Reaction of 3-aryl-2-cyanothioacrylamides with dimethyl acetylenecarboxylate,methyl propiolate,and <Emphasis Type="Italic">N</Emphasis>-phenylmaleimide

The reaction of cyanothioacrylamides with dimethyl acetylenedicarboxylate, methyl propiolate, and N-phenylmaleimide was studied. The reaction follows a cycloaddition pathway to give thiopyrans, irrespective of the electronic or spatial effects of the substituents in the thioamide group and in position 3 of the 1-thiabuta-1,3-diene system. The reaction is regio-and stereoselective. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2784–2792, December, 2005.     

Diastereoselective Diels-Alder Reaction of 2-Thienyl and 2-Furyl Substituted 3-Propenethioamides with Electron Deficient Dienophiles

Summary. The hetero-Diels-Alder reaction of N-aryl-3-(2-thienyl)-2-propenethioamides with N-phenylmaleimide and maleimide yielded a mixture of endo- and exo-2-arylimino-4-(2-thienyl)tetrahydrothiopyran[2,3-c]pyrroles. Cycloaddition to diethyl fumarate required acylation and furnished a mixture of diastereoisomeric 5-(N-acetylphenylamino)-2,3-bis-(ethoxycarbonyl)-4-(2-thienyl)-3,4-dihydro-2H-thiopyrans. Reactions of 3-(2-furyl)-2-propenethioamides with N-arylmaleimides furnished the correspondent 2-arylimino-4-(2-furyl)tetrahydrothiopyran[2,3-c]pyrroles. In the cycloadditions of the heterodienes with N-arylmaleimides the endo-cycloadducts were formed as the major products.     

Preparation of 3-(2H-pyran-2-on-6-yl)indolizines and the diels-alder reactions with some olefinic and acetylenic dienophiles

3-(2H-Pyran-2-on-6-yl)indolizines 6a-d were prepared by 1,3-dipolar cycloaddition reactions of N-(2H-pyran-2-on-6-yl)methylpyridinium bromides 5a,b with dimethyl acetylenedicarboxylate (DMAD). All of the cycloaddition reactions of 6b with N-phenylmaleimide, p-benzoquinone, and DMAD took place at the 2-pyrone ring to give 3-substituted indolizines.     

The synthesis of hexahydrooxoepithiopyridinedicarboximides by the reaction of thioamides with N-substituted maleimides

The synthesis of hexahydrooxoepithiopyridinedicarboxyimide (5: X₂ = N-Ph) by the reaction of thioamides 1 with N-substituted maleimide ( 2a ) was examined. The reaction of primary thioamides, such as thiobenzamide and p-toluthioamide with N-phenylmaleimide gives compounds 5 together with corresponding 4-hydroxy-1,3-thiazoles 4 . However, a similar reaction of secondary thioamides, such as N-methylthioacetamide, thiobenzanilide, with N-phenylmaleimide did not provide compounds 5 without addition of acid. The reaction pathway and the configuration of 5 were also investigated.     

Synthesis of substituted N-phenylmaleimides and use in a Diels–Alder reaction: a green multi-step synthesis for an undergraduate organic chemistry laboratory

ABSTRACT

This paper describes the design and implementation of a minimally hazardous, environmentally friendly, and energy efficient sequential reaction sequence within a sophomore level Organic Chemistry lab course to efficiently synthesize N-phenylmaleimide precursors for a Diels–Alder reaction. Substituted N-phenylmaleimides are a class of very expensive precursors of considerable interest due to their biological properties and use as intermediates in synthesis. The synthesis described herein produces a substituted N-phenylmaleimide in two steps from maleic anhydride and a substituted aniline followed by its Diels–Alder reaction with 2,5-dimethylfuran. The experiment exposes students to the green chemistry principles of atom economy, use of safer chemicals, design for energy efficiency, waste reduction, and inherently safer chemistry for accident prevention and enables students to use ¹H NMR spectroscopy to characterize the products.     

First Synthesis of 2-Vinylindole and its diels-Alder Reactions with CC-Dienophiles

By means of an intramolecular Wittig process, 2-vinylindole ( 2 ) was prepared. The indole 2 functions as a heterocyclic, donor-activated 1,3-diene and undergoes [4+2] cycloaddition reactions with dimethyl acetylenedicarboxylate, N-phenylmaleimide, and p-benzoquinone leading to the novel carbazole dervatives 3 , 4 , 5c , 6 and 7 respectively. The reaction of 2 with acceptor (A)-Substituted dienophiles (e.g.) ACH?CH₂, AC≡(CH) does not yield products that can be isolated.     

Tetrakis(alkylthio)thieno[3,4-c]thiophene: Synthesis,stability, and reactivity

The synthesis of tetrakis(alkylthio)thieno[3,4-c]thiophenes la-e by the dimerization reaction of bis(alkylthio)cyclopropenethiones is described. The remarkable thermodynamic and kinetic stability suggests the significant electron-accepting conjugation of the alkylthio substituents to the carbanionic 1, 3, 4, and 6 carbons in the framework. The isopropylthio- and ethylthio-substituted thienothiophenes 1d and 1e undergo cycloaddition reactions with dienophiles such as N-phenylmaleimide and dimethyl acetylenedicarboxylate to give the cycloadducts in moderate yields.     

Synthesis of 3-(2-benzothiazolylthio)propanenitrile and related products

The reaction of 2-mercaptobenzothiazole, 2-mercaptobenzoxazole or 5-chloro-2-mercaptobenzothiazole with either acrylonitrile or acrylamide under basic conditions afforded the N-cyanoethylated products 1, 2 and 3 or the N-amidoethylated products 4, 5 and 6 , respectively. The reaction of the sodium salts of the same thiazolethiols with 3-chloropropionitrile furnished a mixture containing the N-cyanoethylated products 1, 2 and 3 and the unknown S-cyanoethylated products 7, 8 and 9 , respectively. Whereas, substituting 3-chloropropionamide for 3- chloropropionitrile in the same reaction gave only the S-substituted products 10, 11 , and 12 , respectively. The treatment of 10, 11 or 12 with phosphorus oxychloride or thionyl chloride in DMF afforded 7, 8 and 9 in excellent yields. Possible mechanisms and supporting nmr data are discussed.     

The Effect of Onium Salt Additives on the Diels-Alder Reactions of a 1-Phenyl-1,2-dihydrophosphinine Oxide under Microwave Conditions

The microwave absorbing ability of toluene is increased in the presence of a slight amount (2–4 mg/3 mL) of quaternary ammonium or phosphonium salts. These additives somewhat accelerated the Diels-Alder reaction of 1-phenyl-1,2-dihydrophosphinine oxide 1 with N-phenylmaleimide and maleic acid anhydride to afford phosphabicyclo[2.2.2]octene derivatives.     

Reaction of 2,3-dichloro-1,4-naphthoquinone with dithiooxamide. Synthesis of dibenzo[b,i]thianthrene-5,7,12,14-tetrone

The reaction of 2,3-dihalogeno-1,4-naphthoquinone with dithiooxamide gave dibenzo[b,i]thianthrene-5,7,12,14-tetrone in high yield but not 2,2′-bis(naphtho[2,3-d]thiazole-4,9-dione) which was previously reported. A similar reaction of 3,4-dichloro-N-phenylmaleimide with dithiooxamide also gave the corresponding sulfur heterocycles but not the reported bisthiazole.     

Heterodiene synthesis. Synthesis of fused thiopyrano [2,3-d]thiazole,Benzopyrano[3′,4′:4,5]thiopyrano[2,3-d]thiazole and thiazolo[3,4-c]triazine derivative

5-Salicylidenethiazolidine-2,4-dithione ( 1 ) reacts with acrylonitrile, N-phenylmaleimide and dimethyl acet-ylenedicarboxylate to afford the fused thiopyrano[2,3-d]thiazolidinethione derivatives 2, 4 and 6 , respectively. The salicylidene derivative 1 reacts with ethyl acrylate and malononitrile to afford the fused [1]benzopyrano[3′,4′:4,5]thiopyrano[2,3-d]thiazoles 3 and 9 , respectively. 4-Phenylhydrazono-2-thiazolidinethione ( 11 ) reacts with ethyl bromoacetate and/or phenacyl bromide to yield the fused thiazolo[3,4-c]triazines 13 and 14.     

Diels-alder cycloadditions of diene-substituted N-ethoxycarbonyl-2-methyl-1,2-dihydropyridines with N-phenylmaleimide

The ten possible substitution patterns for N-Ethoxycarbonyl-2-methyl-1,2-dihydropyridines 5 in which one or two olefinic sites are alkyl substituted were synthesized and reacted with N-phenylmaleimide 2 to provide cycloadducts 6. N-Ethoxycarbonyl-5,6-cyclohexyl-2-methyl-1,2-dihydropyridine 51 provided the novel spirocycle 61.     

Hydrophobic acceleration in the Diels—Alder reaction of 9-hydroxymethylanthracene with <Emphasis Type="Italic">N</Emphasis>-phenylmaleimide

The Diels—Alder reaction rates of 9-hydroxymethylanthracene with N-phenylmaleimide and N-ethylmaleimide in water, butan-1-ol, ethylene glycol, acetonitrile, chloroform, and 1,4-dioxane have been compared.     

A study of the relative reactivity of maleic anhydride and some maleimides in free radical copolymerization and terpolymerization

Composition data for the free radical copolymerization of maleic anhydride with N-phenylmaleimide in toluene at 60°C have been obtained. Relative reactivity ratios in terminal and penultimate models using nonlinear least-squares optimization routine have been determined. The standard error was found to be somewhat smaller in the penultimate model, but is still larger than the uncertainty estimated for the copolymer composition. Terpolymers of maleic anhydride and styrene with maleimide, N-butylmaleimide, N-phenylmaleimide, and N-carbamylmaleimide were obtained. On the basis of analysis of the product composition at various monomer feeds the relative reactivity of maleic anhydride and maleimides in these reactions is compared and the influence of the structure of thesemonomers on the rate of some chain growth reactions is discussed.     

Aza-Michael reaction of 12-N-carboxamide of (–)-cytisine under high pressure conditions

The first example of aza-Michael reaction of 12-N-carboxamide of quinolizidine alkaloid (–)-cytisine with α,β-unsaturated ketones, dimethyl acetylenedicarboxylate and β-nitrostyrene under high pressure condition has been described. It has been shown that the [4+2]-cycloaddition takes place in the case with N-phenylmaleimide.     

Poly(hydroxy urethane) coatings prepared from copolymers of 3-(2-vinyloxyethoxy)-l,2-propylene carbonate and <Emphasis Type="Italic">N</Emphasis>-phenylmaleimide

Poly(hydroxy urethanes) and coatings based on them were prepared by ammonolysis of copolymers of 3-(2-vinyloxyethoxy)-l,2-propylene carbonate and N-phenylmaleimide.     

Polymerization of vinyl monomers with salts of bronsted acids

The polymerization of vinyl monomers (N-phenylmaleimide, acrylamide, acrylonitrile, methyl vinyl ketone, methyl methacrylate, vinyl chloride, and styrene) with sodium salts of Brønsted acids (sodium cyanide, sodium nitrite, sodium hydroxide, etc.) were investigated at 0°C in dimethylformamide. N-Phenylmaleimide, acrylonitrile, and methyl vinyl ketone were found to undergo polymerization with sodium cyanide, however the other monomers were not polymerized with this salt. In the polymerizations of acrylonitrile and N-phenylmaleimide with sodium cyanide, the rates of the polymerizations were found to be proportinal to the initiator concentration and to the square of the monomer concentration. The activation energy of acrylonitrile polymerization was 3.7 kcal/mole, and that of N-phenylmaleimide ws 3.0 kcal/mole. The results of the copolymerization of acrylonitrile with methyl methacrylate at 0°C in dimethyl-formamide with sodium cyanide confirm that these polymerizations proceeded by an anionic mechanism initiated by the Michael addition reaction of the monomers with the salts. In these polymerizations, the monomer reactivity increased with increase in the e values. The initiation ability of sodium salts increased with increasing pK_a of the conjugate acids and with decreasing electronegativity of metal ion in the series of lithium, sodium, and potassium cyanide. The polymerizations took place only in aprotic polar solvents, and did not occur in weak polar solvents and in protonic solvents.     

Synthesis and characterization of new N-phenylmaleimide thioglycosides

Thioglycosides derivatives of N-phenylmaleimide have been prepared by the reaction of derivatives of 1-thio-d-glucopyranose, d-galactopyranose, d-lactose, and d-maltose with 3,4-dichloro-N-phenylmaleimide. The reaction of 3,4-dichloro-N-phenyl maleimide with sugar thiols (protected or unprotected) took place by displacement of both chlorine atoms by sulfide nucleophile giving the corresponding bis-thioglycoside products.     

Products derived from oxidations of 3,4-dimethyl-1-phenylphosphole-1-oxide: A 3-phenyl-5,6-dimethyl-2,3-oxaphosphabicyclo[2.2.2]octene-3-oxide derivative as a precursor of phenyl metaphosphonic anhydride

Oxidation of 3,4-dimethyl-1-phenylphosphole with peracids or peroxides gives a relatively stable P-oxide, which can be used in Diels-Alder reactions to give derivatives with the 7-phosphanorbornene framework. Oxygen insertion into a C–P bond of this framework occurs smoothly with m- chloroperbenzoic acid (MCPBA) providing derivatives of the 2,3-oxaphosphabicyclo [2.2.2] octene ring system. The phosphole can be converted to this system in a one-pot synthesis by reaction with excess MCPBA in the presence of N-phenylmaleimide as dienophile. The phosphole oxide undergoes mono-epoxidation with MCPBA. Thermal or photochemical fragmentation of the 2,3-oxaphosphabicyclo [2.2.2] ocetene is a useful source of the 3-coordinate species Ph–PO₂, a meta-anhydride of phenylphosphonic acid. This species was trapped successfully with a variety of alcohols.     

Umsetzung von 3-Amino-2H-azirinen mit Salicylohydrazid

Reaction of 3-Amino-2H-azirines with Salicylohydrazide 3-Amino-2H-azirines 1a–g react with salicylohydrazide ( 7 ) in MeCN at 80° to give 2H, 5H-1,2,4-triazines 10 , 1,3,4-oxadiazoles 12 and, in the case of 1d , 1,2,4-triazin-6-one 11a (Scheme 3). The precursor of these heterocycles, the amidrazone of type 9 , except for 9c and 9g , which could not be isolated, has been found as the main product after reaction of 1 and 7 in MeCN at room temperature. 3-(N-Methyl-N-phenylamino)-2-phenyl-2H-azirin ( 1g ) reacts with 7 to give mainly the aromatic triazines 15b₁ and 15b₂ . In this case, two unexpected by-products, 16 and salicylamide ( 17 ), occurred, probably by disproportionation of a 1:1 adduct from 1g and 7 (Scheme 8). Oxidation of 10f with DDQ leads to the triazine 15a . The structure of 10c, 11a, 12c, 13 (by-product in the reaction of 1b and 7 ), the N′-phenylureido derivative 14 of 9d (Scheme 4) as well as 15b₂ has been established by X-ray crystallography. The ratio of 10/12 as a function of substitution pattern in 1 and solvent has been investigated (Tables 1, 3, 4, and 7). A mechanism for the formation of 10 and 12 is proposed in Scheme 7.