Preparation and root growth-inhibitory activity of N-substituted 2-(2-chloroacetamido)-3-(furan-2-yl)propanamides

A series of N-substituted 2-(2-chloroacetamido)-3-(furan-2-yl)propanamides (16--18) was prepared through the reaction of chloroacetyl chloride with N-substituted 2-amino-3-(furan-2-yl)propanamides (15), which were obtained via condensation of 2-(tert-butoxycarbonylamido)-3-(furan-2-yl)propanoic acid (Boc-furylalanine) (8) with amines (9, 11, 13), followed by hydrolysis of the resultant N-substituted Boc-furylalanine acid amides (10, 12, 14) in the presence of HCl/dioxane. The biological activity of the prepared 16, 17 and 18 as root growth inhibitors was examined by germination assay using rape seed. At the concentration of 5.0 x10 (-5) M, the most active compound, 2-(2-chloroacetamido)-N-(2,6-diethylphenyl)-3-(furan-2-yl)propanamide (16 n), showed potent root growth-inhibitory activity of 76% towards rape seedlings.     

The synthesis of 5-substituted 3-benzoylamino-6-(2-substituted amino-1-ethenyl)-2H-pyran-2-ones and their transformations into 2H-pyrano[3,2-c]pyridine derivatives

A new approach to the 2H-pyrano[3,2-c]pyridine system is described. 5,6-Disubstituted 3-benzoylamino-2H-pyran-2-ones 3a,b , prepared from the corresponding 1,3-dicarbonyl compounds 1a,b and methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate ( 2 ), were converted into 3-benzoylamino-6-(2-dimethylamino-1-ethenyl)-5-ethoxycarbonyl-2H-pyran-2-one ( 4a ) and 5-acetyl derivative 4b . The exchange of the dimethylamino group in 4a,b with aromatic amines 5a-f,m , héteroaromatic amines 5g-i , and benzylamines 5j-l produced 5-ethoxycarbonyl-3-benzoylamino-6-(2-arylamino- or heteroarylamino-or benzylamino-1-ethenyl)-2H-pyran-2-ones 6a-l , and its 5-acetyl analog 6m . The compounds 6 were cyclized in basic media into 2H-pyrano[3,2-c]pyridine derivatives 7a-h . Analogously react also α-amino acid derivatives 8a-c and 11 as nitrogen nucleophiles producing 9a-c, 10 and 12 .     

Preparation of N'-[2-(5,6-dimethylbenzothiazolyl)]-N-furfuryloxamide with plant growth regulatory activity

The reaction of the N-furfuryloxamic acid sodium salt (12) with 1,1'-oxalyldiimidazole (ODI) yielded the imidazolide (13) as an intermediate, and this directly reacted with 2-aminothiazole derivatives (14) or 2-aminobenzothiazole derivatives (15) under essentially neutral conditions to afford the N'-12-(substituted thiazolyl)]- or N'-[2-(substituted benzothiazolyl)]-N'-furfuryloxamides (6 or 7). The prepared compounds (6 and 7) were examined for plant growth regulatory activity in a seed germination assay. The examination resulted in the discovery of some new revelations that N'-[2-(5,6-dimethylbenzothiazlyl)]-N-furfuryloxamide (7c) at the concentration of 1.0 x 10(-3) M completely inhibited the radicle growth of both rape and leek seedlings.     

Syntheses in the methyl-2-furylketone series

3-Hydroxy- (I),3-mercapto- (II), and 3-amino-5-(2-furyl)-1,2,4-triazines (III) are prepared by cyclizing respectively the semicarbazone, thiosemicarbazone, and guanidylhydrazone of 2-furylglyoxal. Treatment of III with nitrous acid converts it to I. Iodine oxidizes II to the disulfide. Depending on the reaction conditions,2-furylglyoxal hydrate and aminoguanidine, give 5- and also 6-(2-furyl)-substituted 3-amino-1,2,4-triazines. Under the same conditions the undehydrated furylglyoxal and aminoguanidine give only the 5-(2-furyl) derivative. Hydrochlorides and N-acetyl derivatives of the two amines are prepared.For Part X see [1].     

β-Carbolines as agonistic or antagonistic benzodiazepine receptor ligands. 1. Synthesis of some 5-, 6- and 7-amino derivatives of 3-methoxycarbonyl-β-carboline (β-CCM) and of 3-ethoxycarbonyl-β-carboline (β-CCE)

Condensation of diethyl formylamino- or diethyl acetylaminomalonate with 4-, 5- or 6-nitrogramine 1 afforded the diethyl formylamino- or the diethyl acetylamino[(nitroindol)-3-ylmethyl]malonates 2 ; reduction of the nitro group followed by N-formylation or acetylation of the resulting amino compounds 3 , led to the 4-, 5-and 6-acylamino derivatives 4 . Cyclization of 4 in the presence of polyphosphoric esters gave the 3,3-bis(ethoxycarbonyl)-3,4-dihydro-β-carbolines 5 , which underwent lithium chloride/water catalyzed monodeethoxycarbonylation to the corresponding 5-, 6- and 7-acylamino-3-ethoxycarbonyl-β-carbolines 6 , whose acidic hydrolysis led finally to the 5-, 6- and 7-amino-3-ethoxycarbonyl-β-carbolines 9 . The 6-amino compounds 9b-e were obtained also by direct nitration of 3-methoxycarbonyl-β-carboline 7a and of 3-ethoxycarbonyl-β-carboline 7c , followed by the nitro group reduction of the resulting nitro carbolines 8 . Preliminary studies of the binding to rabbit brain benzodiazepine receptor sites indicate compounds 9b and 9c to inhibit the ³H-diazepam binding at 10^?8 M concentrations.     

Thiocyanation, Halogenation, Dehalogenation, Transhalogenation, and Nitration of 2-Substituted 4-(2-Furyl)thiazoles

Bromination and thiocyanation of 2-amino- and 2-acetylamino-4-(2-furyl)thiazoles when 1 mol of reagent is used at 10°C are directed to the 5 position. Formation of 5'-bromo-substituted derivatives when the reaction temperature is raised is the result of a secondary, thermodynamically controlled process. Monohalogenation and mononitration of 4-(2-furyl)-2-methylthiazole are directed to the 5' position. Nitration of 2-acetylamino-4-(5-nitro-2-furyl)thiazole by a nitrating mixture is accompanied by oxidative cleavage of the 5-nitrofuran moiety and leads to formation of 5,5'- and 3',5'-dinitro derivatives.     

2-(3-Acetylamino-2,2-dimethylcyclobutyl)-methyl-4(3H)-quinazolinones

Beckmann rearrangement of N-[3-(1-hydroxyimino)ethyl-2,2-dimethylcyclobutyl]acetylanthranilic acid, and its 5-bromo and 4-chloro derivatives gives the corresponding N-(3-acetylamino-2,2-dimethylcyclobutyl)acetylanthranilic acids. Treatment of these acylanthranilic acids with formamide gives 2-(3-acetylamino-2,2-dimethylcyclobutyl)methyl-4(3H)-quinazoline and its 6-bromo and 7-chloro derivatives.     

Studies on heteroaromaticity. XV . the 1,3-dipolar cycloaddition reaction of 5-nitro-2-furyldiazomethane

The 1,3-dipolar cycloaddition reaction of 5-nitro-2-furyldiazomethane ( 1 ) with acrylonitrile, acrylamide, methyl acrylate, diethyl fumarate, methyl methacrylate and methyl cinnamate afforded the corresponding 3-substituted pyrazolines. ( 2a-f ). Similarly the pyrazoles ( 3b-d ) were prepared by addition of 1 to acetylenic compounds such as diethyl acetylenedicarboxylate, methyl phenylpropiolate and cyanoacetylene. Reaction of 1 with fumaronitrile and ω-nitro-styrene gave also the corresponding pyrazoles ( 3a and 3e ) instead of the pyrazolines. 3-(5′-Nitro-2′-furyl)-4-phenyl-5-carbomethoxypyrazoline ( 2f ) was oxidized with lead tetraacetate to the corresponding pyrazole ( 3f ), which was different from 3c , an addition product of 1 with methyl phenylpropiolate. 3-(5′-Nitro-2′-furyl)-5-carbamidopyrazoline ( 2b ) was pyrolyzed to the corresponding cyclopropane derivative 4 in low yield.     

Synthesis and Crystal Structure of 5-Amino-7-benzylseleno-8-cyano-3-ethoxycarbonyl-4-(2-furyl)-1,2-dimethyl-1,4-dihydro-1,6-naphthyridine

5-Amino-7-benzylseleno-8-cyano-3-ethoxycarbonyl-4-(2-furyl)-1,2-dimethyl-1,4-dihydro-1,6-naphthyridine was obtained by N-alkylation. X-ray crystallography showed the presence of two symmetrically conformers in the crystal.     

(3-Hydroxy-3-methylbutyn-1-yl)cycloalkan-1-ols in the Ritter Reaction

(3-Hydroxy-3-methylbutyn-1-yl)cycloalkan-1-ols were prepared by the action of (2-lithiooxy-2-methylbutyn-3-yl)lithium on cyclopentanone, cyclohexanone, cycloheptanone, and cyclododecanone. The products react with acetonitrile under Ritter reaction conditions. Therewith, in the presence of 8 g-equiv of sulfuric acid, a 2:1 mixture of 1-acetylamino-1-(2-acetylamino-2-methylbutyn-3-yl)cycloalkanes and 1-acetylamino-1-(3-acetylamino-3-methylbutyryl)cycloalkanes is formed, whereas in the presence of 2 g-equiv of the acid, a mixture of 1-acetylamino-1-(2-acetylamino-2-methylbutyn-3-yl)cycloalkanes and 1-acetylamino-1-(3-methyl-2-butenoyl)cycloalkanes in the same ratio.     

Synthesis and root growth-inhibitory activity of 2- and 3-(haloacetylamino)-3-(2-furyl)propanoic acids

A convenient synthesis of 2- and 3-(chloroacetylamino)-3-(2-furyl)propanoic acids (6a, 7a) and their fluoro analogs were developed. Both 6a and 7a showed 51-55% root growth-inhibitory activity towards rape seedlings at the concentration of 1.0x10(-4) M.     

Folic acid analogs. Modifications in the benzene-ring region. 5. 2′,6′-diazafolic acid

The synthesis of 2′,6′-diazafolic acid was accomplished by the condensation of 2-acetylamino-4(3H)pteridinone-6-earboxaldehyde (XIV) with diethyl N-[(5-amino-2-pyrimidinyl)carbonyl]-L-glutamate (XIII) followed by reduction of the anil double bond and alkaline hydrolylic cleavage of the N²-acetyl and ethyl ester protecting groups. Intermediate XIII was prepared by starling with 5-nitro-2-styrylpyrimidine (VI) and proceeding via 5-arnino-2-styrylpyrimidine (IX). The henzyloxycarbonyl derivative of IX was prepared and oxidized to the corresponding 5-benzyloxycarbonylaminopyrimidine-2-carboxylic acid (XI). The coupling of XI with diethyl L-glutamate followed by hydrogenolysis of the henzyloxycarbonyl function afforded the desired intermediate XIII. 2′,6′-Diazafolic acid was a potent inhibitor of Streptococcus faecium and displayed marginal activity against leukemia 1,1210 in mice.     

Hypbrvalent Iodine Oxidation of 3-(2-Furyl)-1-(2-hydroxyaryl)prop-2-enones : Synthesis of Novel 2-(2-Furyl)-cis-3-hydroxvchromanones and Derived 3-Hydroxychromones

The synthesis of novel 2-(2-furyl)-cis-3-hydroxychro-manones(3a-c) has been achieved from 3-(2-furyl)-1-(2-hydroxy-aryl)-2-enones (1a-c) via acid catalyzed hydrolysis of dimethylacetals (2a-c), formed by hypervalent iodine oxidation using iodobenzene diacetate in methanolic potassium hydroxide. Action of dil. alkali on 3a and 3b provides a new synthesis of 2-(2-furyl)-3-hydroxychromones (6a, 6b).     

A synthesis of 3-phenyl-1,2,3,4-tetrahydroisoquinoline and 2-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepine via Pummerer-type cyclization: enhancing effect of boron trifluoride diethyl etherate on the cyclization

A synthesis of 6,7-dimethoxy-3-phenyl-1,2,3,4-tetrahydroisoquinoline (14a) and 7,8-dimethoxy-2-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepine (14b) was achieved via the cyclization of N-(3,4-dimethoxyphenyl)methyl-1-phenyl-2-(phenylsulfinyl)ethylformamide (6a) and N-2-(3,4-dimethoxyphenyl)ethyl-1-phenyl-2-(phenylsulfinyl)-ethylformamide (6b) using the Pummerer reaction as a key step, respectively. The Pummerer reaction of 6a,b under usual conditions using trifluoroacetic anhydride yielded the vinyl sulfides (8a, b), non-cyclized products, as a major product. The cyclization proceeded when boron trifluoride diethyl etherate was used as an additive reagent, thus giving rise to the corresponding cyclized products (7a) and (7b) in moderate yields. We propose that the enhancing effect of the Lewis acid on the cyclization may be attributable to the involvement of a dicationic intermediate, sulfonium-carbenium dication (23).     

Alkyl (E,Z)-2-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-3-dimethylaminopropenoates in the synthesis of fused pyrimidinones. A facile route to 3-aminoazino-4H-pyrimidin-4-ones

Alkyl (E,Z)-2-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-3-dimethylaminopropenoates 1a,b react with het-eroarylamines 2 to give alkyl 2-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-3-heteroarylaminopropenoates 3-13 . These were cyclized into fused 3-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-4H-azolo- (or azino)-pyrim-idin-4-ones 14-18 . 2-Benzoyl-2-ethoxycarbonyl-1-ethenyl group can be easily removed from 3-(2-benzoyl-2-ethoxycarbonyl-1-emenyl)amino-8-memyl-4H-pyrido[1,2-a]pyrimidin-4-one ( 14 ) to give 3-amino-8-methyl-4H-pyrido[1,2-a]pyrimidin-4-one ( 19 ). The structure of 1a was confirmed by X-ray analysis.     

Synthesis of some 3-EthoxycarbonyI-5-hydroxy-4-oxo-2-pyrroline derivatives from 3(2H)furanones

A number of 3-ethoxycarbonyl-5-hydroxy-2-methyl-5-or-1,5-substituted 4-oxo-2-pyrrolines have been prepared, respectively, by the action of ammonium hydroxide or primary aliphatic amines on 2-arylidene or 2-N-acetyl-N-arylaminomethylene-4-ethoxycarbonyl-5-methyl-3(2H)furanones. The structures of these prepared compounds have been determined by spectroscopic data and chemical means.     

The bromination of 2-amino- and 2-acetylamino-4-(2-furyl)-thiazoles

The bromination of 2-amino-and 2-acetylamino-4-(2-furyl)thiazoles has been studied, and it has been shown that bromination takes place first in the furan ring and then, with an excess of bromine, also in the thiazole ring in position 5.     

Synthesis and Diazotization of Diethyl 6-Amino-2-Hydroxyazulene-1,3-Dicarboxylate and Its 2-Acetoxyl Derivative

Diethyl 6-amino-2-hydroxyazulene-1,3-dicarboxylate ( 6a ) and 2-acetoxyl derivative ( 6b ) were synthesized by reduction of the 6-azido derivatives ( 5a,b ) with zinc/acetic acid in excellent yields. 5a and 5b were prepared by azidation of diethyl 2-acetoxy-6-bromoazulene-1,3-dicarboxylate (4). Diazotization of 6a with sodium nitrite in the presence of concentrated sulfuric acid in dioxane gave diethyl 2-hydroxy- ( 7a ), 2,6-dihydroxy- ( 8a ), and 2-hydroxy-6-[2-(2-hydroxyethoxy)ethoxy]-azulene-1,3-dicarboxylates ( 9a ), in 5, 35 and 20% yields, respectively. Similar reaction of 6b gave the corresponding acetates 7b, 8b , and 9b , compounds of the same type from 6a . No evidence for the formation of 6-diazo-1,3-diethoxycarbonyl-2(6H) azulenone ( 2b ) was obtained in the employed reaction conditions.     

Synthesis of 2(3)-ethoxycarbonyl-5,6,7,8-tetrafluorochromones

The hitherto unknown ethyl pentafluorobenzoylpiruvate was prepared by condensing pentafluoroacetophenone with diethyl oxalate. Intramolecular cyclization of this ester or of its copper(II) chelate, as well as of ethyl 2-(ethoxymethylene)pentafluorobenzoylacetate affords 2- and 3-ethoxycarbonyl-5,6,7,8-tetrafluorochromones. Hydrolysis of the latter followed by decarboxylation gives 5,6,7,8-tetrafluorochromone.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 362–364, February, 1993.     

Aminoacids in the synthesis of heterocyclic systems. The synthesis of methyl 2-acetylamino-3-dimethylaminopropenoate and 2-(N-methyl-N-trifluoroacetyl)amino-3-dimethylaminopropenoate and their application in the synthesis of heterocyclic compounds

Methyl (Z)-2-acetylamino-3-dimethylaminopropenoate (3) was prepared from N-acetylglycine (1), which was converted with N,N-dimethylformamide and phosphorus oxychloride into 4-dimethylaminomethylene-2-methyl-5(4H)-oxazolone (2), followed by treatment with methanol in the presence of potassium carbonate, into 3. The compound 3 was shown to be a versatile reagent in the synthesis of various heterocyclic systems. With N-nucleophiles, such as heterocyclic amines 4, either methyl 2-acetylamino-3-heteroarylaminopropenoates 5 or fused pyrimidinoncs 6 were formed, dependent on the reaction conditions and/or heterocyclic substituents: C-nuclcophiles with an active or potentially active methylene group, such as 1,3-dicarbonyl compounds 7, 8 and 9, substituted phenols 10a,b, naphthols 11, 12a-c, and substituted coumarin 13a, afforded substituted pyranones 20 and 22, and fused pyranones 21, 23–26. The nitrogen containing heterocycles 14–19 produced pyranoazines 27–31 and pyranoazole 32. In all of these systems the acetylamino group is attached at position 3 of the newly formed pyranone ring. The orientation around the double bond for methyl (Z)-2-(N-methyl-N-trifluo-roacetyl)-3-dimethylaminopropenoate (36) was established by X-ray analysis.