Formation of para-quinomethanes via 4-aminobutylcatechol oxidation and ortho-quinone tautomerism

Enzymatic and chemical oxidation of 4-(4-N,N-dialkylaminobutyl)catechols leads to formation of 1,1-dialkyl-pyrrolidinium salts in good yield. It is proposed that these products are formed by tautomerism of the initially formed ortho-quinones to para-quinomethanes. The corresponding secondary amines do not form para-quinomethanes but cyclise giving tetrahydro-1H-benzo[b]azepine-7,8-diones. The failure of the dialkylaminobutyl derivatives to cyclise to bicyclic betaines, in a manner analogous to lower homologues and monoalkylaminobutyl derivatives, is attributed to steric hindrance. This proposal is supported by evidence that the sterically hindered N-tert-butylaminobutyl derivative, in contrast to other secondary amines, does not cyclise but gives a para-quinomethane-derived product. Based on pulse radiolysis and spectrophotometric evidence, para-quinomethane formation appears to be much slower than cyclisation and only occurs when cyclisation is unfavourable. The ortho-quinones formed from 5-aminopentylcatechols neither cyclise nor tautomerise suggesting that the chain length in these derivatives is too long for both cyclisation and intramolecular deprotonation.     

One-pot synthesis of polycyclic heterocyclic compounds by condensation of 1-carbamoylmethyl-2,3,3-trimethyl-3H-indolium salts with pyridine-2, 3, and 4- and quinoline-4-carboxaldehydes

A one-pot synthesis of new polycyclic heterocyclic compounds was carried out via the condensation of 1-carbamoylmethyl-2,3,3-trimethyl-3H-indolium chloride with pyridine- and quinolinecarboxaldehydes. The heating of the aforementioned 3H-indolium salts with 1 eq. of pyridine-2, 3, and 4- or quinoline-4-carboxaldehyde in ethanol in the presence of piperidine as a catalyst provided 9a-[2-(pyridyl)ethenyl]- or 9a-[2-(quinolyl)ethenyl]-9,9a-dihydro-1H-imidazo[1,2-a]indol-2(3H)-one derivatives as the main products. However, reaction outcome was dramatically different for the analogous reactions in acetic acid. In this case, the heating of the chloride with 2 eq. of pyridine-2-carboxaldehyde afforded derivatives of 9a-[3-(pyridin-2-yl)indolizin-2-yl]-9,9a-dihydro-1H-imidazo[1,2-a]indol-2(3H)-one as the major product, while the use of 2 eq. of pyridine-3 and 4- or quinoline-4-carboxaldehyde led to the formation 2-heteroaryl-1-heteroarylmethyl-9H-pyrrolo[1,2-a]indole-3-carboxamides. Plausible pathways for the cyclization reactions are discussed. The structural assignments were based on ¹H, ¹³C and ¹⁵N NMR spectroscopy, HRMS and single-crystal X-ray diffraction data.     

Extension of Bischler-Napieralski reaction—I Synthesis of isoquinoline derivatives: A synthesis of rac.-apomorphine dimethyl ether

The scope of Bischler-Napieralski reaction has now been extended to include acyl cyclo-hexa-1:4-dienylethylamide types, which cyclise smoothly to yield various isoquinolines after dehydrogenation. 1-(2-Nitro-3:4-dimethoxybenzyl)-3:4-dihydroisoquinoline, hitherto difficultly accessible, could be prepared and converted to rac.-apomorphine dimethyl ether.     

The reaction of phenylarsenazo with chromium(III)

The conditions for the reaction between phenylarsenazo (PAA) (2-[(2-arsonophenyl)azoj-7-(phenylazo)-1, 8-dihydroxynaphthalene-3,6-disulphonic acid) and chromium(III) have been studied. A blue 1:1 complex is formed at pH 2.2 on heating the reactants at 100 degrees for 15 min. It has maximum absorption at 635 nm and is stable for at least 24 hr. The molar absorptivity is 3.3 x 10(4) 1.mole(-1).cm(-1). Beer's law is obeyed in the chromium concentration range 0-1.4 mug ml . The reaction has been successfully applied to determination of chromium in alloy steel.     

Mass spectra of some substituted imidazoles

Comparison of fragmentation pathways and high resolution measurements has revealed that the molecular ions of 1-(2-hydroxy-2-phenylethyl)imidazoles undergo elimination of benzaldehyde. The parent ions of trans-1-styrylimidazoles also cyclise in a manner similar to their photochemical reactivity. A rearrangement involving OH or OMe transfer between the trans-1-styryl and 5-acid or 5-methyl ester group of an imidazole is also described.     

Benzyne cyclisation with carbanion activated aromatic rings1

Attempts to cyclise o-chlorophenyl benzyl ether, sulphide, sulphoxide and sulphone by treatment with KNH₂/NH₃ were unsuccessful. Similar reaction of 1-(o-chlorophenyl)-2,2-diphenylethane led to amination whereas α-(o-chlorobenzyl)phenylacetic acid gave a dihydrocoumarin. Reaction of 4- and 2-(o-chlorophenethyl)-pyridines, however, afforded products comprising benzisoquinolines and 1-pyridylbenzocyclobutenes.     

Preparation of oxime oxalate amides and their use in free-radical mediated syntheses of lactams

Photosensitized decomposition of oxime oxalate amides is a useful new route to carbamoyl radicals that may cyclise to afford beta- or gamma-lactams.     

Cycloalkanes XI. Friedel-Crafts Condensation of Polynuclear Aromatic Compounds with Cis-4-Cyclohexene-1, 2-Dicarboxylic Acid Anhydride

The anhydride of cis-4-cyclohexene-1,2-dicarboxylic acid was condensed with phenanthrene, acenaphthene and fluorene in the presence of anhydrous aluminium chloride to give the corresponding 2-(aroyl) cyclohex-4-ene-1-carboxylic acids. These keto acids when subjected to Wolf-Kishner reduction yielded the corresponding 2-(aryl) cyclohex-4-ene-1-carboxylic acids, which were then converted into their respective acid chlorides by refluxing with thionyl chloride in benzene. The acid chlorides in turn were cyclised by anhydrous aluminium chloride in carbon disulphide to give the corresponding cyclic ketones. These cyclic ketones were then reduced by Wolf-Kishner method to furnish the desired hydrocarbons, 2,3-cyclohex-2′-ene-5,6-substituted cyclohexanes.     

Abstraction Versus Electrophilic Substitution: Metaphosphate-Mediated Reactions in the Gas Phase

Abstract

Whereas arylmetaphosphates (ArOPO₂) tend to cyclise by intramolecular C-H insertion (phosphorylation) when generated in the gas phase, their alkyl-substituted counterparts exhibit non-electrophilic behaviour and give rise to alkenes by an unusual 1,2-methyl shift induced by a combination of hydrogen abstraction with concomitant elimination of metaphosphoric acid (HOPO₂).     

Thermische Cyclodehydratisierung von Salicylalkoholen; eine einfache Synthese von 4-substituierten 2H-Chromenen

Heating of 1-(o-hydroxyaryl)-2-propen-1-ols ( 9–13 ; see scheme 1) in diglyme solution at 147° leads to a 1,4-elimination of water to yield ω-vinyl-o-quinomethides ( b ; see scheme 2) as intermediates which cyclise rapidly to form 2H-chromenes ( 17–21 ). 1-(o-Hydroxyphenyl)-5-hexen-1-ol ( 14 ) on heating at 147° is transformed into o-(1,5-hexadienyl)-phenol ( 23 ). This phenol rearranges at higher temperature (270°) in N,N-diethylaniline to yield a mixture of 2,4-propanochromane ( 25 ) and cis- and trans-3,4-propanochromane (cis- and trans- 26 ). The kinetically controlled ratio of these compounds is 2,8:1:2,9. The formation of 25 and 26 can be explained by an intramolecular Diels-Alder reaction (see scheme 3).     

X=Y-ZH systems as potential 1,3-dipoles: Part 17. Sequential michael addition-5-endo-trig cyclisation of arylidene imines of α-amino acid esters

Imines of α-amino acid esters undergo regiospecific Michael addition to methyl acrylate or acrylonitrile in good yield in benzene at 25°C catalysed by benzyItrimethyl ammonium methoxide (BTAM). The Michael adducts cyclise to a mixture of two stereoisomeric polysubstituted proline ester derivatives in the presence of 1 mol. of BTAM. Mechanistic studies, involving chiral intermediates, show this cyclisation to be an example of a disfavoured 5-(enolexo)-endo-trig process.     

A new access to ring-fused cyclopropanols through samarium diiodide-induced 3-exo-trig-cyclisations

Benzobicyclic δ-oxo-α,β-unsaturated esters easily prepared from tetralones or benzosuberone, readily cyclise in the presence of samarium diiodide and tert-butanol according to a totally syn mode, leading selectively to ‘cis’ ring-fused cyclopropanols that spontaneously lactonise to tetracyclic compounds.     

Farbstoffsensibilisierte Photo-Oxygenierung von 6,6-Dimethylfulven. Eine neue 1,2-Dioxolan-Umlagerung

The dye sensitized photo-oxygenation of 6,6-dimethylfulvene ( 1 ) in solution at 15° gives enol lactone 2 , along with ketoles 3 and 4. The following mechanism is proposed: initially formed endoperoxide 11 undergoes a 1,2-dioxolan rearrangement to give allen epoxide 12 , which then isomerizes to cyclopropanone 13. 13 can then cyclise to give 2 and 3 .     

The stobbe condensation with substituted succinic esters. II A synthesis of benzothiophene derivatives

The condensation of some thienyl carbonyl compounds with dimethyl phenylsuccinate using either sodium hydride or potassium t-butoxide as condensing agents, gave a stereoisomeric mixture of (E)- and (Z)-half-esters (3). The (E)-half-esters la-c were either cyclised to the corresponding benzothiophene derivatives or hydrolysed to the (E)-dibasic acids VIa-e, which were cyclised to the corresponding anhydrides VIIa-c. Methylation of VIIa,c gave the isomeric half-esters VIIIa,c. The (Z)-half-ester Id can cyclise easily to the lactone IX.     

Optimising stereoselectivity in intramolecular Diels-Alder reactions of pentadienyl acrylates: synthetic and computational investigations into the "steric directing group" approach

Experimental conditions for the intramolecular cycloaddition of four related pentadienyl acrylates 3, 4, 5 and 6 are reported. In contrast with several previous reports, pentadienyl acrylates do undergo synthetically useful intramolecular Diels-Alder reactions: 3, 4, 5 and 6 cyclise at reasonable rates at temperatures of 132-180 degrees C at atmospheric pressure in moderate to good yields. The stereochemical outcome of each of these reactions was accurately measured and the results are in good agreement with transition structure populations predicted using B3LYP/6-31+G(d) theory. The parent system 3 cyclises with moderate endo selectivity; the presence of either a C5-methyl substituent or a C3-bromine atom results in a slight shift towards the trans-fused exo stereoisomer but--overall--a less selective reaction. The presence of both C3-Br and C5-CH3 substituents results in a marked improvement in stereoselectivity with the exo,lk-product predominating. Interpretation of B3LYP/6-31+G(d) transition structures allows insights into the improvement in stereoselectivity obtained by incorporating a removable "steric directing group" into a 5-methyl-1,3,8-nonatriene precursor.     

Rearrangement of ketone hydrazones derived from 4-hydrazino-1H-2,3-benzoxazines

The ketone hydrazones IV, derived from 4-(1-methylhydrazino)-1H-2,3-benzoxazines and various ketones, rearrange by the action of anhydrous acids and/or heating to the phthalanylidene compounds V, which are the first reported examples of α-aminoazoaliphatic derivatives. The structure assignment was based on spectroscopic (ir, pmr, and uv) data and on the study of the hydrolysis products. A mechanism for the rearrangement is proposed and briefly discussed.     

Studies on pyridazine azide cyclisation reactions

Reaction of sodium azide with 4-methyl-3,5,6-tribromopyridazine results in the formation of 3,5,6-triazide intermediate which could cyclise to give two possible bicyclic products while ab initio calculations show that the formation of a tricyclic compound is extremely energetically unfavourable. However, experimentally, only one major product is isolated. The structure of this unstable product has been conclusively established by X-ray crystallography as 3,5-diazido-4-methyl[1,5-b]tetrazolopyridazine confirming theoretical predictions.     

Diastereoselective SmI2-mediated cyclisation of δ-oxo-α,β-unsaturated esters to cyclopropanols

In the presence of samarium diiodide and a proton source, δ-oxo-γ,γ-disubstituted-α,β-unsaturated esters readily cyclise with complete diastereocontrol to give anti-cyclopropanol products.     

Lewis acid mediated cyclisations of silylated methylenecyclopropyl hydrazones

Silylated methylenecyclopropyl hydrazones on treatment with BF3 x Et2O cyclise to give heterocyclic products involving a novel sequence of hydride and silyl shifts via a series of increasingly stable cationic intermediates.     

A pincer auxiliary to force difficult lactamisations

A new method to cyclise peptides is reported based on insertion of a salicylaldehyde derived pincer auxiliary in the linear precursor sequence. H-betaAla-Phe-OH and H-Phe-betaAla-OH were chosen as representative model peptides.