Aromatic and Heteroaromatic Chemistry Volume 6

A Review of the Literature Abstracted between July 1976 and June 1977

By H. Suschitzky, O. Meth-Cohn

The Royal Society of Chemistry

Copyright © 1978 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-803-5

Contents

Chapter 1 Three-and Four-Membered Ring Systems By S. M. Roberts, 1,
Chapter 2 Five-membered Ring Systems By G. V. Boyd, 14,
Chapter 3 Six-membered Heterocycles By R. K. Smalley, 81,
Chapter 4 Seven-membered Ring Systems By G. R. Proctor, 146,
Chapter 5 Medium-sized Rings and Macrocycles By O. Meth-Cohn, 153,
Chapter 6 Electrophilic Substitution Reactions By J. H. Ridd, 165,
Chapter 7 Nucleophilic Substitution Reactions By G. M. Brooke, 205,
Chapter 8 Aromatic Substitution by Free Radicals, Carbenes, and Nitrenes By R. S. Atkinson, 223,
Chapter 9 Porphyrins and Related Compounds By A. H. Jackson, 239,
Chapter 10 Naturally Occurring Aromatic Oxygen-ring Compounds By R. D. H. Murray, 258,
Chapter 11 Other Naturally Occurring Aromatic Compounds By J. R. Lewis, 282,
Erratum, 302,
Author Index, 303,

CHAPTER 1

Three-and Four-membered Ring Systems

BY S. M. ROBERTS

1 Three-membered Carbocyclic Systems

A theoretical investigation into the structure and geometry characteristics of stationary points on energy hypersurfaces belonging to the cyclopropenyl cation, radical, and anion established that there is an unusual type of Jahn-Teller distortion that is peculiar to symmetric cyclic systems.

E.s.r. measurements suggest that the tri-t-butylcyclopropenyl radical is best considered to be a rapidly equilibrating trio of equivalent σ-radicals.

The thermodynamic potentials for the one-and two-electron reduction of the cyclopropenyl cation and some alkyl and aryl derivatives have been determined by second-harmonic a.c. voltammetry. The data indicate that cyclopropenyl radicals are destabilized by alkyl substituents and are also destabilized relative to the corresponding unconjugated radicals. The basicity of the various cyclopropenyl anions so formed was also deduced.

Ab initio M.O. calculations on C4H5+ cations showed that the methyl-cyclopropenyl cation is more stable than the homocyclopropenyl cation: the calculated geometry of the latter species was closer to that expected of an open ‘cyclobutenyl’ structure rather than a tightly bridged bicyclic form. In contrast, Jorgensen has calculated that cyclobutenyl cations benefit from homoaromatic delocalization and that the geometry of the cations is decidedly puckered.

Evidence has been offered for the participation of the non-classical tris-homocyclopropenyl cations (1) and (2) in the acetolysis of some alkyl-substituted endo-bicyclo[3,1,0]hexan-3-ol tosylates.

The stable bis(tetramethylhomocyclopropenyl) dication (3) has been prepared from syn-octamethyltricyclo[4,2,0,02’5]octadiene. The homocyclopropenyl cations (4) are remarkably stable, and n.m.r. data have established the importance of 1,3-π-overlap in these instances. The latter cations can be employed in the synthesis of novel fluorinated cyclobutenones (Scheme 1).

The appropriate counterion must be employed to effect successful Friedel–Crafts reactions between trihalogenocyclopropenium ions and unsaturated substrates. With a non-activated aromatic substrate, the trifiate salt should be employed. The counterion of choice in the reactions involving alkenes and alkynes is SbCl6-; novel di-and tri-vinylcyclopropenium salts have been prepared in this way (Scheme 2).

Trichlorocyclopropenyl triftate, when it reacts with dimethyl sulphide, selenide, or telluride, yields the corresponding trimethylchalcogenocyclopropenium salt (Scheme 3). The chlorodimethylthiocyclopropenium salt (5), prepared by the reaction of tetrachlorocyclopropene with methyl(bismethylthio)sulphonium hexa-chloroantimonate, is a convenient precursor of the previously unknown thiodeltic acid methyl ester (6).

The reaction of 2,3,3-trichloro-1-phenylcyclopropene with amines or dialkyl-aminotrimethylsilanes gives bisalkylaminophenylcyclopropenium cations, which are readily converted into the corresponding ketones and thiones (Scheme 4). The thiones are readily converted into the salt (7) (Scheme 4): methods for hydrolysis and for mono-and di-methylation of this salt have been described.

Tris(dialkylamino)cyclopropenium perchlorates give cyclopropenimine derivatives on reaction with iminopyridinium ylides, and a novel synthesis of pyridazinium perchlorates through the reaction of diaminocyclopropenium salts with diazoalkanes has been reported.

Trialkylthiocyclopropenium ion or dialkylthiocyclopropenethione react with tri-alkyl phosphites to give novel esters of cyclopropenylphosphonic acid. A new synthesis of a pyrrole derivative was accomplished by treatment of the former ion with hexamethylphosphortriamide (Scheme 5).

The quinarene (8) has been prepared from p-bromotolan in five steps. Spectral evidence suggests that there is an appreciable contribution from the dipolar form.

Full details of the synthesis of deltic acid (dihydroxycyclopropenone) and of dilithium deltate through the photolysis of bis(trimethylsilyloxy)cyclobutenedione have been published. Some properties of the system have been described. The dissociation constants for deltic acid in water indicate that the molecule is not particularly acidic.

The structure of diphenylcyclopropenone has been investigated, using i.r. and Raman spectroscopy to derive force constants, and using calculations to determine the π-electron bond order. Dicyclopropylcyclopropenones are available via addition of dichlorocarbene to the appropriate alkyne; they are intermediate between diphenylcyclopropenone and di-t-butylcyclopropenone in their thermal and hydrolytic stability. The photoelectron spectra of cyclopropenone and of some alkyl and aryl derivatives have also been described.

Further work on the use of cyclopropenones in cycloaddition reactions to form heterocyclic systems has involved the treatment of methylphenylcycloprupenone with 2-aminopyridines to give cis-3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-2-ones.

The highly reactive methylenecyclopropene (9) has been obtained by a dehy-drobromination procedure. Transformation into a cyclopropenone and an alkynone occurs on treatment with water. Treatment of 1,2-dichloro-1-methyl-cyclopropane with potassium t-butoxide gives t-butoxymethylenecyclopropane (10); the elusive compound methylenecyclopropene has been postulated to be an intermediate.

Labelling studies have confirmed that bicyclo[3,1,0]hexatriene (11) is formed when exo, exo-4,6-dibromobicyclo[3,1,0]hex-2-ene is treated with base. The triene and the 2-methyl and 2-t-butyl derivatives give the corresponding 6-dimethyl-aminofulvene on reaction with dimethylamine.

2 Three-membered Heterocyclic Systems

3-Dimethylamino-2H-azirine derivatives are available by thermal isomerization or photo-isomerization of appropriately substituted isoxazoles (Scheme 6). Similarly, the conversion of 3-phenylisoxazoles into 2-phenyloxazoles proceeds through the intermediate formation of the 3-phenyl-2H-azirine (Scheme 6).

New and facile syntheses of ethyl 2-azidoalk-2-enoate and ethyl 3-azidoalk-2-enoate, and the photolytic conversion of these compounds into 2-alkyl-3-ethoxy-carbonyl-2H-azirines and 3-alkyl-2-ethoxycarbonyl-2H-azirines, respectively, have been reported. 3-Diazopyrazoles give 2-cyano-2H-azirines on pyrolysis.

3-Dimethylamino-2,2-dimethyl-2H-azirine reacts with activated isothiocyanates to form the dipolar compounds (12), which were characterized by hydrolysis and methylation (Scheme 7). These dipolar compounds react readily with a second and a third mole of isothiocyanate. The reaction of the same azirine with carbon disulphide gives the iminium salt (13), which exists in the non-polar isocyanate form in solution. The latter product is very reactive, and has been used to form new heterocyclic systems by treatment with simple reagents.

On the other hand, 2-pyridyl isothiocyanate cycloadds to 3-phenyl-2H-azirines to give 5-phenyl-2-pyridylaminothiazoles.32

The photochemical reactions of 2H-azirines have been reviewed. Recent advances in this area include the intramolecular trapping of the first-formed nitrite ylide with alkene, aldehyde, and alcohol functions. A new synthesis of cycloalkanones has been based on the trapping of the nitrile ylide formed on photolysis of a spiro-azirine with methanol followed by acid-catalysed hydrolysis.

Benzonitrile ylides generated from 3-phenyl-2H-azirines react with vinyl-phosphonium salts or vinyl sulphones to give 2H-pyrroles and pyrroles (Scheme 8).

It was already known that 3-aryl-2H-azirines give 2,5-diarylpyrazines on reaction with Group VI metal carbonyls. Now it has been shown that the same reaction can be accomplished using silver perchlorate. The reaction of 3-aryl-2H-azirines with Fe2(CO)9 affords 2,5-diarylpyrroles (together with dinuclear iron carbonyl complexes), while with Co2(CO)8 or chlorocarbonylrhodium(I) complexes the corresponding 2-styrylindole is formed, in good to excellent yield.

Lithio-and magnesio-methylenecyclopentane and also zinc enolates have been found to add across the imine bond in 3-phenyl-2H-azirines in the expected manner.

The structures of the adducts formed between 3-phenyl-2H-azirine and diphenylcarbene, and the products obtained from this azirine on treatment with N-amino-pyridines and base, have been elucidated.

The trifiate salt of 1-methyl-2,3-diphenyl-2H-azirine has been postulated to be an intermediate in the conversion of 2,3-diphenyl-2H-azirine into the open-chain salt (14).

In studies aimed at the elucidation of the mechanism of the Wolff rearrangement, a non-empirical S.C.F. M.O. study has been carried out on oxirine and formyl-methylene. In the ground state, the total energy of the former lies 11.8 kcal mol-1 above the latter, the ring-opening reaction having an activation energy of 7.3 kcal mol-1.

The stable silacyclopropene 1,1-dimethyl-2,3-bis(trimethylsilyl)-1-siliren (15) has been prepared from hexamethylsiliran and bis(trimethylsilyl)ethyne. Results obtained from Si n.m.r. spectroscopy show that the ring silicon atom is highly shielded, an effect which may be due to π-bonding thut involves participation of vacant silicon 3d orbitals. Photolysis of (pentamethyldisilanyl)phenylethyne in benzene gives a solution containing, inter alia, the 1-silacyclopropene (16). Similarly, tetramethyl-1-silacycloprop-2-ene (17) has been obtained as the product of addition of dimethylsilylene (Me2Si:) to but-2-yne. This silacyclopropene proved to be stable as a solution in dimethoxydimethylsilane at temperatures up to 75°C, in the absence of air and moisture.

The mechanism of the photolytic conversion of 3-chloro-3-methyldiazirine (18) into vinyl chloride, ethyne, hydrogen chloride, and nitrogen has been discussed, and evidence has been gained for the intermediacy of diazoalkane in the thermal decomposition of 3-n-butyl-3-phenyldiazirine (19).

A thiazirine is a plausible intermediate in the thermolysis of N-thiocarbonyl diphenylsulphimides, accounting for the formation of a nitrite and sulphur and for the formation of isothiazoles on conducting the thermolysis in the presence of excess ethyne (Scheme 9).

3 Four-membered Carbocyclic Systems

The electronic configuration and the shape of cyclobutadiene continue to be hotly debated. Maier has provided evidence that cyclobutadiene forms a charge-transfer complex with any species having electron-acceptor properties. This complexation probably complicates the i.r. spectra of cyclobutadiene generated at low temperature, extra bands being due to the complex and not to free cyclobutadiene. In confirmation of this, the i.r. spectrum of cyclobutadiene generated from (20) is very simple, and indicates a square geometry for the molecule. Assuming a dynamic Jahn-Teller effect, it becomes understandable why this molecule exhibits singlet character instead of the triplet character predicted earlier on theoretical grounds. Singlet character is displayed, for instance, in the stereospecific Diels-Alder reaction of cyclobutadiene with maleate or fumarate, which is not affected by the presence of a free-radical scavenger.

The converse behaviour is also possible: viz. the rectangular tri-t-butylcyclo-butadiene undergoes a reaction typical of a triplet molecule (Scheme 10). Alternative explanations are that the tetrahalogenomethane rapidly interconverts the rectangular (ground-state singlet) and square (ground-state triplet) forms of the molecule or that an electronic transition within a complex such as (21) leads to the Cl3C radical in the initiation reaction.

Both theory and experiment indicate that the maxima of electron density lie significantly off the lines joining the carbon atoms in the four-membered ring of compound (22). Thus bent bonds are to be assumed for the four-membered ring (and also for cyclobutadiene itself) such as are generally accepted for three-membered rings. The crystal and molecular structures of the nickel dibromide complex of (22) have been determined by X-ray diffraction.

Photoelectron, ESCA, n.m.r., and u.v. data suggest that the ‘push-pull’ substituted cyclobutadiene (23) is the first well-established example of a delocalized [4]annulene. Calculations show that such substitution on the four-membered ring does lead to a large decrease in anti-aromaticity. The effect is based on electronic as well as steric factors, and consequently it has been predicted that fluorine atoms have the same stabilizing effect as the dialkylamino-groups.

A full report on the preparation, spectroscopic properties, and stability of the cyclobutadiene dications (24) has appeared. The degree of conjugative interaction between the phenyl substituents and the aromatic dication has been determined, and a general comparison between this system and the cyclopropenium system has been made.

The sulphur analogue (25) of squaric acid dianion has been prepared. Spectroscopic data and intramolecular distances, as determined by X-ray diffraction methods, indicate a symmetrical, delocalized electron system.

A full description of the preparation of the monothiosquarate ion (26) and the dithiosquarate ion (27) from diethoxycyclobutenedione has been published. These thiosquarate ions are readily alkylated at sulphur, whilst silylation takes place on the oxygen atoms.

Using the same methodology, the olive-green diselenosquarate dianion (28) has been prepared; alkylation takes place on selenium. Similarly, the salts (29) and (30) have been prepared and some of their reactions investigated.

The new squaric acid bis-amidinium salt (31) has been synthesized and characterized by spectral means.

Orbital symmetry arguments have been presented to show that the thermal barrier to fluxional isomerism of cyclobutadienes may be reduced by having a diamond-like transition state.

A novel synthesis of substituted pyridines by the reaction of AlCl3 σ-complexes of cyclobutadienes with ethyl cyanoformate has been reported (Scheme 11).

Wittig reactions on the dialdehyde (32) have been used to effect annulation onto a cyclobutadiene ring (Scheme 12). The synthesis of similar bicyclo[6,2,0]decane systems from other cyclobutadiene iron tricarbonyl derivatives has also been reported.

4 Four-membered Heterocyclic Systems

The photolysis of a fluorinated pyridazine gives products that are dimers of a possible intermediate azacyclobutadiene (azete) derivative (33).

A new method for the preparation of the diazaphosphete (34) has been disclosed, and the stabilities of various unsaturated four-membered heterocyclic ring systems, inter alia the uretes (35), have been discussed from a theoretical stand-point.

5 Fused Four-membered Carbocyclic Systems

1,2-Dimethylbenzocyclobutadiene dication (36), an eight-carbon-atom six-π-electron Hückeloid system, is stable below -30°C: 13C n.m.r. spectroscopy confirms the presence of a fully delocalized 67T-electron aromatic system.

The first example of a peralkylbenzocyclobutadiene (37) has been prepared by the reaction of trans-3,4-dichloro-1,2,3,4-tetramethylcyclobut-1-ene with t-butyl-ethynylmagnesium bromide followed by thermal isomerization.

The bicyclo-octadienedione (38) has been synthesized. No tendency to give the bis-enolized form (the anti-aromatic benzocyclobutadiene system) could be detected.

Theoretical calculations on reactions carried out by Breslow (1970) involving the formation of the quinone (39) by electrolytic oxidation of the corresponding hydroquinone have confirmed that this process is more difficult to accomplish than in those analogous cases where the anti-aromatic cyclobutadiene feature is missing.

The ease of formation of the dianion (40) by electrochemical reduction of the appropriate cyclobutenedione suggests that fusion of the two anti-aromatic [4n]π-electron systems in (40) (whose core is a cyclobutadieno-cyclo-octatetraene π-system) has resulted in stabilization. In such a system the two component [4n]π-systems are fused in an overall [4n +2]π-electron periphery.

(Continues…)Excerpted from Aromatic and Heteroaromatic Chemistry Volume 6 by H. Suschitzky, O. Meth-Cohn. Copyright © 1978 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.