Synthesis and Analgesic Activity of Some Substituted 1-Benzofurans and 1-Benzothiophenes

2000 ◽  
Vol 65 (7) ◽  
pp. 1093-1108 ◽  
Author(s):  
Stanislav Rádl ◽  
Petr Hezký ◽  
Petr Konvička ◽  
Ivan Krejčí
Keyword(s):  
Acetic Anhydride ◽  
Analgesic Activity ◽  
Ethyl Chloroformate ◽  
Ethyl Bromoacetate ◽  
Boron Tribromide ◽  
Glycine Derivatives ◽  
Mild Hydrolysis ◽  
Hydrolysis Of ◽  
Substituted 1

2-Benzoyl- and 2-(pyridylcarbonyl)-1-benzofuran-3-amines were prepared from 2-hydroxybenzonitrile and corresponding bromoethanone derivatives. 2-Benzoyl- and 2-(pyridylcarbonyl)-1-benzothiophene-3-amines were prepared analogously from 2-sulfanylbenzonitrile. 2-Benzoyl-1-benzofuran-3-amine treated with acetic anhydride or ethyl chloroformate provided the corresponding N-acetyl or N-ethoxycarbonyl derivatives. These N-activated compounds were alkylated with ethyl bromoacetate to provide ethyl N-acetyl-N-(2-benzoyl-1-benzofuran-3-yl)glycinate and ethyl N-(2-benzoyl-1-benzofuran-3-yl)-N-ethoxycarbonylglycinate, respectively. Their mild hydrolysis gave the corresponding glycine derivatives. Methylation of ethyl N-(2-benzoyl-1-benzofuran-3-yl)carbamate gave the corresponding N-methyl carbamate, which was hydrolyzed to N-methyl-(2-benzoyl-1-benzofuran-3-yl)amine. 2-Benzoyl-7-methoxy-1-benzofuran-3-amine and 2-(4-methoxybenzoyl)-1-benzofuran-3-amine were demethylated with boron tribromide to the corresponding hydroxy derivatives; their O-alkylation with ethyl bromoacetate than gave ethyl [(3-amino-2-benzoyl-1-benzofuran-7-yl)oxy]acetate and ethyl {4-[(3-amino-1-benzofuran-2-yl)carbonyl]phenoxy}acetate, respectively. The mild hydrolysis of these esters provided corresponding acids. Similarly, alkylation of the hydroxy derivatives with (dimethylamino)propyl chloride gave corresponding (dimethylamino)propoxy derivatives. 2-Hydroxybenzonitrile treated with 2-bromo-1-(2-, 3-, or 4-pyridyl)ethan-1-one provided the respective 2-(pyridylcarbonyl)-1-benzofuran-3-amine. Similar 2-(pyridylcarbonyl)-1-benzothiophene-3-amines were prepared analogously from 2-sulfanylbenzonitrile. 2-Benzoyl-3-(bromomethyl)-1-benzofuran treated with dimethylamine, 1-methylpiperazine, and sodium 1-methylpiperidine-4-thiolate gave the corresponding alkylation products. Several compounds were found to exhibit considerable analgesic activity.

Synthesis of conjugates of 1-(carboxymethyl)cytosine and 1-(5-O-carboxymethyl-β-D-arabinofuranosyl)cytosine with proteins

1979 ◽  
Vol 44 (10) ◽  
pp. 3023-3032 ◽  
Author(s):  
Helmut Pischel ◽  
Antonín Holý ◽  
Günther Wagner
Keyword(s):  
Human Serum Albumin ◽  
Acetic Anhydride ◽  
Serum Albumin ◽  
Human Serum ◽  
Activated Esters ◽  
Hydrolysis Of

1-(Carboxymethyl)cytosine (Ia), 1-(5-O-carboxymethyl-β-D-arabinofuranosyl)cytosine (IIa) and 5'-O-carboxylmethylcytidine (IIIa) were transformed by treatment with acetic anhydride and 4-dimethylaminopyridine to the peracetyl derivatives Ib-IIIb. These products reacted with p-nitrophenol in the presence of N, N'-dicyclohexylcarbodiimide to give the activated esters Ic-IIIc which on reaction with ammonia, dimethylamine or 2-aminoethanol afforded the corresponding carboxamides Id-IIId, IIe,f. Reactions of Ic and IIc with human serum albumin and bovine γ-globulin at pH 9.2, followed by hydrolysis of the N- or O-acetyl groups at pH 9.5, gave 50% up to 64% yields of the respective conjugates Ig, IIg and Ih, IIh.

The synthesis of norbornanes with functionalized carbon substituents at a bridgehead. 1-(3-Oxonorborn-1-yl)ethanone and 1-(3-oxonorborn-1-yl)-2-propanone

1992 ◽  
Vol 70 (5) ◽  
pp. 1492-1505 ◽  
Author(s):  
Peter Yates ◽  
Magdy Kaldas
Keyword(s):  
Acetic Acid ◽  
Carboxylic Acid ◽  
Hydrogen Bromide ◽  
Tertiary Alcohol ◽  
Ethyl Bromoacetate ◽  
Second Molar ◽  
Molar Equivalent ◽  
Acid Lactone ◽  
Basic Hydrolysis ◽  
Hydrolysis Of

Treatment of 2-norobornene-1-carboxylic acid (7) with one equivalent of methyllithium in ether followed by a second molar equivalent after dilution with tetrahydrofuran gave 1-(norborn-2-en-lyl)ethanone (10) and only a trace of the tertiary alcohol 11. Reaction of 7 with formic acid followed by hydrolysis gave a 4:3 mixture of exo-3- and exo-2-hydroxynorbornane-1-carboxylic acid (16 and 17), whereas oxymercuration–demercuration gave only the exo-3-hydroxy isomer 16. Oxidation of 16 and 17 gave 3- and 2-oxonorbornane-1-carboxylic acid (27 and 29), respectively. Oxymercuration–demercuration of 10 gave exclusively 1-(exo-3-hydroxynorborn-1-yl)ethanone (30), which was also prepared by treatment of 16 with methyllithium in analogous fashion to that used for the conversion of 7 to 10. Oxidation of 30 gave 1-(3-oxonorborn-1-yl)ethanone (1). Dehydrobromination of exo-2-bromonorbornane-1-acetic acid and dehydration of 2-hydroxy-norbornane-2-acetic acid derivatives gave 1-(norborn-2-ylidene) acetic acid derivatives to the exclusion of norborn-2-ene-1 -acetic acid derivatives. Treatment of exo-5-acetyloxy-2-norobornanone (52) with ethyl bromoacetate and zinc gave ethyl exo-5-acetyloxy-2-hydroxynorbornane-(exo- and endo-2-acetate (53 and 54). Reaction of 53 with hydrogen bromide gave initially ethyl endo-3-acetyloxy-exo-6-bromonorbornane-1-acetate (59), which was subsequently converted to a mixture of 59 and its exo-3-acetyloxy epimer 61. Catalytic hydrogenation of this mixture gave a mixture of ethyl endo- and exo-3-acetyloxynorbornane-1 -acetate (62 and 63). Basic hydrolysis of this gave a mixture of the corresponding hydroxy acids, 70 and 71; the former was slowly converted to the latter at pH 5. Oxidation of the mixture of 70 and 71 gave 3-oxonorbornane-1-acetic acid (72). Treatment of the mixture with methyllithium as for 16 gave a mixture of 1-(endo- and exo-3-hydroxynorborn-1-yl)-2-propanone (73 and 74), which was oxidized to 1-(3-oxo-norborn-1-yl)-2-propanone (2). Reaction of exo-2-hydroxynorbornane-1-acetic acid lactone (75) with methyllithium in ether gave (1-(exo-2-hydroxynorborn-1-yl)-2-propanone (76), which on oxidation gave the 2-oxo isomer 78 of 2.

A synthesis and some reactions of 7-Oxabicyclo[2.2.1]heptan-2-one

1983 ◽  
Vol 36 (12) ◽  
pp. 2473 ◽  
Author(s):  
J Moursounidis ◽  
D Wege
Keyword(s):  
Thermal Decomposition ◽  
Alder Reaction ◽  
Diels Alder ◽  
Acid Mixture ◽  
Diels Alder Reaction ◽  
Reaction Proceeds ◽  
Atom Migration ◽  
Acyl Azide ◽  
Mild Hydrolysis ◽  
Hydrolysis Of

Diels-Alder reaction between furan and α-chloroacrylonitrile gives a mixture of exo-2-chloro-and endo-2-chloro-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitrile (4) and (5). Mild hydrolysis affords the corresponding α-chloro acid mixture, from which the endo carboxylic acid may be removed through iodo lactone formation. Catalytic hydrogenation of (4) and (5) followed by hydrolysis, acyl azide formation, Curtius rearrangement, and hydrolysis of the resulting mixture of a-chloro isocyanates yields 7-oxabicyclo[2.2.l]heptan-2-one (1) in preparatively useful amounts. Reduction of (1) gives only endo alcohol, and Baeyer-Villiger reaction proceeds with exclusive bridgehead atom migration. Thermal decomposition of the sodium salt of the p-toluenesulfonylhydrazone of (1) affords 7-oxatricyclo[2.2.1 .02,6]heptane.

Mild hydrolysis of nitriles by the immobilized nitrilase from Aspergillus niger K10

2006 ◽  
Vol 39 (1-4) ◽  
pp. 55-58 ◽  
Author(s):  
Vojtěch Vejvoda ◽  
Ondřej Kaplan ◽  
Karel Bezouška ◽  
Ludmila Martínková
Keyword(s):  
Aspergillus Niger ◽  
Mild Hydrolysis ◽  
Hydrolysis Of

NMR study of the synthesis of17O-enriched acetic acid by hydrolysis of acetic anhydride with17O-enriched water

2003 ◽  
Vol 41 (11) ◽  
pp. 959-961 ◽  
Author(s):  
Heidi M. Hultman ◽  
Kristina Djanashvili ◽  
Joop A. Peters
Keyword(s):  
Acetic Acid ◽  
Acetic Anhydride ◽  
Nmr Study ◽  
Hydrolysis Of

The heat of hydrolysis of boron tribromide

1955 ◽  
Vol 51 ◽  
pp. 19 ◽  
Author(s):  
H. A. Skinner ◽  
N. B. Smith
Keyword(s):  
Boron Tribromide ◽  
Hydrolysis Of ◽  
Heat Of Hydrolysis

Synthetic application of cyclobutanes V. α-Carbalkoxymethylation of α, β-unsaturated ketones

1977 ◽  
Vol 55 (5) ◽  
pp. 822-830 ◽  
Author(s):  
Hsing-Jang Liu ◽  
Patrick Chi-Lin Yao
Keyword(s):  
Hydrogen Peroxide ◽  
Acetic Acid ◽  
Acetic Anhydride ◽  
Potassium Carbonate ◽  
Alkyl Iodide ◽  
Keto Ester ◽  
Unsaturated Ketones ◽  
Synthetic Application ◽  
Hydrolysis Of ◽  
Villiger Oxidation

Two general methods for α-carbalkoxymethylation of both enolizable and nonenolizable (towards the γ-position) α,β-unsaturated ketones have been developed. Method A involves three synthetic steps: photocycloaddition of the starting enone to 1,1-dimethoxyethylene, hydrolysis–oxidation of the adduct with acetic acid and 30% hydrogen peroxide, and O-alkylation of the resulting mixture of lactone and acid using anhydrous potassium carbonate and an alkyl iodide, e.g., 13 → 17 → 21 + 22 → 23. Method B differs from method A in the means of securing the required cyclobutanone intermediate. Thus, photocycloaddition of 13 to vinyl acetate followed by hydrolysis of the adduct gave two epimeric keto alcohols 39 whose oxidation with dimethyl sulfoxide and acetic anhydride afforded diketone 40. Baeyer–Villiger oxidation of 40 followed by methylation of the products 21 and 22 completed the overall α-carbomethoxymethylation process to give keto ester 23.

The Synthesis of Zinquin Ester and Zinquin Acid, Zinc(II)-Specific Fluorescing Agents for Use in the Study of Biological Zinc(II)

1996 ◽  
Vol 49 (5) ◽  
pp. 561 ◽  
Author(s):  
IB Mahadevan ◽  
MC Kimber ◽  
SF Lincoln ◽  
ERT Tiekink ◽  
AD Ward ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Crystal Structures ◽  
Electrophilic Substitution ◽  
Ethyl Acrylate ◽  
Heck Coupling ◽  
Ethyl Bromoacetate ◽  
Reaction Conditions ◽  
Bromo Derivative ◽  
Boron Tribromide

The syntheses of Zinquin ester [ethyl [2-methyl-8-(p- tolylsulfonylamino )-6-quinolyloxy]acetate] and the corresponding acid, both of which are zinc(II)-specific fluorophores , are described. 6-Methoxy-2-methyl-8-(p- tolylsulfonylamino ) quinoline (2) can be demethylated , with boron tribromide, to form either the expected phenol or a mixture of the phenol and the corresponding 5-bromo derivative depending upon the reaction conditions. These compounds react with ethyl bromoacetate to give the corresponding esters, as well as the 5-ethoxycarbonyl derivative formed by electrophilic substitution. Halogenation of the sulfonamide (2) occurs readily at the 5-position. The 5-iodo product undergoes a Heck coupling with ethyl acrylate . The crystal structures of ethyl [5-ethoxycarbonylmethyl-2-methyl-8-(p- tolylsulfonylamino )-6-quinolyloxy]acetate and [5-carboxymethyl-2-methyl-8-(p- tolylsulfonylamino )-6-quinolyloxy]acetic acid are described.

Sign in / Sign up

Export Citation Format

Share Document