Condensation Of Ethyl Research Articles

One-step synthesis and some reactions of ethyl 10-(ethoxycarbonyl-3,4-dimethylpyrrol-2-yl)-1,2-dimethylpyrrolo[1,2-b]isoquinoline-3-carboxylate

The title compound 2 has been synthesized by the acid-catalysed condensation of ethyl 3,4-dimethylpyrrole-2-carboxylate 1 with phthalaldehyde and its structure has been confirmed spectroscopically. The photodimerization and Diels–Alder reactions of compound 2 have been investigated. The X-ray crystal structure of the photodimer 3, which indirectly provides evidence for the identity of compound 2, has been determined.

Ethylp-(2-methyl-3-oxopropyl)- andp-(2-methyl-3-oxo-1-propenyl)benzoates: preparation and use in the synthesis of biologically active derivatives ofp-(nor-polyprenyl)benzoic acids

Novel ways for preparing the title compounds have been developed. Saturated (1) and unsaturated (2) aldehydoesters, which are easily accessible by a Pd-catalyzed reaction of ethyl 4-bromobenzoate with methallyl alcohol and aldol condensation of ethyl 4-formyl-benzoate with propanal, respectively, are strategically advantageous intermediates for the synthesis. The results of thein vitro assays of some of the synthesized compounds are compared with the known data on their pharmacological effectsin vivo.

Synthesis of 6,13‐Dihydroxyimino‐5,12‐Dimethyl‐ 7,14‐Dioxo‐1,4,8,11‐Tetraazacyclotetradeca‐4,11‐Diene

Abstract6,13‐Dihydroxyimino‐5,12‐dimethyl‐7,14‐dioxo‐1,4,8,11‐tetraazacyclotetradeca‐4,11‐diene 2 was prepared by condensation of ethyl α‐oximinoacetoacetate with ethylenediamine in tetrahydrofuran at room temperature. Reduction of 2 gave the corresponding 6,13‐dihydroxyimino‐5,12‐dimethyl‐7,14‐dioxo‐1,4,8,11‐tetraazacyclotetradecane 3. Acylation of 2 afforded 6,13‐bis(O‐acetoxyimino)‐5,12‐dimethyl‐7,14‐dioxo‐1,4,8,1 l‐tetraazacyclotetradeca‐4,11‐diene 4. The structures of 2, 3 and 4 were determined by IR, NMR and mass spectroscopy.

Iodonium ion-assisted synthesis of a haptenic tetrasaccharide fragment corresponding to the inner cell-wall glycopeptidolipid of Mycobacterium avium serotype 4

Condensation of ethyl 2,4-di- O-benzoyl-1-thio-α- l-rhamnopyranoside with ethyl 3- O-benzyl- 4- O-chloroacetyl-2- O-methyl-1-thio-β- l-fucopyranoside in the presence of iodonium di- sym- collidine perchlorate afforded exclusively ethyl 2,4-di- O-benzoyl-3- O-(3- O-benzyl-4- O- chloroacetyl-2- O-methyl-α- l-fucopyranosyl)-1-thio-α- l-rhamnopyranoside. This disaccharide derivative was extended at C-1 with 3-benzyloxycarbonylaminopropyl 6-deoxy-3,4- O- isopropylidene-α- l-talopyranoside, using N-iodosuccinimide and triflic acid as the catalyst, to furnish 3-benzyloxycarbonylaminopropyl 6-deoxy-2- O-[2,4-di- O-benzoyl-3- O-(3- O-benzyl- 4- O-chloroacetyl-2- O-methyl-α- l-fucopyranosyl)-α- l-rhamnopyranosyl]- 3,4- O-isopropylidene-α- l-talopyranoside ( 20). Selective removal of the chloroacetyl group from 20, followed by condensation with ethyl 2,3-di- O-benzoyl-4- O-methyl-1-thio-α- l-rhamnopyranoside in the presence of the same thiophilic promoter, yielded a fully protected tetrasaccharide derivative. Deprotection of the latter gave the target compound 3-aminopropyl 6-deoxy-2- O-{3- O-[2- O-methyl-(4- O-methyl- α- l-rhamnopyranosyl)-α- l-fucopyranosyl]-α- l-rhamnopyranosyl}-α- l-talopyranoside ( 1).

Synthesis of a selectively protected trisaccharide building block that is part of xylose-containing carbohydrate chains from N-glycoproteins

The synthesis is reported of ethyl 4- O-[3- O-allyl-4,6- O-isopropylidene-2- O-(2,3,4-tri- O-acetyl-β- d- xylopyranosyl)-β- d-mannopyranosyl]-3,6-di- O-benzyl-2-deoxy-2-phthalimido-1-thio-β- d-glucopyranoside ( 16), a key intermediate in the synthesis of xylose-containing carbohydrate chains from N-glycoproteins. Condensation of ethyl 3,6-di- O-benzyl-2-deoxy-2-phthalimido-1-thio-β- d-glucopyranoside ( 5) with 2,4,6-tri- O-acetyl-3- O-allyl-α- d-glucopyranosyl bromide, using silver triflate as a promoter, gave the β-linked disaccharide derivative 8 (84%). O-Deacetylation of 8 and then isopropylidenation afforded 10, which was converted via oxidation-reduction into ethyl 4- O-allyl-4,6- O-isopropylidene-β- d-mannopyranosyl)-3, 6-di- O-benzyl-2-deoxy-2-phthalimido-1-thio-β- d-glucopyranoside ( 12). Silver triflate-promoted condensation of 12 with 2,3,4-tri- O-acetyl-α- d-xylopyranosyl bromide gave 16 (71%). The Xyl p unit in 16 and in de-isopropylidenated 16 ( 17) existed in the 1 C 4( d) conformation, but that in O-deacetylated 17 ( 18) existed in the 4 C 1( d) conformation.

SYNTHESIS AND APPLICATION OF 4-(COUMARIN-3-YL)-THIOPHENES

Abstract A facile synthesis of 4-(coumarin-3-yl)thiophenes (6a-6j) was achieved by the condensation of ethyl 2-acetamido-3, 5-dicarbethoxythiophene-4 acetate (4) with selected o-hydroxyaldehydes (5a-5j) in the presence of piperidine. The key intermediate, ethyl 2-acetamido-3, 5-dicarbethoxythiophene-4-acetate (4) was synthesized by cyclocondensation of diethyl acetonedicarboxylate (1), sulfur and ethyl cyanoacetate (2) by a Gewald synthesis followed by acetylation. 4-(Coumarin-3-yl)thiophenes (6a-6j) were applied on polyester fibers as fluorescent disperse dyes and their fluorescence and dyeing properties were studied.

Synthesis and properties of 2-amino-4,6-dimethylnicotinic acid arylamides

It is shown that on boiling 2-amino-4,6-dimethylnicotinic acid arylamides with triethyl orthoformate in acetic anhydride, derivatives of 3-aryl-5,7-dimethyl-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidine are formed. The same compounds are obtained by ternary condensation of ethyl 2-amino-4,6-dimethylnicotinate with triethyl orthoformate and alrylamines. On reaction with urea or ammonium thiocyanate, the ethyl ester or anilides of 2-amino-4,6-dimethylnicothinic acid are converted to 2,4-dioxo- or 4-oxo-2-thio-pyrido[2,3-d]pyrimidines respectively.

Synthesis of trisaccharide methyl glycosides related to fragments of the capsular polysaccharide of Streptococcus pneumoniae type 18C

The synthesis is reported of methyl 3- O-(4- O-β- d-galactopyranosyl-α- d-glucopyranosyl)α- l-rhamnopyranoside ( 1), methyl-2- O-α- d-glucopyranosyl-4- O-β- d-glucopyranosyl-β- d-galactopyranoside ( 3), methyl 3- O-(4- O-β- d-galactopyranosyl-α- d-glucopyranosyl)-α- l-rhamnopyranoside 3″-( sn-glycer-3-yl sodium phosphate)( 2), and methyl 2- O-α- d-glucopyranosyl-β- d-galactopyranoside 3- ( sn-glycer-3-yl sodium phosphate) ( 4), which are trisaccharide methyl glycosides related to fragments of the capsular polysaccharide of Streptococcus pneumoniae type 18C ({→4)-β- d-Glc p-(1→4)-[α- d-Glc p-(1→2)]-[Glycerol-(1-P→3)]-β- d-Gal p-(1→4)-α- d-Glc p-(1→3)-α- l-Rha p-(1→} n ). Ethyl 4- O-acetyl-2,3,6-tri- O-benzyl-1-thio-β- d-glucopyranoside ( 10) was coupled with benzyl 2,4-di- O-benzyl-α- l-rhamnopyranoside ( 6). Deacetylation of the product, followed by condensation with 2,4,6-tri- O-acetyl-3- O-allyl-α- d-galactopyranosyl trichloroacetimidate ( 18), gave benzyl 2,4-di- O-benzyl-3- O-[2,3,6-tri- O-benzyl-4- O-(2,4,6-tri- O-acetyl-3- O-allyl-β- d-galactopyranosyl)-α- d- glucopyranosyl]-α- l-rhamnopyranoside ( 19). Acetolysis of 19, followed by methylation, deallylation (→ 22), and further deprotection afforded 1. Condensation of methyl 2,4-di- O-benzyl-3- O-[2,3,6-tri- O-benzyl-4- O-(2,4,6-tri- O-acetyl-β- d-galactopyranosyl)- α- d-glucopyranosyl]-α- l-rhamnopyranoside ( 22) with 1,2-di- O-benzyl- sn-glycerol 3-(triethylammonium phosphonate) ( 24), followed by oxidation and deprotection, yielded 2. Condensation of ethyl 2,3,4,6-tetra- O-benzyl-1-thio-β- d-glucopyranoside ( 27) with methyl 3- O-allyl-4,6- O-benzylidene-β- d-galactopyranoside ( 28), selective benzylidene ring-opening of the product, coupling with 2,3,4,6-tetra- O-acetyl-α- d-glucopyranosyl trichloroacetimidate ( 31), and deallylation afforded methyl 6- O-benzyl-4- O-(2,3,4,6-tetra- O-acetyl-β- d-glucopyranosyl)-2- O-(2,3,4,6-tetra- O-benzyl-α- d-glucopyranosyl)- β- d-galactopyranoside ( 33). Deprotection of 33 gave 3, and condensation of 33 with 24, followed by oxidation and deprotection, gave 4.

A convenient synthesis of ethyl 2‐(4‐nitrophenyl)‐3,4‐disubstituted and c‐fused thiophene‐5‐carboxylates

AbstractA convenient one step synthesis of the hitherto unknown ethyl 2‐(4‐nitrophenyl)‐3,4‐disubstituted and c‐fused thiophene‐5‐carboxylates was achieved by the condensation of ethyl 4‐nitrobenzylthioacetate with a variety of 1,2‐dicarbonyl compounds using sodium ethoxide in refluxing ethanol.

Chemistry of ethyl 2-{[t-butoxycarbonyl(methyl)amino]methyl}-3-hydroxy-3-phenyl (or 3-vinyl)propionate: mechanistic considerations in the formation of tetrahydro-1,3-oxazin-2-ones

The threo- and erythro-selective aldol condensation of ethyl 3-[t-butoxycarbonyl(methyl)amino]- propionate with benzaldehyde gave the benzylic alcohol-substituted aminopropionate ethyl 2-{[t-butoxycarbonyl(methyl)amino]methyl}-3-hydroxy-3-phenylpropionate as a diastereoisomeric mixture. On treatment with methanesulphonyl chloride and triethylamine, the threo-isomer was converted into ethyl 3-methyl-2-oxo-6-phenyl-3,4,5,6-tetrahydro-2H-1,3-oxazine-5-carboxylate, and the erythro-isomer gave simply its corresponding mesate derivative. The mechanism for this transformation is discussed.

Deuterium labelling of the antidepressant drug doxepin for disposition studies in human subjects

AbstractTwo methods have been developed for the introduction of deuterium into the doxepin molecule. The key intermediate (6,11‐dihydro‐1,2,3,4‐2H4‐dibenz[b,e]oxepin‐11‐one, 5) was prepared by condensation of ethyl 2‐bromomethylbenzoate with [2H6]‐phenol, saponification of the resulting ester, and dehydration with trifluoroacetic anhydride. Using this key intermediate, E‐(1,2,3,4)‐2H4‐doxepin was prepared for administration to human subjects. (1,2,3,4)‐2H4‐N‐desmethyldoxepin, (1,2,3,4,1′,2′,2′)‐2H7‐doxepin, (1,2,3,4)‐2H4‐(N2H3)2‐doxepin (2H10‐doxepin) and (1,2,3,4,1′,2′,2′)‐2H7‐N‐desmethyldoxepin were also prepared for use as internal standards in GC/MS assays. The deuterated compounds contained less than 0.5% protium impurity.

The synthesis and biological activity of 8‐fluoro‐9‐(4‐methyl‐1‐piperazinyl)‐6‐oxo‐6H‐benzo[c]quinolizine‐5‐carboxylic acid

AbstractA one‐pot synthesis of ethyl 8,9‐difluoro‐6‐oxo‐6H‐benzo[c]quinolizine‐5‐carboxylate 11 has been developed. The condensation of ethyl 2‐pyridylacetate and 2,4,5‐trifluorobenzoyl chloride followed by intramolecular nucleophilic aromatic substitution gave the desired ring system. This intermediate was converted to the title compound and its in vitro biological activity is reported.

A Synthesis of imidazo‐ and pyrimido[1,2‐g][1,6]naphthyridinones

AbstractArylmethylimidazolines and (3‐chlorophenyl)methyl‐1,4,5,6‐tetrahydropyrimidine amidated 2‐chloro‐3‐pyridinecarbonyl chloride, and potassium t‐butoxide cyclized the products to linearly fused, tricyclic imidazo‐and pyrimido[1,2‐g][1,6]naphthyridinones. Condensation of ethyl 2‐chloro‐3‐pyridinecarboxylate with 2‐(phenylmethyl)imidazoline in the presence of sodium methoxide directly formed the isomeric, angularly fused 8,9‐dihydro‐6‐phenylimidazo[1,2‐a][1,8]naphthyridin‐5(7H‐one.

ChemInform Abstract: Cyclocondensation of 3‐Aryl‐2‐cyano‐2‐butenoic Acid Esters with Schiff Bases.

The condensation of ethyl 3-aryl-2-cyano-2-butenoates with benzylideneanilines in the presence of aluminum chloride affords 1,4,6-triaryl-2-oxo-1,2,5,6-tetrahydropyridine-2-carbonitriles; the reaction with hydrobenzamide gives N-unsubstituted tetrahydropyridine.

Cyclocondensation of 3-aryl-2-cyano-2-butenoic acid esters with schiff bases

The condensation of ethyl 3-aryl-2-cyano-2-butenoates with benzylideneanilines in the presence of aluminum chloride affords 1,4,6-triaryl-2-oxo-1,2,5,6-tetrahydropyridine-2-carbonitriles; the reaction with hydrobenzamide gives N-unsubstituted tetrahydropyridine.

Synthesis of 4-Methoxy-2,3,5-trimethylpyridine: a Specific Building Block for Compounds with Gastric-acid Inhibiting Activity.

A new synthesis of 4-methoxy-2,3,5-trimethylpyridine (2), an important building block for the preparation of gastric-acid inhibiting compounds, is described. Condensation of ethyl 3-amino-2-methyl-2-butenoate (3) and diethyl 2-methylmalonate (4) gives 4-hydroxy-3,5,6-trimethyl-2(1H)-pyridone 5. Reaction of 5 with phosphoryl chloride affords 2,4-dichloro-3,5,6-trimethylpyridine (9a), which, upon hydrogenolysis with palladium on charcoal, gives 2,3,5-trimethylpyridine (10). However, selective hydrogenolysis in acidic solution yields 4-chloro-2-3-5-trimethylpyridine (11). Substitution of the chlorine in 11 with methoxide ion gives 4-methoxy-2,3,5-trimethylpyridine (2), which can be oxidized to the corresponding N-oxide (13). This constitutes a new and efficient route to compound 2 in an overall yield of 43%.

Condensation of ethyl and methyl 4-(triphenylphosphoranylidine)-3-oxobutanoate with enals

The manipulation of the mode of reaction of 4-(phosphoranylidene)-3-oxobutanoates with enals and a resulting new synthesis of ethyl β-safranate have been explored.

Studies on pesticides based on coumarin. II. Synthesis and antifungal activity of ten 2‐alkyl‐7, 8‐dihydro‐3‐hydroxynaphtho[1,2‐c]chromen‐6‐ones

AbstractA series of 2‐alkyl‐7, 8‐dihydro‐3‐hydroxynaphtho[1,2‐c]chromen‐6‐ones was synthesised by the condensation of ethyl 3, 4‐dihydro‐1‐oxonaphthalene‐2‐carboxylate with substituted phenols in the presence of POCl3. The compounds were characterised and tested for their toxicity towards the mycelial growth of seven phytopathogenic fungi in culture. Drechslera oryzae, Rhizoctonia solani and Colletotrichum falcatum exhibited maximum sensitivity to these compounds whereas Macro‐phomina phaseolina, Fusarium solani, Alternaria alternata and Pythium aphanidermatum were less sensitive. 2‐Ethyl‐7, 8‐dihydro‐3‐hydroxy‐naphtho[1,2‐c]chromen‐6‐ones possessed greatest toxicity with EC50 values ranging from 0.2 to 2.5 μg ml−1 against all fungi except A. alternata and P. aphanidermatum.

Synthesis of 1‐(β‐D‐ribofuranosyl)indol‐3‐acetic acid

AbstractBy condensation of ethyl indolin‐3‐acetate (4) and 2,3,5‐tri‐O‐benzoylribofuranosyl‐1‐acetate (5), ethyl 1‐(2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)indolin‐3‐acetate (6) was obtained in good yield. The indoline nucleoside 6 was aromatized to ethyl 1‐(2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)indol‐3‐acetate (7) with DDQ. The treatment of the indole nucleoside with barium hydroxide and methanol gave the methyl ester 8, which was further treated in water to give the desired 1‐(β‐D‐ribofuranosyl)indol‐3‐acetic acid (9).

A FACILE, STEREOCONTROLLED ENTRY TO KEY INTERMEDIATES FOR THIENAMYCIN SYNTHESIS FROM ETHYL (S)-3-HYDROXYBUTANOATE

Abstract A new synthetic approach to optically active key intermediates for thienamycin synthesis is described which involves the highly stereocontrolled transformation of the 2-azetidinone obtained via the condensation of ethyl (S)-3-hydroxybutanoate with the N-silylimine of trimethylsilylpropynal.