Addition of 1,2- and 1,3-Dithiols to 2-alkoxypropenals - a New Method for the Production of Substituted Dithiacycloalkanes

The reaction of 2-alkoxypropenals with ethane-1,2-dithiols and propane-1,3-dithiols under various conditions was studied by ¹H NMR and chromato-mass spectrometry. Under kinetically controlled conditions at 20° in the absence of catalysts the addition of dithiols takes place according to the Markovnikov rule. The primary adducts are unstable and are quickly converted into the corresponding substituted 1,4-dithiacycloheptane or 1,4-dithiane. The latter in turn can be converted under the reaction conditions or at high temperature into a thiolane derivative. The reaction of 2-ethoxypropenal with a twofold excess of ethane-1,2-dithiol at 60°C in the presence of p-toluenesulfonic acid leads to 2-methyl-2,2'-bi(dithiolane)     

Reaction of 2-Alkoxypropenals with 2-Mercaptoethanol

The reaction between 2-alkoxypropenals and 2-mercaptoethanol was studied at 20 and 60°C by means of ^1HNMR and GC-MS methods. Under kinetically controlled conditions (20°C, 7-30 days) with no catalyst the addition of 2-mercaptoethanol to 2-alkoxypropenals occurs along Markownikoff rule. The arising 2'-hydroxyethylthio-2-alkoxypropanal undergoes isomerization into the 2-hydroxy-3-alkoxy-3-methyl-1,4-oxathiane that at heating in the presence of catalytic amounts of acids is converted into 2-methyl-2-formyl-1,3-oxathiolane. The reaction of 2-alkoxypropenals with 2-mercaptoethanol at heating (60°C, 3 h) in the presence of acids affords 2-methyl-2,2'-bi(1,3-oxathiolane) even at 2-mercaptoethanol deficit. At the double excess of the latter the 2-methyl-2,2'-bi(1,3-oxathiolane) was obtained in quantitative yield. The presumable schemes of conversion of 2-hydroxy-3-alkoxy-3-methyl-1,4-oxathiane into 2-methyl-2-formyl-1,3-oxathiolane and 2-acetyl-1,3-oxathiolane are discussed.     

Reaction of 2-Alkoxypropenals with 2-Aminoethanethiol and Ring-Chain Tautomerism of the Resulting 2-(1-Alkoxyvinyl)-1,3-thiazolidines

2-Alkoxypropenals react with 2-aminoethanethiol to give tautomeric mixtures of the corresponding 2-(1-alkoxyvinyl)-1,3-thiazolidines and 2-(2-alkoxy-2-propenylideneamino)ethanethiols in quantitative yield. The state of the ring-chain tautomeric equilibrium depends on the polarity and acidity of the medium and initial reactant ratio, and it does not change on raising the temperature and is only slightly affected by microwave irradiation.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 4, 2005, pp. 529–534.Original Russian Text Copyright © 2005 by Keiko, Funtikova, Stepanova, Larina.     

Reactions of 2-Alkoxypropenals with Thiols in Neutral and Acid Media

Addition of thiols to 2-alkoxypropenal in neutral medium at 20°C in the absence of a catalyst occurs regioselectively, following the Markownikoff pattern. The resulting 2-alkoxy-2-R-thiopropanals are capable of undergoing spontaneous isomerization to 1-alkoxy-1-R-thiopropanones. The addition and isomerization processes are accelerated by heating to 60°C or in the presence of acid catalysts (TsOH, HCl). The reaction is also accompanied by partial disproportionation of 2-oxopropanal O,S-acetals to give O,O- and S,S-acetals.     

Condensation of 2-alkoxypropenals with N,N- and N,O-1,2-binucleophiles. A route to 2-(1′-alkoxyvinyl)imidazo-lidines and -oxazolidines

Condensation of 2-ethoxypropenal with diaminoethylene in different solvents (CHCl₃, MeCN, H₂O, DMSO) at room temperature gives an equilibrium mixture (1:1–1.5) of tautomeric 2-(1′-ethoxyvinyl)-1,3-imidazolidine and 2-aminoethylimine of 2-ethoxypropenal as well as 1,2-bis(2′-ethoxypropenyl-ideneamino)ethylene. The latter is readily prepared in quantitative yield using a twofold excess of the aldehyde. ¹H NMR was used to demonstrate the effect of heating on the dynamics of the ring-chain tautomeric equilibrium. Reaction of the 2-alkoxypropenals with N-methyl- and N,N′-diphenyl-1,2-diaminoethylenes and with N-phenylaminoethanol gives only the corresponding substituted imidazolidines in 43–95% yield. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov in his 70^th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1809–1815, December, 2008.     

The kinetics and mechanism of cyclodimerization of alkylthiopropenals

The kinetics of 2-alkylthiopropenals cyclodimerization was studied in the temperature range from -7 to +42 °C in heptane and at 20 °C in various solvents. The rate constants for cyclodimerization of 2-alkylthiopropenals are four orders of magnitude higher than those for dimerization of the oxygen-containing analogs, 2-alkoxypropenals, and are independent of the solvent polarity and substituent steric constant. The activation parameters for 2-butylthiopropenal cyclodimerization were estimated. The distribution of electron density in the 2-methoxy- and 2-methylthiopropenals molecules was calculated by the ab initio method. From comparison of the HOMO and LUMO energies for these aldehydes it was concluded that the ratio between the cyclodimerization rates for 2-alkylthio-, 2-ethoxypropenals, and propenal is determined by the HOMO–LUMO gap.     

Regioselectivity of the hydrolysis of 2-(1-alkoxyvinyl)-substituted imidazolidines, 1,3-thiazolidines,and 1,3-oxazolidines

2-(1-Alkoxyvinyl)-1,3-thiazolidines reacted with H₂O or D₂O in the presence of 105 mol % of p-toluenesulfonic acid or trifluoroacetic acid (20°C, 1 h) to give 2-acetyl-1,3-thiazolidine in quantitative yield. 2-(1-Alkoxyvinyl)-3,5-diphenylimidazolidines underwent hydrolysis in the presence of 20 mol % of an acid (20°C, 24 h) at the vinyloxy group with high regioselectivity yielding 2-acetylimidazolidines. Hydrolysis of 2-(1-alkoxyvinyl)-3-phenyl-1,3-oxazolidines in the presence of 10 mol % of p-toluenesulfonic acid (20°C, 5 days) takes two pathways, one of which involves the endocyclic C-O bond with ring opening and the other involves the vinyloxy group to produce 2-acetyl-3-phenyl-1,3-oxazolidine. Unlike phenyl-substituted 1,3-thiazolidines and imidazolidines, hydrolysis of their 3-methyl- and 3,5-dimethyl-substituted analogs in acid medium occurs mainly via ring opening. The observed hydrolysis pathways were interpreted in terms of B3PW91/6-311G(d,p) quantum-chemical calculations.     

Reaction of 2-Alkoxypropenals with α-Hydroxyamino Oximes and 1,2-Bis(hydroxyamino)cyclohexane

Reactions of 2-alkoxypropenals with α-hydroxyamino oximes in neutral medium involve the aldehyde group of the former to afford both acyclic and cyclic azomethine oxides: N-(2-hydroxyiminoalkyl)-N-(2-alkoxy-2-propenylidene)amine oxides and 1-hydroxy-2,5-dihydroimidazole 3-oxides. The state of tautomeric equilibrium between the cyclic and acyclic products depends on the solvent nature and temperature. The reaction in acidic aqueous medium is accompanied by hydrolysis of the vinyl ether moiety in 2-alkoxy-propenals with formation of 2-oxopropionaldehyde which reacts with α-hydroxyamino oxime at the hydroxy-amino group to give substituted pyrazine 1,4-dioxides. The reaction of 2-alkoxypropenals with 1,2-bis-(hydroxyamino)cyclohexane leads to formation of 2-(1-alkoxyvinyl)-1,3-dihydroxyperhydrobenzimidazoles. The structure of the products was proved by IR, UV, and ¹H and ¹³C NMR spectroscopy and X-ray analysis.     

Synthesis of 2-(1-Alkoxyvinyl)oxazolidines by Condensation of 2-Alkoxypropenals with 2-Aminoalkanols and Ring-Chain Tautomerism of the Products

Reactions of 2-alkoxypropenals with 2-aminoalkanols afforded tautomeric mixtures of previously unknown 2-(1-alkoxyvinyl)oxazolidines and imino alcohols. The condensation takes 2 h at room temperature (89-100%) or 1-5 min under microwave irradiation. The tautomeric equilibrium shifts toward the open-chain structure with increase in the solvent polarity (CDCl₃, CD₂OD, DMSO-d ₆, D₂O) and temperature. The presence of substituents in the oxazolidine ring raises the stability of the cyclic tautomer.