Synthesis of 5(and 6)-nitro-4-methyl-2,3-dihydro-1h-1,5-benzo-2-diazepinones

The reaction of 4-nitro-o-phenylenediamine (I) with acetoacetic ester at room temperature under acid catalysis gives ethyl 3-(2-amino-5-nitrophenylamino)crotonate (II), which is readily cyclized to 7-nitro-4-methyl-2,3-dihydro-1H-1,5-benzo-2-diazepinone (III) on heating with alkaline agents. The reaction of I with acetoacetic ester in refluxing xylene gives isomeric 8-nitro-4-methyl-2,5-dihydro-1H-1,5-benzo-2-diazepinone (IVa) or 8-nitro-4-methyl-2,3-dihydro-1H-1,5-benzo-2-diazepinone (IVb), which are readily interconverted. The synthesis of IV is complicated by the side formation of 5-nitro-2-methylbenzimidazole (V) and thermal rearrangement of IVa and IVb to 5-nitro-1-isopropenylbenzimidazolone (VI). 6-Nitro-1-isopropenylbenzimidazolone (VII) is similarly obtained on heating III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 696–699, May, 1972.     

Organotin compounds : X. Organotin hydride addition to methyl cyclohexene-1-carboxylate and methyl indene-3-carboxylate

Free radical hydrostannation of methyl cyclohexene-1-carboxylate (I) and methyl indene-3-carboxylate (III) with trialkyltin hydrides, R₃SnH (R = Me, n-Bu, Ph) gives the energetically unfavourable cis products, 2-trialkylstannyl cyclohexanecarboxylate (II) and 2-trialkylstannyl indane-1-carboxylate (IV) in high yields, via a trans addition of the tin hydrides. The hydride abstractions by the intermediate trialkylstannylcyclohexanyl (VIII) and trialkylstannylindanyl (IX) intermediate radicals take place stereospecifically, and exclusively from the less hindered ring side. The structures of the isomers II and IV were established by (a) their transformation into the corresponding chlorodialkylstannyl derivatives V and VI, which were shown spectroscopically to have cis stereochemistries by intramolecular complexation of the ester group, and (b) their NMR data. Full ¹H, ¹³C, and ¹¹⁹Sn NMR data are given.     

Regioselectivity in nickel(0)/phosphine catalyzed cycloadditions of alkynes and isocyanates

The regioselectivity of Ni(0)-catalyzed cycloadditions of various isocyanates and asymmetrical alkynes to afford pyridones was explored. The use of PEt₃ provided, in most cases, two of the four possible pyridone regioisomers in high overall yields. Mechanistic rationale for the product distribution is provided.     

Studies on the syntheses of heterocyclic compounds. Part CCLXXIII. Synthesis of C-nordihydrocorynantheol and its related compounds

Mannich reaction of tryptamine with 3,3,4-triethoxycarbonylhexaldehyde (IV) gave the cyclized product (VIII), whose hydrolysis, followed by decarboxylation, afforded the acid (IX). After esterification of IX, reduction of ester (X) with lithium aluminum hydride gave the C-nordihydrocorynantheol (II). The syntheses of IV and XV were also described. Furthermore, the Mannich reaction of L-N-benzyl-1-methyltryptophan methyl ester (XV) with IV was also examined. This reaction gave the ester (XVII), which was hydrolyzed and decarboxylated to give the acid (XVIII). Esterification of XVIII, followed by catalytic hydrogenation, gave the lactam (III).     

Pyrans,their analogs,and related compounds

Reaction of 4, 4-dichloroflavine (I) with sulfurylchloride affords 2, 3, 3, 4, 4-pentachloroflavan (II). Hydrolysis of II gives 2-hydroxy-3, 3-dichloro-4-flavanone (III), while alcoholysis with aqueous alcohols yields 2-alkoxy-3,3-dichloro-4-flavanones (IVa, b). Treatment of III with SOCl₂ gives 2,3,3-trlchloro-4-flavanone (V), which with caustic alkali or sodium ethoxide is converted into o-(1-phenyl-2, 2-dichlorovinyloxy)benzoic acid (VIc) or its ethyl ester (VIb), respectively.For Part XLII, see [7].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1167–1170, September, 1970.     

A domino N-amidoacylation/aldol-type condensation approach to the synthesis of the topo-I inhibitor Rosettacin and derivatives

The pot, atom, and step-economic synthesis of Rosettacin topo-I poison and its derivatives has been achieved using a novel domino N-amidoacylation/aldol-type condensation, followed by decarboxylation of the ester function. The key domino procedure simply involves mixing HOBt ester as new reagent with lactam and NaH together in THF or THF/ DMF. The reaction seems to be general and led to suitable N-heterocyclic products in moderate to good yields.     

New synthesis of pyridone derivative from 1-azadiene

The reaction of 1-azabutadienes with enolates of substituted acetates gave 3,4-dihydro-2-pyridones which rearrange or dehydrogenate to other isomeric dihydropyridones or pyridones. Thus 1-azabutadienes were found to be good building blocks for pyridone derivatives.     

Chemie polyfunktioneller moleküle : LXXXVII. Synthese und reaktionsverhalten von 4-methyl-1,2,6-tristiba-tricyclo[2.2.1.0]heptan (Sb3-nortricyclan) gegenüber chrom-, molybdän- und wolframhexacarbonyl

The reaction of CH₃C(CH₂Cl)₃ and NaSb(C₆H₅)₂ in liquid ammonia leads to Sb₂(C₆H₅)₄ (I). Using CH₃C(CH₂Br)₃ instead of CH₃C(CH₂Cl)₃ results in the formation of I and CH₃C[CH₂Sb(C₆H₅)₂]₃ (II). Treatment of II with gaseous HCl in dry CH₂Cl₂ yields CH₃C(CH₂SbCl₂)₃ (III) under elimination of benzene. The reduction of III with Na in THF gives the first all-cis-organocyclotristibane (Sb₃-nortricyclane) CH₃C(CH₂Sb)₃ (IV) which forms the new CH₃C(CH₂Sb)₃M(CO)₅ complexes (Va---Vc) with M(CO)₅THF (M = Cr, Mo, W).     

Synthesis and reactions of 3-carbethoxy and 3-aroyl-3,4-dihydro-1h-2,3-benzoxazin-1-ones

A series of 3-substituted 3,4-dihydro-1H-2,3-benzoxazin-1-ones (IV) (Scheme I) was prepared by reaction of 2-bromomethylbenzoyl chlorides (II) with N-hydroxyethylcarbamate (III) or with benzohydroxamic acids. Acid hydrolysis of 3-carbethoxy (IVa) and 3-benzoyl derivatives (IVb) afforded a mixture of 2-(hydroxyaminomethyl)benzoic acid (V) and 2,3-dihydro-2-hydroxy-1H-1-isoindolinone (VII). Compound IVa reacted with ethanol, amines or hydrazine to yield the ethyl ester X, amides XIV (Scheme II) and the hydrazide XII of 2-(N-carbethoxy-N-hydroxy-aminomethyl)benzoic acid. Diazotization of the hydrazide XII afforded the unstable azide XIII which did not undergo the Curtius reaction but gave the benzoxazinone IVa by loss of hydrazoic acid.     

Benzomorphan related compounds. XIII. Syntheses of 2,6-methanopyrrolo[1,2-d] [1,4]diazocines

Two alternative syntheses of 2,6-methanopyrrolo[1,2-d][1,4]diazocines (I) based in the acidic cyclization of 2-(1-pyrrolylmethyl)tetrahydropyridines are described. In the first synthetic route, lithium aluminum hydride reduction of 2-cyano-1,4-dimethyl-1,2,3,6-tetrahydropyridine (IIa) followed by reaction of the resulting primary amine with 2,5-diethoxytetrahydrofuran affords the requisite tetrahydropyridine IVa. An analogous sequence from 2-cyano-4,6-di-methylpyridine (V) leads to the corresponding 2-(1-pyrrolylmethyl)pyridine VII which by quaternization and borohydride reduction yields a mixture of isomeric tetrahydropyridines, precursors of the pyrrolodiazocine systems Ib and Ic. Structural and stereochemical assignment of the synthesized compounds are discussed.     

Chiral Photochemistry in a Confined Space: Torquoselective Photoelectrocyclization of Pyridones within an Achiral Hydrophobic Capsule

Chiral induction during the photoelectrocyclization of pyridones included within octa acid (OA) capsule has been established. Chiral induction is brought about by a chiral auxiliary appended to the reactive pyridone moiety. Importantly, the same chiral auxiliary while ineffective in acetonitrile solution is found to be effective within the confined space of OA capsule. The diastereomeric excess of 92% obtained here is comparable only to that in solid state. OA capsule, we believe, provides restriction to the rotational motions of the reactant pyridone and chiral auxiliary and thus places the chiral auxiliary in a selective conformation with respect to the reactive pyridone part. A correlation between the position of the methyl group on the pyridone ring and diastereoselectivity was noted. Structures of the host-guest complexes were examined by ¹H NMR and the data were used to obtain preliminary information concerning the mechanism of chiral induction within the confined spaces of OA capsule.     

Selective preparation of pyridines, pyridones, and iminopyridines from two different alkynes via azazirconacycles

Selective preparation of pyridine derivatives from two different alkynes and a nitrile was achieved by a novel procedure in which an alkyne and a nitrile couple first to give an azazirconacyclopentadiene followed by reaction with the second alkyne in the presence of 1 equiv of NiCl(2)(PPh(3))(2). This procedure gives only single products of pyridine derivatives from two different symmetrical alkynes and a nitrile. Our novel procedure can be used even with two similar alkyl-substituted alkynes such as 3-hexyne and 4-octyne. Two possible pyridine isomers from 3-hexyne, 4-octyne, and acetonitrile could be completely and independently prepared as single products by this method. The origin of the selectivity comes from the addition order of two different alkynes. This method was applied for the formation of pyridones and iminopyridines using isocyanate and carbodiimide derivatives instead of nitriles, respectively. Reaction of an alkyne with Cp(2)ZrEt(2) and an isocyanate or a carbodiimide gives an azazirconacycle. Treatment of the azazirconacycle with the second alkyne in the presence of 1 equiv of NiCl(2)(PPh(3))(2) gave a pyridone or an iminopyridine derivative. The use of two different unsymmetrical alkynes afforded the pyridine with five different substituents when the first alkyne has a trialkylsilyl group and the second alkyne has a phenyl group as functional groups. On the other hand, azazirconacyclopentadienes reacted with propargyl bromide in the presence of CuCl with excellent regioselectivity to give tetrasubstituted pyridine derivatives as single products. With the assistance of the trialkylsilyl groups, pyridines with all different substituents including H were also prepared.     

Cyclometallated platinum(II) complexes: oxidation to, and C-H activation by, platinum(IV)

A series of cyclometallated phenylpyridine platinum(II) complexes have been synthesised with a systematic variation in both the phenylpyridine and the ancillary ligand. Oxidation of one of the cyclometallated species leads to a number of isomeric platinum(IV) complexes, all of which eventually isomerize to a single compound. The route to these new compounds has been demonstrated to involve an initial slow oxidation followed by a rapid C-H activation to give doubly cyclometallated complexes. The solid state structures of a number of both the platinum(II) and the platinum(IV) species have been solved; many of the structures exhibited extended interactions that result in complex three dimensional packing.     

Photocycloaddition of four-carbon-tethered pyridones. Intramolecular hydrogen bonding and facilitated amide hydrolysis by a proximal secondary alcohol

Four-carbon-tethered pyridones undergo photocycloaddition to give exclusively trans-[4 + 4] products. The presence of a tether alcohol engenders a solvent-dependent diastereoselectivity for the cycloaddition by intramolecular hydrogen bonding to the adjacent pyridone. Following cycloaddition, the alcohol can deliver a carbonyl group to the proximal, hindered amide nitrogen, leading to a very facile amide hydrolysis.     

Reaction de Cycloaddition dipolaire-1,3-des thiazolones et des selenazolones mesoioniques avec l'acetylene dicarboxylate de methyle—II: Influence de la nature des substituants sur la reactivite observee et sur la nature des produits obtenus

Mesoionic thiazolones and selenazolones react with dimethyl acetylene dicarboxylate to give thiophenes or pyridones. We show that the reactivity of the mesoionic thiazolones towards dimethyl acetylene dicarboxylate may be explained by second order perturbation theory, limited to frontier orbitals. The influence of the temperature and of the nature of the substituants on the evolution of the primary cycloadduct can be explained by a competition between a retro Diels-Alder reaction giving a thiophene and a desulfurisation or a deselenurisation giving a pyridone.     

Cobalt-mediated [2+2+2] cycloaddition versus C-H and N-H activation of pyridones and pyrazinones with alkynes: an experimental study

The reactivity of a range of pyridone and pyrazinone derivatives towards alkynes in the presence of cyclopentadienylcobaltbis(ethene) has been investigated. Depending on the nature of the substrates, [2+2+2]- or [2+2] cycloaddition, C-H, or N-H activation may occur. In the case of pyridones, the first three predominated with N-protected derivatives, whereas substrates containing N-H bonds followed an N-H activation pathway. The [2+2+2] cycloaddition of an N-butynylisoquinolone was applied successfully to the total synthesis of anhydrolycorinone. Pyrazinone substrates showed similar patterns of reactivity.     

Enyne [4+4] Cycloaddition/Oxidation: Ring Contraction via Cyclopropanones and Their Anionic Ring‐Opening Reactions

Irradiation of a 1,3‐enyne tethered to a 2‐pyridone, in the presence of oxygen, leads to formation of a seven‐membered ring product, an overall [4+4−1] reaction. This transformation involves two unstable intermediates and a sequence of unusual reactions. An initial [4+4] photocycloaddition of the enyne with the pyridone yields a 1,2,5‐cyclooctatriene. Photooxidation of this triene forms a cyclopropanone and subsequent photoextrusion of carbon monoxide gives the observed 1,4‐cycloheptadiene product. The first‐formed cyclooctatriene and the cyclopropanone could be observed and characterized spectroscopically. The cyclopropanone underwent CO extrusion both photochemically and thermally to give the cycloheptadiene product. Addition of fluoride or acetylide to the most stable cyclopropanone occurred chemoselectively at the two different silicon groups rather than the carbonyl group. The resulting cyclopropanone ring openings gave unsaturated aldehydes.     

Oxidative cleavage of a tricyclic pyridone to a bicyclic lactam-dione

Two equivalents cf anhydrous m-chloroperbenzoic acid (m-CPBA) cleaved the pyridone ring of 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naph forming; the ten-membered lactam α-diketone 12-(3-chlorophenyl)-7,8,9,10-tetrahydropyrido[2,3-b]azecine-5,6,11(12H)-trione. Under aqueous conditions, one equivalent of m-CPBA and the same pyridone formed the lactam α-ketol 12-(3-chlorophenyl)-7,8,9,10-tetrahydro-6-hydroxypyrido[2,3-b]azecine-5,11(6H, 12H)-dio     

Plant-polyphenols and related compounds. A mass-spectrometric study of the trimethylsilyl derivatives of hydroxy- and/or methoxy-substituted cinnamic acids and of their methyl esters

The low resolution 70 eV mass spectra of the TMS (Trimethylsilyl) derivatives of eight naturally occurring hydroxy- and/or methoxycinnamic acids are presented in detail. The TMS derivatives studied are I, of o-coumaric acid; II, of m-coumaric acid; III, of p-coumaric acid; IV, of isoferulic acid; V, of ferulic acid; VI, of 3,4-dimethoxycinnamic acid; VII, of sinapic acid; VIII, of caffeic acid; Ia to Va, VIIa, of the corresponding methyl esters; and VIa, methyl 3,4-dimethoxycinnamate. The derivatives studied show a high degree of stability under conditions of electron-impact. The major fragmentation processes for the free acid TMS derivatives begin with methyl radical loss from either the ester or ring TMS group. The spectra of the methyl ester TMS derivatives have enabled the site of initial methyl loss to be determined. Accurate mass measurements and analysis of the second field-free region metastable peaks provide support for suggested fragmentation schemes. The spectra are sufficiently different to permit identification except between compounds IV and V (and IVa and Va) where the major fragmentation process involves a common ion, thought to be the silicon analogue of an acetonide.     

PHOTOCHEMISTRY OF 4-AMINOPYRIMIDINES 2,6-DIMETHYL-4-AMINOPYRIMIDINE

Abstract— Ultraviolet irradiation (2537 Å) of 2,6-dimethyl-4-aminopyrimidine (I) results in an intramolecular rearrangement with the formation, either in aqueous or anyhdrous medium, of only one photoproduct, 2-amino-3-cyanopent-2-enemine (II), in quantitative yield. The quantum yield for this reaction is 0.043 einsteins/mole.
Deamination of II gives, quantitatively, 2-amino-3-cyanopent-2-en-4-one (III) and this, in turn, may be deaminated to give, quantitatively, 3-cyanopent-2-en-2-01-4-0ne (cyanoacetyl-acetone, IV). Identification of II was achieved initially through isolation of III and IV. Some of the chemical and physico-chemical properties of these compounds are reported, as well as methods for obtaining all of them on a preparative scale.
The mono-protonated form of I also gives II on irradiation, but in lower quantum yield, 7.3times10⁸ einsteins/mole. Irradiation of the doubly protonated form of I in strongly acid medium leads directly to the formation of a mixture of II, III and IV, with approxi mately the same quantum yield.
The possible mechanisms for the foregoing photochemical reactions are discussed and their significance related to the photochemistry of 4-aminopyrimidines in general and to those of nucleic acid derivatives in particular.