Nitropyridyl isocyanates in 1,3‐dipolar cycloaddition reactions

The reactivity of 3‐nitro‐4‐pyridyl isocyanate ( 7 ) and 5‐nitropyridin‐2‐yl isocyanate ( 9 ) in 1,3‐dipolar cycloaddition reactions with azides and pyridine N‐oxides has been investigated. 1,3‐Dipolar cycloaddition to trimethylsilylazide (TMSA) afforded the respective tetrazolinones, 1‐(3‐nitropyridin‐4‐yl)‐1H‐tetrazol‐5(4H)one ( 8 , 50 %) and 1‐(5‐nitropyridin‐2‐yl)‐1H‐tetrazol‐5(4H)one ( 11 , 64 %). Respectively, 1,3‐dipolar cycloaddition of nitropyridyl isocyanates 7 and 9 to 3,5‐dimethylpyridine N‐oxide ( 14 ), 3‐methylpyridine N‐oxide ( 21 ) and pyridine N‐oxide ( 22 ) gave the substituted amines, 3,5‐dimethyl‐N‐(3‐nitropyridin‐4‐yl)pyridin‐2‐amine ( 17 ), 3,5‐dimethyl‐N‐(5‐nitropyridin‐2‐yl)pyridin‐2‐amine ( 20 ), N‐(5‐nitropyridin‐2‐yl)pyridin‐2‐amine ( 24 ), 5‐methyl‐N‐(5‐nitropyridin‐2‐yl)pyridin‐2‐amine ( 23 ) and 3‐methyl‐N‐(5‐nitropyridin‐2‐yl)pyridin‐2‐amine ( 25 ) in 65 ‐ 80 % yield, obtained by cycloaddition, rearrangement and decarboxylation. The results demonstrate that the nitropyridyl isocyanates ( 7,9 ) readily undergo 1,3‐dipolar cyloaddition reactions similar to phenyl isocyanates.     

[2 + 2] Cycloaddition reactions of unsymmetrically substituted carbodiimides

N-Alkyl-N′-arylcarbodiimides add alkyl and aryl isocyanates to the N-alkyl substituted CN double bond to yield 4-arylimino-1,3-diazetidine-2-ones 3. In the case of bulky alkyl substituents the reaction still proceeds across the sterically hindered CN double bond. N-Aryl-N′-[(4-dimethylamino)phenyl]carbodiimides form [2 + 2] cycloadducts with aryl isocyanates preferentially across the CN double bond not attached to the electron-rich aryl groups. However, steric crowding on this CN double bond directs the reaction to the adjacent double bond of the heterocumulative system. The rate of the [2 + 2] cycloaddition reaction of N'-methyl-N′-phenylcarbodiimide with 4-nitrophenylisocyanate is about 2.5 times faster in acetonitrile than in benzene.     

Efficient synthesis of 1,2,4-dithiazolidine-3,5-diones (dithiasuccinoyl-amines) and observations on formation of 1,2,4-thiadiazolidine-3,5-diones by related chemistry

An efficient synthesis of 1,2,4-dithiazolidine-3,5-diones ( 1 ) from chlorocarbonylsulfenyl chloride ( 3 ) plus O-dimethylaminoethyl-N-alkyl or aryl thiocarbamates ( 4 ) has been worked out. In this synthesis, 1,2,4-thiadiazolidine-3,5-diones ( 5 ) have been shown to arise as low-level by-products, and experiments were conducted to elucidate the mechanism of the side reaction. N,N′-Dimethyl-1,2,4-thiadiazolidine-3,5-dione ( 5a ) was prepared in one step from N,N′-dimethylurea plus 3 , or from 4a plus one equivalent of sulfuryl chloride. A general route to 5 involved reaction of equimolar amounts of isocyanates ( 6 ), isothiocyanates ( 7 ) and sulfuryl chloride followed by hydrolysis of intermediate 9 . Heterocycles reported have been characterized by nmr, ir, uv, ms, and hplc.     

Studies on the synthesis of heterocyclic compounds. Part IV. Further investigation of the pschorr reaction with some pyrazole derivatives

Thermal decomposition of the diazonium sulfate derived from N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-aminobenzamide afforded products formulated as 1-phenyl-3-methyl[2]benzopyrano[4,3-c]pyrazol-5-one (yield 10%), 1,4-dimethyl-3-phenylpyrazolo[3,4-c]isoquinolin-5-one (yield 10%), N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-hydroxybenzamide (yield 8%) and 4′-hydroxy-2,3′-dimethyl-1′-phenylspiro[isoindoline-1,5′-[2]-pyrazolin]-3-one (yield 20%). Decomposition of the diazonium sulfate derived from N-methyl-(1,3-diphenylpyrazol-5-yl)-2-aminobenzamide gave products formulated as 7,9-dimethyldibenzo[e,g]pyrazolo[1,5-a][1,3]-diazocin-10-(9H)one (yield 8%), 4-methyl-1,3-diphenylpyrazolo[3,4-c]isoquinolin-5-one (yield 7%) and 4′-hydroxy-2-methyl-1′,3′-diphenylspiro[isoindoline-1,5′-[2]pyrazolin]3-one (yield 10%). The spiro compounds 6a,b underwent thermal and acid-catalysed conversion into the hitherto unknown 2-benzopyrano[4,3-c]pyrazole ring system 7a,b in good yield. Analytical and spectral data are presented which supported the structures proposed.     

Aziridination of the uracil 5,6-olefinic bond of 3-N-3′,5′-Di-O-tribenzoyl-5-vinyl-2′-deoxyuridine

Oxidation of N-aminophthalimide with lead tetra-acetate at -50° gives N-acetoxyaminophthalimide ( 3 ) which selectively aziridinates the 5,6-double bond present in 3-N-3′,5′-di-O-tribenzoyl-5-vinyl-2′-deoxyuridine ( 1a ) to yield 2-[1′-(2′-deoxy-β-D-ribofuranosyl)]-7-(1-phthalimido)-4-N-3′,5′-di-O-tribenzoyl-6-vinyl-2,4,7-triazabicyclo[4.1.0]heptan-3,5-dione ( 5 ).     

Synthesis of 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones and their conversion into 2-aryl-1,2,4-triazine-3,5-(2H,4H)odiones. A new synthesis of 1-aryl-6-azauracils

Treatment of 6-amino-5-arylazo-1,3-dimethyluracils with urea or N,N′-carbonyldiimidazole gave the respective 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones, which were hydrolyzed with alkali to afford 2-aryl-2,3,4,5-tetrahydro-3,5-dioxo-1,2,4-triazine-6-carboxylic acids (1-aryl-6-azauracil-5-carboxylic acids). Thermal decomposition of these carboxylic acids gave the corresponding 2-aryl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-6-azauracils). Methylation of the latter with methyl iodide gave the corresponding 2-aryl-4-methyl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-3-methyl-6-azauracils).     

Reactions of 2-hydroxybenzonitrile with isocyanates

Triethylamine catalyzes the reaction of 2-hydroxybenzonitrile ( 1 ) with aryl isocyanates to form the corresponding carbamates 2a-c , as well as the cyclization of the latter compounds to either 4[N-(N-arylcarbamoyl)-imino]-3-aryl-2H-1,3-benzoxazin-2-ones 4a-c , or 4-arylamino-2H-1,3-benzoxazin-2-ones 7a-c , depending on the reaction temperature. Under analogous conditions, the carbamates obtained from 1 and 2-chloroethyl isocyanate, 3-chloropropyl isocyanate and ethyl isocyanatoacetate undergo a double cyclization yielding imidazo- and pyrimido[1,2-c|1,3]benzoxazinones 13a,b,17 . Upon heating in phenyl ether, compounds 7a-c , rearrange to 2-(2-hydroxyphenyl)-4(3H)-quinazolinones 10a-c .     

Synthesis of 1′-substituted and 1′,3′-disubstituted (±)-2R*, 11bS*-9,10-Dimethoxy-1,3,4,6,7,11 b-Hexahydrospiro-[benzo[a]quinolizin-2,5′-imidazolidine]-2′,4′-diones

The results of the reaction between (±)-2R*,11bS*-2-alkyl(aryl)amino-1,3,4,6,7,11b-hexahydrobenzo[a]-quinolizine-2-carbonitriles 2 and isocyanates under a variety of experimental conditions are discussed. The ureides 3 and iminohydantoins 4 thus obtained were used to prepare N₃-monosubstituted and N₁,N₃-disubstituted derivatives of the (±)-2R*,11bS*-9,10-dimethoxy-1,3,4,6,7,11b-hexahydrospiro[benzo[a]quinolizin-2,5′-imidazolidine]-2′,4′-dione system 1 . The stereochemistry of these compounds is discussed, on the basis of spectroscopic evidence and study of their chemical reactivity.     

Reaction of N-(2-pyridylmethyl)-3,5-dimethylbenzamide and N-(3-pyridylmethyl)-3,5-dimethylbenzamide N-oxides with acetic anhydride

As a continuation of our work on the reaction of N-pyridylmethyl-3,5-dimethylbenzamide N-oxides with acetic anhydride, we now report a study of the reaction of N-(2-pyridylmethyl)-3,5-dimethylbenzam.de N-oxide ( 5 ) and N-(3-pyridylmethyl)-3,5-dimethylbenzamide N-oxide ( 6 ) with acetic anhydride. Compound 5 gave N,N′-di(3,5.dimethylbenzoyl)-1,2-di(2.pyridyl)ethenediamine ( 7 ) and 3,5-dimethylbenzamtde ( 8 ). Compound 6 afforded three products formulated as 2-acetoxy-3-(3,5-dimethylbenzoylaminomethyl)pyridine ( 12 ), 3-(3,5-dimethylbenzoylaminomethyl)-2-pyridone ( 13 ) and 5-(3,5-dimethylbenzoylaminomethyl)-2-pyridone ( 14 ). Analytical and spectral data are presented which support the structures proposed.     

Umsetzung von 3-(Dimethylamino)-2H-azirinen mit 1,3-Oxazolidin-2-thion zu 3-(2-Hydroxyethyl)-2-thiohydantoinen

Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Oxazolidine-2-thione to 3-(2-Hydroxyethyl)-2- thiohydantoins The reaction of 3-(dimethylamino)-2H-azirines 1 and 1,3-oxazolidine-2-thione ( 6 ), in MeCN at room temperature, yields, after hydrolytic workup, 3-(2-hydroxyethyl)-2-thiohydantoins 7 (Scheme 2). In the case of the spirocyclic 1c , crystallization of the crude reaction mixture leads to spiro [cyclopentane-1, 7′(7′aH)-imidazo [4, 3-b] oxazole] -5′-thione 8c . The mechanism is discussed.     

Reaction of 5-hydroxy-L-tryptophan with alkyl isocyanates

5-Hydroxy-L-tryptophan 4 with potassium cyanate gives 5-(5-hydroxy-3-indolylmethyl)hydantoin 5 or N_b-carbamoyl-5-hydroxy-L-tryptophan 6 depending on the reaction conditions. Reaction of 4 with methyl iso-cyanate in acetone provides 5-hydroxy-N_b-methylcarbamoyl-L-tryptophan 7 . Treatment of 4 with ethyl, propyl and isopropyl isocyanates in acetone gives rise to the formation of the corresponding 2-[(3-alkyl-4,4-dimethyl-2-oxo)-1,3-diazetidinyl]-3-(5-hydroxy-3-indolyl)propionic acids 8–10 .     

Synthesis and polymerization of 1-(2,4,6-tricyanophenylthio)-3-[3,5-bis(n,n-dimethylamino)phenoxy]-2-propyl methacrylate; polymer effect on intramolecular charge–transfer interaction

1-[3,5-Bis(N,N-dimethylamino)phenoxy]-ω-(2,4,6-tricyanophenylthio)alkanes ( 1a–c ), where an electron-accepting 2,4,6-tricyanophenylthio group and an electron-donating 3,5-bis(N,N-dimethylamino)phenoxy one are linked with a spacer such as ethylene, trimethylene, and tetramethylene, were prepared in order to examine an effect of the spacer chain length on intramolecular charge–transfer interaction between the 2,4,6-tricyanophenylthio and 3,5-bis(N,N-dimethylamino)phenoxy groups. From the UV-vis spectra measurements of 1a–c , 1-[3,5-bis(N,N-dimethylamino)phenoxy]-3-(2,4,6-tricyanophenylthio)Propane ( 1b ) carrying the trimethylene chain as a spacer was found to have the strongest intramolecular charge–transfer interaction. A new methacrylate-type monomer carrying the 1b unit as a side chain, 1-(2,4,6-tricyanophenylthio)-3-[3,5-bis(N,N-dimethylamino)phenoxy]-2-propyl methacrylate ( 2 ), was prepared successfully in 9.2% total yield in seven steps. The monomer 2 homopolymerized in benzene, tetrahydrofuran, acetone, and dimethyl sulfoxide in the presence of 2,2′-azobis(isobutyronitrile) at 60°C to give polymers [poly( 2 )] with molecular weights of 6,000 to 98,000. An intramolecular charge–transfer interaction in the poly( 2 ) was found to be larger than that in the monomer 2 and to increase with an increase in the degree of polymerization of the poly( 2 ), suggesting that there is an existence of polymer effect other than the polymer effect due to the high local concentration of the donor-acceptor pair. © 1995 John Wiley & Sons, Inc.     

Synthesis of new functionally substituted hetarylcarbamates from methyl {4-[(2<Emphasis Type="Italic">E</Emphasis>)-3-(4-methoxyphenyl)-prop-2-enoyl]phenyl}carbamate

Three-component condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}- carbamate with ninhydrin and L-proline in methanol–water (10: 1) afforded methyl {4-[1,3-dioxo-1′- (4-methoxyphenyl)-1,1′,2′,3,5′,6′,7′,7a′-octahydrospiro[indene-2,3′-pyrrolizin]-2′-ylcarbonyl]phenyl}carbamate. Heating of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}carbamate with isatin and benzylamine in methanol gave methyl {4-[4′-(4-methoxyphenyl)-2-oxo-5′-phenyl-1,2-dihydrospiro[indole-3,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate. The condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2- enoyl]phenyl}carbamate with sarcosine and 11H-indeno[1,2-b]quinoxalin-11-one generated in situ from ninhydrin and o-phenylenediamine in boiling ethanol led to the formation of methyl {4-[4′-(4-methoxyphenyl)-1′-methyl-11,11a-dihydro-5aH-spiro[benzo[b]phenazine-6,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate.     

Synthesis of 3,3′-(1,6-hexanediyl)bis-pyrimidine derivatives and 3,4-dithia[6.6](1.3)pyrimidinophane

Several 3,3′-(1,6-hexanediyl)bis[6-methyl-2,4(1H,3H)-pyrimidinedione] derivatives ( 4a, 4b , and 4c ) were synthesized from 1,6-(hexanediyl)bis[6-methyl-2H-1,3-oxazine-2,4(3H)-dione] (3) . Compound 4c was converted to 6, which reacted with thiourea giving thiuronium salt 7 . 3,3′-(1,6-Hexanediyl)bis [1-(2-mercaptoethyl)-6-methyl-2,4(1H,3H)-pyrimidinedione] (9) was obtained by the hydrolysis of 7 , and then 9 was oxidized to 12,22-dimethyl-3,4-dithia[6.6] (1.3)-1,2,3,4-tetrahydro-2,4-dioxopyrimidinophane (10) .     

Allgemeiner Zugang zu Polyaminen mit Ethan-1,2-diamin-Einheiten: Synthese von nicht natürlich vorkommenden homologen und isomeren N1,4-Di(4-cumaroyl)sperminen

█tl="American"█The synthesis of the three N,N′-di(4-coumaroyl)tetramines, i.e., of (E,E)-N-{3-[(2-aminoethyl)amino]propyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(ethane-1,2-diyl)bis[prop-2-enamide] ( 1a ), (E,E)-N-{4-[(2-aminoethyl)amino]butyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(ethane-1,2-diyl)bis[prop-2-enamide] ( 1b ), and (E,E)-N-{6-[(2-aminoethyl)amino]hexyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(ethane-1,2-diyl)bis[prop-2-enamide] ( 1c ), is described. It proceeds through stepwise construction of the symmetric polyamine backbone including protection and deprotection steps of the amino functions. Their behavior on TLC in comparison with that of 1,4-di(4-coumaroyl)spermine (=(E,E)-N-{4-[(3-aminopropyl)amino]butyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(propane-1,3-diyl)bis[prop-2-enamide]; 2 ) is discussed.     

Syntheses of folic acid models, 6-(N-acylarylamino)methyllumazines

Folic acid models, 1,3-dimethyl-6-(N-acylarylamino)methyllumazines 9 , were synthesized from 6-bromomethyl-1,3-dimethyllumazine ( 6 ), which was derived from 5,6-diamino-1,3-dimethyluracil ( 1 ) by the condensation with 1,3-dihydroxyacetone, followed by bromination. The bromide 6 was also prepared by the cycloaddition between 3,6,8-trioxo-5,7-dimethyl-5,6,7,8-tetrahydro-3H-pyrimido[5,4-c][1,2,5]oxadiazine ( 4 ) and 1-propenyl trimethylsilyl ether followed by bromination. The folic acid models 9 were also directly synthesized from the oxadiazine 4 and 3-(N-acylaryl)amino-1-propenyl trimethylsilyl ether 8 by cycloaddition.     

Ring transformations of heterocyclic compounds. XVI. Spiro[cyclohexadiene-dihydroacridines]. A novel class of spirodihydroacridines by ring transformation of pyrylium salts with 9-methylacridine and its quaternary salts

2,4,6-Triarylpyrylium salts 1 react with the in situ generated anhydrobase of 9,10-dimethylacridinium methosulfate ( 2a ) in the presence of anhydrous sodium acetate in ethanol by a 2,5-[C₄+C₂] pyrylium ring transformation to give the hitherto unknown 6-aroyl-3,5-diaryl-10′-methylspiro[cyclohexa-2,4-diene-1,9′-9′,10′-dihydro-acridines] 3 . When the pyrylium perchlorate 1a is treated under the same conditions with the N-ethyl, N-allyl or N-benzyl substituted acridinium salts 2b-d a dealkylation of these salts occurs and the N-unsubstituted spiro[cyclohexadiene-dihydroacridine] 4a is formed. The same compounds 4 can also be obtained by transformation of the pyrylium salts 1 with 9-methylacridine ( 7 ) and triefhylamine/acetic acid in ethanol. Structure elucidation is performed by an X-ray crystal structure determination of the spiro[cyclohexadiene-dihydroacridine] 3a . Spectroscopic data of the transformation products and their mode of formation are discussed.     

Reaction of 5-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide with electrophilic reagents: Bromine and nitric acid

Reactions of 5-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide with bromine and nitric acid lead to the electrophilic substitution of the hydrogen atom in the meta-position with respect to the nitro group. At thebromination the primarily formed 4-bromo-6-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide when kept in the solution loses an oxygen atom forming 4-bromo-6-nitrospiro[benzimidazole-2,1′-cyclohexane] 1-oxide and an isomerization product, 8-bromo-6-nitrospiro[3H-[2,1,4]benzoxadiazine-3,1′-cyclohexane] 4-oxide. The latter exposed to light turns into 4-bromo-6-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide. The reaction of the initial 1,3-dioxide with nitric acid afforded 4,6-dinitrospiro[benzimidazole-2,1′-cyclohexan]-7-ol 1-oxide whose heating in o-dichlorobenzene resulted in 3,5-dinitro-1,8-diazatricyclo[7.5.0.0^2,7] tetradeca-2(7),3,5,8-tetraen-6-ol.     

Synthesis of new imidazo[4,5-d][1,3]diazepine derivatives from 5-amino-4-(cyanoformimidoyl)imidazoles

N¹-[(Z) -2- Amino-1,2-dicyanovinyl]formamidines 1a-d react readily with tosyl isocyanate to form novel 8-amino-3-substituted-5-oxo-7-tosylaminoimidazo[4,5-d][1,3]diazepines 6a-d rather than the 6-cyano-2-oxopurine derivatives 5a-d expected. Compound 5a has been synthesized from 1a by reaction with ethyl chloroformate and base-catalyzed cyclization of the resultant 5-ethoxycarbonylamino-4-(cyanoformimidoyl)imidazole. Treatment of the 5-amino-4-cyanoimidazoles 7a and b with tosyl isocyanate under similar conditions gives the 4-cyano-5-(3′-tosylureido)imidazoles 8a and b , which on treatment with ethanolic ammonia cyclizes to the corresponding isoguanines 10a and b .     

Furopyridines. XXIX. Reactions of furo[2,3-b:4,5-c‘]-, -[3,2-b:-4,5-c’]-, -[2,3-c:4,5-c‘]- and -[3,2-c:3,2-c’]dipyridine

Furo[2,3-b:4,5-c‘]- 1a , -[3,2-b:4,5-c’]- 1b , -[2,3-c:4,5-c‘]- 1c and -[3,2-c:4,5-c’]dipyridine 1d were derived to the N-oxides 2a-d , N‘-oxides 2′b , 2′c or N,N’-dioxide 3b-d by N-oxidation with m-chloroperbenzoic acid. Chlorination of these N-oxides, N′-oxide and N,N′-dioxides with phosphorus oxychloride afforded compounds chlorinated at the α-position(s) to the ring nitrogen 4a-d , 4′c , 14b-d and 14′b . Acetoxylation of N-oxides 2a-d and 2′c with acetic anhydride gave the corresponding pyridone compounds 6a-d and 6′c in good yields, while the acetoxylation of N,N′-dioxides gave a complex mixture from which no compound could be isolated. Cyanation of 2a-d, 2′c and 3b-d with trimethylsilyl cyanide yielded the cyano compounds 7a-d , 7′c , cyano-N-oxides 15b-d and dicyano compounds 15′c and 15′d . Monocyano compounds 7a-d and 7′c were converted to the imino esters 8a-d and 8′c by treatment with sodium ethoxide. Imino esters were derived to the carboxylic esters 9a-d and 9′c , from which the corresponding alde hydes 10a-d and 10′c were obtained by reduction with diisobutylaluminum hydride. Dicyanide 15′c was converted to dialdehyde 19 by the treatment with sodium ethoxide, and the subsequent hydrolysis of the imino ester and reduction of the carboxylic ester with diisobutylaluminum hydride.