Chemistry of Heterocyclic Compounds vol.40Pyrrole Oximes:
Synthesis, Reactions, and Biological Activity. (Review) 1-15
Heterocyclic Quinones in ihe Nenitzescu Reaction. Synthesis of
Furo- And Pyrroloquinolines from
2Methoxycarbonyl-4-oxo-5,8-quinolinequinone 16-21 Preparative
Synthesis of 7-Carboxy-2-R-isoindol-1-ones 22-28 Investigations in
the Area of Amines and Ammonium Compounds. 237. Synthesis of
2,2-Dialkyl-4Hydroxymethylbenzo[f]isoindolinium and
2,2-Dialkyl-4-hydroxymethylisoindolinium Salts 29-36 Synthesis and
Anti-HIV-1 Activity of
2-[2-(3,5-Dimethylphenoxy)ethylthio]pyrimidin-4(3H)-ones 37-42
Multicomponent Synthesis of 2,5-Dioxo- and
4-Aryl-5-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydroquinazolines 43-46
Heterocyclization of Functionalized Heterocumulenes with C,N- and
C,O-Binucleophiles. 1. Cyclocondensation of
1-Chloroalkylheterocumulenes and N-(1-Chloroalkylidene)urethanes
with 2-Cyanomethylpyridine 47-57 Anomalous Beckmann Reaction in a
Series of Oximes of
4-Aryl-2,7,7-trimethyl-5-oxo-5,6,7,8tetrahydroquinolines in
Polyphosphoric Acid. 2. Unexpected Synthesis of
3'-Ethoxycarbonyl-4',7',7'-trimethyl-4oxo-2',6',7',8'-tetrahydrospiro(cyclohexa-2,5-diene-1,2'-pyrrolo[4,3,2-d,e]quinolines)
58-64 Trifluoromethyl-substituted Di- and
Tetrahydroazolopyrimidines 65-69 Synthesis of Novel Condensed
Binuclear Heterocycles Based on 1,3- and 1,5-Dicarbonyl Derivatives
of 2,2Dimethyltetrahydropyran 70-74 Condensed Pyridopyrimidines. 7.
Synthesis of Condensed Triazolo[4,3-c]- and
Tetrazolo[1,5-c]pyrimidines 75-78 Condensed Thienopyrimidines. 19.
Study of the Heterocyclization of
2-Hydrazino-6,6-dimethyl-5,6-dihydro-8Hpyranothieno[2,3-d]pyrimidin-4-one
79-83 Thiazolecarboxylic Acid Derivatives. 1. N-Substituted
2-Amino-4-methylthiazole-5-carboxylic Acid Derivatives 84-89
Synthesis of New Branched Hydrazones as Potential Hole-transporting
Materials 90-93 Reactions of 3,4-Dichloro-N-R-maleimides with
Substituted 2-Thiouracils 94-100 1,1-Dichloro-2,2,2-trihaloethyl
Isocyanates and N-(1-Chloro-2,2,2-trihaloethylidene)urethanes in
the Synthesis of 4-Trihalomethyl-2H-1,3-benzoxazin-2-ones 101-105
Synthesis and Study of the Properties of
7,8-Polymethyleneimidazo[4,5-d]-1,3,2-diazaphosphorin-2-thiones
106-113 Synthesis of Lactone from Adamantane-2-spiro-2'-oxirane
114-115 Convenient Method for Synthesis of
6-(N,N-Diethylamino)-9-(2-carboxyphenyl)-1,2,3,4-tetrahydroxanthylium
Perchlorate 116-117 Spiro-bisheterocyclization of
5-Methoxycarbonyl-2,3-dihydro-2,3-pyrrolediones when Treated with
Activated Enamines 118-119 Derivatives of
3,4,5,6-Tetrahydro-6a,10b-diazaindeno[1,2,3-c,d]azulene 120-122
Synthesis of 1-(2-Oxo-2-arylethyl)-3-arylcarbamoylpyridinium
Bromides 123-124 Synthesis of a Novel Heterocyclic System:
7-Methyl-3-methylthio-7,8-dihydro[1,2,4]triazolo[3,4-f][1,2,4]triazine
125-126 Synthesis of 1,6-Polymethylene Pyrimidines Based on
4-(1-Azacycloalkylidene)-1,3-oxazol-5-ones 127-128 Carbon Disulfide
in Synthesis of Thiazolo[3,4-a]quinoxalines Based on
3-(-Chlorobenzyl)quinoxalin-2-(1H)-ones 129-131 Synthesis,
Structure, and Chemical Properties of N-Substituted
2(3)-Imino-2,3-dihydrofuran-3(2)-ones. (Review) 133-152
Isomerization of (Het)arylbenzoins in Basic Media 154-160
Investigation of the Oxidation-Reduction Characteristics of
Heterocyclic Quinones 161-165 Synthesis and Some Chemical
Conversions of 2-([2,2]-5-Paracyclophanyl)pyrrole 166-176
Cyclization of
Dialkyl-(4-hydroxy-2-butynyl)(3-alkenylpropargyl)ammonium Salts and
Recyclization of the 2,2Dialkyl-4-hydroxymethylisoindolinium Salts
Obtained 177-182 Chemistry of Modified Flavonoids. 24. Synthesis of
4- Aryloxy-3-(2-hydroxy-4-hydroxy/alkoxyphenyl)pyrazoles 183-187
Heterocyclic Derivatives of Fullerene C60. 1. Synthesis of New
Fulleropyrazolines by the 1,3-Dipolar Cycloaddition of Nitrile
Imines 188-193 Two Directions of the Reaction of
4-Bromobenzaldehyde with Substituted Acetophenones and Urea.
Synthesis of Aryl-substituted Pyrimidin-2-one and
Hexahydropyrimido[4,5-d]pyrimidin-2,7-dione 194-202 Synthesis and
Properties of Azoles and Their Derivatives. 52. Periselectivity of
[2+3] Cycloaddition of Nitrones to trans--Cyanonitroethylene in the
Light of FMO Theory 203-205 Synthesis and Properties of Azoles and
Their Derivatives. 54. The Regioselectivity of [2+3] Cycloaddition
Of C,C,N-Triphenyl- and Z-C,N-Diphenylnitrones With - and
-Substituted Nitroethylenes in Light of Frontier Molecular Orbital
Theory 203-210 Condensation of Ethyl 2-Oxoindoline-3-glyoxylate
with o-Aminophenol and o-Phenylenediamine 211-213 Synthesis of
3-(3-Acetyl-5-aryl-2,3-dihydro-1,3,4-oxadiazol-2-yl)chromones
214-218 Synthesis of Some Biologically Active Pyrazole,
Thiazolidinone, and Azetidinone Derivatives 219-226 Synthesis and
Properties of 12(E)-Ethoxyimino Derivatives of
8-Aza-16-thiagona-12,17-diones 227-230 Novel Approaches to
Synthesis of 4-Alkyl-6-amino-5-cyano-3-methyl(propyl,
phenyl)-2H,4H-pyrano[2,3c]pyrazoles 231-240 4-Nitrophenyl
N-(1-Aryl-2,2,2-trifluoroethylidene)urethanes: Novel
1,3-Electrophilic Components of Reactions Leading to 6- and
7-Membered Heterocycles 241-244 Characteristic Features of a Hetero
DielsAlder Reaction: the Reaction of Aroylketene with Allobetulone
as an Example 245-246 Regioselective Cycloaddition of Azomethines
and Carbodiimides to Aroyl(quinoxalinyl)ketenes 247-248 Cyclization
of o-Carboxyanilides of Aroylacetic Acids: a Route to a Novel Class
of Heterocyclic Enamino Ketones 249-250 Instructions to Authors
251-256 The Pfitzinger Reaction. (Review) 257-294
Trimethylsilylcyanation of
N-[3-(2-Furyl)-2-propenylidene]trifluoromethylanilines 295-300
Interaction of 5-Aryl-2,3-dihydrofuran-2,3-diones with Functionally
Substituted Hydrazides and Diaminoglyoxal Diphenylhydrazone 301-307
Synthesis of Some Halogen- and Nitro-substituted Nicotinic Acids
and Their Fragmentation Under Electron Impact 308-314 Regioisomeric
Acetoxy Derivatives of 8-Aza-D-homogona-12,17a-dione. Annelation of
1-Methyl-3,4dihydroisoquinoline with
4-Acetoxy-2-acetylcyclohexane-1,3-dione 315-319 The Kost-Sagitullin
Rearrangement in a Series of
1-Alkyl-2-(carbamoylmethyl)-4,6-dimethylpyrimidinium Iodides
320-325 Heterocyclization of Oximes of
3,5-Dimethyl(1,3,5-trimethyl)-2,6-diphenylpiperid-4-ones and
N-Benzylpyrrolid-3ones with Acetylene in a Superbasic Medium
326-333 Novel Aspects of the Reaction of
3-(Benzimidazol-2-yl)-2-iminocoumarins with Aromatic Aldehydes
334-342 Synthesis of Lariat Diazacrown Ethers with Terminal Amino
Groups in the Side Chains 343-350 Acylation of
3,4-Dihydropyrrolo[1,2-a]pyrazines 351-360
Conversion of Amino Group in Position 6 of Uracil 361-363 [3+2]
Cycloaddition of Dimethyl Acetylenedicarboxylate, Methyl Acrylate,
and Ethyl Acrylate to
4,5-Dihydro-5methyl-3H-spiro[benz-2-azepine-3,1'-cyclohexane]
N-Oxide 364-369 Synthesis of
2-Trihalomethyl-3,4-dihydrothieno[2,3-d]pyrimidin-4-ones 370-376
Synthesis and Properties of Substituted
Isoxazolo[3',4':4,5]thieno[2,3-b]pyridines 377-386 N. D. Zelinsky
Institute of Organic Chemistry, Russian Academy of Sciences: 70
Years 387-391 Modification of the Peripheral Substituents in
Chlorophylls a and b and Their Derivatives (Review) 393-425
Phosphorylation of Furfural by Secondary Phosphine Oxides 426-429
Indole Derivatives. 142. Some Properties of
[4-(2-Indolyl)phenyl]phenylmethane and
1-[4-(2-Indolyl)phenyl]-2phenylethane 430-435
Dipyrrolo[1,2-a:2',1'-c]pyrazines. 8. Electrophilic Substitution in
Dipyrrolo[1,2-a:2',1'-c]pyrazines and
5,6Dihydrodipyrrolo[1,2-a:2',1'-c]pyrazines. Acylation of
Dipyrrolo[1,2-a:2',1'-c]pyrazines 436-445 Synthesis and
Heterocyclization of -Aroyl--diphenylphosphorylpropionic Acids
446-451 Synthesis and Antimicrobial Activity of Substituted
5-Cyano-6-oxo-2-styrylnicotinic Acids 452-455 Investigation of
H-Complex Formation of Derivatives of Naphthalimide with Phenol by
IR Spectroscopy 456-459 Interaction of Methyl
5,6-Dialkyl-2-amino-3-cyanopyridine-4-carboxylates with Primary
Amines 460-464 Investigation of the Nucleophilic Rearrangement of
2-(Cyanomethyl)-1,4,6-trimethylpyrimidinium Iodide Into
4,6Dimethyl-2-methylaminonicotinic Acid Nitrile 465-468 Synthesis
and Properties of Symmetrical and Asymmetrical Phthalocyanines with
D,L-Leucine Fragments 469-474 Synthesis and Rotamerism of
9,10-Diarylsubstituted
1,2,3,4,5,6,7,8,9,10-Decahydroacridine-1,8-Diones 475-480 Acylation
and Cyclodehydration of Benzofuran-, Benzothiophene-, and
Indolyl-3-acetic Acid Arylamides. Synthesis of Novel
Benzofuro[2,3-c]-, Benzothieno[2,3-c], and Indolo[2,3-c]pyrilium
and Pyridine Derivatives 481-489 Condensation of
1-Amino-4-azafluorene with -Diketones and ,-Unsaturated Ketones
490-495 Cyclizations of
N-(1-Chloro-2,2,2-trihaloethylidene)-O-methylurethanes with
5-Amino-3-methylisoxazole and 3Amino-5-methylisoxazole 496-499 New
Derivatives of Thiazole with Mesomorphous Properties 500-502
Reaction of 1,2,3-Selenadiazoles with Phosphines 503-506
Psychotropic Preparations Sydnophen and Sydnocarb as Donors of
Nitrogen Monoxide 507-509 Synthesis of Derivatives of
8-Cyano-6-ethoxycarbonyl-3-hydroxy-5-methylimidazo[1,2-a]pyridine
and 9Alkoxycarbonyl- (or
9-Carboxy)-3-ethoxycarbonyl-2-methyl-10H-benzo[b]-1,8-naphthyridine-5-one
from the Reaction of
2-Chloro-5-ethoxycarbonyl-6-methylnicotinonitrile with Amino Acids
510-515
6-Arylamino-3-methyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines:
Novel N-Arylamidine Structures 516-518 Unusual Reaction of
5-Ethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine with Ethyl
Propiolate 519-520 Unusual Reaction of
1-Acetyl-5-bromo-1H-indole-2,3-dione with Ethyl
(Triphenylphosphoranylidene)acetate 521-522 Novel Synthesis of
Substituted Benzimidazoles by Reduction of Esters of
4-Alkylamino-3,5-dinitrobenzoic Acids by Tin Chloride 523-524 Novel
Stereoselective Synthesis of Chiral Nonracemic cis- and
trans-3-Alkyl-4-aminopiperidines 525-527 7-Oxo-3,7-dihydro- and
1,2,7-Trioxo-1,2,3,7-tetrahydropyrano[3,2-e]indoles 528-529 Unusual
Condensation of
6,7-Dimethoxy-1,3,3-trimethyl-3,4-dihydroisoquinoline with
4-Antipyrylidenebarbituric Acid
530-531 Novel Synthesis Route for Pyrrolo[1,2-a]quinazolines
532-533 Novel Synthesis for 4-Hydroxy-2-phenyl-2H-benzotriazoles
534-535 Oxidation of Heterocyclic Compounds by Permanganate Anion.
(Review) 537-560 Synthesis of N-Substituted
-Alkoxy-3-aryl-4-methyl-2,5-dihydro-2-pyrrolones 561-569 Conditions
for the Selective Conversion of Quaternary
3-Anilino-1,5-dimethylpyrazolium Salts into
3-Anilino-1,5dimethylpyrazole 570-574 Interaction of ,-Unsaturated
Ketones of the Adamantane Series with N,N'-Binucleophiles 575-581
Stereodirected Catalytic Synthesis of Perhydroacridines and Their
Isologs from Decahydroacridine-1,8-diones 582-593 Simple Synthesis
of 6-Substituted 4a-Methyl-1,2,3,4,4a,10b-hexahydrophenanthridines
and -9,10Benzophenanthridines 594-598 Synthesis of Formyl
Derivatives of 2-Hetarylimidazoles Annelated with Naphthalene and
Phenanthrene Rings 599-602 Condensed Isoquinolines. 16. Enamine
Properties of Benzo[4,5]imidazo[1,2-b]isoquinolin-11(5H)-one in
Terms of Its Acylation Reactions 603-615 Synthesis of 2-Substituted
and 2,3-Disubstituted Quinazolin-4-ones Containing a Sterically
Hindered Phenol Residue 616-621 Some Chemical Transformations of
4,5-Dihydro-5-methyl-3H-spiro[benz-2-azepine-3,1'-cyclohexane]
N-Oxide 622-630 A Facile Synthesis of Substituted Benzodiazepines
Using Solid Support 631-634 Synthesis of
3-(3-Alkyl-5-thioxo-1H-4,5-dihydro-1,2,4-triazol-4-yl)aminocarbonylchromones
635-640 Oxidative Reactions of Azines. 11. The Influence of
Manganese Dioxide on the Reaction of Tetrahydropyridines with
Formaldehyde: Synthesis and Molecular Structures of
3-Oxa-7-azabicyclo[3.3.1]- and 6-Oxa-2azabicyclo[3.2.1]octanes
641-649 A New Route to Partially Hydrogenated
Thiazolo[3,2-a]pyridine 650-659 Halocyclization of Substituted
2-(Alkenylthio)pyrimidin-6-ones 660-666 Reaction of
2-Aminothiazoles and Their Benzo- and Naphtho Derivatives with
-Sulfonyltrifluoromethylvinyldiols 667-675 Quantum-chemical Study
of the Structure of 1,2,2,3,4,4-Hexachloro-1,3-diphosphetane
Isomers 676-679 Third Balticum Organicum Syntheticum Conference in
Riga 681-683 Heterocalixarenes. (Review) 683-700 Hydrosilylation Of
(Hetero)aromatic Aldimines in the Presence of a Pd(I) Complex
701-714 Synthesis and Cytotoxic Activity of 4-Substituted
3-Cyano-6,6-dimethyl-5,6-dihydro-2-pyranones 715-724 Unnatural
Amino Acids. 2. Simple Method of Obtaining Esters of
Aziridine-2-carboxylic Acids by a Transesterification Reaction
725-733 Interaction of Hydroxylamine with Esters of 2-Oxobutenoic
Acids. Synthesis of 1-Hydroxy-3-hydroximino-2pyrrolidinones 734-741
Synthesis and Cytotoxicity of Derivatives of Di(3-indolyl) Selenide
742-746 Nitrogen NMR Shieldings of Some Nitro Derivatives of
2-Amino-4-methylpyridine Systems 747-752 Electrochemical Oxidation
of Compounds Containing 1,4-Dihydropyridine and Pyridinium Rings
Analogs of Gene Transfection Agents 753-758 Activation of
Pyridinium Salts for Electrophilic Acylation: a Method for
Conversion of Pyridines into 3Acylpyridines 759-766
Condensation Products of
1-Aryl-3-ethoxycarbonyl-2-methyl-1,4,5,6-tetrahydro-4(1H)pyridones
with Hydrazine, Phenylhydrazine, and Hydroxylamine 767-775
Synthesis of Quinoline-8-selenol, Its Complex Compounds with Metals
and Their Cytotoxic Activity 776-780 Synthesis and Cyclization of
N-(4-Phenoxyphenyl)--alanines 781-787 Synthesis and Reactions of
(6-Methyl-2-methylsulfanyl-4-oxo-3,4-dihydro-3-pyrimidinyl)acetyl
Azide 788-791 Cyclization of the Reaction Products of
p-Phenylenediamine with Maleic Acid 792-796 Addition of Nitrile
Oxides to Aryl Allyl Ethers 797-800 Reaction of N-Phenylbenzamidine
with O-Acetylbenzeneoximoyl Chloride 801-806 Oxidative
Recyclization of
4,6,7-Trichloro-5-hydroxy-2-(2-pyrimidylamino)-2,3-dihydrobenzo[b]furan
807-810 Synthesis of Substituted
5,6-Dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines 811-815
Synthesis of Cytotoxic 4-Sulfonyl-, 4-Sulfonylthio-and
4-Sulfothioazetidinones-2 816-822 Gunars Duburs Seventieth Birthday
823-828 The Seventieth Birthday of Professor Andris Strakovs
829-830 Oleg Nikolaevich Chupakhin Seventieth Birthday 831-833
Benzo[b]tellurophene, Dibenzo[b,d]tellurophene, and Their
Derivatives. (Review) 834-853 Acylation of Amines with
5-Phenyltetrazol-2-ylacetyl Chloride 854-861 Synthesis of
6-Bromomethyl-substituted Derivatives of Pyridin-2(1H)-ones and
Their Reaction with Nucleophiles 862-867 Reaction of
3,5-Carbonyl-substituted 1,4-Dihydropyridines with Hydrazine
Hydrate 869-875 Synthesis, Cardiovascular Activity, and
Electrochemical Oxidation of Nitriles of
5-Ethoxycarbonyl-2-methylthio1,4-dihydropyridine-3-carboxylic Acid
876-887 Cyclocondensation of 2-Fluoro-5-nitrobenzaldehyde with
Amidines. New Synthesis of Isoquinolines 888-894 Oxidative Addition
of N-Aminophthalimide and 3-Amino-2-methylquinazolin-4(3H)-one to
Conjugated Azocyclopentenes and Azocyclohexenes 895-902 Ring-Chain
Tautomerism of 1,2,3,4-Tetrahydroquinazolines. The Products of
Reaction of 1,3-Dicarbonyl Compounds with 2-Aminomethylaniline
903-910 Regioselectivity of Nucleophilic Attack on the Reactions of
1,2,4-Triazine 4-Oxides with Certain C-Nucleophiles 911-915
Synthesis of Derivatives of 1,3,4-Oxadiazoles Based on
Monohydrazides of 2-Aryl-4-methyl-4-cyclohexen-1,2dicarboxylic
Acids 916-918 Synthesis of 2-Aryl and 2-Hetaryl Derivatives of
2'-Aminospiro[(1,3-dioxane)-5,5'-thiazolin]-4'-one and
Spiro[(1,3dioxane)-5,5'-thiazolidine]2',4'-dione 919-926 Tautomeric
and Conformational Isomerism of Mercaptoacetylhydrazones of Methyl
Alkyl Ketones 926-930 Candida Rugosa Lipase-catalyzed Kinetic
Resolution of 3-(Isobutyryloxy)methyl
4-[2-(Difluoromethoxy)phenyl]-2methyl-5,5-dioxo-1,4-dihydrobenzothieno[3,2-b]pyridine-3-carboxylate
931-937 Reactions of 2-Amino-4-methyl-6-(2-pyridyl)- and
2-Amino-4-methyl-6-phenyl-7,8-dihydroindazolo[4,5-d]thiazoles with
Aldehydes 938-943
10-Aryl-7,7-dimethyl-5,6,7,8,9,10-hexahydro-11H-pyrido[3,2-b][1,4]benzodiazepin-9-ones
944-948 11-Aryl-3,3-dimethyl-7- and 7,8-Substituted
1,2,3,4,10,11-Hexahydro-5H-dibenzo[b,e]-1,4-diazepin-1-ones 949-955
Selective Cyclopropanation of Chromenes with a Phenylacryloyl
Substituent by Bromine-containing Zinc Enolates 956-957
Unexpected O-Methylation of
N-(2-Hydroxyethyl)-1,2,3,4-tetrahydroquinoline and
-1,2,3,4-Tetrahydroisoquinoline in Silylalkylation by
Trimethylchloromethylsilane under Phase-transfer Catalysis
Conditions 958-959 Cyclization of N,N-Bis(2-chloroethyl)methylamine
in Aqueous Hydrazine 960-961 Kishner Reduction of
3,3-Dimethyl-6-trifluoromethyl-1,2,3,4-tetrahydroindolo[2,3-c]quinolin-1-one
962-963 Transformations of 5-Amino-4-(3,4-dimethoxyphenyl)pyrazoles
in the Diazotization Reaction 964-965 Synthesis and Characteristics
of Tetracyclic Systems of Benzo[b]furoindoles and Their
Derivatives. (Review) 967-978 Investigation in the Area of Furan
Acetal Compounds. 13. Synthesis and Structure of 1,3-Dioxacyclanes
Based on Furfural and Glycerol 979-985 Features of the Reaction of
Heterocyclic Analogs of 2'-Alkoxychalcones with Lanthanide Shift
Reagents 986-991 Reactions of Amidines with
5-Methylene-1,3-dioxolan-2-ones 992-1001 Synthesis of Arylidene
Derivatives of 1-Aryl-3H-pyrrol-2-ones 1002-1006 Synthesis of Ethyl
cis- and trans-4-Chloro-5-oxo-1,2-diphenylpyrrolidine-2-carboxylate
1007-1008 Synthesis, Structure, and Some Properties of Substituted
3-Carbethoxy(methoxy)-5-cyano-1,2,3,4tetrahydrospirocyclohexane-4-pyridine-2-thiones
1009-1016 Regioselective Synthesis and Properties of
6-Amino-3-carbamoyl-5-cyano-3,4-dihydrospirocyclohexane-4pyridine-2-thiol
and 5-Cyano-3-thiocarbamoyl-4-spirocyclohexanepiperidine-2,6-dione
1017-1023 Reaction of Polyfluorinated -Diimines with Ketones. A
Novel Method for the Synthesis of Fluorinated Pyridines 1024-1030
Characteristics of the Dissociative Ionization of
9-Aryl(hetaryl)-3,3,6,6-tetramethyldecahydroacridine-1,8-diones
under the Influence of Electron Impact 1031-1035 Synthesis of
3,3-Dialkyl-1-(3-coumarinyl)-3,4-dihydroisoquinolines 1036-1038
Studies on Reactions of Cyclic Oxalyl Compounds with Hydrazines or
Hydrazones. 2. Synthesis and Reactions of
4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic Acid
1039-1046 Synthesis of Pyridazinone Derivatives 1047-1051 Condensed
Isoquinolines. 17. Enamine Properties of
Benzimidazo[1,2-b]isoquinolin-11(5H)-one in Alkylation Reactions
1052-1062 4-Oxo-3,4-dihydroquinazolinyl- and
Benzimidazolylacetonitriles in Annelation Reactions of a
Haloquinoline Ring 1063-1069 Interaction of Cyclic Schiff's Bases
with 2-Methylthiopyrimidine-4,6-dione Enol Acetate. Synthesis of
5-(2-Acetyl6,7-dimethoxy-1,2,3,4-tetrahydro-1-isoquinolyl)-6-hydroxy-2-methylthio-1,4-dihydro-4-pyrimidinones
1070-1076 Study of the Products of Iodocyclization of
4-Allyl-5-phenyl-1,2,4-triazole-3-thione 1077-1082 Reactions of
1,3-Substituted Benzothieno[2,3-c]pyrylium Salts with Primary
Amines 1082-1086 Reaction of Substituted
2-Allylthiopyrimidin-4(3H)-ones with Sulfenyl Chlorides 1087-1091
2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones
1092-1096 Substituted and Spiro-annelated
Perhydro-1,2,3-oxathiazine 2,2-Dioxides and
1-Benzyl-4-methylazetidines 1097-1105 Hetarylcyanamides. (Review)
1107-1123 The Use of
4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one as Masked
-Bromo-'-Hydroxy Ketone in the Synthesis of Heterocyclic Systems
1124-1130 Synthesis and Reactions of
1-(3-Chloropropyl)-6,7-dimethoxy-3-methylbenzo[c]pyrylium
Perchlorate 1131-1136 Synthesis and Structure of
Di-N-arylpyrrolo[1,2-c;5,6-c]cyclooctanes 1137-1141 Reactions of
Hydroxyazolidines with -Donor Heterocycles. 3. Reaction of
1-Acetyl-5-hydroxypyrazolidines with Oxindoles
1142-1149 Heterocyclic Derivatives of Fullerene C60. 2.
Cycloaddition to Fullerene C60 of the Products of
Dehydrochlorination of N-Benzyltrifluoroacetimidoyl Chlorides
1150-1154 Interaction of
5-Acetyl(alkoxycarbonyl)-3-alkoxycarbonyl-6-methylpyridin-2(1H)-ones
with Primary Aromatic Amines and Hydrazine Hydrate 1155-1161
Derivatives of sym-Triazine. 3. Synthesis and Some Conversions of
Monoazides of the Triazine Series 1162-1168 Derivatives of
sym-Triazines. 6. Some Special Features of the Addition of
Substituted Acetylenes to Triazine Monoazides 1169-1173 Reactions
of 2,3-Dioxopyrrolo[2,1-a]isoquinolines with Ammonia and Aliphatic
Amines 1174-1178 Condensed Isoquinolines. 18. Enamine Properties of
Benzimidazo[1,2-b]isoquinolin-11(5H)-one in the Michael Reaction
1179-1184 Studies on Pyrazine Derivatives. 38. Synthesis,
Reactions, and Tuberculostatic Activity of Pyrazinyl-substituted
Derivatives of Hydrazinocarbodithioic Acid 1185-1193 Synthesis of
Substituted 1,2,4-Triazoles and 1,3,4-Thiadiazoles 1194-1198
Isomerization in the Oxidative Cyclocondensation of
2-Aroylmethyl-1H-benzimidazoles with o-Aminothiophenol 1199-1206
Unexpected Direction of Iodocyclization of
3-Allylthio-5-phenyl-4H-1,2,4-triazole 1207-1211 Reaction of
10-Methyl(phenyl)-5,10-dihydrophenarsazine 10-Oxides with Hydriodic
Acid 1212-1215 Novel Route to 2,6-Diphenyl-1,4-dithiine 1216-1217
3-Aryl-2-chloropropanals in Hantzsch Synthesis of Pyrroles
1218-1219 Synthesis of Amino Acid Esters: Derivatives of
1,2,3,4-Tetrahydroisoquinoline 1220-1221 Novel Variant of
Recyclization of N-Arylmaleimides when Reacted with Aminoazoles
1222-1223 Reductive Cyclization of N-(2,4-Dinitrophenyl)pyridinium
Chloride by Tin(II) Chloride 1224-1225 Reaction of
10-Cyanotetrahydrobenzo[b][1,6]naphthyridines with
Acetylenedicarboxylic Ester 1226-1227 Unexpected Reaction of
Thiosemicarbazide with
3,6-Bis(vinylsulfonyl)-1,2,4,5-tetrafluorobenzene 1228-1229 Aleksei
Vsevolodovich Bogatsky (75th Anniversary of his Birth) 1230-1234
Vadim Aleksandrovich Pestunovich (January 6, 1942 -- July 4, 2004)
1235-1242 Reactivity of pyrrol-2-ones. (review) 1243-1261
Phenyl-substituted porphyrins. 1. Synthesis of
meso-phenyl-substituted porphyrins 1262-1270 Derivatives of indole.
143.* synthesis of photochromic derivatives of 2-arylindoles
1271-1278 Polyfunctional pyrazoles. 3.* Synthesis of
3-(3-aryl-4-formyl-1-pyrazolyl)propionic acids and their amides
1279-1282 A novel spiroheterocyclization: synthesis of
1-ethoxycarbonylmethylidene-8-(2-ethoxycarbonylmethylidene-5,5dimethyl-3-pyrrolidinylidene)-3,3,6-trimethyl-2-azaspiro[4,5]deca-6,9-diene
1283-1287 [3 + 3] Cyclocondensation of
1-alkyl-3,4-dihydroisoquinolines with -keto esters. New annelation
reaction in a series of cyclic Schiffs bases 1288-1294 Chemistry of
Acyl(imidoyl)ketenes. 8. Thermolysis of
3-Alkoxycarbonyl-5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones.
Structure of
2-(3-oxo-4-phenyl-3,4-dihydro-2-quinoxalinyl)-2,4-di(ethoxycarbonyl)-6phenyl-2,3,5,6-tetrahydro-1h-pyrido[1,2-a]quinoxaline-1,3,5-trione
1295-1299 Reaction of 3-acylamino- and 3-alkoxybenzo[c]pyrilium
salts with hydrazine 1300-1304 Dehydration of
4-hydroxy-4-methyl-3-phenylamino-oxazolidin-2-ones 1305-1309
Regioselectivity of the interaction of
(1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol with some
symmetrical ketones 1310-1314 Novel schemes for the synthesis of
pyrrolocoumarins 1315-1322 Recyclization of 2-iminocoumarins using
nucleophilic reagents. 6. Reaction of
2-iminocoumarin-3-carboxamides with 2-aminobenzophenones 1323-1331
Intramolecular cyclization of
5-aryl-3-arylamino-4-benzoyl-1h-3-pyrrolin-2-ones to
pyrrolo[3,4-b]quinolines 1332-1334 Synthesis of
7-oxopyrrolo-[3,2-d]pyrimidine 5-oxides by the rearrangement of
6-alkynyl-5-nitropyrimidines 1335-1338 Synthesis of derivatives of
7,8-dihydrothiazolo[2,3-i]purine by halocyclization of
6-allylthiopurine 1339-1341 Condensed pyridopyridimines. 8.
Synthesis of new derivatives of
pyrano[3,4:6,7]pyrido[2,3-d]pyrimidine 1342-1345 Formation of the
pyrroline N-oxide ring by interaction of -isonitrosoketones
derivatives of tetrahydrobenzofurazan and -furoxan with aldehydes
and morpholine and some of the reactions of these compounds
1346-1351 New method for the synthesis of thieno[2,3-d]pyrimidines
1352-1358 Annelation of 3,4-dihydroisoquinolines by
3-acyl-5,5-dimethylthiopyran-2,4-diones. Synthesis and properties
of 8aza-17-thia-d-homogona-12,17a-diones 1359-1369 First example of
hydro-thiophosphorylation of 3-thiolene 1,1-dioxide 1370-1372
Synthesis of
3-chloro-6,6-diphenyl-6,11-dihydropyrido[1,2:1,2]imidazo-[4,5-b]quinoline
based on reaction of 2chloromethyl-4,4-diphenyl- 4h-3,1-benzoxazine
with 2-amino-5-chloropyridine 1373-1374 A. N. Nesmeyanov Institute
of Organoelement Compounds (INEOS), Russian Academy of Sciences: 50
years 1375-1379 Antibiotics produced at the G. F. Gauze
Scientific-Research Institute of new antibiotics, Russian Academy
of Medical Sciences (marking the fiftieth anniversary of the
institute). (review) 1381-1395 Antibiotics produced at the G. F.
Gauze Scientific-Research Institute of New Antibiotics, Russian
Academy of Medical Sciences (marking the Fiftieth Anniversary of
the Institute). (Review) 1381-1395 Self-oscillating reaction In the
Furan series 1396-1401 Self-oscillating reaction in the furan
series 1396-1401 Heterocyclic synthesis using Nitrile imines. 4.
synthesis of 3-substituted 1-aryl-1,2,4-triazaspiroalk-2-enes
1402-1407 Heterocyclic synthesis using nitrile imines. 4. Synthesis
of 3-substituted 1-aryl-1,2,4-triazaspiroalk-2-enes 1402-1407
Chemistry of 3-hetarylcoumarins. 2*. 3-(2-thiazolyl)coumarins
1408-1420 Chemistry of 3-hetarylcoumarins. 2.
3-(2-thiazolyl)coumarins 1408-1420 Reactions of
4-Cyanobenzo-[c]pyrylium salts with Nitrogen-containing
nucleophiles 1421-1426 Reactions of 4-cyanobenzo[c]pyrylium salts
with nitrogen-containing nucleophiles 1421-1426 Concerning the
product of [2 + 2] cyclodimerization of 9-allenylcarbazole
1427-1434 Concerning the product of [2 + 2] cyclodimerization of
9-allenylcarbazole 1427-1434 New derivatives of 3-Aminoindole.
Synthesis of 2-Aryl(Hetaryl)-3-(3,5-Dimethyl-1-Pyrazolyl)indoles
1435-1441 New derivatives of 3-aminoindole. Synthesis of
2-aryl(hetaryl)-3-(3,5-dimethyl-1-pyrazolyl)indoles 1435-1441
Alkylation of 3-cyano-4-methoxymethyl-6-methyl-2(1h)-pyridone by
active Halomethylene compounds. The Molecular structure of
3-amino-2-benzoyl-4-methoxymethyl-6-methylfuro[2,3-b]pyridine
1442-1453 Alkylation of
3-cyano-4-methoxymethyl-6-methyl-2(1h)-pyridone by active
halomethylene compounds. The molecular structure of
3-amino-2-benzoyl-4-methoxymethyl-6-methylfuro[2,3-b]pyridine
1442-1453 Synthesis and reductive reactions of
2,3-dioxo-2,3-dihydrobenzo-[b]furo[2,3-f]-, -[2,3-g]-, and
-[3,2-e]indoles
1454-1459 Synthesis and reductive reactions of
2,3-dioxo-2,3-dihydrobenzo[b]furo[2,3-f]-, -[2,3-g]-, and
-[3,2-e]indoles 1454-1459 Synthesis of
3,9,9,9a-tetramethyl-1,2,3,9a-tetrahydro-9h-imidazo[1,2-a]-indol-2-ones
by reaction of 2,3,3trimethyl-3h-indole with 2-bromopropionamides
1460-1464 Synthesis of
3,9,9,9a-tetramethyl-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]-indol-2-ones
by reaction of 2,3,3trimethyl-3H-indole with 2-bromopropionamides
1460-1464 Synthesis of
1,2,3,9a-tetrahydro-9h-imidazo[1,2-a]indole-2-thione and
1,5,6,10b-tetrahydroimidazo[2,1-a]isoquinoline-2(3h)-thione
derivatives 1465-1469 Synthesis of
1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indole-2-thione and
1,5,6,10b-Tetrahydroimidazo[2,1-a]isoquinoline-2(3H)-thione
derivatives 1465-1469 Reactions of 5-diazoimidazoles With steroid
hydrazones 1470-1476 Reactions of 5-diazoimidazoles with steroid
hydrazones 1470-1476 Synthesis of
2-r-4,5,7-trimethyl-1-vinyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridines
1477-1484 Synthesis of
2-R-4,5,7-trimethyl-1-vinyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridines
1477-1484 Synthesis of
6-aryl-1,6-dihydro-dipyrazolo[3,4-b:4,3-c]pyridines 1485-1489
Synthesis of 6-aryl-1,6-dihydrodipyrazolo[3,4-b:4,3-c]pyridines
1485-1489 A convenient one-pot synthesis of
benzopyrimido[1,8]naphthyridines by knoevenagel condensation
1490-1492 A convenient one-pot synthesis of
benzopyrimido[1,8]naphthyridines by Knoevenagel condensation
1490-1492 Cyclization of -[(s)-1-phenylethyl]-amino alcohols to
form chiral 1,3-disubstituted phthalanes 1493-1494 Cyclization of
-[(S)-1-phenylethyl]-amino alcohols to form chiral
1,3-disubstituted phthalanes 1493-1494 Efficient route to
substituted 2-aminoquinoline 1495-1496 Efficient route to
substituted 2-aminoquinoline 1495-1496 Novel cyclocondensation of
2-acylethynyl-1-amino- and
2-alkoxycarbonylethynyl-1-amino-anthraquinones with pyridines
1497-1498 Novel cyclocondensation of 2-acylethynyl-1-amino- and
2-alkoxycarbonylethynyl-1-amino-anthraquinones with pyridines
1497-1498 Unexpected reaction of
3-benzoyl-4-hydroxy-1-methyl-4-phenylpiperidine with
1,2-diaminobenzene 1499-1501 Unexpected reaction of
3-benzoyl-4-hydroxy-1-methyl-4-phenylpiperidine with
1,2-diaminobenzene 1499-1501 Method for synthesis of
2-amino-5-(2-thienylmethyl)thiazole 1502-1503 Method for synthesis
of 2-amino-5-(2-thienylmethyl)thiazole 1502-1503 Unusual reaction
of 3,6-dimethoxy-benzonorbornadiene with
2-chloro-sulfenyl-1-pyridine 1-oxide 1504-1505 Unusual reaction of
3,6-dimethoxy-benzonorbornadiene with 2-chloro-sulfenyl-1-pyridine
1-oxide 1504-1505 Novel method for synthesis of polynuclear
heterocyclic systems with a pyridazine ring 1506-1507 Novel method
for synthesis of polynuclear heterocyclic systems with a pyridazine
ring 1506-1507 Unexpected oxidation of azafluoren-9-ones under
Baeyer-Villiger conditions 1508-1509 Spirothiazolo[4,2]- and
thiazolo-[3,4-a]quinoxalines based on
3-(-bromoethyl)quinoxalin-2-ones and thiourea 1510-1512 Emilija
Gudriniece (August 3, 1920 October 4, 2004) 1513-1515 4,7-Dihydro-,
4,5,6,7-tetrahydro-, and octahydroisoindoles (and
methanoisoindoles). (Review) 1517-1535
Synthesis of 5-amino-4-hetaryl-2,3-dihydro-1h-3-pyrrolones
1536-1542 2-(1-Adamantyl)-7-methylimidazo-[1,2-]pyridine and its
reactions with N-bromosuccinimide 1543-1545 Preparation of
1-amino-4-methylpiperazine 1546-1549 Investigation of the products
of interaction of cyclic diketones with nitrogen-containing
1,4-binucleophiles 1550-1559 Investigation of naphthyridines. 16.
Synthesis of derivatives of
2,5-dioxo-1,2,5,6,7,8-hexahydro-1,6naphthyridine-3-carboxylic acids
from anilides (hydrazides) of 6-oxo-2-styrylnicotinic acids
1560-1563 New synthesis of the dihydroindolizinoquinoline system by
intramolecular cyclization of sulfur ylide 1564-1567
Quantum-chemical study of the structure and thermochemical
properties of nitropiperazines and nitrosopiperazines 1568-1587
2-R-6-ethyl-7-hydroxy-3-(5-phenyl-1,3,4-thiadiazolyl-2)chromones
1588-1594 Reactions of -acetylenic ketones with
n-3-amidinothioureas. 1. Synthesis and properties of new
derivatives of 1,3-thiazine 1595-1599 Synthesis and properties of
(thieno[2,3-b]pyridin-3-yl)iminotriphenylphosphoranes. Molecular
structure of
(2benzoyl-4-methoxymethyl-6-methylthieno[2,3-b]pyridin-3-yl)iminotriphenylphosphorane
1600-1608 Study of nitrogen- and sulfur-containing heterocycles.
54. Properties and conversions of
pyrimido[4,5-b]-1,4benzothiazepines. Synthesis of a novel
heterocyclic system: Pyrimido[5,4-c]isoquinoline 1609-1617 Study of
reaction of 5-aryl-2,3-dihydro-2,3-furandiones with
n-cyanotriphenylphosphinimine. Molecular and crystal structure of
the solvate of
6-p-tolyl-2-triphenylphosphinimino-4H-1,3-oxazin-4-one with
acetonitrile 1618-1625
Chemistry of Heterocyclic Compounds, Vol. 40, No. 1, 2004
PYRROLE OXIMES: SYNTHESIS, REACTIONS, AND BIOLOGICAL ACTIVITY.
(REVIEW)E. Abele, R. Abele, and E. Lukevics Data on the production
methods and reactions of pyrrole aldoximes and ketoximes and their
derivatives are reviewed. The synthesis of new heterocycles from
the pyrrole oximes is examined separately. The principal results
from investigation of the biological activity of pyrrole oximes are
described. Keywords: oximes, pyrrole, biological activity. Pyrrole
oximes are widely used as intermediates in fine organic synthesis.
In the present work the methods for the production and the
reactions of pyrrole oximes are reviewed. Methods for the synthesis
of new heterocycles from derivatives of these oximes are dealt with
in a separate section. The principal methods for investigation of
the structure of pyrrole oximes with regard to isomerism are also
briefly examined. The main paths for the selective production of
the E- and Z-isomers of the oximes and their O-ethers are
described. The last section of the paper gives the results from
research into the biological activity of derivatives of pyrrole
oximes.
1. SYNTHESIS AND STRUCTURE OF PYRROLE OXIMES 1.1. Synthesis of
Pyrrole Oximes The classical method for the synthesis of pyrrole
oximes is based on the reaction of an aldehyde or ketone with
hydroxylamine hydrochloride in pyridineethanol [1, 2], sodium
acetatemethanol or ethanol [3-6], sodium carbonateethanolwater [7],
or potassium hydroxideethanol [8] systems. By modifying these
methods it is possible to obtain the pyrrole oxime 2 from
5-bromo-2-dimethylmethylene-3,4-dimethyl-2H-pyrrole (1).
Debromination of the oxime 2 in the system containing palladium on
barium sulfatesodium methoxidesodium hydroxide leads to
3,4-dimethylpyrrolecarbaldehyde oxime (3) [9].Me
Me
NH2OH .HCl MeONa
Me
Me
Me
Me
Pd, BaSO4BrN
Br
N
CHNMe2
CH=NOH
MeONa
N
CH=NOH
1
H 2
H
3
__________________________________________________________________________________________
Latvian Institute of Organic Synthesis, Riga; e-mail: [email protected].
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp.
3-19, January, 2004. Original article submitted August 19, 2003.
0009-3122/04/4001-00012004 Plenum Publishing Corporation 1
Unexpected deiodination during the synthesis of pyrrole oxime
was described in [10]. Thus, the reaction of the aldehyde 4 with
hydroxylamine hydrochloride in the presence of 10% aqueous sodium
hydroxide gives the oxime 5 with a yield of 81% [10].HOOCCH2CH2 I
CH2COOHNH2OH.HCl, NaOH, H2O
HOOCCH2CH2
CH2COOH CH=NOH
N H
CHO
N H
4
5
2-Methoxy-1-pyrroline (6) and hydroxylamine in alcohol give
2-pyrrolidone oxime (7) [11].NH2OH N 6 OMe N H NOH 7
A series of methods for the synthesis of pyrrole oximes were
based on the nitrosation of indole derivatives [12-15]. For
example, pyrrole (8) and alkyl nitrites in the presence of sodium
alcoholates give a salt of the oxime 9 [16]. The ketoxime 11 is
formed as the only product during the nitrosation of
2-acetylpyrrole (10) with amyl nitrite [17]NOH AlkONO, AlkONa N H 8
Me N H 10 O C5H11ONO, NaOEt N H 11 O NOH N 9
The nitrosation of 2-(dimethylaminomethyl)pyrrole (12) with
sodium nitrite in acetic acid gives a mixture of the oxime 13,
N-nitrosodimethylamine, and formaldehyde [18].NO O N H 12 13 NOH +
MeNMe + CH2O
NMe2 N H
NaNO2, AcOH
2
The pyrrole oximes 16 and 17 (ratio 90:10, overall yield 74%)
were obtained successfully by the reaction of pyrrole with the
bromo oxime 14 in the presence of sodium carbonate. The products
are formed through the cycloadduct 15 as intermediate
[19]._PhSO2CBr=NOH (14) K2CO3
_ O N N SO2Ph 15 SO2Ph
N H 8 _
H
SO2Ph N H 16 + NOH N H 17
NOH
1-Methylpyrrole (18) reacts readily with the oxime of ethyl
bromopyruvate in a basic medium and forms the oxime 19 with a 67%
yield [20].NOH Na2CO3 N Me 19 CO2Et
N Me 18
+
Br
CO2Et NOH
The condensation of 3-ethoxycarbonyl-2,4-dimethylpyrrole (20)
with the -diketone monoxime 21 gives the gem-dipyrrolyl derivative
22 [21].EtO2C Me + Me N H Me NOH O Me Me Me N H Me HN Me 20 21 22
CO2Et Me Me HON
EtO2C
The reaction of the dioxime 23 with acetone and morpholine leads
to the formation of
3-hydroxy-2methyl-2-morpholino-4-hydroxyimino-2,3,4,5,6,7-hexahydro-3H-indole
1-oxide (24) with a yield of 80% [22]. 3
NOH O NOH 23
MeCOMe, O
NH
NOH OH Me N N O 24 O
1.2. The Structure of Pyrrole Oximes One of the most reliable
methods for the determination of the structure of isomeric pyrrole
oximes is NMR spectroscopy. In [23] the stereochemistry of the
oximes of 2-carbonyl derivatives of 1-nitrophenylpyrroles was
studied in detail. 2-Formyl-1-nitropyrroles readily give oximes in
reaction with hydroxylamine and always as a mixture of two isomers,
s-trans-syn (25) and s-trans-anti (26), which can be separated by
chromatography. The ratio of the isomers amounts to 2:1 in the case
of 1-(4-nitrophenyl)-2-formylpyrrole oxime and 4:1 for the
3-isomer. This means that conjugation of the nitro group with the
pyrrole ring stabilizes the s-trans-syn isomer.OH H N N NO2 25 26
OH N N H NO2
The difference between the chemical shifts of -H and OH amounts
to 2.91-2.92 for the syn isomer and 4.30 ppm for the anti isomer.
The 15N1H spinspin coupling constant (12.5 Hz) was determined for
the anti isomer of pyrrole 2-aldoxime in acetone [24]. Several
papers have been devoted to the synthesis, structure, and
transformations of pyrrole aldoximes and ketoximes [25-27]. Thus,
the two isomeric anti (27) (mp 164.5C) and syn (28) (mp 70-71C)
products are formed in the synthesis of 2-pyrrolecarbaldehyde
oxime. The syn isomer of the oxime is less stable and is readily
transformed into the anti isomer on heating, during storage, during
irradiation, or in the presence of HCl. In reaction with copper
acetate the anti isomer 27 forms a 1:1 complex, while the syn
isomer 28 forms a 1:2 complex. It was also shown that the syn
isomer of 2-acetylpyrrole oxime is converted into the anti isomer
in the presence of HCl.Cu(OAc)2 N H 27 N H Cu(OAc)2 N H HON 28 N Cu
N O CHO HCl NOH N NOH Cu/2
4
The structure of pyrrole oximes has also been investigated by UV
spectroscopy [28, 29], polarography [30], spectrophotometry [30,
31], and potentiometry [31].
2. REACTIONS OF PYRROLE OXIMES 2.1. Synthesis of the Ethers of
Pyrrole Oximes The chief method for the synthesis of the O-ethers
of pyrrole oximes is based on the reaction of O-alkyl derivatives
of hydroxylamine with carbonyl derivatives in the presence of
sodium acetate in aqueous ethanol [6]. Another method for the
synthesis of the O-ethers of pyrrole aldoximes is based on the
reaction of the salts of the oximes with alkyl halides. It should
be noted that only the E-isomers of pyrrole aldoximes give O-alkyl
derivatives. Z-Aldoximes give mainly the N-alkylated products
nitrones [32]. Phase-transfer catalysis systems alkyl bromide
(RBr)10% aq. NaOHOct4N+BrPhH or RBrsolid K2CO318-crown-6PhH were
used successfully by the authors for the O-alkylation of pyrrole
oximes. The ketone oximes 29 react with hexacyanocyclopropane (30)
in the presence of metallic sodium and give
2-amino-4,4-di(alkylideneaminooxy)-1,5,6,6-tetracyano-3-azabicyclo[3.1.0]hex-2-enes
31 with yields of up to 74%. The further reaction of compound 31
with the oxime (RR'C=NOH) and sodium leads to the tricyclic
derivatives of oximes 32 [33].RR'C=NO NC NC RR'C=NOH + NC NC 29 30
CN CN CN H2N N 31 R, R' = Alk Na NC CN CN ON=CRR' ON=CRR' N 29, Na
H2N H2N N 32 ON=CRR' CN CN ON=CRR' ON=CRR'
The formamidoximes 33 react with aldehydes in the presence of
DBU and give the tautomeric oximes 36 and 37 with yields of 29-68%.
The products are formed through the intermediates 34 and 35 [34]._
H NC NC N NOR NOR H NC NH2 _ HN O H _ _ O H NH N Ar N H2N _ _ H N N
Ar 35 _ Ar H O N H N NH NOR H NOR Ar H H O N H N NH2 _ NOR H
ArCHO, DBUH
N
36
33
34
N H
R = Me, CH2Ph
37
5
2-Acetylpyrrole O-acetyloxime was obtained by acylation of the
oxime in the acetyl chloride triethylamine system [35]. The pyrrole
ketoxime 38 was also acylated by acids (RCOOH) in the
4-dimethylaminopyridine
(DMAP)3-(dimethylaminopropyl)-1-ethylcarbodiimide (EDCI)methylene
chloride system and gave the acyl derivatives 39 with yields of up
to 78% [36].NOH N Me 38 R = Alk, Py Me RCOOH , EDCI , DMAP , CH2Cl2
N Me 39 NOCOR Me
The pyrrole oxime carbamate (41) was obtained with a yield of
67% from N-(4-nitrobutyl)pyrrole (40) in the presence of phenyl
isocyanate and triethylamine [37].
N NO 2 40
PhNCO, Et3 N
N OCONHPh N
41
2.2. Reactions of Pyrrole Oxime Groups and Rings Recent advances
in the chemistry of oxime derivatives were reviewed in [38]. In
this section the chemistry of pyrrole oximes will mainly be
discussed. The dehydration of the oximes was described extensively
in the review [39]. In addition, pyrrole oximes are easily
transformed into the corresponding nitriles in the presence of
acetic anhydride [5, 40-45], acetic anhydridesodium acetate [46],
p-toluenesulfonic acidDMF [47], or epichlorohydrinsodium methoxide
[48]. Pyrrole aldoximes and ketoximes were hydrogenated to the
corresponding derivatives of primary pyridine amines in the
presence of Raney nickel in dioxane or ethanol [49],
rhodiumaluminum oxide or Raney nickel in methanol [50], or platinum
dioxideacetic acid [51]. During hydrogenation with Raney nickel
4-aryl-5formyl-3-methoxycarbonyl-1,2-dimethylpyrrole oximes (42)
give a mixture of primary amines 43 (yields 32-40%) and dimeric
products 44 (yields 30-35%) [52]. Pyrrole aldoximes were also
reduced to primary amines in the presence of sodium amalgam [53].
The transformation of 2-pyrrolecarbaldehyde oxime to the
corresponding aldehyde (yield 88%) takes place readily in the
presence of cetyltrimethylammonium permanganate [54].R MeO2C MeNi
H2 / MeOH
R MeO2C MeO2C Me
R R
+Me N Me43 R = H, OAlk
CO2Me H N N Me44
N Me42
CH=NOH
CH2NH2
N Me
Me
6
It should also be noted that C-(2-pyrrolyl)
N-[2-(4'-chlorophenylsulfonamido)ethyl] nitrone (46) can be
generated by the reaction of the salt of the pyrrole oxime 45 with
N-(4-chlorophenylsulfonyl)aziridine in the presence of sodium
hydride [55].
N
SO2NaH
Cl H N
N H
CH=NONa
N H
N + -O46
SO2
Cl
45
2.3. The Synthesis of New Heterocycles from Pyrrole Oximes
Advances in the synthesis of heterocyclic systems from oximes were
reviewed in [56], and in this section we will dwell on the specific
reactions of pyrrole oximes. In the presence of Raney nickel,
generated in situ, the oximes 47 give a mixture of several
pyrrolo[2,3-b]pyrrolones 48 and 49 (overall yield 16-41%) and 50
(yield 4-48%) [57].H Ph O Ph NOH N R 47 Me Ni-Al EtOH Ph O Ph N Me
+ N R 48 Ph Ph Me Ph O Ph H N Me + N R 49 Me
N
Me
+O N R 50 R = H, Alk Me
Several papers have been devoted to synthesis of the isoxazole
derivatives of pyrrole oximes. The reaction of
3-hydroxyimino-2,5-diphenylpyrrole (51) with NH2OHHCl in methanol
leads to the trioxime 52 and then to a mixture of
3-benzoyl-5-phenylisoxazole oxime (53) and
3-phenyl-4-phenylacetyl-1,2,5-oxadiazole (54). Under similar
conditions 3-hydroxyimino-2-methyl-5-phenylpyrrole only gives
3-acetyl-5-phenylpyrrole oxime [58].NOHNH2OH.HCl, MeOH
NOH Ph Ph NOH NOH52
NOH Ph Ph N O 53 Ph54 +
Ph O N O N
Ph
N51
Ph
7
In the presence of methylene chloride and water the
meso-formylporphyrin oximes 55 give the isoxazoles 56 with a yield
of ~50% [59].R' R N Ni N R''' R'' 55 R, R', R'', R''' = Alk R' N R
R'' 56 R' N CH=NOH R''' R'' R''' CH2Cl2, H2O R N Ni N N R R' R'' O
N R'''
O N
The sodium salt of the oxime 9 in the hydroxylamine
hydrochloridepotassium hydroxidewater system gives the oxadiazole
57 with a yield of 78% [16].NOH NH2OH HCl, KOH, H2O N 9.
HO O N O 57
NH2 N
The nitroxyl radical of
2,2,3,3-tetramethyl-4-phenylethynyl-2,5-dihydro-1H-pyrrole-3-carbaldehyde
(58) reacts in the hydroxylamine hydrochloridepotassium
carbonateethanolwater system with the formation of the
pyrrolo[3,4-c]pyridine radical 60 with a yield of 82%. The product
60 is formed through the oxime 59 as intermediate [60].Ph NH2OH,
CHO K CO 2 3 Me Me N O. 58 Me Me Me Me N O. 59 Ph CH=NOH Me Me Me
Me N O. 60 Me Me Ph N O
The hydroxyiminopyrroles 61 react with hydrazine with cleavage
of the ring and form dihydropyridazine oximes 62 as the only
product [61].R' R' NOH NH2NH2 R'' N 61 R, R', R'' = H, Alk R R'' HN
N 62 NOH
R
8
Cyclization of 2,5-diphenylpyrrole (63) with the oxime of ethyl
bromopyruvate in the sodium carbonatemethylene chloride system
leads to ethyl
4a,6-diphenyl-4,4a,7,7a-tetrahydropyrrolo[2,3-e]-1,2oxazine-3-carboxylate
(64) with a yield of 36% [20].CO 2Et NOH Na2 CO 3 Ph N Ph 64 CO 2Et
O N
+ Ph N H 63 Ph
Br
The reaction of compound 24 with hydrazine hydrate in acetic
acid leads to tetrahydrocinnoline oxime 65 with a 32% yield. The
reaction of compound 24 with hydroxylamine hydrochloride gives the
spiro derivative of isoxazoline 66 (yield 75%) [22].NOH OH Me N N
65 O 24 NH2OH.HCl NOH N O NH2NH2.H2O O N N NOH Me
Me
NOH 66
The reaction of the Z-isomer of 2-pyrrolecarbaldehyde oxime 28
with 4-bromo-1-butene leads to C-2-pyrrolyl N-3-butenyl nitrone 67
with a yield of 43%. Intramolecular thermocycloaddition of 67 leads
to exo-C-2-pyrrolyl-1-aza-7-oxabicyclo[2.1.1]heptane (68) with a
yield of 49% [62]._
O PhMe 110oC
Br N H 28 CH=NOH EtONa, EtOH N H 67
+ O N
N N H H 68
The thermal cyclization of 1-allyl-2-pyrrolecarbaldehyde (69)
was described in [63]. In this case in boiling xylene the oxime 69
gives the dimer 70 with a yield of 52%.Me N CH=NOH 140 oC H N O N H
N H CH=NOH
69
70
9
2.4. The Beckmann Rearrangement of Pyrrole Oximes The Beckmann
rearrangement is one of the most characteristic reactions of
oximes. In the presence of phosphorus pentachloride [27] or
hydrochloric acid [7] the E- and Z-isomers of pyrrole ketoximes
give acylaminopyrroles. A simple method was also developed for the
synthesis of the isomeric derivatives of pyrroloazepines 73 and 74
by the rearrangement of syn- and
anti-4-tosyloxyimino-4,5,6,7-tetrahydroindoles 72 [64].
N
O
SO2
Me H N HN NH
O
N Me 71 Me SO2O
N DMF 73 O N H N Me
N 72 Me 74
N Me
Reaction 1,3-dimethyl-1,5,6,7-tetrahydro-4H-indol-4-one oxime in
polyphosphoric acid leads to
1,3-dimethyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one [65].
During the treatment of
3-ethoxycarbonyl-2-methyl-4,5-dioxobenzo[g]indole 5-monoxime (75)
in an alkaline medium
5-(2-cyanophenyl)-3-ethoxycarbonyl-2-methyl-1-phenyl-4-pyrrolecarboxylic
acid (76) was formed with a yield of 87% as a result of a Beckmann
rearrangement [66].OH N N Ph 75 76
O
COOEt PhSO2Cl, NaOH Me
HOOC CN N Ph
COOEt Me
3. THE BIOLOGICAL ACTIVITY OF DERIVATIVES OF PYRROLE OXIMES 3.1.
Action on the Cardiovascular System The pyrrole oximes 77, which
exhibited anti-serotonin 5-HT2-receptor activity, were proposed as
antihypertensive and anticoagulation drugs [67, 68]. 10
HON HON N N (CH2)n O N O 77 R = H, Alk; n = 35 N R N F N Me O 78
N Ph
The oxime derivatives of pyrroloazepines also exhibited
vasodilating activity. Among these compounds the oxime 78 was
mentioned as one of the most active [69, 70]. The blocking action
of pyrrole O-(2-alkylamino-2-hydroxypropyl)oximes 79 on
-adrenoceptors has also been investigated [71].
N Me
CR=NOCH2CH(OH)CH2NHCMe2R' 79 R = H, Alk, Ar; R' = H, Me
3.2. Antidepressant Activity The tricyclic derivatives of the
pyrrole oximes 80 and 81 exhibited high antidepressant activity
[72, 73].
R
N
N
S
N 80
O-(CH2)n-NR'R''
N R 81
O-(CH2)n-NR'R''
R,R',R'' = H, Alk; n = 2, 3
3.3. Analgesic and Anti-inflammatory Activity Oxime derivatives
containing pyrrole and pyridine fragments were studied as
inhibitors of Raf kinase [74]. All these compounds can be used as
analgesics and agents against migraine, and the oxime 82 is one of
the most active.
11
N
N H HON 82 O NMe2
The O-lauroyl- and O-nicotinoyloximes of
1-methyl-2-acetylpyrrole possess anti-inflammatory activity
[36].
3.4. Bactericidal Activity Derivatives of 2-pyrrolecarbaldehyde
oximes have exhibited high bactericidal activity [75-77]. The
pyrrole oxime fragment also enters into the structure of certain
penicillin antibiotics [78]. It was recently shown that ethers of
pyrrole oximes 83 have high bactericidal activity against resistant
strains of bacteria [79].Me O O O Me O N H O 83 R, R' = Alk OH Me O
NOR' R
Me MeO
3.5. Pyrrole Oximes as Fungicides and Plant Growth Regulators
The ethers of pyrrole oximes exhibit high fungicidal, insecticidal,
and acaricidal activity [80]. Among these compounds, in particular,
the ether 84 should be mentioned [81].NOMe N MeO 2C 84 Me CHOMe
The ethers of pyrrole amidoximes
[(pyrrolyl)C(NH2HCl)=NOCHR'CO2R", where R', R" = alkyl] exhibited
good herbicidal activity [82].
12
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15
Chemistry of Heterocyclic Compounds, Vol. 40, No. 1, 2004
HETEROCYCLIC QUINONES IN THE NENITZESCU REACTION. SYNTHESIS OF
FUROAND PYRROLOQUINOLINES FROM
2-METHOXYCARBONYL-4-OXO-5,8-QUINOLINEQUINONET. I. Mukhanova1, L. M.
Alekseeva1, A. S. Shashkov2, and V. G. Granik1 Derivatives of
furo[2,3-f]quinoline were synthesized by the reaction of the
enamines of acetylacetone and benzoylacetone with
2-methoxycarbonyl-4-oxo-5,8-quinolinequinone. A derivative of
pyrrolo[2,3-h]quinoline was obtained from N-benzyl--aminocrotonic
ester. Keywords:
3-acyl-5-hydroxy-7-methoxycarbonyl-9-oxofuro[2,3-f]quinolines,
1-benzyl-3-ethoxycarbonyl-8-hydroxy-5-methoxycarbonyl-2-methyl-7-oxopyrrolo[2,3-h]quinoline,
2-methoxycarbonyl-4oxo-5,8-quinone, enamine, Nenitzescu reaction.
The new path that we developed for the synthesis of tricyclic
systems containing indole or benzofuran rings as fragments is based
on the use of heterocyclic quinones in the Nenitzescu reaction and
the use of derivatives of indazolequinone [1], benzofuranquinone
[2], and isoquinolinequinone [3] for this purpose. The present work
was devoted to the use of an arbitrary quinone
2-methoxycarbonyl-4-oxo-5,8-quinolinedione (1), synthesized by the
method in [4]. It is known [5] that the electron density at the
-positions of 4-pyridones is substantially increased and it is at
these positions that the reactions with electrophilic reagents are
directed. From this it can be concluded that the carbonyl at the
position 5 of the quinone 1 (added to the -position of the pyridine
ring) is a weaker electron acceptor than the quinone carbonyl at
position 8 (structure A), while the reactions with nucleophilic
reagents, which the enamines (the second component of the
Nenitzescu reaction) are, will take place preferentially at
position 6.O4 3 2 8 8a
O6 7 5 4a
O
O
_
O _
O
_ O
O
N1 H 1
COOMe O
+ N H
COOMe O
+ N H
COOMe O A
+ N H
COOMe
O
__________________________________________________________________________________________
Federal State Unitary Enterprise "The State Scientific Center
NIOPIK" (Scientific-Research Institute of Organic Intermediates and
Dyes), Moscow 103787; e-mail: [email protected]. 2 N. D. Zelinsky
Institute of Organic Chemistry, Russian Academy of Sciences, Moscow
117913. Translated from Khimiya Geterotsiklicheskikh Soedinenii,
No. 1, pp. 20-26, January, 2004. Original article submitted July
19, 2001. 16 0009-3122/04/4001-00162004 Plenum Publishing
Corporation1
In addition it can be supposed that, as for isoquinolines, the
presence of the electron-withdrawing pyridone ring will lead to
difficulty in the oxidation of the intermediate hydroquinone
adducts [3], and this must give rise to the preferential formation
of the furo- and not the pyrrolotricyclic systems. The reaction of
the quinone 1 with the enamino ketones 2a-e leads exclusively to
3-acyl-5-hydroxy-7methoxycarbonyl-2-methyl-9-oxofuro[2,3-f]quinolines
3a,b. Compounds 3a,b were subjected to O-acetylation in order to
increase the solubility, and their NMR spectra were investigated in
this form 4a,b. In spite of the theoretical treatment, which
determines the probability of the formation of compounds 3a,b, it
is still necessary to consider the possible production of the
isomeric structures 5.Me O O COR" O R"OC AcOH Me NRR' 2ae N OH H
3a,b a R" = Ph, b R" = Me Ac2O OH5 4 5a 9a 9 9b
O
+N O 1 H COOMe
COOMe
O6 7 8
Me R"OC COOMe2 1 3 3a 4 5 5a
O9b 9a
OCOMe9 8
R"OC Me
3a 3 2 1
O
N H 5
N
7
OCOMe MeCOO OCOMe
6
COOMe
4a,b
R"OC Me
N O 5A
N
COOMe
a R = H, R' = R" = Me; b R = H, R' = p-MeC6H4, R" = Me; c R = R'
= Me, R" = Ph; d R = H, R' = CH2Ph, R" = Ph; e R = H, R' =
p-MeOC6H4, R" = Ph
The 1H NMR spectra of the obtained compounds correspond well to
both structures 4 and 5 (see Experimental), and it is impossible on
their basis to provide an unambiguous answer to the question as to
whether annelation of the furan ring is in fact realized at the 5,6
bond of the quinoline ring. Examination of the HMBC spectra (1H13C
correlations through two and three bonds, see Table 1) of the
obtained acetyl derivatives shows that the derivatives 3 are in
fact formed as a result of condensation of the quinone 1 and the
enamines 2. Thus, in the HMBC spectrum of compound 4a the signal of
the 8-H proton (8.11 ppm) has two correlation peaks with the
signals of C(9a) and C(9) (112.2 and 152.6 ppm respectively), while
the signal of the 4-H proton (7.72 ppm) has three correlation peaks
with signals at 139.5, 142.2, and 144.6 ppm, belonging to C(9b),
C(5a), and C(5). (It is not possible to assign these signals
specifically, which incidentally is not important for solution of
the main task, i.e., determination of the structure of the
synthesized compounds.) The presence of three correlation peaks for
the 4-H signal with the signals of the carbon atoms, observed in
the 17
TABLE 1. The 13C NMR Chemical Shifts of Compounds 4a,b, and 8
and the Proton-Carbon Correlations in the HMBC spectrum (1H13C
Correlation through Bonds 2 and 3)*Carbon atoms 2 3 3 4 5 5 7 8 9 9
913
, , ppm 4b 164.1 (2-3) 117.8 (2-3) 124.4 (nc) 116.5 (nc) *3 *4
*3 115.4 (nc) 152.6 (8-) 111.9 (8-) *4
4 163.1 (2-3) 117.1 (2-3) 125.1 (nc) 115.9 (nc) *2 *2 146.9 (nc)
115.7 (nc) 152.6 (8-) 112.2 (8-) *2
Carbon atoms 2 3 3a 3b 5 6 7 7 8 9 9 1-CH2C6H5
13
, , ppm 8
2-3 3-R
5( and 9)OCOCH3
7-O3
14.5 190.4 (-2'6') CO 138.3 (-3'5') 1 128.7, 128.8 2'6'3'5'
133.1 (-2'6') 4' 168.5 (3) 169.4 (3) 20.5 CH3 20.7 CH3 164.1 (3)
52.9 3
15.3 193.4(CH3) 30.5 CH3
CO
2-3 3-OC2H5
145.8 (1-CH2, 2-CH3) 105.5 (2-CH3) 112.1 (9-H) *5 *5 112.2 (NH)
176.3 (nc) 114.3 (9-H, NH, 6-H) 145.4 9-) 102.3 (nc) 135.4 (1-2)
46.3 CH2 136.0 (3',5'-H) C1' 125.8 C2'6' 128.6 C3'5' 127.3 C4' 13.8
167.1 (2) CO 61.1 CH2 12.9 CH3 162.2 (3, 6-, NH) CO 53.1 CH3
169.0(CH3) 20.8 CO CH3
168.4 (3) 5-COOCH3 169.3 (3) 20.4 CH3 20.6 CH3 164.1 (3,8-) CO
8-OCOCH3 52.8 3
_______ * The numbers of the protons with which correlation
peaks are observed in the HMBC spectrum are given in parentheses
(nc = no correlation). The signals of the protonated carbon atoms
were assigned by means of the HSQC spectrum. *2 139.6 (4-), 142.2
(4-), 144.6 (4-). *3 144.8 (nc), 147.0 (nc). *4 139.4 (4-), 141.8
(4-). *5 135.2 (nc), 136.7 (nc).
downfield region, indicates conclusively in favor of structure
4. If compounds with structure 5 were obtained, the signal of the
proton of the pyrimidine fragment would have correlation peaks
similar to those observed in the spectrum, but a correlation peak
with an upfield signal for the C(5a) atom (identical with C(9a),
112.2 ppm in structure 4) would be observed for the 4-H signal in
addition to the two correlation peaks with the downfield atoms
C(9b) and C(5). This is the main argument in favor of the idea that
structure 5 is not realized; a general correlation peak for the
signals of the two aromatic protons and a signal for a carbon atom
with 112.2 ppm are not observed in the spectrum. The same logic
indicates that compound 4b has an analogous structure.
Consequently, it is possible to state that the reaction of the
quinone 1 with the enamines 2 takes place at the position 6 of the
quinone with the formation of compounds having structure 3.
18
In a continuation of the present research a compound having a
weaker electron-withdrawing substituent at the -position, i.e.,
N-benzyl--aminocrotonic ester 6, was chosen as enamine component.
The reaction of the quinone 1 and the enamine 6 led to the
tricyclic compound 7, which was converted into the O-acetyl
derivative 8. The data from the 1H NMR spectrum, the HMBC spectra
(Table 1), and also the ROESY spectrum and the results from the
mass spectra make it possible to determine reliably the structure
of compound 8. Its highresolution mass spectrum contains a
molecular-ion peak with m/z 476.1582 and ion peaks at 434 (M+
MeCO), 388 (M+ MeCOEtOH), 343 (M+ MeCOPhCH2), and 297 (M+
MeCOEtOHPhCH2). In the ROESY spectrum there is a strong correlation
peak at 5.59/7.27 ppm. This means that the PhCH2 group and the 9-H
proton are sterically close. (It is not possible to imagine any
other ring closure in which the benzyl substituent would be close
to 6-H.) In the HMBC spectrum at 176.3 ppm there is a downfield
signal not having a correlation peak with the signals of any
protons and assigned to the 7-CO carbon atom. The presence of the
pyridone fragment is also favored by the presence of the NH signal
in the 1H NMR spectrum in the region of 14 ppm. It can be supposed
on the basis of these data that the reaction in this case takes
place in the unusual direction:O COOEt 1 O
+Me NHCH2Ph Me PhCH2NH OH H N N OH H COOEt COOMe O N OH H COOEt
COOMe
OH
O
PhCH2
PhCH2 Me
N
N H COOEt 7
COOMe
Me
O8 9 7a
O7 6 4 5
PhCH2
N
1
9a 2 3
3b 3a
N H 8
COOMe
Me
COOEt
The HMBC spectrum supports the proposed structure; the signal of
the proton at position 9 (7.27 ppm) has two correlation peaks with
the upfield carbon atoms 112.1 (C(3a)) and 114.3 (C(7a)). Thanks to
the presence of a correlation peak in the spectrum at 6.57/114.3
(H-6/C(7a)) it is possible to assign these signals having chemical
shifts of similar value. The signal of the 9-H proton also has a
correlation peak with a downfield signal at 145.4 ppm, assigned to
C(8) (correlation with C(8) through two bonds). The signal of the
6-H proton (6.57 ppm) has two correlation peaks with C(7a) (114.3
ppm) and with 5-CO (162.2 ppm). (In the spectrum there is a
correlation peak at 4.00/162.2 (OMe/5-CO)). For the signal of the
NH proton (14 ppm) there are three correlation peaks with the
following signals: 5-CO (162.2), C(6) (112.2), and C(7a) (143.3
ppm). The obtained data undoubtedly indicate that the interaction
of the quinolinequinone 1 and the enamino ester 6 leads to
1-benzyl-8-hydroxy-2-methoxycarbonyl-3-ethoxycarbonyl-7-oxopyrrolo[2,3-h]quinoline
(7), containing a 6-hydroxyindole fragment. Whereas the retardation
of the benzofuran synthesis with decrease in 19
the electron-withdrawing strength of the substituent at the
-position of the enamine does not seem unusual the benzofuran
cyclization of the intermediate hydroquinone adduct depends
directly on the electron deficiency at the -position of the enamine
fragment the formation of 6-hydroxyindoles has until now only been
observed in cases with variation of the structures of the initial
enamines (but not quinones), e.g., in the transition from N-alkyl-
to N-aryleneamines or to enamines having strong electron acceptors
such as cyano and particularly nitro groups at the -position [6].
In view of the fact that the Nenitzescu reaction very often takes
place ambiguously and the yield of the obtained 6-hydroxy
derivative is low it is not possible to claim that the use of the
heterocyclic quinone 1 in reaction with the enamine 6 changes the
direction of this reaction completely and fundamentally and
excludes the formation of the normal 5-hydroxyindoles for the
Nenitzescu reaction. However, the fact that the structure of the
quinone can change this direction so dramatically is a new
previously unknown and unexpected phenomenon and requires further
detailed investigation.
EXPERIMENTAL The 1H NMR spectra were recorded on a Bruker AC-200
spectrometer (200 MHz). The 2D HMBC NMR spectra (1H and 13C) were
obtained on a Bruker DRX-500 spectrometer (at 500 and 125 MHz
respectively) using the manufacturer's standard procedures. The
high-resolution mass spectra were obtained on a Finnigan MAT TCQ
700 spectrometer (triple quadrupole) with direct injection of the
sample into the ion source. The purity of the obtained substances
was monitored on Silufol UV-254 and Kieselgel 60 F-254 (Merck) in
ethyl acetate.
3-Benzoyl-5-hydroxy-7-methoxycarbonyl-2-methyl-9-oxofuro[2,3-f]quinoline
(3a). A mixture of the quinone 1 (0.23 g, 10 mmol),
2-p-anisidino-3-benzoyl-2-propene (2e) (0.27 g, 10 mmol), and
glacial acetic acid (4 ml) was heated to 60-70C, kept at this
temperature for 5 min, and then left at room temperature. The next
day the crystals that separated were filtered off, washed on the
filter with petroleum ether, and dried, and 0.14 g (37.1%) of the
furoquinoline 3a was obtained; mp >300C (DMF) (decomp.).
High-resolution mass spectrum. Found: m/z 377.0888 [M]+. 21H15NO6.
Calculated: M = 377.359.
3-Acetyl-5-hydroxy-7-methoxycarbonyl-2-methyl-9-oxofuro[2,3-f]quinoline
(3b). The compound was obtained similarly to compound 3a from the
quinone 1 and the enamine 2b with a yield of 59%; mp >300C (DMF)
(decomp.). High-resolution mass spectrum. Found: m/z 315.077 [M]+.
1613N6. Calculated: M = 315.288.
1-Benzyl-3-ethoxycarbonyl-8-hydroxy-5-methoxycarbonyl-2-methyl-7-oxopyrrolo[2,3-h]quinoline
(7). The compound was obtained similarly to compound 3a from the
quinone 1 and the enamine 6 with a yield of 32%. After
recrystallization from dioxane the pure pyrroloquinoline 7 was
isolated with a yield of 13%, calculated on the initial quinone 1;
mp 285-287C. High-resolution mass spectrum. Found: m/z 434.1487
[M]+. 2422N2O6. Calculated: M = 434.486.
5,9-Diacetoxy-3-benzoyl-7-methoxycarbonyl-2-methylfuro[2,3-f]quinoline
(4a). To compound 3a (0.38 g, 10 mmol) acetic anhydride (15 ml) and
three drops of sulfuric acid were added. The reaction mixture was
heated until the precipitate had dissolved, kept at room
temperature for 24 h, and poured into cold water (150 ml). The
precipitate was filtered off, washed with water on the filter, and
dried. The yield of compound 4a was 0.38 g (82%). The compound was
purified by column chromatography on silica gel. The eluent was
ethyl acetate. The solvent was distilled, and compound 4a was
obtained with a yield of 43%; mp 192-194C (ethanol).
High-resolution mass spectrum. Found: m/z 419.099 [M]+. 2317N7.
Calculated: M = 357.32. 1H NMR spectrum, , ppm: 2.40 (3, s,
5(9)-3); 2.51 (3, s, 9(5)-3); 2.49 (3, s, 2-3); 3.95 (3, s, 7-C3);
7.43 (2, t, 3'-, 5'-H); 7.70 (1, t, 4'-H); 7.72 (1, s, 4-); 7.83
(2, d, 2'-, 6'-H); 8.11 (1, s, 8-). 20
5,9-Diacetoxy-3-acetyl-7-methoxycarbonyl-2-methylfuro[2,3-f]quinoline
(4b). The compound was prepared similarly to compound 4a from the
furoquinoline 3b and acetic anhydride with a yield of 50%. The
individual compound was likewise isolated by column chromatography
on silica gel. High-resolution mass spectrum. Found: m/z 357.084
[M]+. 1815N7. Calculated: M = 357.32. 1H NMR spectrum, , ppm: 2.47
(3, s, 5(9)-3); 2.58 (3, s, 9(5)-3); 2.67 (3, s, 3-C3); 2.93 (3, s,
2-3); 3.98 (3, s, 7-3); 8.13 (1, s, 8-); 8.29 (1, s, 4-).
8-Acetoxy-1-benzyl-3-ethoxycarbonyl-5-methoxycarbonyl-2-methyl-7-oxopyrrolo[2,3-h]quinoline
(8). The compound was prepared similarly to compound 4a from the
pyrroloquinoline 7 and acetic anhydride with a yield of 90%; mp
245-247C (methanol). High-resolution mass spectrum. Found: m/z
476.1582 [M]+. 2624N27. Calculated: M = 476.49. 1H NMR spectrum:
1.40 (3, t, 3-23); 2.27 (3, s, 8-3); 2.69 (3, s, 2-C3); 4.00 (3, s,
5-3); 4.44 (2, t, 3-23); 5.59 (2, s, C2Ph); 6.57 (1, s, 6-); 7.02
(2, d, 2'-, 6'-H); 7.27 (2, m, 9-, 4'-H); 7.32 (2, t, 3'-, 5'-H);
14.00 (1, N). The work was carried out with financial support from
the Russian Fund for Fundamental Research (grant No.
99-03-32973).
REFERENCES 1. 2. 3. 4. 5. 6. V. M. Lyubchanskaya, L. M.
Alekseeva, S. A. Savina, and V. G. Granik, Khim. Geterotsikl.
Soedin., 1482 (2000). V. M. Lyubchanskaya, L. M. Alekseeva, S. A.
Savina, and V. G. Granik, Khim. Geterotsikl. Soedin., 1012 (2003).
T. I. Mukhanova, L. M. Alekseeva, and V. G. Granik, Khim.
Geterotsikl. Soedin., 670 (2002). J. Baxter and W. R. Phillips, J.
Chem. Soc. Perkin Trans. I, 2374 (1973). D. Barton and W. D. Ollis,
Comprehensive Organic Chemistry [Russian translation], Vol. 8,
Khimiya, Moscow (1985), p. 30. V. G. Granik, V. M. Lyubchanskaya,
and T. N. Mukhanova, Khim.-Farm. Zh., 27, No. 6, 37 (1993).
21
Chemistry of Heterocyclic Compounds, Vol. 40, No. 1, 2004
PREPARATIVE SYNTHESIS OF 7-CARBOXY-2-R-ISOINDOL-1-ONESA. V.
Varlamov, E. V. Boltukhina, F. I. Zubkov, N. V. Sidorenko, A. I.
Chernyshev, and D. G. Grudinin A preparative method for the
synthesis of 7-carboxy-2-R-isoindol-1-ones was developed on the
basis of the [4+2] cycloaddition of secondary furfurylamines to
maleic anhydride. Keywords: isoindolones, furfurylamines,
intramolecular DielsAlder reaction. Isoindolones, or phthalimides,
can be obtained from phthalic anhydride [1] and various derivatives
of phthalic acid [2, 3] by the oxidation of
2-R-1-methoxycarbonylisoindoles [4]. Functionally substituted
isoindolones, from which various condensed heterocyclic systems
containing an isoindole fragment can be obtained, are of interest
at the synthetic level. Great promise in this direction is opened
up by the recently developed method for the synthesis of
1-isoindolones based on the transformation of nitrogencontaining
tricyclic compounds
2,3,7,7a-tetrahydro-3a,6-epoxy-2-R-isoindol-1-ones, which can be
obtained with high yields from N-alkyl(aryl)-N-furfurylacrylamides
by intramolecular [4+2] cycloaddition [5-12]. The epoxyisoindolones
can also be obtained by the four-component condensation of furfural
and benzylamine or furfurylamine and benzaldehyde with derivatives
of maleic and fumaric acids [13]. In the context of the development
and study of the applicability limits for the last method we
propose a two-stage preparative method for the synthesis of
7-carboxy-2R-isoindol-1-ones 2, based on the [2+4] cycloaddition of
maleic anhydride to N-substituted furfurylamines 1a-j. The initial
furfurylamines 1a-j were prepared by reduction of the respective
Schiff bases with sodium borohydride in ethanol. Cycloaddition of
maleic anhydride to the amines 1a-j was conducted in benzene at
25C. The reaction takes place stereoselectively and in most cases
with high yields (Table 1). The carboxy-substituted
epoxyisoindolones 2a-j are formed through the initial formation of
the N-furfurylamide of maleic acid 2*, which is then transformed
through an exo transition state into the epoxy derivative 2. It is
significant that N-acetyl-N-phenylfurfurylamine does not enter into
[4+2] cycloaddition with maleic anhydride even after prolonged
boiling in xylene, which provides indirect evidence for the
described reaction path. It is interesting to note the important
role of the substituent R at the nitrogen atom of the
furfurylamines 1. Thus, Z-4-(2-furylmethylamino)-4-oxobut-2-enoic
acid, which does not undergo an intramolecular DielsAlder reaction
and does not enter into reaction with an excess of maleic anhydride
even after heating to 150C, is formed with a quantitative yield
during the reaction of furfurylamine with maleic anhydride.
__________________________________________________________________________________________
Russian University of the Friendship of Peoples, Moscow 117198;
e-mail: [email protected], [email protected].
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp.
27-33, January, 2004. Original article submitted December 25, 2001.
22 0009-3122/04/4001-00222004 Plenum Publishing Corporation
10
O7 6
H O 1aj N R
O
O
O1 2 3 5
COOH O H3PO4 70100 oC
COOH
O N R
C6H6, 25 oC
N R 2aj
3ai
O N R
O COOEt O O COOH N 2* Ph 4
COOEt
O N Ph
5
O
a R = Ph; b R = Bn; c R = C6H4Cl-m; d R = C6H4NO2-p; e R =
C6H4NO2-m; f R = tetrahydrofuryl; g R = cyclohexyl; h R =
methoxyethyl; i R = cyclopropyl; j R = furfuryl
In spite of existing data on the effective [4+2] cycloaddition
of maleic anhydride to furfuryl alcohols [14, 15], we were unable
to realize the reaction of maleic anhydride with secondary
furfurylamines containing the reactive functional groups OH or NR2
in the radical R. During an attempt at cycloaddition to
N-(-hydroxyethyl)-, N-(-pyridyl)-, and N-(-pyridyl)furfurylamines
rapid polymerization of the reaction mixtures occurred. TABLE 1.
The Characteristics of Compounds 2a-j, 3a-i, 4, and 5Compound 1 2a
2b 2c 2d 2e 2f 2g 2h 2i 2j 3a 3b Empirical formula 2 C15H13NO4
C16H15NO4 C15H12NO4Cl C15H12N2O6 C15H12N2O6 C14H17NO5 C15H19NO4
C12H15NO5 C12H13NO4 C15H13NO5 C15H11NO3 C16H13NO3 Found, %
Calculated, % 4 4.79 4.79 5.27 5.26 3.95 3.93 7.82 7.80 7.84 7.80
6.08 6.09 6.84 6.86 5.87 5.93 5.53 5.53 4.72 4.73 4.37 4.35 4.85
4.87 mp, N 5 5.18 5.17 4.93 4.91 4.59 4.58 8.84 8.86 8.90 8.86 5.03
5.01 5.04 5.05 5.27 5.53 5.93 5.96 5.05 5.09 5.52 5.53 5.26 5.24 6
184-185.5* 164 179-181* 202-204 205-207 134-136 191-192 127-128.5
168-171.5 146-148 227-230 177-178.5* Yield, % 7 86 90 89 74 80 37
90 92 35 95 46 33
C 3 66.43 66.42 67.35 67.37 58.90 58.92 56.99 56.96 56.95 56.96
60.23 60.21 64.97 64.98 56.73 56.92 61.29 61.28 65.44 65.45 71.13
71.15 71.94 71.91
23
TABLE 1 (continued)1 3c 3d 3e 3f 3g 3h 3i 4 5 2 C15H10NO3Cl
C15H10N2O5 C15H10N2O5 C14H15NO4 C15H17NO3 C12H13NO4 C12H11NO3
C17H17NO4 C17H15NO3 3 62.62 62.60 60.41 60.40 60.38 60.40 64.34
64.36 69.50 69.49 61.55 61.28 66.34 66.36 68.22 68.23 72.59 72.60 4
3.49 3.48 3.35 3.35 3.36 3.35 5.78 5.75 6.56 6.56 5.51 5.53 5.04
5.07 5.60 5.69 5.56 5.34 5 4.89 4.87 9.36 9.39 9.38 9.39 5.33 5.36
5.40 5.40 5.81 5.92 6.48 6.45 4.70 4.68 4.95 4.98 6 229.5-230* 297
(dec.)*2 239-240*2 130-132* 245-246* 168.5-170.5 213-213.5
133-134*3 106-107*4
7 48 30 52 56 37 30 22 75 86
_______ * Recrystallization from a mixture of i-PrOH and DMF. *2
DMSO. *3 Ethyl acetate. *4 from a mixture of hexane and ethyl
acetate.
TABLE 2. The Spectral Characteristics of Compounds 2a-5Compound
2a 2b 2c 2d 2e 2f 2g 2h 2i 2j 3a 3b 3c 3d 3e 3f 3g 3h 3i 4 5
Molecular mass Found [] 271 285 305, 307 316 316 279 277 253 235
275 253 267 287, 289 298 298 261 259 235 217 299 281+
IR, , cm-1 NCO 1669 1659 1680 1680 1675 1680 1660 1625 1630 1660
1610 1600 1583 1610 1589 1690 1615 1610 1600 1615 1610 1690 1640
COO 1729 1729 1730 1705 1728 1720 1730 1715 1710 1725 1714 1713
1710 1705 1711 1705 1700 1720 1715 1725 1715 OH 2460 2485 2480 2400
2500 2480 2400 2460 2460 2460 2300 2370 2400 2410 2380 2380 2300
2280
Calculated 271 285 305, 307 316 316 279 277 253 235 275 253 267
287, 289 298 298 261 259 235 217 299 281
24
TABLE 3. The 1H NMR Spectra of
N-R-4-Oxo-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic
Acids 2a-j and Ethyl
N-Phenyl-4-oxo-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylate
(4) (TMS)Compound 2a 2b 2c 2d 2e 2f 2A-H d 2B-H d 4.06 d 3.44 d
4.06 d 4.18 d 4.19 d 3.92 d Chemical shift, , ppm* 6-H d 7-H 8-H
2.60 d 2.51 d 5.05 d 4.98 d 6.49 dd 6.40 dd SSCC (J, Hz) 7,8 8,9
1.8 1.5 1.3 1.7 1.5 0 5.9 5.7 5.6 5.7 5.5 5.8
COOH
5-H d 3.07 d 2.84 d 3.07 d 3.15 d 3.14 d 2.89 d
9-H 6.64 d 6.54 d
Others
2, 2B
5,6 9.1 9.2 9.2 9.1 9.2 9.2
Others
12.15 br. s 4.55 d 3.89 d 4.52 d
2.59 d 5.02 br. s 6.47 br. d 6.62 d 2.67 d 2.65 d 2.80 d 5.03 d
5.07 d 5.26 6.48 dd 6.51 dd 6.45 d 6.62 d 6.66 d 6.50 d
4.58 d 12.25 br. s 4.64 d 9.41 br. s 4.23 d
2g 2h 2i 2j
3.84 d 4.05 d 3.91 d 3.96 d
3.82 d 3.62 d 3.46 d 3.78 d
2.86 s 2.74 d 2.46 d 3.20 d 2.80 d 2.79 d 2.50 d
5.32 s 4.96 d 4.97 d 5.35 d
6.48 s 6.42 dd 6.57 d 6.41 dd 6.50 dd 6.53 d 6.46 d
4
4.42 d
4.19 d
2.98 d
2.79 d 5.19 br. s 6.48 br. d 6.58 d
7.66 (2, d); 7.38 (2, t); 11.7 7.14 (1, t) 7.33-7.21 (2H, m);
4.42 (1H, d); 11.7 4.34 (1, l) 7.88 (1H, br. s); 7.49 (1H, d); 11.5
7.40 (1H, t); 7.17 (1H, d) 8.22 (2H, AA'); 7.91 (2H, BB') 11.6 8.76
(1H, t); 7.96 (2H, dd); 11.6 7.69 (1H, t) 4.07(1H, dd); 3.95-3.65
(3H, m); 12.5 3.16 (1H, dd); 2.10-1.75 (2H, m); 1.70-1.50 (2H, m)
3.85 (1H, m); 1.90-1.60 (10H, m) 11.5 3.60-3.40 (3H, m); 3.26 (3H,
s); 11.6 3.17 (1H, m) 2.67 (1H, m); 0.66 (4H, m) 11.5 7.38 (1H,
dd); 6.34 (1H, dd); 12.2 6.30 (1H, dd); 4.78 (1H, d); 4.30 (d) 7.58
(2H, d); 7.35 (2H, t); 11.4 7.14 (1H, t); 4.27 (m, 23); 1.32 (t,
23)
Jm = Jmp = 7.3 JAB = 15.3 (2Ph) J5'6' = J4'5' = 8.0 JAB 9.2
J5'6' = J4'5' = 8.2 J2'4' = J2'6' = 2.1 JAB = 14.0 JA2' = JB2' =
7.0 (2CHO) J1'2' = J1'3' 5.6 JAB = 15.6; J' = 3.4 J' = 0.8; J = 1.8
(CH2furyl) Jm = Jmp = 7.6 JCH2CH3 = 7.0
9.2 9.2 9.0
1.8 1.3 1.5
5.8 5.6 5.8
8.9
1.0
5.5
_______ * Solvent: DMSO-d6 (compounds 2a-i) and CDCl3 (compounds
2j and 4).
25
26
TABLE 4. The 1H NMR Spectra of Solutions of
2-R-7-Carboxyisoindolin-1-ones 3a-i and
7-Ethoxycarbonyl-2phenylisoindolin-1-one (5) (TMS)Compound 3a 3b 3c
3d 3e 3f Chemical shift,, ppm* 4-H 5-H 6-H 7.85-7.70 m 7.80-7.76 m
7.88 br. d 7.82 t 8.49 dd 8.08 br. d 7.97 br. d SSCC, (J, Hz) 5,6
6.3 7.2 7.3 7.2
COOH 15.53 s 15.74 br. s
3A-H
3B-H
Others 7.76 (1H, d); 7.50 (2H, t); 7.34 (2H, t) 7.39-7.26 (5H,
m); 4.57 (2H, s) 8.02 (1H, t); 7.80 (1H, dd); 7.51 (1H, t); 7.33
(1H, dd) 8.27 (2) and 8.12 (2, 'BB') 8.83 (1H, br. s); 8.23 (1H,
dd); 8.09 (1H, dd); 7.78 (1H, t) 4.16 (1H, dq); 3.97 (1H, dd); 3.87
(1H, t); 3.77 (1H, dd); 3.55 (1H, dd); 2.10 (1H, dd); 1.93 (2H, );
1.63 (1H, dd. d) 4.08 (1H, m); 1.93-1.18 (10H, m) 3.82 (2H, t);
3.64 (2H, t); 3.29 (3H, s) 3.16-3.03 (1H, m); 1.00-0.85 (4H, m)
7.83 (2H, d); 7.40 (2H, t); 7.16 (1H, t); 4.50 (m, 23); 1.43 (t,
23)
3A,3B 18.5
4,5
4,6 2.6
Others Jom = Jmp = 7.5 J5'6' = J5'4' = 7.9; J2'6' = J2'4' = 1.3
JAB 9.1 J5'6' = J5'4' = 8.2; J4'6' = 1.3
5.04 s 4.81 s 5.18 s 5.09 s 5.25 s 4.83 d 4.64 d
7.2 7.3 7.2
0 0 0
7.91 d 7.65 d
7.70-7.60 m 7.85 t 7.99 d 7.69 t 8.38 d
3g 3h 3i 5
15.94 br. s
4.69 s 4.76 s 4.63 s 4.83 s
7.88 d 7.91 dd 7.86 br. d
7.79 t 7.81 t 7.79 t 7.60 br. s
8.16 d 8.16 dd 8.15 br. d
7.4 7.6 7.3
0 1.4 0
7.4 7.6 7.3
Jom = Jmp = 7.6; JCH2CH3 = 7.2
_______ * Solvent: DMSO-d6 (compounds 3b-i) and CDCl3 (compounds
3a and 5).
To convert the epoxy derivatives 2a-j into the
7-carboxyphthalimidines 3a-i we used hydrochloric and sulfuric
acids at various concentrations, 85% phosphoric acid, and boron
trifluoride etherate in boiling dioxane. The largest yields of
compounds 3 were obtained with BF3Et2O, but from the practical
standpoint it is better to use 85% phosphoric acid in the range of
70-100C. In spite of the fact that the yield of the desired
products here is reduced by 10-15% the procedure for the synthesis
and the isolation of the isoindolones 3 is greatly simplified. It
was not possible to select conditions for the aromatization of the
N-furfuryl-substituted epoxide 2j. During esterification of the
acids 2a and 3a the corresponding monoesters 4 and 5 were obtained.
The mass spectra of compounds 2 and 3 (Tables 1 and 2) contain
low-intensity peaks of molecular ions, corresponding to their
molecular formulas. The readily occurring elimination of a CO2
molecule and retrodiene dissociation (in the case of the adducts 2)
are the reason for the insufficient reliability of this method of
obtaining evidence for the structure of the synthesized substances.
In the IR spectra of the carboxylic acids 2a-j and 3a-i there are
characteristic bands for the stretching vibrations of the amide and
carboxyl groups in the regions of 1610-1690 and 1705-1730 cm-1
respectively, and there is also a broad band for the associated
hydroxy in the region of 2280-2485 cm-1. In the IR spectra of the
esters 4 and 5 the band of the ester group appears at 1715-1725
cm-1. The 1H NMR spectra of compounds 2a-j (Table 3) contain three
characteristic signals for the interacting protons 7-H, 8-H, and
9-H with chemical shifts of 4.96-5.35, 6.40-6.51, and 6.46-6.66 ppm
respectively and spinspin coupling constants 3J78 = 1.3-1.8 and
3J89 = 5.5-5.9 Hz. The absence of the 3J67-exo spinspin coupling
constant in the bicyclooxaheptene fragment of the molecule
indicates unambiguously the endo arrangement of the 5-H and 6-H
protons (J56 = 9.0-9.3 Hz) and the exo arrangement of the carboxyl
and amide substituents. The protons of the 2-CH2 group in compounds
(2a-j) are chemically nonequivalent and are observed in the
spectrum in the form of an AB system. Conversely, in the 1H NMR
spectra of compounds 3a-e,g-i the signals of the 3-CH2 protons are
equivalent and are observed in the form of a singlet at 4.63-5.25
ppm. Only in the case of the magnetically anisotropic
tetrahydrofuryl substituent R do these protons become nonequivalent
and appear in the form of an AB system (Table 4).
EXPERIMENTAL The IR spectra were recorded on a Specord IR-75
spectrometer in tablets with potassium bromide. The mass spectra
were recorded on an HP MS 5988 mass spectrometer with direct
injection of the sample into the ion source with ionizing potential
70 eV. The 1H NMR spectra were recorded in deuterochloroform and
DMSO-d6 solutions on Bruker WP-200 (200 MHz) or Bruker WH-400 (400
MHz) instruments with TMS as internal standard. Silufol UV-254
plates were used for thin-layer chromatography (development with
iodine vapor).
3-R-4-Oxo-3-azatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic Acids
(2a-j). A mixture of maleic anhydride (0.1 mol) and
N-R-furfurylamine 1a-j (0.1 mol) in benzene (100 ml) was stirred at
25C for 2-3 days. The precipitate was filtered off, washed with
benzene, and dried at 90C to constant weight. Compounds 2a-j were
obtained in the form of finely crystalline powders. The spectral
data and physicochemical characteristics of the tricyclic compounds
2a-j are given in Tables 1-3. 2-R-Carboxyisoindolin-1-ones (3a-i).
The epoxyisoindolinones 2a-i (0.01 mole) were heated at 70-100C for
1 h in 85% phosphoric acid (40 ml). The reaction mixture was cooled
and poured into water. The crystals that separated were filtered
off, washed with water to a neutral reaction in the wash water,
dried, and recrystallized from a mixture of isopropyl alcohol and
DMF. The spectral data and physicochemical characteristics of the
isoindolones 3a-i are given in Tables 1-3.
27
Ethyl
4-Oxo-3-phenyl-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylate
(4) and 7-Ethoxycarbonyl-2-phenylisoindolin-1-one (5). To a
suspension of compound 2a (or 3a) (0.01 mol) in ethanol (50 ml) we
added concentrated hydrochloric acid (1 ml). The mixture was boiled
for 10-12 h (monitored by TLC). The reaction mixture was poured
into water and extracted with ether (3 50 ml), and the extract was
dried with magnesium sulfate. The residue after distillation of the
ether was recrystallized from ethyl acetate. The esters 4 and 5
were obtained in the form of white crystals (Tables 1-4). The work
was carried out with financial support from the Russian Fundamental
Research Fund (grant No. 01-03-32844).
REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. D.
T. Minh and J. E. Johnson, J. Org. Chem., 42, 4217(1977). J. D.
White and M. E. Mann, Adv. Heterocycl. Chem., 10, 113 (1969). R.
Bonnett and S. A. North, Adv. Heterocycl. Chem., 29, 341 (1981). R.
Fryor, J. V. Early, and L. U. Sternbach, J. Org. Chem., 34, 649
(1969). M. S. Bailey, B. J. Brisdon, D. W. Brown, and K. M. Stark,
Tetrahedron Lett., 24, 3037 (1983). D. D. Sternbach, D. H. Rossane,
and K. D. Onan, Tetrahedron Lett., 26, 591 (1985). M. E. Gung and
J. Gervay, Tetrahedron Lett., 29, 2429 (1988). S. C. Hirst and A.
D. Hamilton, J. Am. Chem. Soc., 113, 382 (1991). M. Suzuki, T.
Okada, T. Taguchi, Y. Hanzawa, and Y. Iitaka, J. Fluorine
Chemistry, 57, 239 (1992). D. Prajapati, D. R. Borthakur, and J. S.
Sandhu, J. Chem. Soc. Perkin Trans. I, 1197 (1993). K. H. Doetz, D.
Boettcher, and M. Jendro, Inorg. Chim. Acta, 222, 291 (1994). J. B.
F. N. Engberts, Pure Appl. Chem., 67, 823 (1995). K. Paulvannan,
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28
Chemistry of Heterocyclic Compounds, Vol. 40, No. 1, 2004
INVESTIGATIONS IN THE AREA OF AMINES AND AMMONIUM COMPOUNDS.
237.* SYNTHESIS OF 2,2-DIALKYL-4-HYDROXYMETHYLBENZO[f]ISOINDOLINIUM
AND 2,2-DIALKYL4-HYDROXYMETHYLISOINDOLINIUM SALTSE. O.
Chukhadzhyan1, A. R. Gevorkyan1, El. O. Chukhadzhyan1, K. G.
Shakhatuni1, F. S. Kinoyan1, and G. A. Panosyan2 The ability of the
4-hydroxy-2-butynyl group to participate as ,-unsaturated fragment
in basecatalyzed intramolecular cyclization was established.
2,2-Dialkyl-4-hydroxymethylbenzo[f]isoindolinium and
2,2-dialkyl-4-hydroxymethylisoindolinium salts were obtained by the
cyclization of dialkyl(4-hydroxy-2-butynyl)(3-phenylpropargyl)- or
dialkyl(4-hydroxy-2-butynyl)(3-alkenylpropargyl)ammonium salts.
Keywords: alkenylpropargyl and phenylpropargyl groups,
4-hydroxy-2-butynyl
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