Study of aromatic nucleophilic substitution with amines on nitrothiophenes in room-temperature ionic liquids: are the different effects on the behavior of para-like and ortho-like isomers on going from conventional solvents to room-temperature ionic liquids related to solvation effects?

The kinetics of the nucleophilic aromatic substitution of some 2-L-5-nitrothiophenes (para-like isomers) with three different amines (pyrrolidine, piperidine, and morpholine) were studied in three room-temperature ionic liquids ([bmim][BF4], [bmim][PF6], and [bm(2)im][BF4], where bmim = 1-butyl-3-methylimidazolium and bm(2)im = 1-butyl-2,3-dimethylimidazolium). To calculate thermodynamic parameters, a useful instrument to gain information concerning reagent-solvent interactions, the reaction was carried out over the temperature range 293-313 K. The reaction occurs faster in ionic liquids than in conventional solvents (methanol, benzene), a dependence of rate constants on amine concentration similar to that observed in methanol, suggesting a parallel behavior. The above reaction also was studied with 2-bromo-3-nitrothiophene, an ortho-like derivative able to give peculiar intramolecular interactions in the transition state, which are strongly affected by the reaction medium.     

Catalysis in aromatic nucleophilic substitution. Note II. Piperidino substitution reactions of some 2-l-3-nitrothiophenes and 2-l-5-nitrothiophenes in methanol and benzene

The rates of piperidino substitution of some 2-L-3-nitrothiophenes (I) and 2-L-5-nitrothiophenes (II) (L = Cl, Br, I, OC₆H₄NO₂-p, and SO₂Ph) have been measured in methanol and in benzene at various piperidine concentrations. The reactivity of compounds (I) is not affected by the piperidine concentration in both methanol and benzene, except for the case of L = I (Ic). Probably due to association effects, the reactivity of Ic in benzene decreases as the piperidine concentration is increased. The reactions of compounds II follow overall second order kinetics in methanol while in benzene a different behaviour is observed as a function of the nature of the leaving group. In fact, the piperidino substitutions of IIa-c (L = Cl, Br, I) are mildly accelerated at high piperidine concentrations (a moderate solvent effect); on the contrary the reactivity of IId and e shows a strong dependence on the piperidine concentration, pointing out a genuine base catalysis.     

Effects of ring substituents on the reactivity of thionphenoxide ions towards some nitro-activated thiophene derivatives

The rates of nucleophilic substitution of bromine on 3-bromo-2-nitrothiophene (1) and 2-bromo-3-nitrothiophene (II) by o-, m-, and p-substituted thiophenoxide ions bave been measured in methanol at 20.02°. The rate of thiophenoxy-debromination is always higher when the reaction center is in the β-position (substrate I) rather than in α-position (substrate II). Plots of the log k against σ°-constants for the reaction of the substituted thiophenoxides towards I and II have ρ-values of -0.78 (for substrate I) and -0.76 (for substrate II). Deviations from linearity for p-substituents with strong +M and -M effect are discussed. A comparison of proton basicity, carbon basicity, and nucleophilicity of the thiophenoxide ions has also been made.     

Synthesis of 2-(5-halogeno-2-f uryl)-2,3-dihydroperimidines

By boiling naphthylene-1,8-diamine with 5-halogeno- and 5-nitrofurfural in benzene or xylene, 90–95% yields of the corresponding 2-(5-halogeno-2-furyl)- and 2-(5-nitro-2-furyl)-2, 3-dihydroperimidines have been obtained. The dehydrogenation of 2-(5-bromo-2-furyl)-2, 3-dihydroperimidine with palladium on carbon has given 2-(5-bromo-2-furyl)perimidine. The compounds obtained have been characterized by their UV and IR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1001–1003, July, 1973.     

meta-Photoaddition reactions of 2-chloro-, 2,5-dichloro-, and 2-halo-5-isopropyl-tropones with 9,10-dicyanoanthracene

Photoreactions of 2-halotropones with the excited 9,10-dicyanoanthracene gave a meta-adduct and substitution products occurred at the C-2 position of troponoids. The mechanism of the meta-adduct was proved by the product analysis of the reaction of 3,7-dideuterio-2-bromo-5-isopropyltropone and 9,10-dicyanoanthracene. In the photoreaction of 2-chloro-5-isopropyltropone and 9,10-dicyanoanthracene in a mixed solvent of benzene and methanol, a benzaldehyde with a dibenzo-2-oxabicyclo[3.2.2]nonane system was obtained to support occurrence of an [8+4] cycloaddition reaction between them.     

Thiophene series. Substituent effect on thiophenoxy debromination of various 2-nitro-3-bromo-5-X-thiophenes

The kinetics of the reaction of a series of 2-nitro-3-bromo-5-X-thiophenes with sodium thiophenoxide in methanol were determined. The plot of log k against σ-values gave ρ-value + 4.51 at 20°. Good correlation was observed pointing out the validity of the Hammett relationship for reactions occurring directly on the thiophene ring at the β-position with respect to the heteroatom.     

Novel copolymers of styrene. 7. Some ring-disubstituted propyl 2-cyano-3-phenyl-2-propenoates

Novel trisubstituted ethylenes, ring-disubstituted propyl 2-cyano-3-phenyl-2-propenoates, RPhCH = C(CN)CO₂C₃H₇ (where R is 2-bromo-5-methoxy, 3-bromo-4-methoxy, 5-bromo-2-methoxy, 2-chloro-3-methoxy, 3-chloro-4-methoxy, 2-fluoro-3-methoxy, 2-fluoro-4-methoxy, 3-fluoro-4-methyl, 4-fluoro-3-phenoxy) were prepared and copolymerized with styrene. The monomers were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and propyl cyanoacetate and characterized by CHN elemental analysis, IR, ¹H- and ¹³C-NMR. All the ethylenes were copolymerized with styrene (M₁) in solution with radical initiation (ABCN) at 70°C. The composition of the copolymers was calculated from nitrogen analysis, and the structures were analyzed by IR, ¹H and ¹³C-NMR, GPC, DSC, and TGA. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200–500°C range with residue (3–7% wt.), which then decomposed in the 500–800°C range.     

Synthesis of n-(2-chloro-5-bromo-4-pyrimidyl)- and N-(2-chloro-5-iodo-4-pyrimidyl)amino acids

The previously unreported N-(2-chloro-5-bromo-4-pyrimidyl)- and N-(2-chloro-5-iodo-4-pyrimidyl) amino acids were synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 527–529, April, 1971.     

Oxidative nucleophilic substitution of hydrogen versus ring-opening in the reaction of 4-R-2-nitrothiophenes with amines. The crucial effect of 4-alkyl groups

4-Alkyl-2-nitrothiophenes [10: R = CH3, CH(OH)CH3, CH(OCH3)CH3] react with secondary aliphatic amines, in the presence of AgNO3, to give 3-alkyl-2-amino-5-nitrothiophenes (12) through an oxidative nucleophilic substitution of hydrogen (ONSH) of synthetic interest. This behavior is in striking contrast with that of the parent 2-nitrothiophene (6), which was found to undergo ring-opening in analogous reaction conditions. A possible rationale for the crucial effect of alkyl groups is suggested, grounded also on a study of the corresponding Meisenheimer-like adducts.     

Novel copolymers of styrene. 7. Some ring-disubstituted butyl 2-cyano-3-phenyl-2-propenoates

Novel trisubstituted ethylenes, ring-disubstituted butyl 2-cyano-3-phenyl-2-propenoates, RPhCH?C(CN)CO₂C₄H₉ (where R is 2-bromo-5-methoxy, 3-bromo-4-methoxy, 5-bromo-2-methoxy, 2-chloro-3-methoxy, 3-chloro-4-methoxy, 2-chloro-6-methyl, 3-chloro-4-methyl, 2-fluoro-4-methoxy) were prepared and copolymerized with styrene. The monomers were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and butyl cyanoacetate, and characterized by CHN analysis, IR, ¹H and ¹³C-NMR. All the ethylenes were copolymerized with styrene in solution with radical initiation (ABCN) at 70°C. The compositions of the copolymers were calculated from nitrogen analysis and the structures were analyzed by IR, ¹H and ¹³C-NMR. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200-500ºC range with residue (1-6% wt.), which then decomposed in the 500–800ºC range.     

Mechanism of the electrochemical reduction of 2-halo-5-nitrothiophenes in dimethylformamide

The reduction of 2-bromo-5-nitrothiophene and 2-iodo-5-nitrothiophene in dimethylformamide (DMF) was studied by means of classical and commutated polarography, EPR spectroscopy, a rotating platinum disk electrode with a ring, and preparative electrolysis. It was established that, depending on the nature of the halogen, their anion radicals may undergo further reduction to 2-nitrothiophene anion radicals or decomposition with splitting out of a halide anion and conversion to nitrothienyl radicals, which were identified on the ring electrode. The latter are capable of undergoing dimerization to 2,2-dinitro-5,5-dithienyl. The spectra of the anion radicals of 2-nitrothiophene and 2,2-dinitro-5,5-dithienyl were recorded by means of EPR. A mechanism for the reduction of halonitrothiophenes is proposed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 195–198, February, 1981.     

Über halogen- und stickstoffhaltige Derivate aliphatischer Carbonsäuren, 9. Mitt.: 2-Halogen- und 2-Amino-3-alkylchinoxaline

Zusammenfassung 3-Alkyl-2-chinoxalone lassen sich mit Phosphoroxyhalogeniden zu den entsprechenden 2-Chlor- und 2-Brom-3-alkyl-chinoxalinen umsetzen. Am Beispiel des 2-Chlor-3-decylchinoxalins wird die Reaktion mit nucleophilen Substanzen (Methanol, Äthanol, Ammoniak, Anilin) untersucht. Aus den 2-Halogeno-3-alkylchinoxalinen werden die entsprechenden 2-Hydrazino-3-alkylchinoxaline hergestellt.

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3-Alkyl 2-quinoxalones and phosphorus oxyhalides give the corresponding 2-chloro- and 2-bromo-3-alkyl quinoxalines. The reaction with nucleophiles (methanol, ethanol, ammonia and aniline) was investigated for 2-chloro-3-decyl quinoxaline. From 2-halogeno-3-alkyl quinoxalines the corresponding 2-hydrazino-3-alkyl quinoxalines have been prepared.

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8. Mitt.:H. Reinheckel, Mh. Chem.99, 2203 (1968).     

Alkylatlon orientation rules in conjugate addition of grignard reagents to nitropyrrole and nitrothiophene systems

Conjugate addition of various Grignard reagents to 1-alkyl-2-nitropyrroles and to 2-nitrothiophene has been investigated. 1-Alkyl-2-nitropyrroles undergo alkylation at 3 and 5 positions with prevalence of the latter isomer. On the contrary, in 2-nitrothiophene system, formation of the 3-isomer prevails. In both systems, a bulkier Grignard reagent favours the 5-isomer formation. This trend can be reversed increasing steric hindrance exerted by the 1-substituent of 2-nitropyrrole. 1-(Tri-isopropylsilyl)-3-nitropyrrole and 3-nitrothiophene give exclusively the 2-isomer. This rection allows 2-alkyl-3-nitrothiophenes and pyrroles to be synthesized with a one-pot procedure instead of the classical multi-stage reaction.     

On the synthesis and animation of 5-chloro-and 5-bromo-1,7-naphthyridine

A new synthesis of 5-chloro- and 5-bromo-1,7-naphthyridine, using 8-amino-1,7-naphthyridine as starting material is described. On amination with potassium amide in liquid ammonia, the 5-bromo compound undergoes a tele-amination into 8-amino- and 2-amino-1,7-naphthyridine and a Chichibabin reaction yielding 8-amino-5-bromo-1,7-naphthyridine. The reaction with the 5-chloro compound occurs at a much lower rate than the 5-bromo compound and only gives 8-amino-5-chloro-1,7-naphthyridine in a small yield. Convincing ¹H-nmr evidence is presented, showing that the 5-bromo- and 5-chloro-1,7-naphthyridine give addition of the amide ion at position 8 and that the 5-chloro compound also gives addition at position 2.     

Versatile synthesis of 3,5-disubstituted 2-fluoropyridines and 2-pyridones

5-bromo-2-fluoro-3-pyridylboronic acid (3) was prepared in high yield by ortho-lithiation of 5-bromo-2-fluoropyridine (1), followed by reaction with trimethylborate. Suzuki reaction of 3 with a range of aryl iodides gave 3-monosubstituted 5-bromo-2-fluoropyridines 4 in excellent yields. A second Suzuki reaction utilizing the bromo constituent of 4 with aryl and heteroaryl boronic acids provided 3,5-disubstituted 2-fluoropyridines 5, which in turn could be converted to the corresponding 2-pyridones 6.     

Thiophene series. Note IX . The absence of secondary steric effects in nucleophilic substitutions of thiophene derivatives: Kinetics of the reactions of 2-bromo-3,5-dinitrothiophene and 2-bromo-3,5-dinitro-4-methylthiophene with piperidine

The kinetics of the reactions of piperidine with 2-bromo-3,5-dinitrothiophcne (IV) and 2-bromo-3,5-dinitro-4-methylthiophene (III) have been measured in methanol, ethanol and benzene. Molecular model predictions were confirmed when the kinetic results (k_IV/k_III ? 2) demonstrated, for the first time, the absence of secondary steric effects for nucleophilic substitutions in thiophene compounds.     

Studies on silyl furans. II. Halodesilylation of 2-trimethylsilyl-3,4-bis(methoxycarbonyl)furans

Reactions of 2-trimethylsilyl-3,4-bis(methoxycarbonyl)furans 1a,b with sulfuryl chloride, bromine, and iodine monochloride in acetonitrile afforded the corresponding 2-halo-3,4-bis(methoxycarbonyl)furans 2a-f via chloro-, bromo-, and iododesilylation in good yields, respectively. However, the reaction of 1a with bromine in carbon tetrachloride mainly gave 2-bromo- 2b and 2-bromo-5-trimethylsilyl-3,4-bis(methoxycarbonyl)furan ( 3 ) in 37% and 45% yields. Similarly, the reaction of 1a with iodine monochloride afforded 1a , 2-chloro- 2a and 2-iodo-3,4-bis(methoxycarbonyl)furan ( 2c ) in 50%, 27%, and 23% yield.     

Synthèse et réactions de didésoxy-5,6-halogéno-6-α-D-xylo-hepténo-5-furannurononitriles. Communication préliminaire

Synthesis and reactions of 5,6-dideoxy-6-halogeno-α-D-xylo-hept-5-eno-furanurononitriles The 5,6-dideoxy-6-chloro-, 6-iodo- and 6-fluoro-3-O-methyl-α-D -xylo-hept-5-eno-furanurononitriles have been prepared, their properties described as well as the methods used for the assignment of the configuration of the geometrical isomers. Some new reactions of the 6-bromo analog ( 1 ) of these compounds are reported. For example, when reacted with 2-mercaptoethanol or N,N′-dimethyl-ethylenediamine in the presence of NaOH, 1 gave the corresponding six-membered ring, stereo-isomers of an oxathiane or of a perhydrodiazine respectively. When the base used was Et₃N and the binucleophile the N-methyl-ethanolamine or the N,N′-dimethyl-ethylene-diamine the major product was a cyano-enamine which could be hydrolysed to a β-cyanoketone or cyclized to a five-membered ring, an oxazolidine or an imidazolidine respectively.     

On the reaction of methoxide ion with bromoiodothiophenes

The reaction of 3-bromo-2-iodothiophene with sodium methoxide in methanol, pyridine or hexamethylphosphoric triamide and the same reaction of 4-bromo-2-iodo- and 4-bromo-3-iodo-thiophene in pyridine led to a halogen-dance, giving the same mixture of 3-bromothiophene, bromo-iodothiophenes, diiodo-bromothiophenes and triiodo-bromothiophenes. The reaction of all three isomeric bromo-iodothiophenes with sodium methoxide in methanol in the presence of cupric oxide gave 4-bromo-2-methoxythiophene.     

Reactions of 3-iodo-7-dialkylaminocoumarins with secondary amines

The reaction of 3-iodo-7-diethylaminocoumarin and 2,3,6,7-tetrahydro-10-iodo-1H,5H-quinolizino[9,9a,1-gh]coumarin with secondary amines (diethylamine, piperidine, morpholine, imidazole, and benzimidazole) leads to 4,7-diaminocoumarins. The corresponding 3-iodo-4-chloro-7-dialkylaminocoumarins under similar conditions give 3-iodo-4,7-diaminocoumarins. 4-Aminomethyl derivatives of coumarins are formed in the reactions of 3-iodo-4-methyl-7-diethylaminocoumarin and 2,3,6,7-tetrahydro-9-methyl-10-iodo-1H,5H-quinolizino[9,9a,1-gh]coumarin with these secondary amines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 609–618, May, 1991.