10 Aromatic Compounds By W. CARRUTHERS Department of Chemistry The University Stocker Road Exeter 1 Introduction Reviews on naturally occurring compounds of the shikimic acid pathway’ and on the biosynthesis of aromatic hemiterpenes2 have been published. Resonance energies of conjugated compounds in the electronically excited states have been calculated and the ‘allowedness’ of some pericyclic reactions predicted using these resonance energies. The predictions based on the difference in resonance energy between the pericyclic transition state and the reactants were in general agreement with e~periment.~ Qualitative potential energy surfaces for electrophilic photoelectrophilic nucleophilic and photonucleophilic aromatic substitutions have been constructed and selection rules derived.The regiochemistry of electrophilic and photonucleophilic aromatic substitution is predicted to be controlled by the electron density of the highest occupied molecular orbital of the aromatic substrate while the regiochemistry of nucleophilic and photoelectrophilic substititution is controlled by the electron density of the lowest unoccupied molecu- lar orbital of the aromatic ~ubstrate.~ The benzene radical anion is of interest in experimental organic chemistry as the species formed in the first stage of the Birch reduction of benzene. Ab initio MO calculations have been carried out for the radical anions of benzene and fluoroben- zene. In accordance with the Jahn-Teller theorem benzene radical anion is predic- ted to be distorted from regular hexagonal (&h) symmetry to structures of DZh symmetry having either four longer and two shorter carbon-carbon bonds or two longer and four shorter carbon-carbon bonds.’ An MO study of the effect of substituents in benzene radical ions has been reported.The effects of various types of substituent (OH CH3 CN SiH,) in benzene radical cations were investigated using INDO-SCF computations with and without consideration of n-conjugation between the substituents and the adjacent substrate.6 Experimental data for 1,2- and 1,4-dihydroxybenzene and 1,2,4-trihydroxybenzene correlate well with the results of INDO calculations of proton hyperfine coupling constants of free radicals from some hydroxybenzenes.’ Theoretical geometries and relative energies are ’ B.Ganem Tetrahedron 1978,343353. * M.F.Grundon Tetrahedron 1978,34,143. J. Aihara Bull. Chem. SOC.Japan 1978,Sl. 1788. ‘N.D.Epiotis and S. Shaik J. Amer. Chem. SOC.,1978,100 29. A. L. Hinde D. Poppinger and L. Radon J. Amer. Chem. SOC.,1978,100,4681. F. Bernardi M.Guerra and G. D. Pedulli Tetrahedron. 1978,34,2141. Y. Shinagawa and Y. Shinagawa J. Amer. Chem. Soc.. 1978,100.67. 199 200 W. Carruthers reported for aliphatic and aromatic diazonium ions. Open structures are preferred for both with NGN bond lengths in both cases similar to that in molecular nitrogen.' Further studies have been made of quantum mechanical tunnelling in the iso- merization of sterically hindered aryl radicals. The isomerization of 2,4,6-tri-t- butylphenyl (1) to (2) which occurs by quantum-mechanical tunnelling of a (cH3)3cyJcH3)3 (CH3)3c~c(cH3)2cH2* C(CH3)3 C(CH313 (1) (2) hydrogen atom from an ortho-t-butyl group occurs at the same rate in matrices as formerly found for solutions.The rate of this process has been measured at temperatures down to 28 K; at such low temperatures the rate is virtually indepen- dent of temperature. A number of less hindered aryls decay by intermolecular abstraction of hydrogen from the surrounding medium.' The benzenium (3) naphthalenium and meso-anthracenium cations have been prepared and studied by 'H and I3C n.m.r. spectroscopy. The pattern of delocal- ization of positive charge in (3)suggests approximate Cz symmetry for this species Q +' ,-.I .,* HH (3) and the absence of antihomoaromatic character in this potentially anti-Hiickel system." The dianions of phenanthrene and 1,2,3,4-dibenzocyclo-octatetraene have been prepared by metal reduction of the neutral compounds.A descriptionof the charge distribution can be achieved which is consistent with both MO models and the spin-density distribution of the corresponding radical anions. Thus the dianion of 1,2,3,4-dibenzocyclo-octatetraene appears as a 7r-bond-delocalized species with the excess of charge concentrated in the eight-membered ring.lla The charge distribution in the dianion of pyrene as revealed by 'H n.m.r. spectroscopy suggests that it can be regarded as essentially a 4nr perimeter an approach'which is satisfactorily rationalized by simple MO models and supported by e.s.r.measure- ments of the spin density in the corresponding radical anion.'lb Ionization reactions of anti-9-chloro-9-methoxybicyclo[4.2.l]nona-2,4,7-triene (4) proceed without skeletal rearrangement. From the relatively low reaction rate of the triene it is concluded that the cation is destabilized by homoantiaromatic interaction between the cationic centre and the butadiene moiety. The 'H and 13C n.m.r. spectra point to an interaction of the cationic centre with one of the double H. A. Vincent and L. Radom J. Amer. Chem. SOC..1978,100,3306. G. Brunton J. A. Gray D. Griller L. R. C. Barclay and K. U. Ingold J. Amer. Chem. Soc.,1978,100 4197. lo G. A. Olah J. S. Staral G. Asencio G.Liang D. A. Forsyth and G. D. Mateescu,J. Arner. Chem. SOC. 1978,100,6299. (a)K.Miillen Helv. Chim. Am 1978 61 1296; (b)ibid p. 2307. Aromatic Compounds (4) bonds of the butadiene moiety. The mode of conjugative interaction is obviously controlled by orbital symmetry.12 In a series of eighteen papers J. Michl and his co-workers have considered the magnetic circular dichroism of a number of benzenes naphthalenes and anthracenes some aza derivatives of these some polycyclic aromatic hydrocarbons azulene and benzazulene. A general classification of chromophores with a (4n+2) T-electron perimeter is proposed and rules for the effects of substituents on magnetic circular dichroism spectra of such T systems are derived. In many cases excellent agreement between experiment and theory was found.13 A detailed analysis of the electronic structure of p,p’-dibenzene (5) and related molecules based on quantitative perturbational MO treatment reveals that through-bond coupling of the four w systems is responsible for an elongation of the (T bonds which mediate the intera~tion.’~ (5) ‘Is antiaromaticity absolute?’ it has been asked.In reply it is said that theoretical and experimental evidence do not support the idea of absolute antiaromaticity at least in the monocyclic series. Relative antiaromaticity is affirmed but only for the three smallest monocyclic systems; cyclopropenide cyclobutadiene and cyclo- pentadienylium.l5 2 Benzene Isomers Oxides and Homobenzenes Reaction of l,2,5,6-tetramethyl-3,4-dimethylenetricyclo[3.l.0.02*6]hexane(6)with reactive dienophiles gives derivatives of benzvalene benzene or homofulvene depending on the dienophile and the reaction conditions.16 With tetracyanoethylene the benzvalene derivative (7) is obtained but with maleic anhydride and 4-phenyl- I I (6) (7) P.Schipper and H. M. Buck J. Amer. Chem. Soc. 1978,100,5507. l3 J. Michl etal.,J. Amer. Chem. Sac. 1978,100,6801,6812,6819,6824,6828,6834.6838,6844,6853 6857,6861,6867,6872,6877,6882,6884,6887,6892. l4 I).A. Dougherty H. B. Schlegel and K. Mislow Tetrahedron 1978,34,1441. Is N. L. Bauld T. L. Welsher J. Cessac and R. L. Holloway J. Amer. Chem. Soc. 1978 100,6920. l6 H. Hogeveen and W. F. J. Huurdeman,I. Amer. Chem. Soc. 1978,100,860. 202 W.Carruthers 1,2,4-triazoline-3,5-dione reaction leads directly to the corresponding homofulvene derivative (as 8) probably by way of the benzvalene. Acid-catalysed (Ag’) re-arrangement of (7)leads to the corresponding benzene derivative (9). Similarly reaction of (6) with maleic anydride and with the triazolinedione in presence of Ag’ gives not the homof ulvene but the corresponding benzene derivative. Less reactive dienophiles such as methyl acrylate do not react with (6) under ordinary conditions but in the presence of silver perchlorate benzene derivatives are formed in high yield. Both the acid lability as well as the preferred pathway of rearrangement of benzvalene derivatives appear to depend on the nature of the substituents. ‘Isobenzvalene’ (lo) a highly strained molecule generated transiently by action of lithium bases on l-chlorotricyclo[3.1 .0.02*6]hexane has now been trapped as the Diels-Alder adduct with anthracene (11).The structure of the adduct was established by X-ray crystallography. l7 n Attempts to prepare the bicyclohexatriene (12) (m-benzyne) by elimination of hydrogen bromide from 4,6-dibromobicyclo[3.1.0]hex-2-ene did not lead to the desired product. Depending on the base employed either bromobenzene or a 6-substituted fulvene was obtained. Labelling experiments suggest that the fulvenes may be formed by way of the triene (12).’* 2-Methoxycarbonyloxepin-benzene oxide (13;R = CH3) and the corresponding carboxylic acid have been synthesized and their aromatization reactions studied.l9 The results obtained support the suggestion that 1,2-oxides of benzoic acids may be ” U. Szeimies-Seebach J. Harnish G. Szeimies M. van Meerssche. G. Germain and J.-P. Declerq Angew. Chem. Internat. Edn. 1978,17,848. l8 W. N. Washburn R. Zahler and I. Chen J. Amer. Chem. Soc. 1978,100,5863. l9 D. R. Boyd and G. A. Berchtold J. Amer. Chem. Soc. 1978,100,3958. 203 Aromatic Compounds ooo2R (13) intermediatesin biological oxidative decarboxylations and that the acid (13; R =H) may be an intermediate in the ortho-hydroxylation of benzoic acid. The ester (14) rearranges quantitatively in trifluoroacetic acid to methyl salicylate with 50% retention of deuterium; a reaction pathway which involves migration of the methoxycarbonyl group is suggested (Scheme 1).1 1 CO,Me Scheme 1 A novel route to 3-substituted benzene oxides which involves consecutive elimination (under mild conditions) of hydrogen bromide and carbon dioxide from bromocyclohexane &lactone epoxides has been applied” to the synthesis of the oxide (15) as shown in Scheme 2. The oxide (15) has been proposed as an intermediate in the biosynthesis of senepoxide (16) one of a number of highly oxygenated cyclohexane epoxides with tumour-inhibitory anti-leukaemic and antibiotic activity and it was successfully converted into (16) in the laboratory. 4,5-Dimethyloxepin (17) is converted into the syn-oxepin epoxides (19) and (20) by a sequence involving Diels-Alder addition of bis(trichloroethy1) azodicarboxylate to the benzene form of (17) followed by epoxidation to give (18).Extrusion of nitrogen from (18) at ambient temperature in deuteriochloroform monitored by n.m.r. spectroscopy gave transiently the oxepin epoxide (29,which was quan- titatively converted into the aldehyde (21).’l 2,7-Dimethyloxepin behaves differently towards the azodicarboxylic ester giving a cyclopropane derivative by initial addition to the oxepin form.’lb 2o B. Ganem G. W. Holbert L. B. Weiss and K. Ishizumi J. Amer. Chem Soc. 1978,100,6483; G. W. Holbert and B. Ganem ibid 1978,100,352. 21 (a)W. H. Rastetter and T. J. Richard Tetrahedron Letters 1978,2995; (b) ibid p. 2999. 204 W. Carruthers n n :OC,H (mainly) (16) (15) Reagents i Brz NaHCO,; ii C,H,COCI-pyridine; iii CF,CO,H Na,HPO,; iv 13-diazabicycloC5.4.Olundec-5-ene(DBU);v reffux in benzene Scheme 2 Me Me Me Me Me 1 "eQe -MeQetMeQMe H CHO 0 (21) (20) (19) A remarkably simple synthesis of anti-benzene dioxide and anti- benzene trioxide from benzoquinone has been reported22 and is outlined in Scheme 3.cis-Benzene dioxide was also made. There is continuing interest in oxides derived from polycyclic aromatic hydro-carbons because of their r61e in carcinogenesis. Biphenyl 2,3-oxide obtained2j by the conventional route from 1-phenyl- 1,4-dihydrobenzene is not stable but a tetrachloro derivative of biphenyl 3,4-oxide one of a number recently prepared,24 is exceptionally stable. The reaction of the 2-3-oxide with water gave 2-phenyl- and 3-phenyl-phenol in the ratio 49 :1.A synthesisof a trans- 1,2-dihydroxy-3,4-epoxy-z2 H. J. Altenbach H. Stegelmeier and E. Vogel Tetrahedron Letters 1978,3333. " M.P. Serve and D. M. Jerina J. Org. Chem. 1978,43,2711. 24 H. J. Reich I. L. Reich and S. Wollowitz J. Amer. Chem. SOC.,1978,100 5981. Aromatic Compounds +&r __+ I,. I1 .. iii 6 fj Br -+) 0 OH Reagents i Br,; ii NaBH,; iii. KOH-ether; iv m-CIC,H,CO,H Scheme 3 1,2,3,4-tetrahydrochrysene has been reported.25 The rates of acid-catalysed solvolysis of and of nucleophilic attack on some polycyclic arene oxides and their variation with the structures of the oxides have been studied.26 A review of homoaromatic ions has been p~blished.~' By analogy with the homoaromatic homocyclopropenyl and homotropylium cations cyclohexadienyl anions might have been expected to be non-planar homoaromatic species.However study of the 'H and 13Cn.m.r. spectra of several such anions indicated that they were planar and not homoaromatic. MIND0/3 calculations on the parent cyclo- hexadienyl anion found the planar form in a shallow energy minimum.28 Analysis of the photoelectron spectrum of nortriquinacene (22) and its 2- methylene and 2-isopropylidene derivatives confirms that the exocyclic double bond in the last two compounds does not interact with the endocyclic w-bonds. These findings agree well with chemical and spectroscopic evidence of the lack of homoaromaticity in these compounds.29 The interesting CI6-hexaquinacene (23) has been synthesized in nine steps from sodium ~yclopentadienide.~'" It is apparent from its 'H and 13C n.m.r.spectra that it does not exist as a highly delocalized ground *' P. P. Fu and R. G. Harvey,J.C.S. Chem. Comm. 1978,585. 26 A. R. Becker J. M. Janusz D. 2.Rogers and T. C. Bruice J. Amer. Chem. SOC.,1978,100,3244. 21 L. A. Paquette. Angew. Chem. Internat.Edn. 1978,17,106. G. A. Olah G. Asensio H. Map and P. von R. Schleyer,J. Amer. Chem. SOC.,1978,100,4347. 29 L. N. Domelsmith K. N. Houk,C. R. Degenhardt and L. A. Paquette J. Amer. Chem. SOC.,1978,100 100. 30 (a)L. A. Paquette R. A. Snow J. L. Muthard andT. Cynkowski J. Amer. Chem. Soc.. 1978. la.1600; (b)G. G. Christoph J. L. Muthard L. A. Paquette M. C. Bohm and R. Gleiter ibid p. 7782. 206 W.Carruthers state. X-Ray crystallographic analysis shows that although the geometry is favour- able the interatomic distances rule out an effective aoverlap of the w-orbitals of the double Thermolysis of trans-tris-a-homobenzene (24) at 380-400 "C in a flow system leads to trans- bicyclo[4.3.0]nona-3,7-diene(26). Studies of the reaction pathway using labelled material established that cis,truns,trans- 1,4,7-~yclononatriene (25) is (24) (25) (26) an intermediate.31" This contrasts with the behaviour of cis-analogues of tris-a-homobenzene which give cis,cis,cis-cyclononatrienesat 60-200 "C. A theoretical study of the rearrangements of tris-o-homobenzenes by MIND0/3 has been carried out.3 3 Benzene and Its Derivatives General.-The orientation of the products formed by meta photocycloaddition of olefins to substituted benzenes can depend critically on the nature of the olefin.The 1-position in the metu-adducts from methylbenzenes does not always bear a methyl group and deactivation of positions metu to the methyl substituent in toluene reported by some workers is not always observed. There is a preference for endu stereochemistry but this also is not in~ariable.~~ The photo-addition of maleimide to anisole has been studied with the object of discovering whether the charge- transfer mechanism found with benzene and substituted benzenes and maleic anhydride as addend but not with maleimide could be induced to oceur with maleimide by choice of a relatively more nucleophilic substituted benzene.In the event irradiation in the maleimide-anisole charge-transfer band gave three isomeric 2 1 adducts resulting formally from initial 1,2- 2,3- and 3,4-addition to the aromatic ring followed by Diels-Alder addition of a second molecule of maleimide.33 Photo-addition of ethylenes and acetylenes to hexafluorobenzene shows some points of resemblance to the corresponding processes with benzene but some differences were noted.34 Both cis-and trans-cyclo-octene gave various 1:1-cycloadducts which arise via 1,2- and 1,3-addition and subsequent isomerization of the initial adducts; no products formed by 1,4-addition to the aromatic ring were detected. In contrast 2,3-dimethylbut-2-ene gave mainly a 1:1adduct formed by substitutive addition. Propyne and but-2-yne gave cyclo-octatetraene derivatives.Two routes to derivatives of resorcinol have been described. Substituted resor- cinol monomethyl ethers are obtained by Diels-Alder reaction of 1,l-dimethoxy-3- trimethylsilyloxy-l,3-butadienewith acetylenic dienophiles or with the readily '' (a) W. Spielmann D. Kaufmann and A. de Meijere Angew. Chem. Internat. Edn.. 1978,17,440;(b) J. Spanget-Larsen and R. Gleiter Angew. Chem. Internat. Edn. 1978,17,441. 32 D.Bryce-Smith W. M. Dadson A. Gilbert B. H. Orger and H. M. Tyrrell Tetrahedron Letters. 1978 1093. 33 D. Bryce-Smith A. Gilbert and B. Halton J.C.S. Perkin I 1978 1172. 34 D. Bryce-Smith A. Gilbert B. H. Orger and P. J. Twitchett J.C.S. Perkin I 1978 232. Aroma tic Compounds available methyl trans-& nitroacrylate.With the latter dienophile the orientation of the addition is controlled by the nitro-group and after elimination of nitrous acid the resorcinol derivative obtained has a different orientation from that formed in the reaction of the diene with methyl acetylenecarboxylate (Scheme 4).35 E-CO,Me TMSO Scheme 4 A route to 5-substituted resorcinols is exemplified in Scheme 5 by the synthesis of 5-phenylresorcinol. The formation of the resorcinol is envisaged as proceeding by base-catalysed Michael addition of the sulphoxide to the double bond followed by cyclization and thermal elimination of phenylsulphenic acid. Olivetol a naturally occurring 5-alkyl-resorcinol was synthesized by this method.36 Reagents i Mg(OMe),-MeOH; ii reflux in benzene Scheme 5 2,3-Bis(trimethylsilyloxy)-173-butadiene is a useful diene in the Diels-Alder reaction.It adds to a variety of olefinic and acetylenic dienophiles giving adducts which may be converted into derivatives of catech01.~' The synthesis and chemistry of cyclopropabenzenes have been reviewed.38 Cyclo- propa[3,4]benzocyclobutene (27),the second isomer to be reported in which a benzene ring is annelated with a three- and a four-membered ring has been '' S. Danishefsky R. K. Singh and R. B. Gammill J. 0%.Chem. 1978,43 379; S. Danishefsky M. P. Prisbylla and S. Hiner J. Amer. Chem. SOC.,1978,100,2918. " A. A. Jaxa-Chamiec P. G. Sammes and P. D. Kennewell J.C.S. Chem. Comm. 1978,118. '' D. R.Anderson and T. H. Koch. I. Org.Chem. 1978,43,2726. '* W.E.Billups Accounts Chem. Res. 1978,ll.245. 208 W. Carruthers synthesizedJg from (28)by reaction with potassium t-butoxide in dimethyl sulphox- ide. The isomer (29) could not be converted into (27) and it is thought that this may be related to the position of the double bond in (29). Benzo[l,2 :4,5]dicyclobutene (30; R = H) and two derivatives (30;R = CH,or Br) have been obtained by pyrolysis of the appropriate cy,a'-dichlor~durenes,~~" and a number of other benzocyclobutenes have been prepared by the same method; pyrolysis of o-methylbenzyl chlorides provides a straightforward route to compounds of this class.4o6 As with benzocyclobutene itself electrophilic substitu- tion of (30) occurs exclusively by ips0 attack giving the corresponding ring-opened products in high yield.For example chloromethylation using paraformaldehyde and hydrogen chloride gave 4-chloromethyl-5-(2-chloroethyl)benzocyclobutene. (30) Pyrolysis of the trisulphone (31) gave not the expected benzo[l,2 3,4 5,6]-tricyclobutene but hexaradialene (32),4' previously obtained by pyrolysis of 1,5,9-cyclododecatriyne. It is most conveniently obtained by pyrolysis of commercially available 1,3,5-tri~hloromethylmesitylene.~~ The 13Cn.m.r. spectrum of hexaradi-alene provides no evidence for a diamagnetic ring current in the six-membered ring. With dimethyl acetylenedicarboxylate it forms the adduct (33). qO,Me C0,Me (33) 39 D. Davahan P. J. Garratt and M. M. Mansuri J. Amer. Chem. SOC.,1978,100,980.*O (a)R. Gray L. G. Harruff J. Krymowski J. Peterson and V. Boekelheide J. Amer. Chem. Soc.,1978 100 2892; (b)P. Schiess M. Heitnnann S. Rutschmann and R. Staheli Tetrahedron Letters 1978 4569. 41 L. G. Harruff M. Brown and V. Boekelheide,J. Amer. Chem. Soc. 1978,100,2893; see also P. Schiess and M. Heitzmann Helv. Chim. Actu 1978,61 844. Aromatic Compounds Naphtho[a]cyclobutene and naphtho[b]cyclobutene have been obtained by reac- tion of benzene with vinylcyclobutene and 1,2-dimethylenecyclobutanerespec-tively followed by dehydrogenation of the initial adducts. Similar reaction of 2,3-dehydronaphthalene with the two dienes gave adducts which could be converted into anthra[a]- and anthra[b]-cy~lobutene.~*It is suggested that the apparent instability of anthra[b]cyclopropene may indicate a higher degree of bond fixation in this compound than in naphtho[b]cyclopropene.1,l-Difluorobenzocyclopropene and 1-chloro-1-fluorobenzocyclopropene have been prepared from butadiene and the appropriate 1,2-dichloro-3,3- dihalogeno- cy~lopropene.~~" The corresponding 2,s -diphenyl derivatives have also been made.436 On ionization in cold fluorosulphonic acid 1,l-difluorobenzocyclo-propene gives fluorobenzocyclopropeniumion. It is well known that aryl halides react readily with olefins in the presence of tertiary amines and palladium catalysts to form vinylic substitution products but attempts to extend the reaction to aryl bromides containing strongly electron- donating substituents such as hydroxyl and amino were generally unsuccessful.It is now found that significant improvements in yield are often obtained when tri-o- tolylphosphine is used in place of triphenylphosphine as the palladium ligand or even better by using the corresponding aryl iodide instead of the bromide when palladium acetate without a phosphine ligand can be employed as the The reaction has been applied to the preparation of 2-arylethylamines by reaction of aryl bromides or iodides with N-~inylamides.~~~ Additional methods for specific ortho-substitution of benzene derivatives have been reported. 0-(1-Hydroxybenzyl)- and 0-(1-hydroxyalkyl)-anilines are obtained specifically by reaction of aldehydes with secondary anilinodichloroboranes them- selves prepared in situ from N-alkylanilines and boron trichloride.Reaction with nitriles leads to the valuable 2-acyl-N-substituted aniline~.~' Another sequence makes use of the new reagents lithium o-lithiobenzyl oxides (34) which are easily obtained from 1-phenylalkanols and butyl-lithium in the presence of tetramethyl- ethylenediamine. They react readily with electrophiles to give derivatives of type (35).46 R R Phenyl isocyanide also undergoes ortho-lithiation when treated with t-butyl- lithium and tetramethylethylenediamine. The resulting o-lithio lithiumaldimines 42 R. P. Thurnrnel W. E. Cravey and W. Nutakul J. Org. Chem. 1978,43,2473. 43 (a) P. Miiller. J. F'fyffer E. Wentrup-Byrne and U. Burger Helu. Chim. Ada 1978 61 2081. P. Muller R. Etienne J. Pfyffer.N. Pineda and M. Schipoff Tetrahedron Letters 1978 3151; (b)P. Miiller R. Etienne J. Pfyffer N. Pineda and M. Schipoff Helu. Chim. Acta 1978,61 2482. 44 (a)C. B. Ziegler and R. F. Heck J. Org. Chern. 1978,43,2941; J. E. Plevyak and R. F. Heck J. Org. Chem. 1978,43,2454; (b)C. B. Ziegler and R. F. Heck J. Org. Chem. 1978,43,2949. *' T. Sugasawa. T. Toyoda M. Adachi and K. Sasakura,J. Org. Chem. 1978,43,4842. 46 N. Meyer and D. Seebach Angew. Chem. Internat. Edn. 1978.17.521. 210 W. Carruthers (36) react with a variety of electrophiles to form ortho-substituted anilines and with metal dihalides they give novel heterocyclic sy~tems.~’ R / \ Li (36) A method for alkylating aromatic rings which provides 1,2,3-trisubstituted ben- zene derivatives conveniently and in high yield has been described.48 Following- earlier work by other workers the bis-oxazolinylbenzene (37) which is readily available from isophthalic acid gave the lithio derivative (38) on treatment with lithium di-isopropylamide in the presence of tetramethylethylenediamine.Alkyl-ation with methyl iodide followed by hydrolysis gave the methylisophthalic acid (40; R = CH3).Further lithiation of (39),reaction with ethyl iodide and hydrolysis gave (40; R =C&) (see Scheme 6).R (40) Reagents i LiNPri2-MezNCH2CH2NMe2;ii MeI; iii aqueous HCI Scheme 6 Following on his earlier work [cf. Ann. Reports (B),1977,74,235] Gassman has developed a method for specific ortho-benzylation formylation and vinylation of anilines involving [2,3]sigmatropic rearrangement of ylides derived from azasul- phonium salts (Scheme 7).49“ A similar principle was used to make o-alkyl- and o-formyl-phen~ls.~~~ A useful synthesis of a variety of ortho-substituted phenyl- acetic esters by [3,3]sigmatropic rkarrangement of benzyl vinyl ethers derived from derivatives of ethyl mandelate and orthoesters has been de~cribed.~’ 4’ H.M. Walborsky and P. Ronman J.Org. Chem. 1978,43,731. 48 T.D.Harris B. Neuschwander and V. Boekelheide J. Oig. Chem. 1978,43,727. 49 (a)P.G. Gassrnan and H. R. Drewes J. Amer. Chem. Soc. 1978,100,7600;(b)P.G. Gassrnan and D. R. Arnick ibid 1978 100 7611. S.Raucher and A. S.-T. Liu J. Amer. Chem. Soc. 1978,100,4902. Aromatic Compounds 211 CI-ns Reagents i Bu'OCI; ii U;iii NaOMe; iv hydrolysis Scheme 7 Oxidative cleavage of aromatic rings is widespread in Nature.Typically the enzyme pyrocatechase catalyses the oxidative cleavage of catechol to &,cis-muconic acid with incorporation of a molecule of oxygen into the muconic acid. Pyro-catechase and related enzymes are known to require either copper or iron for maximum activity. It is now found that smooth oxidative cleavage of catechol to a mono-ester of cis&-muconic acid takes place with copper(1) chloride and molecular oxygen in pyridine at room temperature. Phenol was similarly oxidized although in poorer yield. The reactions have synthetic utility because of the high yields and mild reaction condition^.^^ Further experiments aimed at mimicking the action of the mono-oxygenase group of enzymes by irradiation of derivatives of pyridine N-oxide carrying 2-benzyl 2-phenylethyl and 2-phenoxy substituents have been rep~rted.~' In the presence of boron trifluoride migration of oxygen round the pyridine ring is inhibited resulting in increased nuclear hydroxylation of the 2-substituent.An oxenoid mechanism (i.e. transfer of atomic oxygen) involving transient formation of benzene oxides is proposed. Three reactions have been reported which lead to direct introduction of a hydroxyl substituent into the benzene ring. Reaction of benzene alkylbenzenes and halo- benzenes with hydrogen peroxide in superacidic media at low temperatures gives high yields of monohydroxylated products. The phenols formed are protonated in the superacid and thus are deactivated against further electrophilic attack or secondary oxidation.In some cases 1,2-shifts of methyl substituents occur and it is suggested that benzene oxides may be intermediates in the ~xidations.~' In another reaction peroxydisulphate in the presence of suitable metal ion oxidants notably Cu" brought about ring hydroxylation of a number of benzene derivative~.~~ Hydroxylated products have also been obtained by attack of oxygen ('P) atoms generated by y-radiolysis of liquid carbon dioxide on alk~lbenzenes.~~ " J. Tsuji and H. Tokayanagi Tetrahedron 1978,34 641. '* P.G.Sammes G. Serra-Errante and A. C. Tinker J.C.S. Perkin I 1978,853. s3 G.A.Olah and R. Ohnishi J. Org. Chem. 1978,43,865. " C.Walling D. M. Carnaioni and Sung So0 Kim J. Amer. Ckem. Soc. 1978,100,4814. 55 A Hori H. Matsumoto S. Takamuku and H. Sakurai J.C.S. Chem. Comm. 1978 16. 212 W. Carruthers Anodic oxidation in methanol of a series of alkylanisoles and hydroquinone ethers and of p-xylene leads initially to the corresponding cation radicals Under appropriate conditions reaction then may give either nuclear methoxylated products or in the case of p-alkylanisoles or p-xylene benzyl ethers or benzaldehyde dimethyl acetal~.~~ Anodic oxidation of hexamethylbenzene in acetonitrile with Bu4NBF4as electrolyte at a platinum anode gave mainly 1,3-bis(acetarnidomethy1)2,4,5,6-tetramethylben~ene.~’ Aminocyclohexadienes containing either conjugated or unconjugated double bonds are readily available by metal-ammonia reduction of aniline derivatives.Their reactions as enamines make them of synthetic interest and this is increased if the starting amines contain methoxy substituents for the products of reduction then contain masked carbonyl groups. In an investigation of the potential of this scheme the reduction of N-(m-and o-methoxypheny1)morpholine by metal and liquid ammonia has been studied and some cyclo-addition reactions with the resulting dienamines have been attempted.58 For example reduction of rn-morpholinoanisole gave the 2,5-dihydro-compound which on distillation iso- merized to the conjugated diene (Scheme 8). Scheme 8 ElectrophilicSubstitution.-Previous studies have suggested that tritiation of alkyl- benzenes with Lewis acid and a tritium source occurs randomly in the benzene ring and is confined to the aromatic protons.New work using 3Hn.m.r. spectroscopy now shows that exchange can follow the normal electrophilic substitution pattern and may not be confined to the aromatic proton~.’~ In order to ascertain the extent to which hydrogen exchange may be hindered in very crowded molecules the rates of protodetritiation and protodesilylation of each position in tri- and tetra-phenyl- methane were determined in trifluoroacetic acid. In both reactions tetraphenyl- methane was more reactive than expected possibly due at least in part to steric enhancement of neighbouring group participation.60 Electrophilic aromatic substitution by vinyl triflates is thought61 to proceed by way of vinyl cations and a number of other aromatic substitutions with unsaturated progenitors such as vinyl halides and alkynes may also proceed by way of vinyl cations.Surprisingly Friedel-Crafts benzylation of 2,6-dimethylphenol under a variety of conditions gave approximately 40% of the rneta-substitution product. s6 A. Nilsson U. Palmquist T. Pettersson and A. Ronlan J.C.S. Perkin I 1978 708. ” A. Bewick G. J. Edwards and J. M. Mellor Annalen 1978,41. A. J. Birch and S. F. Dyke Austral. J. Chem. 1978.31 1625. ” M. A. Long J. L. Garratt and J. C. West Tetrahedron Letters 1978,4171. H. V. Ansell and R. Taylor J.C.S. Perkin 11 1978,751. “ P. G. Stang and A. G. Anderson J. Amer. Chem. SOC.,1978,100,1520. Aroma tic Compounds 213 With 2,6-dimethylanisole and isopropyl 2,6-dimethylphenyl ether the metu benzyl derivatives were the main products.It is believed that these products are formed by direct attack at the meta position and not by initial ortho or para attack.62a Unexpectedly high yields of rneta-substitution products were also observed in Friedel-Crafts allylation of 2,6-dimethylphenol and 2,6-dimethylani~ole.~~~ Reac-tion of a variety of benzene derivatives with nitroniethane and manganese(II1) acetate gave nitromethyl derivatives; substitution by nitromethyl radicals is pro- Metal acetates including manganese(rI1) acetate have also been used to obtain diarylmethanes from alkylben~enes.~~ Treatment of aromatic hydrocarbons with sodium nitrite in trifluoroacetic acid is reported to give nitroarenes in high yield.65 Nitrosodemetallation at the ips0 position occurs to give nitrosoarenes by similar treatment of arylmetal compounds.The former reaction proceeds through attack by NO2+,while NO' or its carrier N203is the attacking species in the latter reaction. Rate profiles for nitration of rn-xylene and several other reactive benzene derivatives in aqueous perchloric acid are all closely similar and probably reflect the rate of encounter between nitronium ions and the aromatic compound in these media.66 Study of the aromatization of 4-methyl-4-nitrocyclohexadienonesto o-nitro- phenols which takes place in a wide variety of solvents by a formal 1,3-shift of the nitro-group strongly suggests that it proceeds by a radical dissociation-recom- bination pathway (Scheme 9).67 47 + *NO 1 Scheme 9 Migration of the nitro-group in 1,2-dimethyl- 1-nitro-[3,5-2H2]cyclohexadienyl cation (41b) obtained by solvolysis in 85% sulphuric acid of the cyclohexadienol (41a) gave equal amounts of 1,2-dimethy1-3-nitr0-[4,6-~H~]benzene (formed by a single 1,2-migration of the nitro-group) and 1,2-dimethyl-3-nitr0-[5-~H~]benzene 62 (u) M.P. McLaughlin V. Creedon and B. Miller Tetrahedron Letters 1978 3537; (b)B. Miller and M. P. McLaughlin ibid p. 3541. M. E. King and T. R. Chen J. Org. Chem. 1978,43,239. S. Tanaka S. Uemura and M. Okano J.C.S. Perkin Z 1978,431. 63 64 63 S. Uemura,A. Toshimitsu and M. Okano J.C.S.Perkin Z 1978 1076.R. B. Moodie K.Schofield and P. N. Thomas,LCS. Perkin ZZ 1978,318. '' C. E. Barnes and P. C. Myhre J. Amer. Chem. SOC.,1978,100,973; see also R. G. Coombes and J. G. Golding. Tetrahedron Letters 1978,3583. 214 W. Carruthers Me NO Me NO D H' 'OH (414 (4 1 b) (formed by two successive ly2-migrations via the neighbouring ips0 position). No 1,2-dimethy1-4-nitrobenzenewas detected. It can be estimated from these data that the rate of a ly2-shift of a nitro-group to an unsubstituted position is about one fiftieth the rate of migration to an equivalent ips0 position.68 The absence of lY2-dimethyl- 4-nitrobenzene from the reaction products is difficult to reconcile with Perrin's suggestion[cf.Ann. Reports (B),1977,74,224] that migration of nitro-groups occurs uia an aromatic cation-radical pair.Perrin's suggestion is also not supported by the observation that the composition of the product from reactions of the cation radical of mesitylene differs from that found in direct nitration of mesitylene even when the cation radical is generated in the nitrating medium and in the presence of added dinitrogen tetr~xide.~' The behaviour of the nitro Wheland intermediates formed by solvolysis of 4-methyl-4-nitrocyclohexa-2,5-dienyl acetate and some of its homo- logues has also been studied7' and confirms earlier views of the results of nitrating methylbenzenes in aqueous sulphuric acid. Nitration of a series of benzene derivatives with nitric acid in acetic anhydride has been studied;71 a series of ipso-nitration products were isolated and their re-aromatization was examined.A number of reactions other than nitration which appear to involve ipso-attack on an aromatic substrate have been reported. Thus kinetic suggest that oxidation of NN-dimethylaniline with peroxydisulphate to give the o-aminoaryl sulphate takes place by ipso-attack of reagent followed by rearrangement and cyclization of suitably labelled 7-1-naphthylbutyric acid with boron trifluoride etherate shows that this also involves some ip~o-reaction.~~ Several examples of free-radical substitution which appear to proceed by ipso-attack have been re- ported.74" Thus photo-chlorination of p-nitrobromobenzene gave among other products some 3-bromo-4-chloronitrobenzene and some 2,4-dichloronitroben- zene.74 The sulphonation of 1-methylnaphthalene and polymethylbenzenes has been The mechanistic conclusion that sulphonation with H3S04+has a later transition state than this with H2S2O7 is in agreement with the results of Huckel MO calculations.Sulphonation of a number of biphenyl derivatives containing de- activating substituents with concentrated sulphuric acid at 25 "Ctakes place in the C. E. Barnes and P. C. Myhre J. Amer. Chem. SOC.,1978,100,975. 69 M. R. Draper and J. H. Ridd J.C.S. Chem. Comm. 1978,445. 70 H.W.Gibbs R. B. Moodie and K. Schofield J.C.S. Perkin I 1978 1145. " A.Fischer and Khay Chuan Teo Canad. J. Chem. 1978,56,258,1758; A.Fischer and C. C. Greig ibid p. 1863;A. Fischer and S. S. Seyan ibid p. 1348;A. Fischer G.N.Henderson and R. J. Thompson, Austral. J. Chem. 1978 31 1241. '2 E. J. Behrman and I).M. Behrman J. Org. Chem. 1978,43,4551. 73 A.H.Jackson P. V. R. Shannon and P. W. Taylor J.C.S. Chem. Comm. 1978,734. 74 (a) L.Benati P. C. Montevecchi and A. Tundo J.C.S. Chem. Comm. 1978,530; L. Testaferri U. Tiecco M. Tingoli M. Fiorentino and L. Troisi ibid 1978,93;(6)C. R.Everly and J. G. Traynham J. Amer. Chem. SOC.,1978,100,4316. 75 K. Lammertsma C. J. Verlaan and H. Cerfontain J.C.S. Perkin IZ 1978 719. Aromatic Compounds 215 unsubstituted ring predominantly at the 4’-po~ition.~~” At 180“Cin 75% aqueous sulphuric acid all biphenyldisulphonic acids are eventually converted into the 3,4’- isomer.76b NucleophilicSubstitution.-A review of nucleophilic substitution of aromatic nitro- groups has been p~blished,’~ and aromatic substitution by the SRN1mechanism i.e.a radical chain mechanism of nucleophilic substitution has been reviewed.” Nucleophilic attack on aromatic nitro-compounds by nucleophiles which them- selves contain substituents able to leave as anions results in substitution products resulting from formal displacement of hydride ion. The leaving group departs in the form of an anion and at the same time hydride ion migrates to the carbon atom of the nucleophile vacated by the leaving group. Hence the whole process could be considered as a nucleophilic substitution of a hydride ion in the aromatic ring whereas actually the leaving group is present in the nucleophilic agent.The term ‘vicarious substitution’ has been coined to designate the process (Scheme 10).The tendency for substitution of hydride is so strong that reaction of p-chloro-nitrobenzene as in Scheme 10gave mainly the product formed by replacement of an ortho hydrogen without notable substitution of the chlorine in the aromatic ring.” + CICH,SO2C,H f c1-NO2 Scheme 10 Nucleophilic displacement of aryl fluorides is well known to occur readily in the presence of strong electron-withdrawing substituents. It is now shown that o-fluoroaryl-oxazolines which are readily obtained from the corresponding benzoic acids react readily with Grignard or organolithium reagents or with lithium amides (all designated RM in Scheme 1l),with replacement of the fluorine substituent.800 o-Methoxyaryl-oxazolines undergo similar displacement of the methoxy substitu- ent.”’ Hydrolysis of the products affords the corresponding benzoic acid derivatives (Scheme 11).Aromatic nitro-compounds also may be alkylated in the ortho and para positions by reaction with alkyl-lithium or alkyl Grignard reagents.81 The formation of an anion radical in the nucleophilic displacement of one nitro- group of p-dinitrobenzene by hydroxide ion in aqueous dimethyl sulphoxide has been demonstrated by visible and e.s.r.spectroscopy. The formation of the anion radical seems to be due to direct electron transfer from hydroxide ion to 76 (a) T. A. Kortekas H. Cerfontain and J. M. Gall J.C.S. Perkin 11 1978,445; (b)T. A. Kortekas and H. Cerfontain ibid 1978 742.77 J. R. Beck Tetrahedron 1978,34 2057. ’18 J. F. Bunnett Accounts Chem. Res. 1978 11,413. 79 J. Golinski and M. Makosza Tetrahedron Letters 1978 3495. 80 (a) A. I. Meyers and B. E. Williams Tetrahedron Letters 1978,223,227; (6)A. I. Meyers R. Gabel and E. D. MiheIich J. Org. Chem. 1978 43 1372. 81 F. Kienzle Helu. Chim. Acta 1978 61,449. 216 W Carruthers Reagents i SOCl,; ii HzN<OH ;iii RM; iv H,O' Scheme 11 p-dinitrobenzene. Kinetic studies suggest that the anion radical is a precursor in the substitution react ion. 82 Dediazoniations of arenediazonium ions are generally considered to be the only nucleophilic aromatic substitutions which proceed by an SN1-like mechanism. Results of further study of the dediazoniation of benzene- and of 2,4,6-tri-methylbenzene-diazonium tetrafluoroborate in solvents of low nucleophilicity and comparison with results in 2,2,2-trifluoroethanol suggest that two reaction inter- mediates are involved a tight nitrogen-aryl cation molecule-ion pair and a (solvated) aryl cation free of or solvent-separated from ArN; S [Ar'N,] +Ar' + N2+ products.Experiments on the scope and mechanism of photostimulated reactions of aryl iodides with diethyl phosphite ion continue [cf.,Ann. Reports (B),1977,74,227]. In SRN 1 reactions of dihalobenzenes with nucleophiles whether one or two halogen atoms are replaced depends on the nucleophile and the halogen involved and on their ~rientation.'~" Results of interrupted photostimulated reaction of diethyl phosphite ion with rn-bromoiodobenzene in liquid ammonia are compatible with the SR,1 mechanism but exclude alternative mechanisms.846 The reaction of rn-bromo-iodobenzene and rn-chloroiodobenzene with diethyl phosphite gives mixtures of a monosubstitution product in which only iodine is replaced and a disubstitution product in which both halogens are replaced.As expected from the SRN1 radical chain mechanism the ratio of monosubstitution to disubstitution product from either substrate increases linearly with increasing concentration of sub~trate.'~' Biary1s.-A new synthesis of unsymmetrical biphenyls proceeds (see Scheme 12) from the Diels-Alder adducts of arylmaleic anhydrides and substituted butadienes." Ar 0 Ar 'OzH (i)Pb(OAc) R'OAr R2 \ 4-CO,H (ii)DDQ' R2 "I$ 0-::a 0 Scheme 12 *' T.Abe and Y. Ikegami Bull. Chem. SOC.Japan 1978,51,196. 83 I. Szell and H. Zollinger J. Amer. Chem. SOC. 1978,100,2811;Y.Hashida R.G. M.Landells G. E. Lewis 1. Szele and H. Zollinger ibid p. 2816. 84 (a)J. F. Bunnett and R. B. Traber J. Org. Chem. 1978,43,1867;(6)J. F.Bunnett and S. J. Shafer ibid p. 1873;(c) ibid p. 1877. '' L. A. Levy J. Org. Chem. 1978,43 3068. Aromatic Compounds Among naturally occurring biphenyl derivatives the lignan (f)-schizandrin (42)86 and the anti-tumour compound (f)-steganacins7 (43) have been synthesized. r-0 Me0 -Me Me0Meow:/ Me0 OMe OMe (42) (43) A number of non-planar polycyclic aromatic compounds including some heli- cenes have been resolved by high-performance liquid chromatography using the chiral cyclic atropisomeric binaphthyl-2,2'-diyl hydrogen phosphate linked to silica gel (44) as stationary phase." (44) Continuing their work on host-guest complexation Cram and his co-workers describes9" the chiral recognition properties of a+series of hosts (45) based on 1,l'-binaphthyl towards guests of the type LMSCNH3 X-,where L M,and S are large medium and small groups respectively.Total optical resolution of three amine or amine ester salt racemates was achieved by chromatography using (45; X=Y = -CHz-O-CHz-).s9b ~6 E. Ghera and Y. Ben-David J.C.S.Chem. Comm. 1978,480. F. E. Ziegler K. W. Fowler and N. D. Sinha Tetrahedron Letters 1978 2767. F. Mikts and G.Boshart J.C.S. Chem. Comm. 1978,173. 89 (a)E. P. Kyba. J. M. Timko,L. J. Kaplan F. de Jong G. W. Gokel and D. J. Cram,J. Amer. Chern. Soc. 1978,100,4555; (b)L. R. Sousa G. D. Y. Sogah D. H. Hoffmann and D. J. Cram ibid p. 4569. 218 W.Carruthers 4 Quinones and Related Compounds Anodic oxidation of 2-bromo- 1,4-dimethoxybenzenes in 1-2% methanolic potas- sium hydroxide affords the bromoquinone bisketal. Metallation of these bromo- bisketals at low temperatures with an alkyl-lithium reagent followed by reaction of the lithiated derivatives with electrophiles provides a convenient route to functionalized quinone bi~ketals.~' An investigation of the anodic methoxylation of phenols and the use of this reaction for the synthesis of quinones quinone hemi- acetals 4-alkyl-4-me thoxycyclohexa-2,5 -dienones and 2-alkyl-2 -met hoxycyclo- hexa-3,5-dienones has been de~cribed.~' The reaction of n-allylnickel bromide complexes with p-quinones which usually leads to 2-allylhydroquinones has been showng2 to proceed through relatively unstable allylquinol intermediates which rearrange to the allylhydroquinones.Some interesting and synthetically useful reactions of p-quinone monoketals leading to p-quinonemethide ketals and thence to benzene derivatives derived formally by nucleophilic aromatic substitution have been de~cribed.'~ Thus the dimethyl ketal (46) reacted with the anion of the trimethylsilylacetamide (47) to give the p-quinone methide ketal (48) converted with boron trifluoride into (49) (Scheme 13).Me0 OMe Me0 OMe CH,SiMe + 0 0 0 (47) (48) 1ii Reagents i LiNPr',; ii BF Scheme 13 The Diels-Alder reaction of o-benzoquinones with acyclic dienes has been used to make derivatives of 9,IO-phenanthraq~inone.~~ Thus reaction of 2,3-dimethyl-butadiene with 3-substituted catechols in the presence of an oxidizing agent (Ag20 Mn02) gave tetrahydrophenanthraquinoneswhich were easily converted into 9,lO- 90 J. S. Swenton,D. K. Jackson M. J. Manning andP. W. Raynolds,J. Amer. Chem. SOC.,1978,100,6182. 91 A. Nilsson U. Palmquist T. Pettenson and A. Ronlan J.C.S. Perkin I 1978,696. 92 L.S.Hegedus and B. R. Evans J. Amer. Chem. SOC.,1978,100,3461. 93 D.J. Hart,P. A. Cain and D. A. Evans J. Amer. Chem. Soc. 1978,100 1548. 94 R. Al-Hamdany and B.Ali J.C.S. Chem. Comm. 1978,397. Aromatic Compounds phenanthraquinones. The addition of 1,l-dialkoxyethenes to 1,4-benzoquinones and 1,4-naphthoquinones has been re-e~amined.’~ Reaction of 1,4-benzoquinones with 1,l-dialkoxyethenes in dimethyl sulphoxide gives high yields of 1,4-naph-thoquinones by 1:2 addition. In boiling hydrocarbon solvents however reaction with 1,4-benzoquinones leads chiefly to 1:1adducts.(Scheme 14). By 1:2 addition to 0 EtO OEt Me + DMSO OEt HO+ EtoyoEt Me6-M~ 25°C / OEt OEt 0 0 0 Scheme 14 naphthoquinones in dimethyl sulphoxide anthraquinones are obtained. Juglone for example gave 1,3-diethoxy-8-hydroxyanthraquinone,and 2-acetylemodin was synthesized from 1,l-diethoxyethene and stypandr~ne.~~ The reaction pathway shown in Scheme 15 is proposed.{6’ PAOR OR OR 0 0 0 X = H or Halogen 1 1 OH OR OR 0 OR 1 1 1 :1 products 1:2 products Scheme 15 95 D. W. Cameron and M. J. Crossley,Austral. J. Chem.. 1978,31 1353. D.W.Cameron M. J. Crossley, G. I. Feutrill and P. G. Griffiths ibid p. 1335. 96 D.W.Cameron M. J. Crossley G. I. Feutrill and P. G. Griffiths Austral.J. Chem. 1978,31,1363;see also D.W. Cameron G. I. Feutrill P. G. Grifiths and D. J. Hodder J.C.S. Chem. Comm. 1978.688. 220 W. Carruthers Several other approaches to anthraquinones involving Diels-Alder additions to naphthoquinones have been reported some of them prompted by synthetic interest in the anthracycline antibiotics. Thus reaction of 6-methoxy-4-methylpyran-2-one with naphthoquinone followed by oxidation and demethylation gave pachybasin 2-methyl-4-hydroxyanthraquinone,in 64% yieldg7 and the synthesis of several methoxylated anthraquinones including two coccid pigments by the Diels-Alder addition of 1,1,4-trimethoxy-3-trimethylsilyloxybutadiene,1,l -dimethoxy-3-tri- methylsilyloxyocta-l,3-diene,and 2-acetyl-l,l-dimethoxy-3-methylbutadiene to appropriate naphthoquinones has been described.98 A related route to tetrahydro- naphthacenequinones which has been extended to the synthesis of 4-demethoxy- daunomycinone proceeds by Diels-Alder addition of a,a'-dibromo-o-quinodi-methane to the appropriate naphthoq~inone.~~ One of the main difficulties in the synthesis of anthracyclines is posed by the dissymmetric arrangement of the substituents in the two terminal rings and in several synthetic approaches this resolves itself into the problem of how to achieve regioselective substitution at C-2or C-3 in an anthraquinone in which there is a substituent at C-5.A possible way round this difficulty lies in the observation'00 that under the appropriate conditions the leuco compound (50) prepared in situ by reduction of 5 -hydroxyquinizarin with alkaline dithionite reacts with aldehydes specifically at C-2or C-3 to give (51) or (52)(Scheme 16).An intramolecular (52) Reagents i C,H,CHO-OH-; ii C2H5CH0 isopropanol piperidinium acetate Scheme 16 version of this procedure has been used to prepare a tetracyclic system.1o' A different approach to this problem exploits the regioselective lithiation of appro- priately substituted benzene derivatives.Thus lithiation of N-phenyl-rn-anis- amide takes place exclusively at the position ortho to both substituents. Reaction of " M.E. Jung and J. A. Lowe J.C.S. Chem. Comm. 1978,95. '' J.-L. Grandmaison and P. Brassard J. Org. Chem. 1978,43 1435; G. Roberge and P. Brassard,J.C.S. Perkin I 1978 1041; K. Krohn and A. Rosner Tetrahedron Letters 1978 353; K. Krohn and K. Tolkiehn Tetrahedron Letters 1978,4023. 99 J. R. Wiseman N. I. French R. K. Hallmark and K. G. Cheong Tetrahedron Letters 1978,3765; see also F. A. J. Kerdesky and M. P. Cava J. Amer. Chem. Soc. 1978,100,3635. loo L. M. Harwood L. C. Hodgkinson and J. K. Sutherland J.C.S. Chem. Comm.1978,712. lo' F. Suzuki S. Trenbeath R. D. Glein and C. J. Sih J. Amer. Chem. Soc. 1978,100 2272. Aromatic Compounds the resulting lithio derivative with an aromatic aldehyde gives a phthalide which can be elaborated to an anthraquinone. Appropriate choice of starting materials pro- vides an unsymmetrically substituted anthraquinone suitable as a precursor for synthesis of anthracyclines102 (Scheme 17) OLi n @NHc6H5 OMe OCH,C,H Reagents i 2 mols. BuLi; ii I ;iii H,O* 0.H. OMe Scheme 17 Interest in the synthesis of anthracyclines has led to some interesting work on the regioselectivity of Diels-Alder addition of dienes to peri-hydroxylated naph- thoquinones. It has long been known that the nature of the oxygen function in 5-hydroxy- and 5-acetoxy- 1,4-naphthoquinone profoundly influences the regio- chemistry of the cycloaddition with 1-acetoxybutadiene and this general trend has been noted more recently for a variety of diene system^."^ The reaction is catalysed by Lewis acids but remarkably with peri-hydroxylated naphthoquinones the regioselectivity varies dramatically with the nature of the catalyst (Scheme lS).'" no catalyst 75 25 BF,.Et,O >99 <1 MgI2 15 85 Scheme 18 J.E. Baldwin and K. W. Blair Tetrahedron Letters 1978,2559; see also I. Forbes R. A. Pratt and R. A. Raphael ibid p. 3965. for example T. R. Kelly,J. Gillard,R. Goemer and J. Lyding J. Amer. Chem. Soc. 1977,99,5513;T. R. Kelly Tetrahedron Letters 1978 1387. '04 T. R.Kelly and M. Montury Tetrahedron Letters 1978.4311.222 W. Carruthers The explanation suggested for the effect in the uncatalysed reaction at any rate is based on the concept that the strong hydrogen bond in 5-hydroxy-1,4-naph- thoquinone serves as an internal Lewis acid polarizing the unsaturated system so that the C-4 carbonyl group controls the direction of cycloaddition. In the cor- responding acetate or methyl ether on the other hand electron donation by the substituent is held to dominate leading to reversal of the direction of addition. It has been suggested however that this picture is oversimplified and that for high regiocontrol the proper choice of the diene might be more crucial.1o5 Phenanthraquinones are obtained in good yield by photocyclization of 1,2-diarylvinylidene carbonates themselves available from benzoins by treatment with phosgene.lo6 A polychloro pigment isolated from certain green soils has been assigned the novel structure (53).lo' 5 Cyclophanes The observed splitting of the first two photoelectron bands and the calculated strain energies of the [n]paracyclophanes are attributed to deformation of the benzene ring.Calculated energies suggest that the aromatic character of the benzene nucleus in [n]paracyclophanes has been largely lost for n =6 and completely lost for n = 5.'08 Diels-Alder reactions of benzene derivatives are rare However sterically strained benzene rings such as that in (54) can act as dienes; 1:l addition of reactive dienophiles leads to bridged ba-rrelenes (55;n =7or 8; R = CF3or CN)."' Insertion of a chromium atom between the benzene rings of [2,2]paracyclophane has been accomplished by condensation of the hydrocarbon with chromium atoms at -196"C.The novel complex can be sublimed and survives eight days in hydrochloric acid."' R (54) (55) R. K. Boeckman T. M. Dolak and K. 0.Culos J. Amer. Chem. Soc. 1978,100,7098. '06 I. Lantes Tetrahedron Letters 1978,2761. lo' D. W.Cameron and M. D. Sidell Austral. J. Chem. 1978,31 1323. 'pa H. Schmidt A. Schweig W. Thiel and M. Jones Chem. Ber. 1978 111 1958. K.-L. Noble H. Hopf M. Jones and S.L. Kammula Angew. Chem. Internat. Edn. 1978,17 602. C. Elschenbroich R.Miickel and M. Zenneck Angew. Chem. Znfernar. Edn. 1978,17,531. Aromatic Compounds The long-sought [2](4,4')orthoterphenylophane (56) has been prepared."' Particular interest attaches to such cyclophanes in which benzene rings are held orthogonal to each other.N.m.r. and U.V. spectroscopic data for (56) suggest that there is very little if any interaction between the ?r-electron clouds of the orthogonal benzene rings. (56) Cyclic sulphones have again shown their worth as precursors of cyclophanes. By vacuum pyrolysis of the appropriate cyclic sulphones a series of sterically hindered [1,n]paracyclophanes some of them not accessible by other methods was obtained in excellent yield,"*" and several [2,2]cyclophanes were obtained by photo- extrusion of sulphur dioxide from the bis-sulphones of 2,ll -dithia[3,3]paracyclo- phanes."*' Tetrasubstituted [2,2]paracyclophanes are formed by cycloaddition of ace tylenic dienophiles to 1,2,4,5 -hexat e traene .I A new route to [4,2]paracyclophanes with unsaturation in the larger bridge proceeds by condensation of vinyl p-xylylene with other xylylene-type inter- mediate~.~~~ Thus pyrolysis of (57) with (58) gave (59) and (60) as well as [2,2]paracyclophane (Scheme 19).+ Scheme 19 ''I N. Jacobson and V. Boekelheide Angew. Chem. Intentat. Edn. 1978.17,46. 'I2 (a) A. Ruland and H. A. Staab Chem. Ber. 1978 111 2997; (b) R.S. Givens and P. L. Wylie Tetrahedron Letters 1978,865. I. Bohm H. Herrmann. K. Menke and H. Hopf Chem. Ber. 1978,111,523. 'I* P. S. Hammond and D. T. Longone Tetrahedron Letters 1978 415. 224 W. Carruthers In the naphthalenoparacyclophane (61)the upfield shift of the internal protons Hi confirms the expected stepped structure in which the para-disubstituted benzene ring is tilted towards the naphthalene ring.'" The variable-temperature 'H n.m.r.spectrum of [2,2](2,6,2',7')naphthalenophan-l,ll-dieneindicates that it undergoes conformational flipping in X-Ray crystallography shows that the furanonaphthalenophane (62) exists in the anti conformation. The non-bridged portion of the naphthalene ring is planar but the bridged ring is puckered and boat-shaped.' l7 In [2,2]anthracenophane also there is slight distortion of the bridged benzene moieties.'" (61) (62) Further examples of highly strained cyclophanes which have two benzene rings held with three or more ethano-bridges have been synthesized.[2,2,2]- (1,2,4)(1,2,5)-and [2,2,2](1,2,4)(1,3,5)-cyclophanes the first examples of [2,2,2}cyclophanes in which the benzene rings are held together in an unsymmetrical manner by three ethano bridges were obtained by the sulphone pyrolysis route. Their U.V. and n.m.r. spectra suggest highly strained structure^."^ The novel triply clamped biphenylophanes (63) and (64) have also been made by the sulphur- @ V (63) (64) (65) extrusion route. Their n.m.r. and U.V. spectra reveal transannular steric and elec- tronic effects.12' The cyclophane (65)has been synthesized. On pyrolysis it gave hexaradialene (cf.p. 208) and not the hoped for [2,2,2,2,2,2]( 1,2,3,4,5,6)cyclophane with six ethano bridges.'*' Nevertheless it appears that direct dimerization of o-xylylenes does provide a convenient route to some multibridged cyclophanes.J. R. Davy M. N. Iskander and J. A. Reiss Tetrahedron Letters 1978 4085. M. N. Iskander and J. A. Reiss Tetrahedron 1978,34 2343. M. Corson B. M. Foxman and P. M. Keehn Tetrahedron 1978,34,1641. T. Toyoda and S. Misumi Tetrahedron Letters 1978,1479. 'I9 M. Nakazaki K. Yamamoto and Y. Miura J. Org. Chem. 1978,43 1041. ''O F. Vogtle and G. Steinhagen Chem. Ber. 1978 111,205. ''I R. Gray L. G. Harruff J. Krymowski,J. Peterson and V. Boekelheide J. Amer. Chem. Soc. 1978,100 2892. L. G. Harruff,M. Brown and V. Boekelheide ibid 1978,100,2893. Aromatic Compounds Thus thermal dimerization of the bis-o-xylylene (66) gave the cyclophane (67) (Scheme 20).122Formation of multibridged paracyclophanes in this way has a bearing on the mechanism of dimerization of o-xylylenes to dibenzocyclo-octa- 1,s-dienes.+ / Scheme 20 Multilayered cyclophanes proliferate and their chemistry has been reviewed. 123 In triple-layered [2,2]metacyclophanes the isomers in which a benzene ring is forced to take up a boat conformation are more stable by at least 17kJ mol-' than the isomers with a benzene ring in the chair conformation. SCF MO calculations confirm that distortion of a benzene ring to a boat is preferred to that to a Using the standard method of ring-contraction with extrusion of sulphur the triple-layered anti-[2,2]metacyclophanes (68; R = H) and (68; R =CH,) have been synthesized --Me\ /R />M;.( ) (68) and shown to have a staircase-type geometry.125 A series of triple-layered [m,m]- [n,n]paracyclophanes has been synthesized.'26 There is continuing interest in paracyclophane quinhydrones. Intramolecular fixation of donor-acceptor systems in the rigid skeleton of cyclophanes provides information on the dependence of charge-transfer interactions on orientation and V. Boekelheide and G. Ewing Tetrahedron Letters 1978,4245. S. Misumi and T. Otsubo Accounts Chem. Res. 1978,11,251. IZ4 H. Iwamura H. Kihara S. Misumi Y. Sakata and T. Umemoto Tetrahedron 1978,34,3427. T. Otsubo D. Stusche and V. Boekelheide J. Org. Chem. 1978 43 3466; D. Kmp and V. Boekelheide ibid 1978,43 3470. T.Otsubo T.Kohda and S. Misumi. Tetrahedron Letters 1978 2507.226 W. Carruthers separation which is inaccessible by the study of intermolecular complexes. The quinhydrone (69)derived from [2,2,2,2 ]( 1,2,4,5)cyclophane is of particular interest in this connection. It shows a broad intense charge-transfer band which is surpris-ingly similar in line shape and position to that of pseudogeminal[2,2]paracyclophane quinhydrone surprising in view of the shorter transannular distances and the completely rigid arrangement of the donor and acceptor units in (69).127Charge-transfer spectra have been observed in triple-and quadruple-layered cyclophanes in which respectively one and two benzene rings are sandwiched between the quinone and hydroquinone rings.'*' The triptycene derivative (70)shows strong transannular & 0 I oqj 0 OH interaction in spite of the apparently disadvantageous molecular framework.'H n.m.r. and U.V. absorption studies and electrolytic reduction clearly indicate that the electron donor-acceptor interaction between the hydroquinone and p-benzo-quinone chromophores in the triptycene is almost as strong as that in quinhydrone itself. A simple through-space interaction between donor and acceptor rings held at 120" to each other is considered not to account for the strong interaction observed and a through-bond homoconjugative interaction between donor and acceptor rings is The use of cyclophanes as components of the host in host-guest compounds is discussed in a review,l3' and the synthesis and characterization of a number of stereoisomeric macrocyclic polyethers (hosts) containing rigid chiral a,a'-binaph-thy1 units for study of chiral recognition in molecular complexation with racemic alkylammonium salts is rep~rted.'~' 6 Condensed Systems A novel route to condensed polycyclic aromatic compounds by intramolecular cyclization of benzynes and heteroarynes has been reviewed,'32 and so has the dehydrogenation of polycyclic hydroaromatic compounds.133 H.A. Staab and V.Schwendemann Angew. Chem. Internat. Edn. 1978,17,756. 12* H. A. Staab U. Zapf and A. Gurke Angew. Chem. Internat. Edn. 1977,16,801;H.Machida, H.Tatemitsu Y. Sakata and S. Misumi Tetrahedron Letters 1978,915; H.A.Staab and U. Zapf Angew. Chem. Internat. Edn. 1978,17 757. 129 H. Iwamura and K.Makino J.C.S. Chem. Comm.. 1978,720. I3O D.J. Cram and J. M. Cram Accounts Chem. Res. 1978,11,8. 13' D.J. Cram,R. C. Helgeson S. C. Peacock L. J. Kaplan L. A. Domeier P. Moreau K. Koga J. M. Mayer Y. Chao M. G. Siegel D. H. Hoffman and G. D. Y. Sogah J. Org-Chem. 1978,43,1930. S. V.Kessar Accounts Chem. Res. 1978,11,283. 133 P.P.Fu and R. V. Harvey Chem. Rev. 1978,78,317. 12' Aromatic Compounds 227 It has been found that the outcome of the reduction and reductive alkylation of many aromatic compounds with an alkali metal and liquid ammonia depends on secondary reactions which occur on quenching and different products are obtained in many instances by using an inverse quench proced~re.'~~ A number of new syntheses of naphthalene derivatives have been described.Michael addition of the anion derived from phthalide to electrophilic olefins under aprotic conditions leads to cyclic products which on dehydration afford substituted naphthols (Scheme 21),13' and in another route naphthalene derivatives are obtained by reaction of phthalide ortho esters with acetylenic and olefinic dien0phi1es.l~~ 00 @C02Me m\ M eMe \ /Me OH Reagents i LiNPriz;ii MeCH=CHCO,Me; iii CF,COZH or BF,. Et,O Scheme 21 Another route by condensation of the anion of 2-ethoxycarbonylbenzyl phenyl sulphone with @unsaturated esters and ketones gives 1-hydroxy-2,3-disubstituted naphthalenes and by suitable modification 1,4-dihydroxy-2,3 -disu bsti tuted nap h-thalene~.'~'A closely similar procedure leads to naphthalene derivatives from ortho-substituted benzyl sulphones and Michael ac~eptors.'~~ Naphtho[b,e]dicyclo-butene (71) has been synthesized by a sequence involving two Diels-Alder reactions with dimethyl cyclobutene- 1,2-dicarboxylate.Preliminary X-ray crystallographic analysis reveals a symmetrical carbon framework. 13' (71) A 180" rotation about a phenyl-naphthyl bond is expected to be effectively blocked for derivatives of the peri-diphenylnaphthalenes.However surprisingly low P. W. Rabideau and E. G. Burkholder J. Org. Chem. 1978,43,4283. 13' N. J. P. Broom and P. G. Sammes J.C.S. Chem. Comm. 1978 162. '" L. Contreras C. E. Slemon and D. B. Maclean TetrahedronLetters 1978,4237. 13' F. M. Hauser and R. P. Rhee J. Org. Chem. 1978,43 179.J. Wildeman P. C. Borgen H Pluim P. H. F. M. Rouwette and A. M. van Leusen TefruhedronLetrers 1978,2213. 139 R. P. Thummel and W. Nutakul J. Amer. Chem. Soc. 1978,100,6171. 228 W. Carruthers rotational energy barriers have been found. For a 3'-substituted derivative of the highly crowded 1,4,5,8-tetraphenylnaphthalenethe barrier to rotation (63 kJ mol-') is even smaller than that (69 kJ mol-') for 1,8-diphenylnaphthalene and consider- ably less than that (141 kJ mol-') of the stereotopically similar [3,4]paracyclophane. The differences are discussed in terms of a rotational transition state with large deformations of the naphthalene ring. 140 Chirality and conformational changes in 4-phenylphenanthrenes and 1-phenylbenzo[c]phenanthrenes have been studied.l4' N.m.r.data for several methyl-substituted 4-phenylphenanthrenes revealed that the crowding in these compounds does not lead to chirality at temperatures as low as -90 "C. The easy rotation of the phenyl substituent observed by n.m.r. spectroscopy implies that although the phenanthrene moiety on average is planar the phenyl group does not experience steric hindrance. With 1-phenylbenzo[c]phenanthrene however some restriction to rotation of the phenyl group was observed. The photocyclization of a series of 2-(P-arylvinyl)biphenyls to 9-aryl-9,1 O-dihy- drophenanthrenes has been studied and quantum yields have been measured. The p ho toreaction consists of a stereoselective probably concerted conro tatory cycliza- tion from the S state of both the cis-and trans-arylvinylbiphenyl to a 9-aryl-8a,9- dihydrophenanthrene derivative followed by a fast thermal suprafacial [1,5]sig-matropic hydrogen shift (Scheme 22).142Photocyclization of stilbene derivatives to Scheme 22 phenanthrenes continues to be of interest.Dicyclobuta[b glphenanthrene and dicyclobuta[b,h]phenanthrene have been made in this way from the appropriate stilbene and a number of 4,4'-dihydroxystilbenes (72),constrained in the cis configuration cyclized on irradiation to the corresponding 4a,4b-dihydro- phenanthrenes which were stabilized by isomerization to the corresponding enones (73) (Scheme 23).144 W. H. Laarhoven W. H. M. Peters and A. H. A. Tinnemans Tetrahedron 1978,34,769. P. H. G. op het Veld and W.H. Laarhoven J.C.S. Perkin ZZ 1978 915. 0 hv -* Me (73) Scheme 23 140 R. L. Clough and J. D. Roberts J. Org. Chem. 1978,43,1328. 143 P. Perkins and K. P. C. Vollhardt Angew. Chem. Internat. Edn. 1978,17,615. 144 M. Maienthal W. R. Benson E. B. Sheinin T. D. Doyle and N. Filipescu J. Org. Chem.. 1978,43,972. 14' Aromatic Compounds 229 Anthracene photo-oxide on thermolysis undergoes changes resulting eventually in the formation of the di-ether (74) uia the diepoxide (75). With naphthacene won / \ / \ 0 0 photo-oxide a similar di-epoxide is formed but subsequent reactions are more complex and a mixture of products results.145a Mixtures were also obtained by photo-rearrangement of the endoperoxides of 9,lO-diphenylanthra~ene’~~~ and of 7,12-dimethylbenz[a Ianthracene.146 The complex triphenylmethyl radical (76) has been prepared by reduction (Na or K mirror in benzene) of the cation. E.s.r. results indicate clearly that it is ~1anar.l~’ A novel route to the benz[a]anthracene ring system by Diels-Alder reaction of 1,4-phenanthraquinone and 1-methoxy- 1,3-~yclohexadiene followed by thermal extrusion of ethylene led to a mixture of 8-and 11-methoxybenz[a]anthra-quinone.14’ A dicarboxylic anhydride of benz[a]pyrene was obtained by photo- addition of maleic anhydride to chrysene in presence of air.’49 Dibenz[a,c]anthracene is conveniently and directly obtained from 2-(9’-phenanth- roy1)benzoic acid with boiling hydriodic acid and red phosphorus.150 The unexpec- ted ease of cyclization of the benzoic acid in comparison with that of analogous keto-acids is ascribed to the relatively high olefinic character of the phenanthrene 9,lO-bond in this compound. Reaction with hydriodic acid and phosphorus of 0-(1-naphthoy1)benzoic acid which lacks such a bond furnished only the product of reduction of the carbonyl group 0-(1-naphthylmethyl)benzoic acid. Dihydro-diols of polycyclic aromatic hydrocarbons have become important because of their r61e in the causation of cancer by some of the hydrocarbons and 14’ (a)J. Rigaudy J. Baranne-Lafont A. Defoin and N. K. Cuong Tetrahedron 1978,34,73; J. Rigaudy and D. Sparfei ibid 113,226; (6)J. Rigaudy C. Breliere and P. Scribe Tetrahedron Letters 1978,687. 146 M.K. Logand W. A. Austin and R. E. Davis Tetrahedron Letters 1978,511. 14’ F. A. Neugebauer D. Hellwinkel and G. Aulmich Tetrahedron Letters 1978,4871. 14’ S. W. Wunderly and W. P. Weber J. Org. Chem.. 1978,43 2277. H. Karpf and 0.E. Polansky Tetrahedron Letters 1978 2069. 1so R. G. Harvey C. Leyba M. Konieczny P. P. Fu and K. B. Sukumaran J. Org. Chem. 1978,43,3423. 230 W. Carruthers several derived from ~hrysene,'~' ben~o[eJpyrene,'~~ have and ben~o[a]pyrene'~~ been synthesized for biological study. The absolute stereochemistry of the cis-l,2- trans- 1,2- and cis- 3,4-dihydro-diol metabolites of phenanthrene has been deter- mined. 154 Several 'bay-region' diol epoxides of phenanthrene and chrysene have been prepared and the rates and products of their hydrolysis compared with those observed for corresponding derivatives of ben~o[a]pyrene.'~~ (77) (78) (79) Heating concentrated ' solutions of 1,3,14,16-tetramethylhexahelicene(77) at 180-300 "C results in the formation of the two spiro compounds (78)and (79);dilute solutions only racemize.Similar behaviour is shown by the 1,16- but not by the 1,3- or 1,14-dimethyl compounds. Presumably the carbon skeleton of the pyrene moiety arises via a sigmatropic hydrogen shift from the C1-CH3 to C19 followed by an electrocyclic reaction.'56 Irradiation of 2-~tyrylbenzo[c]phenanthrene in eleven different chiral solvents led to non-racemic hexahelicene in optical yields of 0.2-2.0%. The r61e of the chiral solvents is ascribed to their influence on the equilibrium between enantiomeric conformations of the cis-styrene.157 Methyl substituents at C-1 and C-16 of hexahelicene lead to a large increase in the free energy of activation in the thermal racemization compared with hexahelicene but methyl substituents in other positions have little effect.ls8 A new helical molecular skeleton (80)has been constr~cted.'~~ The temperature- dependent 'H n.m.r. spectrum shows that the molecule is helical at low tempera- U (80) 15' P. P. Fu and R. G. Harvey J.C.S. Chem. Comm. 1978,585. 152 R. E.Lehr C. W. Taylor S. Kumar H. D. Mah and D. M. Jerina J. Org. Chem. 1978,43 3462. 15' D.R.Boyd G. S. Gadaginamath R. Hamilton H.Yagi and D. M. Jerina Tetrahedron Letters 1978 248. 154 M. Koreeda M. N. Akhtar D. R.Boyd J. D. Neill D. T. Gibson and D. M. Jerina J. Org. Chem. 1978 43 1023. 155 D. L. Whalen A. M. Ross H. Yagi J. M. Karle and D. M. Jerina J. Amer. Chem. Soc. 1978,100,5218. J. H.Borkent P. H. F. M. Rouwette and W. H. Laarhoven Tetrahedron 1978,34,2569. 15' W. H.Laarhoven and T. J. H. M. Cuppen J.C.S. Perkin ZI 1978,315. ''* J. H.Borkent and W. H. Laarhoven Tetrahedron 1978,34,2565. 159 F. Vogtle and E. Hammerschmidt Angew. Chem. Internat. Edn. 1978.11 268. 15' Aromatic Compounds 231 tures; the signals of the benzylic protons appear as singlets at room temperature but display considerable broadening on cooling. 7 Non-benzene Systems Three- and Four-membered Rings.-The first example of an electrophilic substitu- tion in the cyclopropenylium ion has been reported.160a The compound (81; X = H) when treated with D2S04,is converted into the deuteriated analogue (83) presum-ably by way of the a-complex (82).In the same system the synthetically useful lithium derivative (81; X=Li) is obtained by action of butyl-lithium on (81; x = C1)?Ob The results of ab initio SCFand CI calculations for the low-lying singlet and triplet states of cyclobutadiene imply that the square form is the lowest energy intermediate for interconversion of rectangular singlets. 16' Experimental evidence for a rec- tangxiar structure for the ground state of cyclobutadiene comes from a careful infrared study. This rules out the possibility that cyclobutadiene is square and sugpgsts that it is very likely rectangular.'62 X-Ray crystallographic analysis of the benzocyclobutadiene derivative (84) shows that the benzocyclobutadiene moiety is planar and that the bond in the four-membered ring carrying the substituents is as short as an isolated carbon=carbon double bond.The measured bond lengths rule out any contribution from the resonance structure (86),and the ground state is best described in terms of the two resonance structures (84) and (85).163 Hiickel molecular orbital theory predicts the aromatic 2welectron cyclobutadiene dication to have a square-planar ground state. Results of more recent calculations suggest however that the parent dication as well as the tetramethyl derivative is not planar but is puckered.'64 The dianion of dimethyl cyclobut-3-ene-1,2-dicar-boxylate has been prepared.Spectroscopic and chemical evidence suggest that it does not benefit from aromatic delo~alization.'~~ 160 (a)R.Weiss and C. Priesner Angew. Chem. Internat. Edn. 1978,17,445;(b)R.Weiss C. Priesner and H. Wolf ibid 1978 17,446. 161 J. A.Jafri and M. D. Newton J. Amer. Chem. Soc. 1978,100,5012. 162 S. Masamune F.A. Souto-Bachiller T. Machiguchi and J. E. Bertie J. Amer. Chem. Soc. 1978,100 4889;cf. also H.Kollmara and V. Staemmler ibid 1978,100,4304. 163 W. Winter and H. Straub Angew. Chem. Internat. Edn. 1978 17 127. 164 K. Krogh-Jespersen P.von R.Schleyer J. A.Pople and D. Cremer J. Amer. Chem. Soc. 1978,100 4301. 165 P.J. Garratt and R. Zahler J. Amer. Chem. SOC..1978,100,7753. 232 W. Carruthers Five- and Seven-membered Rings.-The highly strained 6,6-dimethylenefulvene (88)has been generated by gas-phase pyrolysis of (87).It is stable at low tempera- tures as a crystalline solid or in dilute solution in deoxygenated hydrocarbon solvents but the neat liquid polymerizes explosively at room temperature.'66 The [6 + 4Jcycloaddition of 1-dialkylaminobutadiene to fulvenes provides an efficient new synthesis of hydroazulenes and with suitable starting materials of azulenes as well.167 A fresh study confirms that the [6+ 41adduct (89) is probably the initial product from reaction of tropone with monocyclic fulvenes.'68 (89) The heat of formation of the tropyl cation is estimated at 882 f8.4kJ mol-' from the helium(1) photoelectron spectrum of the tropyl ~adical.'~' This value is in good agreement with that estimated by ab initiu MO calculations (873 kJ mol-') though it is considerably above the MIND0/3 estimate (822 kJ mol-').All nucleophiles so far investigated react with benzotropylium ion to give mixtures of the 5H-and 7H-benzocycloheptatriene in approximately equal amounts. With the 5-and 7-methoxybenzotropylium ions however the position of attack varies with the nu~leophile.'~~ Nucleophilic capture of cation (90) by methoxide ion yields 9-methoxyfluorene instead of the expected product. This rearrangement of derivatives of 4bH-benzo[3,4]cyclobuta[ 1,2]cycloheptene to derivatives of fluorene appears to be gene~a1.l~~ (90) Tropone and tropolone do not undergo Friedel-Crafts acylation.The tropone- irontricarbonyl complex on the other hand is easily acylated with acetyl chloride and aluminium chloride to a mixture of tautomeric acetyltropone complexes in high yield. The reaction was used in syntheses of P-thujaplicin and P-dolabrin (Scheme 24).172 A new approach to the synthesis of tropolones by rearrangement of appro-166 R. D. Miller and D. Kaufmann J.C.S. Chem. Comm. 1978,496. 16' L. C.Dunn and K. N. Houk Tetrahedron Letters 1978 3411. 16* 1.-M. Tegmo-Larrson and K. N. Houk Tetrahedron Letters 1978,941. 16' T. Koenig and J. C. Chang J. Amer. Chem. Soc. 1978,100,2240. ''* B. Fiihlisch C.Fischer and W. Rogler Chem. Ber. 1978,111 213. 17' L.Lombard0 and D. Wege Austral. J. Chem. 1978,31 1569. 172 M. Franck-Neumann F. Brion and D.Martina Tetrahedron Letters 1978 5033. Aromatic Cornpounds 0 OH Reagents i MeCOCI-AlCI,; ii Me2CN2 Scheme 24 priately substituted bicyclo[4.l.0)hept-3-en-2-ones has been de~cribed.”~ Thus P-dolabrin (91)was obtained as shown in Scheme 25. The ring expansion is viewed as proceeding by electrocyclic ring opening of the enolate of the enone. The sequence has been applied in a promising route to the ring system of colchicine. Me0 4 Me00 0 OSiMe 0 (91) Reagents i KH-THF;ii Me,SiCl; iii chloranil; iv BBr Scheme 25 Oxyallyl species generated from a,a‘-dibromoketones and iron carbonyls react with open-chain and cyclic 1,3-dienes in a 3+4+7 manner giving 4-cyclo- heptenones. Dehydrogenation of these by bromination-dehydrobromination gives substituted tropones.The procedure can be modified to give y-tropolones 43- homotropones and hydroxyhomo trop ylium ions 74 The rearrangement of cycloheptatrienylidene to phenylcarbene in solution has been studied.’” Simple dilution and increase in temperature to 240°C were not sufficient for the rearrangement of the parent cycloheptatrienylidene to be competi- tive with dimerization to heptafulvalene but rearrangement was observed when dimerization was retarded by the presence of substituents at C-2 and C-7. The 173 D. A. Evans D. J. Hart and P. M. Koelsch 1.Amer. Chem. Soc. 1978,100,4593. 174 H. Takaya Y. Hayakawa S. Mikino and R. Noyori J. Amer. Chem. Soc. 1978,100 1765 1778. C. Mayor and W. M. Jones J. Org. Chem. 1978,43,4498. 234 W.Carruthers preparation of several 8,8-dimethylhomotropyliumcations has been reported. They undergo a variety of molecular rearrangements including circumambu- lation. 176 Annulen-.-MIND0 methods are unsuccessful in predicting correct geometries or enthalpies of formation (when geometries are known) for the larger annulenes. One cause of this could be neglect of the correlation energy. The dependence of this energy on the size of the 7r system the symmetry of the molecule and the number of the considered doubly excited configurations has been investigated and some simple rules for estimating the importance of the correlation energy of a Tsystem have been put f0r~ard.l~~ The reaction of 9-anti-methoxy- or 9-anti-chloro-cis-bicyclo[6.l.O]nona-2,4,6-triene with alkali metals in tetrahydrofuran leads stereoselectively to the aromatic cis,cis,cis,trans-[9]annuleneanion which can be isolated as crystalline salts.The isomeric 9-syn-methoxy- and 9-syn-chloro-cis-bicyclo[6.1.O]nona-2,4,6-trienes on the other hand gave the all-cis anion.’78a The topomerization and isomerization of the cis,cis,cis,trans-anion have been A derivative (92) of 1,5-methano[ 10Iannulene has been prepared. Its n.m.r. spectrum suggests that it sustains as large a diamagnetic ring current as 1,6- methano[ lO]ann~lene.’~~ Two aza derivatives of 1,6-methano[ 101annulene have been prepared. Both show evidence of a diamagnetic ring current in their n.m.r. spectra. 180 Experimental evidence has been presented that other things being equal the possibility or not of equivalent ‘Kekult’ structures can have a profound effect on the diatropicity (aromaticity) of an annulene.lgl The two bridged annulenes (93) and (94)were synthesized.Compound (93) for which two equivalent ‘KekulC’ structures can be drawn showed a much more strongly pronounced diamagnetic ring current \ I / I OMe \ @ 176 R. F. Childs and C. V. Rogerson J. Amer. Chem. Soc. 1978,100,649. 177 H. Baumann J. Amer. Chem. SOC..1978,100,7196. 178 (a) G. Boche H. Weber D. Martens and A. Bieberbach Chem. Ber. 1978,111,2480; (6)G.Boche H. Weber and A. Bieberbach ibid 1978,111 2833. G. Boche and A. Bieberbach ibid 1978,111 2850. 179 T. Scott and W. R. Brunsvold J. Amer. Chem.SOC.,1978 100,4320. 180 W. J. Lipa H. T. Crawford P. C. Radlick and G. K. Helmkamp J. Org. Chem. 1978 43 3813. M. Schaffer-Riddler A. Wagner M. Schwarmborn H. Schreiner E. Devrant and E. Vogel Angew. Chem. Internat. Edn. 1978 17 853. H.-J. Goiz J. M. Muchowski and M. L. Maddox ibid 1978 17 855. 181 R. H. Mitchell R. J. Carruthers andL. Mazuch J. Amer. Chem. Soc. 1978,100 1007. Aroma tic Compounds as shown by 'Hand 13Cn.m.r. than did (94) which does not have two equivalent KekulC structures. The hexahydrocoronene (95) has been obtained in solution by photocyclization of [2,2,2]paracyclophan-1,9,17-triene (Scheme 26). It shows a (95) Scheme 26 pronounced diamagnetic ring current and is readily oxidized by oxygen to coronene. A quantitative analysis of the ring current in (95)has been made following Haddon's procedure.The large value of 0.87found for the fraction of maximum calculated ring current for (95) is strong evidence that there is no significant trend toward bond alternation at the ring size of an [18]ann~lene.'~~ The corresponding benzo- and dibenzo-analogues (96) and (97)were also made. The dibenzo analogue (97) shows a larger ring-current contribution to chemical shifts than does the monobenzo analogue (96). This is held to illustrate the important r61e of symmetry in ring- current contributions to chemical shifts. The analogues (98) also show n.m.r. X=H,H; -CH2-CH2-; -S-; or -CH=CH-18' T. Otsubo R. Gray and V. Boekelheide J. Amer. Chem. Soc. 1978,100.2449. 236 W.Carruthers characteristics to be expected for bridged [18]annulenes with a strong diamagnetic ring c~rrent."~ The pentatridecafulvalene (99) has been made as well as a vinylogous pentatridecafulvalene. As in other cases the protons of the cyclo- pentadiene ring of (99)give a singlet in the 'H n.m.r. spectrum; there is no evidence for a ring current.lg4 w (99) The photoelectron and ultraviolet absorption spectra of octamethylcyclododeca- 1,3,7,9-tetrayne (100)have been measured and interpreted with the aid of ab initio Me Me$; -Me ;yML -_-Me Me (100) molecular orbital calculations. The p.e. spectrum gave clear evidence of through- space interaction between the two conjugated diacetylene units situated essentially face-to-face across the twelve-membered ring.The molecule has both in-plane and out-of-plane antiaromatic 8n-electron systems which promote bending of the acetylenic linkages.'*' Kekulene (101) a kind of 'super-benzene' has been synthesized. Its 'H n.m.r. spectrum supports the benzenoid (101a) rather than the annulenoid (101 b) form.186 In continuationof earlier work lO-methylbenzo[d1-6,8- (101a) (101b) 183 R. B. Du Vernet 0.Wennerstrom,J. Lawson T. Otsubo and V. Boekelheide J. Amer. Chem. SOC. 1978,100,2457. 184 P. D. Howes and F. Sondheimer I. Org. Chem. 1978,43,2158. 185 C. Santiago K. N. Houk G. J. De Acco,and L. T. Scott J. Amer. Chem. SOC.,1978,100,692. 186 F. Diederich and H.-A. Staab Angew. Chem. Internat. Edn.. 1978.17,372. Aromatic Compounds bisdehydro[ 1Slannulenone and 12-methylbenzo[fl-8,l0-bisdehydro[ 1Slannul-enone have been synthesized.The 'Hn.m.r. spectra show that the protonated annulenones are diatropic. 18' Cycloheptadecaoctaene has been synthesized from the dimer of cyclo-octatetraene and converted into [17lannulenyl anion by treat- ment with base. The 'H n.m.r. spectrum of the anion shows the presence of a strong diamagnetic ring current.'88 The aromatic character of the annuleno-annulenes has been examined theoreti- cally and found to be dominated by the aromaticity of the two fused rings rather than by that of the molecular peri~hery.'~' The synthesis of the trisdehydroannuleno- annulene (102) has been described. Features of the 'H n.m.r. spectrum are explained in terms of an independent ring current in each ring.'" 18' J.Ojima and Y. Shiroishi Bull. Chem. Soc. Japan 1978 51 1204. lS8 P. Hildenbrand G. Plinke J. F. M. Oth and G. Schroder Chem. Ber. 1978,111 107. lS9 B. A. Hess L. J. Schaad and I. Agranat J. Amer. Chem. Soc. 1978,100,5268. 190 S. Nakatsuji S. Akiyama and M. Nakagawa Tetrahedron Letters 1978,1483.