Ethyl 2-bromomethyl-5-(1,2,3-thiadiazol-4-yl)furan-3-carboxylate in reactions with O-, S-, N-, and P-nucleophiles

Reaction of ethyl 2-bromomethyl-5-(1,2,3-thiadiazol-4-yl)furan-3-carboxylate with nucleophiles of different nature was studied. It is shown that substitution of bromine with acetoxy group takes place under the action of sodium acetate in the acetic acid. Stronger bases, like phenolates, cause considerable decomposition of the labile furylthiadiazole fragment Decomposition can be avoided only when this reaction is carried out in the presence of a phase transfer catalyst under the conditions of the ion pair extraction,. In the reaction with sodium N,N-diethyl dithiocarbaminate the corresponding thioester is formed. Butanethiol and thiophenol are alkylated as potassium thiolates. In the last case S-alkylation proceeds exclusively. Reaction with excess 2-aminoethanol permits to prepare secondary amine, and the reactions with pyrrolidine, piperidine, and morpholine give the corresponding tertiary amines. Phosphorylation with triethyl phosphite under the conditions of Arbuzov reaction leads to the corresponding diethyl phosphonate. In all these transformations furylthiadiazole fragment is retained.     

Reaction of 2,3,5,6-tetrachloro-4-pyridyl vinyl sulfone with nucleophilic agents

The reactions of 2,3,5,6-tetrachloro-4-pyridyl vinyl suifone (I) with nucleophilic agents were studied. It was established that products of addition to the double bond of I are formed in the reaction of equivalent amounts of primary aliphatic amines and mercaptans, while the -alkylamino and -alkylthioethylsulfonyl groups are displaced to give 4-alkyl-amino- or 4-alkylthiotetrachloropyridines in the reaction with excess amines and mercaptans. Aromatic amines, phenols, thiophenols, and alcohols add to the double bond of I. Morpholine and piperidine add to the double bond of I when they are present in equivalent quantities, and the chlorine atom in the 2 position of the pyridine ring is also replaced when excess amine is present.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1634–1637, December, 1972.     

A practical one-pot procedure for the synthesis of pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidinones by a tandem aza-Wittig/heterocumulene-mediated annulation strategy

A simple one-pot and efficient method is described for the synthesis of pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidinone derivatives 6 via a tandem aza-Wittig/heterocumulene-mediated annulation process. The iminophosphorane 3 reacted with aryl isocyanates, followed by heterocyclization on addition of secondary amines to give the corresponding guanidine intermediates 5, which were cyclized in the presence of a catalytic amount of potassium carbonate to tricyclic compounds 6. Similarly, iminophosphorane 3 reacts with phenols, thiophenol, or ROH to give 2-aryl(alkyl)oxy(thio)pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidinone derivatives 7 in good yields. The corresponding carbodiimide 4c and guanidine-type intermediate compounds 5 could be isolated and characterized, thus confirming the suggested reaction pathway. However, two isomeric pyrazinothienopyrimidinones 8 and 9 may be produced in the reaction of iminophosphorane 3 with aromatic isocyanates and subsequent reaction with primary amines in the presence of a catalytic amount of potassium carbonate. The effects of the nucleophiles and isocyanates on the regioselectivity of the cyclization have been investigated.     

Conversions of 2-α-chloroalkylbenzimidazoles

Upon interaction with caustic in a DMSO medium, 2-chloromethylbenzimidazoles are subjected to cyclodimerization, forming 5H,12H-pyrazino[1,2-a:4,5-a]bis-benzimidazoles; in the presence of nucleophiles (ammonia, amines, anions of -diketones), under the indicated conditions, the products are the corresponding substituted amines or derivatives of pyrrolo[1,2a]benzimidazole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 664–672, May, 1993.     

Reaction of Dithiophosphoric Acid Chloride Betaine with Bifunctional Compounds - A New Route to Cyclic Dithiophosphates

Abstract

Dithiophosphoric acid chloride pyrididium betaine, Py. PS₂Cl (1)¹, can be widely used for the synthesis of various organophosphorus compounds. 1 reacts in the presence of a base with an excess of nucleophiles like amines, alcohols or thiols to the corresponding disubstituted thiophosphoric acid derivatives^2–3.     

New approach to nonracemic 1-alkylamino-3-aryloxypropan-2-ols belonging to β-blockers via cyclic sulfites

Nonracemic -blockers, viz., (S)-propranolol and (S)-timolol, were prepared from (S)-glycidol in three steps consisting in the reaction with SOCl₂ followed by the reaction of the resulting (4S)-4-chloromethyl-2-oxo-1,3,2-dioxathiolanes with the corresponding phenol and the final cleavage of (4R)-aryloxymethyl sulfites under the action of amines in DMF.     

Iterative addition of carbon nucleophiles to N,N-dialkyl carboxamides for synthesis of α-tertiary amines

A protocol for the synthesis of α-tertiary amines was developed by iterative addition of carbon nucleophiles to N,N-dialkyl carboxamides. Nucleophilic 1,2-addition of organolithium reagents to carboxamides forms anionic tetrahedral carbinolamine (hemiaminal) intermediates, which are subsequently treated with bromotrimethylsilane (Me₃SiBr) followed by organomagnesium (Grignard) reagents, organolithium reagents or tetrabutylammonium cyanide, affording α-tertiary amines. Employment of (trimethylsilyl)methylmagnesium bromide as the 2^nd nucleophile allowed for aza-Peterson olefination of the resulting α-tertiary (trimethylsilyl)methylamines with acidic work-up, resulting in the formation of 1,1-diarylethylenes.

We herein report a concise protocol for iterative addition of carbon nucleophiles to N,N-dialkyl carboxamides for the synthesis of α-tertiary amines.     

Iridium(I)-catalyzed regio- and enantioselective allylic amidation

Ir(I)-catalyzed intermolecular allylic amidation of ethyl allyl carbonates with soft nitrogen nucleophiles under completely ‘salt-free’ conditions is described. A combination of [Ir(COD)Cl]₂, a chiral phosphoramidite ligand L^∗, and DBU as a base in THF effects the reaction. The reaction appears to be quite general, accommodating a wide variety of R-groups and soft nitrogen nucleophiles, and proceeds with excellent regio- and enantioselectivities to afford the branched N-protected allylic amines. The developed reaction was conveniently utilized in the asymmetric synthesis of N-Boc protected α- and β-amino acids as well as (−)-cytoxazone.     

Kinetics of nucleophilic halogen exchange in 1-alkyl-2-(5′ -halo-2′- furyl) benzimidazoles

The kinetics of the reaction of 1-alkyl-2-(5-halo-2-furyl)benzimidazoles and their corresponding quaternary salts with secondary aliphatic amines were studied. The effect on the activation parameters of this reaction of the nature of the halogen being replaced by the secondary amine residue, the presence of a positive charge on the imidazole ring, the character of the anion in the quaternary salts, and the remoteness of the reaction center from the activating grouping on the activation parameters of this reaction is discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 252–257, February, 1971.     

5,7-Dichloro-1,3-dithiolo[4,5-d]pyrimidine-2-thione and -2-Selone: Synthesis, Crystal Structure, Solvatochromism, and Reactions with Nucleophiles

We have obtained for the first time the halo derivatives of a novel heterocyclic system, 1,3-dithiolo[4,5-d]pyrimidine-2-thione and -2-selone, by reaction of 5,7-dioxo(4H,6H)-1,3-dithiolo[4,5-d]pyrimidine-2-thione and -2-selone with POCl₃. The crystal structure of thione confirms that we had obtained the desired compound. The electronic absorption spectra reveal an interesting solvatochromism connected with the appearance of low-intensity n transitions from selenium and sulfur atoms in the visible region of the spectrum. The chlorine atoms in the studied compounds have significant mobility in reactions with nucleophiles (amines, thiourea, azidione), which ensures that new derivatives of 1,3-dithiolo[4,5-d]pyrimidine-2-selone are obtained, and specifically 7-N,N-dialkylamino, 7-N-alkyl-N-arylamino derivatives and 7-isothiuronium salts. The 2-selones obtained can be used in synthesis of new tetrathiafulvalenes.     

Reactions of Nucleophiles with Reactive Intermediates in the 3,4,6‐Tri‐O‐benzyl‐d‐glucal–TfOH–n‐Bu4NI Reaction System

The unique reactive intermediate formed in the 3,4,6‐tri‐O‐benzyl‐d‐glucal–TfOH (triflic acid)–n‐Bu₄NI reaction system (in dichloromethane) reacted with nucleophiles in a regio‐ and stereoselective manner. These selectivities resulted in hitherto unknown compounds, such as benzyl 4,6‐di‐O‐benzyl‐2,3‐dideoxy‐3‐iodo‐α‐glucopyranoside, which was obtained in the presence of an iodide ion as a nucleophile. The corresponding 2‐deoxy α‐glycosides were obtained exclusively in the corresponding reaction with hydroxylic nucleophiles.     

The rearrangement of cyclopropyl chlorides to allyl chlorides : Stereospecificity in the recapture of the chloride ion

The cyclopropyl chlorides (1 and 2) rearrange on heating to give stereospecifically the allyl chlorides (3 and 4, respectively). In the presence of nucleophiles such as methoxide ion, the corresponding allyl ethers (5 and 6, respectively) are formed. Analysis of the stereochemistry of these products indicates that they are formed from the corresponding allyl chlorides (3 and 4), which are evidently the first-formed products of the reaction even in the presence of strong nucleophiles. The reaction of the allyl chlorides (3 and 4) with sodium phenylthioxide in aprotic non-polar solvents goes predominantly with retention of configuration, but in methanol is normal in giving predominantly inversion of configuration.     

Reaction of 2,2′,3,3′-tetrachloro-6,6′-diquinoxalyl with nucleophilic reagents

The corresponding tetrasubstituted diquinoxalyls were synthesized by reaction of 2,2,3,3-tetrachloro-6,6-diquinoxalyl with sodium methoxide, piperidine, and hydrazine. Tetrahydrazinodiquinoxalyl reacts with nitrous acid to give tetrakistetrazolodiquinoxalyl, which is also obtained by the action of sodium azide on tetrachlorodiquinoxalyl. Tetrahydrazinodiquinoxalyl undergoes cyclization with acetic acid to give tetrakistriazolodiquinoxalyl. A competitive effect of nucleophiles [CN and N(CH₃)₂] was observed in the reaction of tetrachlorodiquinoxalyl with cuprous cyanide in dimethylformamide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 414–416, March, 1977.     

Aminoalkylation with Aldehydes Mediated by Solid Lithium Perchlorate

The solid LiClO₄-mediated one-pot reaction of aldehydes with secondary amines and C nucleophiles afforded the corresponding aminoalkylation products in high yields. Unlike the previous reported procedure, the aminoalkylation of aldehyde was achieved in the presence of only 0.5 equivalents of solid lithium perchlorate in dichloromethane as the solvent with good to high yields at room temperature.     

Aminoalkylation with Aldehydes Mediated by Solid Lithium Perchlorate

Summary. The solid LiClO₄-mediated one-pot reaction of aldehydes with secondary amines and C nucleophiles afforded the corresponding aminoalkylation products in high yields. Unlike the previous reported procedure, the aminoalkylation of aldehyde was achieved in the presence of only 0.5 equivalents of solid lithium perchlorate in dichloromethane as the solvent with good to high yields at room temperature.     

An unusual bicyclic aziridine, 1-azabicyclo[4.1.0]heptan-2-one, and its reaction with nucleophiles

Unexpected reaction pathways have been unravelled that are involved in the generation of 2,2,5,5-substituted tetrahydrofurans from the mesylate of 5-hydroxy-5-methyl-6-oxo-2-phenyl-2-piperidinemethanol (7). Upon treatment of 7 with amines under controlled conditions two reactive intermediates could be isolated. The first is a strained aziridine-fused lactam, 1-azabicyclo[4.1.0]heptan-2-one 10, which reacts further with amines or methoxide at the lactam carbonyl group to form γ-hydroxyalkylaziridines. Final N-acylation results in internal OH attack to give the hydrofuran products. Reaction of 10 with some other nucleophiles led to 3,3,6,6-substituted 2-piperidinones.     

Synthesis and Chemistry of Novel Perhalogenated Imines,Oxaziridines, and Oxazolidines

Imines have been prepared using three different methods. The thermal addition of tetrafluoroethylene to N‐bromoperhalo‐1‐alkanimines (R_fCF=NBr) to give imines of the type R_fCF=NCF₂CF₂Br, the Lewis acid cleavage of perfluorinated amines to give imines of the type R_fN=CFR_f′ and the one pot reaction between hexafluoroacetone and perfluoroamides. Reactions of these imines with m‐chloroperoxy benzoic acid (MCPBA) lead to the corresponding cis‐perfluoro‐2, 3‐dialkyloxaziridines R_f R_F′. The oxaziridines undergo cycloadditions with olefins to give the corresponding oxazolidines. A preliminary investigation was done on the synthesis and reaction chemistry of complex formed between activated zinc and the 4‐iodo and 4‐bromo‐perhalooxazolidines.     

Gas-phase thermolysis of allyl propargyl amine,allyl cyanomethyl propargyl amine,allyl propargyl 2-thiapropyl amine,and allyl methanesulfonyl propargyl amine

The title amines have been pyrolyzed in a stirred-flow reactor, at temperatures of 360–500°C, pressures of 7–16 torr, and residence times of 0.5–2.9 s, using toluene as carrier gas. The reaction products were allene, propene, and the corresponding imines. The ratio allene:propene varied in the range 6.7–1.6. The amines with CH₂CN and SO₂CH₃ substituents also formed HCN and SO₂. These appear to arise from complex free radical decomposition of the imine product. The first-order rate coefficients for the production of allene plus propene followed the Arrhenius equations: Allyl propargl amine: Allyl cyanomethyl propargyl amine: Allyl propargyl 2-thiapropyl amine: Allyl methanesulfonyl propargyl amine: Nonconcerted mechanisms, involving polar six center cyclic transition states, are suggested for the elimination of allene and propene. © 1994 John Wiley & Sons, Inc.     

β-Aziridinylacroleins in reactions with nucleophilic reagents

The reactivities of -aziridinylcinnamaldehyde and -(2-methylaziridinyl)acrylaldehyde with respect to amines, hydrazines, and semicarbazide were studied, -Aminoacroleins were obtained by reaction of secondary amines with aziridinylacroleins. The reaction of aziridinylcinnamaldehyde with primary amines gives the corresponding imines. It was established that in its reaction with hydrazines and semicarbazide aziridinylacrolein is more inclined to undergo heterocyclization reactions (the formation of pyrazoles and pyrazolines) than aziridinylcinnamaldehyde.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 483–488, April, 1978.     

Synthesis of ene-allenes via palladium-catalyzed hydride-transfer reaction of propargylic amines under mild conditions

The palladium-catalyzed allene transformation reaction from propargylic amines proceeded in the presence of Pd₂(dba)₃·CHCl₃ (5 mol %) and (C₆F₅)₂PC₂H₄P(C₆F₅)₂ (10 mol %) in CHCl₃ at room temperature to give the corresponding allenes in good to high yields. Dicyclohexyl groups substituted on the nitrogen of propargylic amines were found to be effective for the current transformation and the conjugated ene-allenes 4 were synthesized from the corresponding propargylic amines 3 under mild conditions.