Mercaptoacetic acid based expeditious synthesis of polyfunctionalised 1,3-thiazines

A novel three-component expeditious synthesis of 3,6-diaryl-5-mercaptoperhydro-2-thioxo-1,3-thiazin-5-ones from 2-methyl-2-phenyl-1,3-oxathiolan-5-one, an aromatic aldehyde and an N-aryldithiocarbamic acid is reported. The synthesis is diastereoselective and involves tandem Knoevenagel, Michael and ring transformation reactions under solvent-free microwave irradiation in a one-pot procedure.     

1H-1,3-diazepines, 5H-1,3-diazepines, 1,3-diazepinones, and 2,4-diazabicyclo[3.2.0]heptenes

Tetrazolo[1,5-a]pyridines/2-azidopyridines 1 undergo photochemical nitrogen elimination and ring expansion to 1,3-diazacyclohepta-1,2,4,6-tetraenes 3, which react with alcohols to afford 2-alkoxy-1H-1,3-diazepines 4 (5), with secondary amines to 2-dialkylamino-5H-1,3-diazepines 16, sometimes via isolable 2-dialkylamino-1H-1,3-diazepines 15, and with water to 1,3-diazepin-2-ones 19. The latter are also obtained by elimination of isobutene or propene from 2-tert-butoxy- or 2-isopropoxy-1H-1,3-diazepines 4 or 5. 1,3-Diazepin-2-one 22B and 1,3-diazepin-4-one 24 were obtained from hydrolysis of the corresponding 4-chlorodiazepines. Diazepinones 19 undergo photochemical ring closure to diazabicycloheptenones 25 in high yields. The 2-alkoxy-1H-1,3-diazepines 4 and 5 interconvert by rapid proton exchange between positions N1 and N3. The free energies of activation for the proton exchange were measured by the Forsén-Hoffman method as DeltaG([double dagger])298= 16.2 +/- 0.6 kcal mol(-1) as an average for 4a-c in CD2Cl2, acetone-d6, and methanol-d4, and 14.1 +/- 0.6 kcal mol(-1) for in 4c acetone/D2O. The structures of 2-methoxy-5,6-bis(trifluoromethyl)-1H-1,3-diazepine 4k, 1,2-dihydro-4-diethylamino-5H-1,3-diazepin-2-one 22bB, and diazabicycloheptanone were 26 determined by X-ray crystallography. The former represents the first reported X-ray crystal structure of any monocyclic N-unsubstituted 1H-azepine.     

The first ionic liquid-promoted one-pot diastereoselective synthesis of 2,5-diamino-/2-amino-5-mercapto-1,3-thiazin-4-ones using masked amino/mercapto acids

The first expeditious synthesis of 2,5-diamino-/2-amino-5-mercapto-1,3-thiazin-4-ones from masked and activated amino/mercapto acids, viz. 2-phenyl-1,3-oxazol-5-one or 2-methyl-2-phenyl-1,3-oxathiolan-5-one, aromatic aldehydes and thioureas using the ionic liquid [Bmim]Br as an environmentally benign reaction promoter is reported. The synthesis is highly diastereoselective and involves tandem Knoevenagel, Michael and ring transformation reactions in a one-pot procedure. The sequential reaction pathway is supported by the isolation of arylidene derivatives and their Michael adducts with thiourea, and quantitative conversion of the latter into the final products under the same reaction conditions.     

Fused pyrimidine systems: XIII. Synthesis and some transformations of 1,3-thiazolo(thiazino)-fused pyrido[3,4-d]pyrimidines

2-[Allyl(propargyl)sulfanyl]pyrido[3,4-d]pyrimidin-4-ones at heating in polyphosphoric acid undergo an intramolecular cyclization with the formation of pyrido[4,3-e]thiazolo-[3,2-a]pyrimidin-5-ones of angular structure. Under similar conditions the cyclization of 2-(cinnamylsulfanyl)pyrido[3,4-d]-pyrimidin-4-one results in a linear pyrido[3′,4′:4,5]pyrimido-[2,1-b][1,3]thiazin-6-one. The iodocyclization of the same substrates affords the corresponding 9-(iodomethyl)(iodomethylidene)pyrido[4,3-e][1,3]thiazolo-[3,2-a]pyrimidin-5-ones and 3-iodopyrido[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-6-one of angular structure. 9-(Iodomethyl)-8,9-dihydro-5H-pyrido[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-5-one treated with sodium azide gave 9-(azidomethyl) derivative whose cyclization with substituted alkynes in the presence of copper compounds provided pyrido [4,3-e][1,3]thiazolo[3,2-a]pyrimidinylmethyltriazoles.     

Diels-Alder cycloaddition of electrophilic 2H-azirines with 3-(3-(tert-butyldimethylsilyloxy)buta-1,3-dienyl)oxazolidin-2-ones. Treatment of the cycloadducts under acidic conditions

3-(3-(tert-Butyldimethylsilyloxy)buta-1,3-dienyl)oxazolidin-2-one was reacted with several electrophilic 2H-azirines to give the expected cycloadducts in moderate to good yields. Treatment of the cycloadducts under acidic conditions gave six-membered ring aminoenones and aziridine derivatives. In the case where anilinium fluoride was used an inversion at the C-2 stereogenic center was observed forming an isomer of the former cycloadduct. The chiral (R)-3-(3-(tert-butyldimethylsiloxy)buta-1,3-dienyl)-4-phenyloxazolidin-2-one was also reacted with an electrophilic 2H-azirine. The reaction showed no diastereoselectivity, but both diastereoisomers were fully isolated by chromatography.     

A facile synthetic approach to novel spiro-oxindoles/acenaphthylen-1-ones containing benzo[1,4]thiazin-3-one ring via 1,3-dipolar cycloaddition

A series of spiro-oxindole derivatives containing spirobenzo[1,4]thiazin-3-one ring were synthesized regioselectively via a multicomponent 1,3-dipolar cycloaddition of isatin, 2-(4-methyl-benzylidene)-4H-benzo[1,4]thiazin-3-one and sarcosine or l-proline in toluene under reflux condition. Also spiro-acenaphthylen-1-ones containing spirobenzo[1,4]thiazin-3-one ring have been synthesized using 2-(4-methyl-benzylidene)-4H-benzo[1,4]thiazin-3-one as dipolarophile. The methodology affords high yields of products in short reaction time.     

Studies in ring-opening polymerization. IV. Thermal polymerization of phenyl-substituted 1,3-dioxolan-2,4-diones

The effect of C-5 phenyl substituents on the thermal decomposition of the 1,3-dioxolan-2,4-dione ring has been examined. Unlike the dimethyl-substituted ring, 5-methyl-5-phenyl-1,3-dioxolan-2,4-dione decomposes smoothly in dry nonhydroxylic solvents to yield polymer and carbon dioxide. The introduction of a second C-5 phenyl substituent produces a similar but more rapid decomposition, with the added complication of a competing ring fragmentation leading to ketone formation. An analogy is drawn between the observed behavior of the phenyl-substituted 1,3-dioxolan-2,4-diones and that of the previously studied 1,3,2-dioxanthiolan-4-one 2-oxides. These monomers therefore provide another example of the thermal polymerisation mechanism first observed with 5,5-dimethyl-1,3,2-dioxathiolan-4-one 2-oxides. In these reactions the rate-determining step is the first-order ring-scission process leading to the formation of an α-lactone intermediate. This intermediate then takes part in a very rapid chain-growth process which governs the characteristics of the polymer formed.     

Selective syntheses of 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones via temperature-dependent Rh(II)-carbenoid-mediated 2H-azirine-ring expansion

The Rh(II)-catalyzed reaction of 2-carbonyl-substituted 2H-azirines with ethyl 2-cyano-2-diazoacetate or 2-diazo-3,3,3-trifluoropropionate provides an easy access to 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones. These compounds can be selectively prepared from the same starting material using temperature as the only varied parameter. The 2-azabuta-1,3-diene intermediate, a common precursor for both heterocyclic products, isomerizes into 2H-1,3-oxazine under kinetic control, while 1H-pyrrol-3(2H)-one is the sole product of the reaction at elevated temperatures. According to DFT-calculations a one-atom oxazine ring contraction involving ring-opening to a 2-azabuta-1,3-diene intermediate, followed by a 1,5- and 1,2-prototropic shift leads to the consecutive formation of imidoylketene and azomethine ylide, which then further undergo cyclization to the pyrrole derivative.     

1,3-Dipolar cycloaddition of β-alkoxyvinyl trifluoromethylketones with aryl (or benzyl) azides: Synthesis of 4-trifluoroacetylated 1H-1,2,3-triazoles

The 1,3-dipolar cycloaddition of aryl (or benzyl) azides with 1,1,1-trifluoro-4-ethoxy-3-butene-2-one proceeded smoothly by heating without solvent. 1-Aryl (or benzyl)-4-trifluoroacetyl-1H-1,2,3-triazoles were formed regiospecifically in good yield. These compounds were readily hydrated when exposed to air. In contrast, the reaction of benzyl azide with 4-trifluoroacetyl-2,3-dihydrofuran only gave minor amounts of 4-trifluoroacetyl-5-benzylamino-2,3-dihydrofuran in addition to an inseparable mixture of other products. 5-Trifluoroacetyl-3,4-dihydro-2H-pyran was inert towards benzyl azide under the same conditions.     

General approach to 6-tosyl-2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones via nucleophile-mediated ring expansion of tetrahydropyrimidines

A general six-step approach to 6-tosyl-2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones has been developed. The key step involves a ring expansion reaction of 4-mesyloxymethyl- or 4-tosyloxymethyl-5-tosyl-1,2,3,4-tetrahydropyrimidin-2-one mediated by nucleophilic reagents.     

Synthesis of adamantane derivatives—38: Synthesis of 1,3-bishoadamantane via ring-expansion of homoadamantan-2-one and homoadamant-4-en-2-one

The ring expansion of homoadamant-4-en-2-one (7) via the corresponding aminomethyl alcohol (9) gave 1,3-bishomoadamant-7-en-4-one (10) as the major product which was converted to 1,3-bishomoadamant-4-ene (14) and 1,3-bishomoadamanta-4,7-diene (16) via the alcohols 13 and 15. Catalytic hydrogenation of 14 and 16 afforded 1,3-bishomoadamantane (2). The ring expansion of homoadamantan-2-one (17) via the aminomethyl alcohol (19) afforded a 9:1 mixture of 1,3-bishomoadamantan-4-one (12) and 5-one (20). The same mixture was also obtained directly from 17 on treatment with diazomethane. The Wolff-Kishner reduction of 12 and 20 gave also 2.     

Synthesis of 2-amino-1,3-diols incorporating the cyclobutane ring

The synthesis of free and protected 2-amino-1,3-diols with threoninol substructure that incorporate a conformational restriction defined by the cyclobutane ring is reported. The key step in the synthesis of these target compounds, namely cis- and trans-c₄-threoninols, is the addition of methylmagnesium bromide to a cyclobutanone derivative. The selectivity of the reaction is modulated by the solvent.     

Dipolar addition of diazomethane to 5-methylene-1,3-dioxolan-4-one

The reactions of 1-pyrazoline-3-spiro-4-(1,3-dioxolan-5-one) were studied; this compound is the product of the 1,3-dipolar addition of diazomethane to 5-methylene-1,3-dioxolan-4-one. Depending on the conditions, thermolysis of the spiro compounds proceeds either with destruction of the pyrazoline ring, or with cleavage of the dioxolane ring, followed by rearrangement to give 1(2)-hydroxymethyl-3(5)-pyrazolecarboxylic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1182–1184, September, 1985.     

Stereoselective synthesis and transformations of pinane-based 1,3-diaminoalcohols

A library of pinane-based 1,3-diaminoalcohols and 5-aminomethyloxazolidin-2-ones was developed from commercially available (1R)-(?)-myrtenol which was transformed to N-trichloroacetyl protected allyl amine via Overmann rearrangement followed by stereoselective epoxidation with mCPBA resulting in key intermedier epoxy-amine. In order to obtain the diaminoalcohol moiety, aminolysis and azidolysis of the oxirane ring was performed. The cleavage of the oxirane ring proceeded regioselectively, affording N-trichloroacetyl protected 1,3-diaminoalcohols and oxazolidin-2-ones, which were obtained also via a thermal cyclisation. Since N deprotection of diaminoalcohols was unsuccessful under varied conditions, the protecting group was changed and Boc-protected analogues were synthesised. In this case, removal of the Boc protecting group was successful resulting in the planned diamino alcohols. An unexpected extreme δ Me_α-9 value (0.11 ppm) was measured for the dibenzylaminomethyl-substituted oxazolidine-2-one, and the stereostructure was refined by means of DFT geometry optimization. The obtained potential catalysts were applied in the test reaction of benzaldehyde and diethylzinc with low to moderate enantioselectivities (up to 74% ee).     

Novel mercaptoacetylative expeditious annulation of 5-mercaptopyrimidine ring on azoles using 1,3-oxathiolan-5-one

Schiff bases of azoles containing the amino group as part of a partial amidine structure undergo mercaptoacetylative expeditious annulation with 2-methyl-2-phenyl-1,3-oxathiolan-5-one to yield highly substituted 6,7-dihydro-6-mercapto-5H-thiazolo/1,3,4-oxa(thia)diazolo[3,2-a]pyrimidin-5-ones stereoselectively. The annulation is effected via an isolable intermediate under solvent-free microwave irradiation conditions in a one-pot procedure.     

Facile catalyst-free pseudo five-component domino reactions in the expedient synthesis of 5-aroyl-1,3-diarylhexahydropyrimidines

The pseudo five-component domino reactions of (E)-3-(dimethylamino)-1-arylprop-2-en-1-one, formaldehyde and aniline afford 5-aroyl-1,3-diarylhexahydropyrimidines in good yields under catalyst-free conditions. This transformation involving 4 C-N and 1 C-C bond formations in a one pot operation presumably proceeds via Michael addition-elimination-Mannich type reaction-condensative annulation-reduction sequence.     

Synthesis of benzimidazolone derivatives based on 2-acylcyclohexane-1,3-diones alkoximes

2-(1-Alkoxyiminoalkyl)cyclohexane-1,3-diones undergo at heating Beckmann rearrangement to give 6,7-dihydro-1,3-benzoxazol-4(5H)-one derivatives that under treatment with amines in acid medium are converted into 1,5,6,7-tetrahydro-4H-benzimidazol-4-ones. In reaction of 6,7-dihydro-1,3-benzoxazol-4(5H)-ones with O-ethylhydroxylamine 4-ethoxyimino derivatives were obtained that treated with hydrochloric acid formed the corresponding N-ethoxybenzimidazolones.     

Some transformations of 3-amino-4-alkoxycarbonyl-6-hydroxy-2H-1-benzopyran-2-ones. The synthesis of [1] benzopyrano[3,4-d]-[1,3]oxazine and [1] benzopyrano[3,4-d]pyrimidine derivatives

Acylation of 4-alkoxycarbonyl-3-amino-6-hydroxy-2H-1-benzopyran-2-one derivatives 3 and 4 gave under mild conditions the O-substituted derivatives 5–10, N,O -disubstituted derivative 11 and N,N-disubstituted derivative 12 . The compound 4 was transformed with benzoyl chloride under more drastic conditions into 13 , a derivative of a new heterocyclic system 2-benzopyrano[3,4-d][1,3]oxazine. The derivatives of 1-benzopyrano-[3,4-d]pyrimidine 19 and 20 were prepared either from 3 and 4 through the corresponding N-heteroarylformamidines 14 and 15 and N-heteroarylformamide oximes 17 and 18 or by cyclization of thiourea derivative 20 .     

Free radical ring expansion and chain extension of 1,3-diketones

Free radical-promoted one carbon ring expansion and chain extension of 1,3-diketones including 1,3-diarylpropane-1,3-diones and 2-aroyl-3,4-dihydro-2H-naphalen-1-one to generate corresponding 1,4-diketones are described.     

Yb(OTf)3-catalyzed cyclization of an N-silylenamine with 2-methylene-1,3-cyclohexanedione to afford a 7,8-dihydroquinolin-5(6H)-one derivative and its application to the one-pot conversion to a 2,3,5-trisubstituted quinoline derivative

A catalytic amount of ytterbium triflate (Yb(OTf)₃) promotes the cyclization of an N-silylenamine with in situ generated 2-methylene-1,3-cyclohexanedione and 2-methylenecyclohexanone to produce the corresponding 2,3-disubstituted 7,8-dihydroquinolin-5-one and 5,6,7,8-tetrahydroquinolin-5-one in moderate to good yields. A one-pot conversion of 7,8-dihydroquinolin-5-one to the quinoline derivative also proceeded in good yield.