determination of other alcohols in various matrices.

3-(7-methoxycoumarin-3-carbonyl)- and 3-(7-dimenthylaminocoumarin-3-carbonyl)-2-oxazolones as new fluorescent labeling reagents for high-performance liquid chromatography.

3-(7-Methoxycoumarin-3-carbonyl)- and 3-(7-dimethylaminocoumarin-3-carbonyl)-2-oxazolones (IIa and IIb) were synthesized as fluorescent labeling reagents for high-performance liquid chromatography (HPLC). Treatment of 7-methoxy- and 7-dimethylaminocoumarin-3-carboxylic acids (Ia and Ib) with diphenyl 2-oxo-3-oxazolinylphosphonate in the presence of triethylamine in dichloromethane gave IIa and IIb in 45% and 26% yields, respectively. Compounds IIa and IIb reacted with primary and secondary amines at room temperature in chloroform to give the corresponding fluorescent 7-methoxy- and 7-dimethylamino-3-carboxamides (IIIa-i and IVa-i). A mixture of primary amines was labeled with IIa and chromatographed on a reversed-phase HPLC column (mobile phase : methanol-water) with a fluorescence detector. The detection limit of a test compound, benzylamine, was 19 fmol/100 μl by the use of IIa.