11 Heterocyclic Chemistry By A. J. BOULTON School of Chemical Sciences University of East Anglia Norwich NR4 7TJ 1 Heterocycles in Functional Group Transformations The 4,4-dimethyl-2-oxazoline substituent already established as a versatile protec- tive group and reaction intermediate continues to assert its value. As a typical electron-withdrawing group in a benzene ring it activates an ortho-fluorine atom to nucleophilic displacement by carbon nucleophiles (e.g. Grignard reagents) as well as amide ions.’ As a 4-substituent in pyridine (l),it allows metallation (MeLi) at the 3-position forming (2) and leading to a variety of 3-substituted isonicotinic acid derivatives2 A similar directive effect of metallation occurs at the thiophene 3- position in (3).3 On the other hand the nicotinic acid derivative in ether adds alkyl lithium (RLi) to produce unusually stable 1,4-dihydropyridines (4) on a~idification.~ (1) R=H (2) R=Li Acylamino-acids can be cyclised to azlactones [oxazolinones; (5)] the anions of which may be alkylated at C-4 hydrolysed and oxidatively degraded to ketones.The alkylidene azlactones (6) undergo conjugate addition of organocuprates and the products can be converted into aldehydes (Scheme l).’Asymmetric induction by the (S)-l-phenylethyl substituent on alkylation of the lithium salts of the imidazol- inones (7)leads to amino-acids (8) in good chemical and optical yields after hydrolysis.6 As a rival to the oxazoline the 2-benzothiazolyl substituent shows promise as revealed in an interesting set of preliminary notes,’ which are sum- marised in Chapter 13 of these Reports.A. I. Meyers and B. E. Williams Tetrahedron Letters 1978,223. * A. I. Meyers and R. A. Gabel Tetrahedron Letters 1978,227. L.DellaVecchia and I. Vlattas J. Org. Chem. 1977,42,2649. C. S.Giam and A. E. Hauck J.C.S. Chem. Comm. 1978,615. R. Lohmar and W. Steglich Angew. Chem. Internat. Edn. 1978,17,450. U.Schollkopf H. H. Hausberg 1. Hoppe M. Segal and U. Reiter Angew. Chem. Intemat. Edn. 1978 17 117. ’ E.J. Corey and D. L. Boger Tetrahedron Letters 1978,5,9 13. 239 240 A. J. Boulton Li(PhSCuBu) R' R-C*-C02H I I NH2 R,R'= alkyl aralkyl (7)R=H (8) A reagent for directing lithiation and at the same time introducing chirality is the N-aminopyrrolidine (9).The aldol product is liberated from (10) by oxidative cleavage (MeOH/H202 or photo-oxidation).* ___* CH,OMe PzH2OMe R'COCH pH I I iii Me,SiCI I OSiMe, I NH NYCH3 R' (9) (10) The conversion RCH2NH2 +RCHO is achieved using the quaternary triazolium salt (11). An imine is formed which is a-oxidised using diethyl azodiformate and the product is hydrolysed by acid to the aldeh~de.~ The reagent (11) is also applicable to condensation reaction^,^ cf. the halo-substituted quaternary salts reviewed in this Section last year. Another condensation reagent for peptide coupling is the tetramethyluronium salt (12) which is reported to have the advan- tage of good shelf stability." The formamidopyridine (13) is found to be an excellent reagent for effecting the conversion RMgX +RCHO." H.Eichenauer E. Friedrich W. Lutz and D. Enders Angew. Chem. Internat. Edn. 1978,17,206. G. Doleschall Tetrahedron Letters 1978,2131. lo V.Dourtoglu. J. C. Ziegler and B. Gross,Tetrahedron Letters 1978 1269. " D. Comins and A. I. Meyers Synthesis 1978,403. Heterocyclic Chemistry 241 2 General Heterocyclic Synthesis Reactions and Properties 0-Acylanilines starting materials for a wide variety of heterocycles are not easy to prepare by direct substitution of the anilines. However a reasonably efficient procedure has been described using nitriles as the acylating agents and boron trichloride with or without aluminium chloride as catalyst. The boron is suggested to direct the attacking reagent by its complexation with the amino-group.Aldehydes and ketones in place of nitriles introduce hydroxyalkyl substituents.” More details are available on the thioacetal procedure for ortho-functionalisation of anilines which has been mentioned in previous re~orts.’~ Details of some cine-substitution reactions of o-dinitro-heterocycles have been published. The relative proportions of the direct (14) and cine (15) substitution products of the reaction of piperidine with 6,7-dinitroquinoxaline are variable the cine-product predominates at high base concentration the normal at low. It is suggested that the cine-substitution reaction is second order in base and the direct substitution is first ~rder.’~ 1-Methyl-3,4-dinitropyrrole with methoxide forms the 2-methoxy compound (16); the dihydropyrrole (17) has been isolated from this reaction and its formation was found to be accelerated by excess of methoxide.” The mechanism in this case is suggested to involve SN2-displacement of nitrite ion by methoxide in (18) and to be different overall from that which occurs in the superficially similar reaction of 3,4-dinitrothiophen with thiolates.I6 H OzNaI> X\ Y Me H (14) X =piperidino Y =H (15) X =H Y = piperidino OMe T.Sugasawa T. Toyoda M. Adachi and K. Sasakura,J. Amer. Chem. Soc. 1978,100,4842. l3 P. G. Gassman and H. R.Drewes J. Amer. Chem. Soc. 1978,100,7600. l4 R.Nasielski-Hinkens D. Pauwels and J. Nasielski Tetrahedron Letters 1978 2125.’’ P. Mencarelli and F. Stegel J.C.S. Chem. Comm. 1978,564. l6 C.Dell’Erba D. Spinelli and C. Leandri Guzzettu 1969,99 535. 242 A. J. Boulton Longer-range cine-displacements are sometimes termed tele-substitutions. An example has been found. in the 1,2,4-triazoIo[4,3-a]pyrazines:the 5-bromo compound (19) with methoxide yields a mixture of the 5-and 8-methoxy deriva- tive~.~’ The bicyclic ‘Dewar’ isomers of both five- and six-membered rings have been known for many years to be involved in photochemical ring interconversion reac- tions and a number of these species have been isolated. The scope and detailed mechanism of these reactions continue to attract attention and 1978 saw a number of interesting publications in this area.2-Picolines carrying electron-withdrawing a-substituents [e.g. (20)] are photochemically converted into anilines (21) with scrambling of the ring substituents as indicated by the suggested mechanism of Scheme 2. ’*2,6-Di-t-butyl-4-pyrone forms 4,6-di-t-butyl-2-pyrone on irradiation _3 HN CHCN Scheme 2 in sulphuric acid,lg implying a Dewar-pyrylium salt intermediate rather than an ‘oxygen walk’ mechanism which is the process usually favoured in this typt of compound.20 Steric hindrance to the formation of the 2,6-bond is suggested to be the reason for the change in mechanism. In five-membered rings the ‘Dewar intermediate’ and ‘heteroatom-walk’ mechanisms amount to the same thing. Irradiation of 2-cyanopyrroles (22) and (23) in methanol and in furan gives adducts formed by trapping of the intermediate bicyclic cup-unsaturated nitrile (24) produced by a one-step nitrogen walk.The furan adduct (25; R = H R’= Me) on heating reverts to the azabicyclopentene (24); at the pyrolysis temperature the nitrogen atom walks freely about the ring eventually ’’ J. Bradac Z. Furek D. Janezic S. Molan I. Smerkolj B. Stanovnik M. Tisler and B. Vercek J. Org. Chem. 1977,42,4197. Is Y. Ogata and K. Takagi J. Org. Chem.. 1978,43,944. l9 J. W. Pavlik and R. M. Dunn Tetrahedron Letters 1978 5071. 2o I$ Ann. Reports (B),1975 72 167 257. Heterocyclic Chemistry producing all four isomeric pyrroles. A footnote to this paper reports that the permutation pattern has been uniquely established by deuterium labelling of one of the two ring hydrogen atoms.21 (Scheme 3) R'OCN %R1 CN A wgc~A furan RNm +-a N H N R' R R' CN (24) (22) R =H R' = Me (25) (23) R=Me,R=H t 11.\ A/ R N -OMe R,QNR A -H RN 4 CN CN Scheme 3 In seven-membered eight r-electron systems 'walk' processes are preceded by thermally-allowed cyclisation; this is possibly what happens with the 1,2-diazepine (26),although the acetoxy-group seems to be necessary and a further intermediate (27) is proposed on the way to the pyridine (28) and the 1,3-diazepine (29) which are formed at 110 "C(Scheme 4).*' M2OAc MP COPh -N phf-jAc H N -NCOPh COPh (27) Scheme 4 The products of methylation (with MeOS02F) of a number of prototropic tau- tomeric systems many of them heterocyclic have been investigated.Naive expec- tation would be that alkylation of the union would give mainly the product of methylation at the site which usually carries the mobile proton but reaction of the neutral species (as here) would favour alkylation at the alternative site. In general. *' J. A. Barltrop A. C. Day and R. W. Ward J.C.S. Chem. Comm.. 1978,131. J. A. Moore,W. J. Freeman R. C. Gearhart and H. B. Yokelson J. Org. Chem. 1978,43,787. 244 A. J. Boulton this seems to be borne out in practice; cases (e.g. 4-pyridone) where the isolated product does not follow this general rule are neatly explained.23 The question of sulphur d-orbital participation seems to be as controversial as ever.In a series of diazoles of structure (30)the thiadiazole had the highest-field ”N chemical shift. It was suggested that structure (31) is an important resonance contributor. Comparison was also made with the sulphur di-imides (32) and (33) which have still higher shifts.24 On the other hand the photoelectron spectroscopy of (33) and (34) has led another group25 to the conclusion that quadrivalent sulphur structures with d-orbital participation are of no importance in the thiadiaz- ine case. Also relevant to this question is the novel heterocycle (33 the protons of which resonate at S 4.45 surely justifying its description as ‘of ambiguous aromatic character’.26 (30) X = 0,S Se (31) (32) (33) x=s (35) (34) X=NMe Nitrogen elimination from cyclic azo-compounds has received a fair share of attention in 1978.Theoretical calculations on the reaction were reported,*’ and many practical results were obtained. When the fragment left after the N2 has departed is a stable molecule the reaction usually proceeds thermally with ease; the azoxy-compounds are then much more stable.28 The meso-and dl-1,2-azetines (36) prepared by stereospecific routes decompose stereospecifically the meso giving the cis- and the dl the trans-olefin. The decomposition is theoretically energetic enough to produce the TIlevel of the olefin but this does not appear to be formed; neither is the [2 (olefin)+ 2 (N2)]retro-addition pathway followed.29 More vigorous conditions of temperature or irradiation are needed for those compounds where removal of nitrogen leaves a biradical.Some of these triplet species have been identified spectroscopically for instance those formed on irradiation in glassy matrices at 77 Kof (37)30 and (38).3’ Another precursor to a related species is (39).32 The cage structure (40) is thermally very stable and being efficiently fluorescent requires special conditions (Xe-Hg radiation at 80-90 “C,in vapour phase) for its successful photoly~is.~~ The 1,l-diazene (41) is reported to form a purple solution 23 P. Beak J. K. Lee and B. G. McKinnie J. Org. Chem. 1978,43 1367. ” I. Yavari R. E. Botto and J. D. Roberts J. Org. Chem. 1978,43 2542. ” R. Bartetzko and R. Gleiter Angew. Chem. Internat. Edn. 1978 17,468. 26 R. C. Haddon M. L. Kaplan and J. H. Marshall J.Amer. Chem. Soc. 1978,100 1235. ” B. Bigot A. Sevin and A. Devaquet I.Amer. Chem. Soc. 1978,100,2639. ’* J. P. Snyder and H. Olsen J. Amer. Chem. SOC.,1978 100 2566. ’’ D. K. White and F. D. Greene J. Amer. Chem. Soc. 1978,100,6760. 30 H. Quast L. Bieber and W. C. Danen J. Arner. Chem. Soc. 1978,100 1306. 31 N. J. Turro M.J.Mirbach,N. Harrit,J. A. Berson and M. J. Platz J. Amer. Chem. SOC.,1978,100,7653. 32 R. J. Busby and M. D. Pollard. Tetrahedron Letters 1978 3855 3859. 33 N. J. Turro K. C. Liu W. Cherry J. M. Liu and B. Jacobson Tetrahedron Letters 1978 555. Heterocyclic Chemistry 245 when the corresponding hydrazine is oxidised (t-butyl hypochlorite in NEt3/Et20).34 3 Three-memberedRings A careful study of the thermal decomposition of the P-benzoylvinyl azide (42) has shown that the benzoylazirine (43)is an important intermediate in the pathway to the heterocyclic products (44)and (45).The oxazole is formed by a base-catalysed process as shown by labelling experiments; the isoxazole is produced by thermal rearrangement of (43). The P-ketonitrile (46) is also formed independently (Scheme 5). When a substituent is present 0-to the azide group an oxazole can still be formed by an alternative acid-catalysed mechanism.35 0 Me (45) Scheme 5 The azomethine ylide (47) which is in thermal equilibrium with the aziridine (48),is stabilised by lithium perchlorate. The complex (49)reacts with bromomalononitrile anion to form the azetidine Some steroidal N-nitroaziridines have been prepared by cyclisation of P-hal~nitramines.~’ Oxidation of N-aminoaziridines gives besides bisaziridinodiazenes by dimerisation some (not much) olefin by extrusion of NZ and when the opportunity is presented nitrene insertion products for instance the interesting example (51).38 34 W.D. Hinsberg and P. B. Dervan J. Amer. Chem. Soc. 1978,100,1608. 35 K.Isomura Y. Hirose H. Shuyama ,Q ’.5e,G.-I. Ayabe and H. Taniguchi,Heterocycles,1978,9,1207. 36 M.Vaultier and R. CarriC Tetrahedron Letters 1978 1195. ’’M.J. Haire and G. A. Boswell J. Org. Chem. 1977,42 4251. L. Hoesch N. Egger,and A. S. Dreiding Helv. Chim. Acta 1978,61,795. 246 A. J. Boulton MeO PhCH C=O, PhCH-C(CO,Me) -PhCH C(CO,Me) LiCI04 \ \\+ / . \/ 7 \\+/ N-C-'ti + N N Ph Ph (+) Ph/\c=o'' Me0/ (47) (49) The photolysis of various 1,2,3-thiadiazoles at 8 K in Ar matrix gives i.r.bands attributable to thiirene~.~~ Details of similar work reported last year4' are criticised but it is clear that the same species was observed. Thiazirines are claimed as intermediates in the formation of nitrile sulphides from various ring systems (e.g. Scheme 6) by irradiation at 10-15 K,in PVC film.4' Substituents which stabilise diazomethane usually tend to destabilise diazirene and vice-versa. So the photoisomerisation of a-carbonyl diazoalkanes has not often led to the isolation of the corresponding cyclic isomers although instances of adiazoamide conversion were noted in these Reports earlier.42 Now examples (e.g. 52+53) in the a-diazoketone field have been and the Meldrum's acid derivative (54) has been prepared.44 Theoretical ab initio SCF calculations have been made on the photochemical diazomethane-diazirine interconversion and also on their decomposition to N2and CH2.45 39 M.Torres. A. Clement 3. E. Bertie. H. E. Gunning and 0.P. Strausz J. Org.Chem. 1978,43,2490. 40 Ann. Reports (B),1977,14253. 41 A. Holm N. Harrit and I. Trabjerg J.C.S. Perkin I 1978 746; A. Holm and N. H. Toubro,ibid. p. 1445. *' cf-Ann. Reports (B),1975,72.252. " T. Miyashi T. Nakajo and T. Mukai J.C.S. Chem. Comm. 1978,442. 44 T. Livinghouse and R. V. Stevens J. Amer. Chem. Soc.,1978,100,6479. 45 B. Bigot R. Ponec A. Sevin. and A. Devaquet J. Amer. Chem. SOC.,1978,100,6575. Heterocyclic Chemistry 247 A report noted in this Section last year46 has turned out to be incorrect X-ray crystallography has shown that the reaction between methanesulphonyl azide and dimethyl N-arylketenimines produces a five- (55) rather than a three-membered NAr Me,C=C=NAr + Me2<I NAr 0NS~3Me2 -+ Me.SO,N NS0,Me /o Me (55) ring.47 X-ray evidence has however confirmed the structure of the adduct (-N2)of tosyl isothiocyanate and diphenyldiazomethane as a stable thiiranimine (56).48 The S-C(sp3) distance is long (1.94A) and on standing for some time in chloroform the compound forms the benzothiophene (57) quantitatively it is suggested uia the zwitterion (or trimethylene-methane analogue) (58).48 (56) (58) (57) Allene episulphide (59)seems to be much more stable than its cyclopropanethione isomer (60); (59) generated in a variety of ways was fully characterised by microwave spectroscopy.No unambiguous evidence for (60) was found but the -cs C2H S (59) (60) formation of ethylene suggested it as an intermediate.49 Some kinetic data on the rearrangement of the optically-active trimethylsilyl methyleneaziridine (61) are available (Scheme 7). The cyclopropane product (62) retains much of the SiMe k values (x lo5) K (sec-’1 at 120 oc NMe (62) Scheme 7 46 Ann. Reports (B),1977,74 256. 47 G. L‘abbC C. C. Yu J.-P. Declercq G. Germain and M. Van Meerssche Angew. Chem. Internut. Edn. 1978,17,352. 48 G. L’abbk J.-P. Dekerk J.-P. Declercq G. Germain and M.Van Meensche Angew. Chem. Inrernur. Edn. 1978,17 195. 49 E.Block,R.E. Penn. M. D. Ennis T. A. Owens and S. L. Yu J. Amer. Chem. SOC..1978,100,7436. 248 A. J. Boulton dissymmetry the rearrangement. of (61) to (62) must be at least partly stereospecific.50 Three-membered rings containing unusual heteroatoms are becoming more common. Silirene chemistry is vigorously investigated in several laboratories. Photochemical addition of nitriles to the derivative (63) results in 2 :1 compounds (64) probably via (65) then (4 + 2)-cycloaddition of another molecule of (63). Acrylonitrile however gives (66) by an alternative (2+2) addition to (65; R= vinyl).’l Siliranes likewise undergo insertion reactions into a ring C-Si bond giving products of type (67) along with ope?-chain compounds (when X =C Y = O).’*The tri-t-butyl phosphirane oxide (68) has been rep~rted.’~ A diphosphaborirane (69) [from (Bu‘P)& +Pr:N.BC12] is said on n.m.r.evidence to have a rapidly-equili- brating structure above -100 “C,with the boron atom n~n-planar;~~ to the Reporter this seems rather strange. The crystal structure of the bridged triarsirane (70) has been determined.” PhkSiMe + RCN Me,Si (65) (63)(R=vinyl) i Ph fPh 4 Four-membered Rings A number of benzo-fused heterocycles undergo ring transformations under the vigorous conditions of flash vacuum pyrolysis to bring a nitrogen atom from a @position to an a-,adjacent to the benzene ring. Examples are the rearrangements H. Quast and C. A. Weise Velez Angew.Chem. Internat. Edn. 1978,17,213. 51 H. Sakwai Y. Karnikama and Y. Nakadaira J.C.S. Chem. Comm. 1978,80. 52 D.Seyferth and D. P. Duncan J. Amer. Chem. Soc. 1978,100,7734. 53 H.Quast and M. Heuschmann Angew. Chem. Internat. Edn. 1978,17,867. 54 M.Baudler A. Marx and J. Hahn 2.Naturforsch. 1978,33b 355. 55 G.Thiele G. Zoubek H. A. Lindner and J. Ellerman Angew. Chem. Internat. Edn. 1978,17,135. Heterocyclic Chemistry (71 -+ 72) of indoxazenes (X = 0),benzisothiazole dioxides (X = SO,) and 2,3-benzoxazin-1-ones (X = COO). Spiro-azirene intermediates of type (73) are suggested to account for this. However in the FVP preparation of 2-phenyl- benzazete (74) from 4-phenyl-1,2,3-benzotriazine,no such transposition takes place as was shown by substituent labelling in the benzo-fused ring.56 2-Phenyl- benzazete adds to diarylnitrilimines with rearrangement finally giving 1,3,5-benzo- triazepines (73,’’ in a way quite analogous to its reaction with nitrile oxides which was reported earlier.The diazomethane adduct (76),which could be isolated forms 2-azido-a-phenylstyrene (77) on mild heating while chromatography on silica results in rearrangement mainly to 2-phenylind0le.~~ A few years ago some malonic anhydrides were reported as formed by carbo- di-imide cyclisation of the acids.’* This claim has now been disputed,” on the grounds that the published5’ properties did not agree with those of compounds formed by ozonolysis of p-lactone ketene dimers (78) and assigned the anhydride structures (79).The compounds were not isolated being very unstable contrary to =~ the earlier claims. The Y~ frequency (only one observed) was in the region of 1820 ~m.-’.~~ Clearly since no alternative explanation for the earlier results was suggested the matter cannot be regarded as closed. The malonimide and related systems (80) have been reported from penicillin sulphoxide precursors.6o The synthesis of ‘penems’ (81) unsaturated and even more unstable analogues of penicillins (penams) has been reported.61 r Ph 1 0 0 (78) X=CR2 (80) X=O S (76) (77) (79) x=o CMe2,CHMe s6 K. L. Davies R. C. Storr and P. J. Whittle J.C.S. Chem. Comm. 1978 9. 57 P. W. Manley R. Sornanathan D. L. R. Reeves and R. C. Storr J.C.S. Chem. Comm. 1978,396; cf.Ann. Reports (B),1975,72 255. ” G. Resofzki M. Huhn B. Hegediis P. Dvorak and K. Kaloy Tetrahedron Letters 1975,3091. 59 C. L. Perrin and T. Arrhenius I. Amer. Chem. Soc. 1978,100,5250. M. D. Bachi 0.Goldberg and A. Gross Tetrahedron Letters 1978 4167. I. Ernest J. Gosteli C. W. Greengrass W. Holick D. E. Jackrnan H. R. Pfaendler and R. B. Woodward J. Amer. Chem. Soc. 1978,100,8214. 250 A. J. Boulton (81) R=H Me Irradiation of 2-cyano- 1-pyrroline- 1-oxides leads via the oxaziridines to ring- contraction forming N-(cyanoformy1)azetidines (82).62Photo-adducts from various heterocyclic thiones and acetylenes have been shown by X-ray crystallography to be spiro-thietes [e.g. (83)],63not thiopyrans as earlier Another thiete (84) is found to be in equilibrium with its open-chain isomer (85).Both forms have been isolated in the solid phase but the equilibration is fairly rapid in solution according to n.m.r. evidence.65 The cycloadduct formed from thiobenzophenone and diphenylketene is shown by 13Cn.m.r. spectroscopy to be the thietan-2-one (86).66 0 SMe & / 030 '0' '0 (84) (85) (86) Other sulphur-containing four-membered rings of note are the oxathietanone S-oxide (87),formed by irradiation of a mixture of SO and CH,CO at 10 K in an argon matri~,~' and the sulphone (88),which has been investigated as a precursor to a trimethylenemethane derivati~e.~~ Flash vacuum pyrolysis of allylsilanes leads to loss of propene in some cases with rearrangement of the residue as in the example (89-+90) which produces a siletene.68 '* D.StC. Black N. A. Blackman and A. B. Boscacci Tetrahedron Letters 1978 175. H. Gotthardt and 0.M. Huss,Tetrahedron Lerters 1978 3617. cfAnn. Reports (B) 1976,73,245. " A. C. Brouwer A. V. E. George D. Seykens and H.J. T. Bos Tetrahedron Letters 1978,4839. H. Kohn P. Charumilind and Y. Gopichand J. Org. Chem. 1978 43,4961. " 1. R. Dunkin and J. G. MacDonald J.C.S. Chem. Comm. 1978 1020. '* E. Block and L. K. Revelle J. Amer. Chem. SOC.,1978,100,1630. Heterocyclic Chemistry 25 1 Cyclic phosphinimines (91) form adducts with i~ocyanates,~~~ isothi~cyanates,~~~ and ketones.69c The ketone adducts are formed reversibly but decompose irrever- sibly to split the four-membered ring in the opposite sense.The isothiocyanate adducts can be formed by addition across the C=S or C=N bonds and in solution rearrangement between isomers was observed. (Scheme 8) I; syNR' E E E Scheme 8 5 Five-membered Rings It has been known for some years that the nitrone tautomers of oximes can be trapped by their reactions with dipolarophiles forming isoxa~ol(id)ines.~~ Ben-zylidene derivatives of a-amino-acids and their esters have now been found to behave in a similar way to generate azomethine ylides which in turn produce a variety of pyrrolidines and 3-pyrrolines with olefins and acetylene~,'l-~~ and aryl- hydrazones similarly give pyrazolines and pyra~olidines.~~*~' Among more con- ventional 1,3-dipole reactions the nitrone cycloaddition to olefins forming isox- azolidines has led to a neat stereospecific synthesis of and to 4-phenylquinolizidin-2-ones (not stereo~pecifically).~~ The reaction of enamines [e.g.(92)] with dimethyl acetylenedicarboxylate (DMAD) in polar solvents (e.g. methanol) follows the pattern of the 3-pyr- rolidinothiophene described here in 1976.78The enamino-ester (93) with phenyl- diazonium fluroborate produces a phenylhydrazone (94) which on heating with a base cyclises with elimination of aniline to give the fused imidazole (95).79Both of 69 (a) A. Schmidpeter and T. von Criegern J.C.S. Chem. Comm. 1978 470; (b) Angew. Chem. Internat. Edn. 1978,17,443;(c) ibid. p. 55. 'O M. Ochiai M. Obayashi and K. Morita Tetrahedron 1967,23 2641;A.Lablache-Combier M.L.Villaume. and R. Jaquesy Tetrahedron Letters 1967,4959;Tetrahedron 1968,246951. 71 R. Grigg J. Kemp G. Sheldrick and J. Trotter J.C.S.Chem. Comm. 1978,109. 72 R. Grigg and J. Kemp Tetrahedron Letters 1978,2823. 73 M.Joucla and J. Hamelin Tetrahedron Letters 1978 2885. 74 R.Grigg J. Kemp and N. Thompson Tetrahedron Letters 1978,2827. " G. Le Fevre and J. Hamelin Tetrahedron Letters 1978,4503. 76 J. J. Tufariello J. J. Tegeler S. C. Wong and S. Asrof Ali Tetrahedron Letters 1978 1733. '' J. J. Tufariello and R. C. Gatrone Tetrahedron Letters 1978 2753. '* D.N.Reinhoudt J. Geevers and W. P. Trompenaars Tetrahedron Letters 1978 1351. 79 C. B.Kanner and U. K. Pandit Heterocycles 1978,9,757. 252 A. J. Boulton these reactions seem to involve electro-cyclisation of conjugated azomethine ylides (96) and (97) respectively to account for the involvement of the pyrrolidine a-positions.0 3 N H,E 9 E (93) b,+ 1 NEt, N ___+ eNaNHPh E (94) (97) (95) E =C02Me or C02Et Cyclisation of 1,5-dipoles remains the theme for the next few papers to be considered. The rate of formation of tetrazoles (98)from azides (99)appears to be N=CHAr’ I Ar’ N=CHArZ Ar lrN\N N3 N.$ N3)=” N=CHAr2 [Ar$N/ (99) (98) controlled by the syn-anti isomerisation rate of the mine group which is very sensitive to the effect of substituents on the remote (Ar2) ring conjugative inter- action of type (100) is said to explain the rate-increasing effect of electron- withdrawing substituents.** A full paper on the cyclisation of azidoximes to 1-hydroxytetrazoles (101) has appeared.81 Evidence (from substituent and kinetic isotope effects) has been presented which suggests that the first step in the thermal decomposition of phenyl 172,3,4-thiatriazole is ring-opening to thiobenzoyl azide.82 For the photochemical decomposition see Section 3.A. F. Hegarty K. Brady and M. Mullane J.C.S. Chern. Cornm. 1978,871. ’* J. Plenkiewin Tetrahedron,1978 34,2961. ’* A. Holm L. Carlsen and E. Larsen J. Org. Chern. 1978,43,4816. Heterocyclic Chemistry 253 Four papers were noted which widen the range of substitution possibilities into the indole nucleus. Lithiation at the 2-position followed by addition to a trialkylborane leads to 2-indolyltrialkylborate ions which are decomposed by iodine introducing a 2-alkyl group into 1-methyl or 1-phenylsulphonyl ind01e.~~ Meldrum's acid an aldehyde and indole undergo a triple condensation to yield a product (102) which may be ethanolysed to an a-substituted indole-3-propionic Indole can be converted directly into the 3-malonic ester using a 2,5-dichloro-1-thiophenium ~lide.~~ The chromium tricarbonyl activation method allows introduction of some nucleophilic substituents into the indole 7-position (103); the scope in terms of R and Nu is still rather limited however.86 P-Nitrostyrenes have been cyclised to oxindoles (104) using acetyl chloride and ferric ~hloride.~' a T aH R J O M e 2 Cr(CO),07t R 03;H Nu (102) (103) (104) 2,3-Dimethylbenzofuran under Friedel-Crafts conditions gives a mixture of the 6-acetyl compound and the rearranged product (105 in which the ethyl group is formed by migration of the 2-methyl onto a 3-methylene group of a dihydro- intermediate.88 a7jMe + ' AcCl ' 'Me SnCI oT)cH2Me 'Ac (105) Thiophene reacts with maleic anhydride in a variety of organic solvents at 100 "C and 15 kbar pressure to form the exo-Diels-Alder adduct (106).No reaction was observed with a number of other common dien~philes.~~ A crystal structure '0 (106) '' A. B. Levy J. Org. Chem. 1978,43,4684. 84 Y.Oikawa H. Hirasawa and 0.Yonemitsu Tetrahedron Letters 1978 1759. 85 R. J. Gillespie and A. E. A. Porter J.C.S. Chem. Comrn. 1979 53. " A. P. Kozikowski and K.Isobe,J.C.S. Chem. Comm. 1978,1076. '' P. Demerseman J. Guillaumel J. M. Clavel and R. Royer Tetrahedron Letters 1978 2011. 88 E. Baciocchi A. Cipiciani S. Clementi and G. V. Sebastiani. J.C.S. Chem. Comrn. 1978 597. 89 H. Kotsuki S. Kitagawa H. Nishizawa and T. Tokoroyama J. Org. Chem. 1978.43 1471. 254 A. J. Boulton determination has been carried out on the thiophenium ylide (107).90 It was made by Rh(OAc)2-catalysed addition of dimethyl diazomalonate to thiophen and on heat- ing it rearranged to the 2-thienylmalonic ester ( 108).91 Although this rearrangement was found to be intramolecular the 2,5-dichloro-derivative of (107) transferred its ylide grouping to cyclopropanate 01efins~~ and substitute activated aromatic rings.85 Bisallenyl sulphide (109) prepared by base-catalysed isomerisation of dipropargyl sulphide forms the dimer (110) when heated (at 50 “Cin CHCl,) presumably via the ‘non-classical’ dimethylene-thiophen (111)(or its equivalent biradical) which can be trapped by 302 [forming (112)] or maleic anhydride.93 Solvent and deuterium- isotope effects on the rate of rearrangement of the selenium analogue (113) to the selenophene (114) are small the first step is probably a rate-determining cyclisation to (115) followed by rapid H-migrati~n.~~ 5) A S(CH=C=CH,) +[sm’”]-CHZ CMe CMe2H Se(CH=C=CMe,) [Sex ] % Se(>x ,,CHZ CMe C I The isoindole structure (116) exists as such rather than in alternative tautomeric forms without NH groups.It is however sensitive to oxygen and gives a 1 2 adduct with N-phenylrnaleimide.9s The pyrroloquinoxaline (117) adds dienophiles across the 1,3-positions.It is made by oxidation of its 1,3-dihydro derivative by Mn02 or of its 4,9-dihydro derivative by 02.96 H b N H a:xNBul (116) (117) 9o R. J. Gillespie J. Murray-Rust P. Murray-Rust and A. E. A. Porter J.C.S. Chem. Comm. 1978 83. 91 R. J. Gillespie A. E. A. Porter and W. E. Willmott J.C.S. Chem. Comrn. 1978,85. ’* J. Cuffe R. J. Gillespie and A. E. A. Porter J.C.S. Chem. Comm. 1978,641. 93 Y. S. P. Cheng E. Dominguez P. J. Garratt and S. B. Neoh Tetrahedron Letters 1978,691. 94 S. Braverman and Y. Duar Tetrahedron Letters 1978,1493. ’’ R. Kreher and K. J. Herd Angew. Chem. Znternat. Edn. 1978 17 68. 96 R.Kreher and G. Use. Tetrahedron Letters 1978,4671. Heterocyclic Chemistry Light was shed on some long-standing puzzles in the year under review. Hector's base an oxidation product of N-phenylthiourea has been known for many years to be a diphenyl diamino-1,2,4-thiadiazole,but the precise location of the two phenyl groups and two mobile protons was not known with certainty. It is now clear that at least in the crystal structure (118) prevail^.^' The structure of its adduct with CS2 is also c~rrected.~~ The products of the action of sodium sulphite on o-diazonioben- zophenones which were originally supposed to be 2-hydroxyindazoles are the 3-hydroxy isomers (119).99Hydrazine and indigo react to form a variety of products. Ph PhNHcNyNH N-s (118) (119) One the so-called desoxyindigo is assigned the complex spirocyclic indoxyl struc- ture (120) while the same reactants under anhydrous conditions produce the very unusual quinazoline derivative (12 1) at low temperatures and its des-imino ana- logue at high temperatures.100 As was briefly mentioned last year the oxidation product of 2,4-di-t-butylphenol which was previously thought to be a spiro-benzo- xete has been found by X-ray crystallography to have the oxepinobenzofuran structure (122).'O' (122) A 2 :1adduct is formed between acetylenic esters and pyrazolo[l,2-~]pyrazoles both with the parent and with the much more stable 1-benzoyl-2-phenyl derivative.Crystallographic confirmation is desirable for the novel cyclophane structures (123) and (124) suggested.It is proposed that they are formed by proton shifts and ring-opening of the cyclazine intermediates (125) and (126) respectively.lo2 The 97 A. R. Butler C. Glidewell and D. C. Liles J.C.S. Chem. Comm. 1978 653; Acta Cryst. 1978,34b 3241. 98 A. R. Butler C. Glidewell and D. C. Liles Acra Cryst. 1978,34B,2570. 99 A.J. Boulton J. S. Khosrowshahi and "hoe K. W. J.C.S. Chem. Comm. 1978 1052. loo J. Bergman B. Egestad and N. Eklund Tetrahedron Letters 1978,3147. lo' H.Meier H.-P. Schneider A. Ricker and P. B. Hitchcock Angew. Chem. Infernut. Edn. 1978,17,121. lo2 K.Matsumoto and T. Uchida Chem Letters 1978. 1093. 256 A. J. Boulton (123) (124) substituted pyrazolopyrazole had earlier been reported to form a 1:1adduct with oxidation,lo3 in a way quite analogous to that which has now been found with the pyrazolo[ 1,2-a][ 1,2,3]triazoles (127) giving the cyclazines (128).The heterocycles (127) are made (R = Ph) by amination of 1-phenacylpyrazole or (R =Me) from C N H,NOSO,H I CH ,COPh E R (127) (128) 1-aminopyrazole by reaction with 3-chloropentane-2,4-dione,followed by dea~etylation.~’~ Another novel cyclazine is the blue polyaza compound (129) formed by decomposition of the tetrazolopyrimidine (130).lo’ Some interesting results have been obtained from the photolysis and pyrolysis of 8-azido-1-arylazonaphthalenes(131). The known naphthotriazine system (132) was observed in only one case and as a minor product and it photo-rearranged to the red-violet azimine isomer (133) which was the main product in all of the reactions.lo6 lo3 V.Boekelheide and N. A. Fedoruk Proc. Nut. Acad. Sci U.S.A.,1966,55,1385 (Chem. Abs. 196665 13 683). lo4 H. Koga M. Hirobe and T. Okamoto Tetrahedron Letters 1978 1291. lo’ A. Konnecke E. Lippmann R. Dorre and P. Lepom Tetrahedron Letters 1978 3687. ‘06 P. Spagnolo A. Tundo and P. Zanirato J. Org. Chem. 1978 43 2508. Heterocyclic Chemistry 257 A number of o-azidobenzoic acid derivatives (134) were photolysed in methanol to produce the azepines (135); in no case was any of the anthranil(l36) dete~ted.~”The amino-compound (136; X=NH2) and the N-H tautomer of the hydroxy- compound (X= OH) are known but the 3-chloro- -alkoxy- -aryloxy- and alkyl- thio-anthranils have proved remarkably resistant to isolation.Possibly these anthranils thermally form the nitrenes rather too easily. Even the 3-styryl derivative (137) rearranges (at 245 OC) the product is (138),rather than the 2-phenylquinolone which might have been expected. The suggested mechanism is outlined in Scheme 9. At lower temperatures (155 “C)(and in a more basic solvent) the indogenide (139) is formed.lo’ Ar X =OMe OPh OH OCOPh SPh NH2 NHPh Ar 1 A new synthesis of pyrazolo[ 1,2-~]pyrazolediones involves treatment of 4- chloropyrazoles with base. It is suggested that the pyrazolones (140) are formed lo’ R. Purvis R. K. Srnalley W. A. Strachan and H. Suschitzky J.C.S. Perkin I 1978 191. R. K. Srnalley R. H. Smith and H. Suschitzky Tetrahedron Letters 1978 2309.258 A. J. Boulton which react with their open-chain tautomers (141) as indicated. Both 1,5-and 1,7-dione (142) isomers are produced in the reaction."' The tetrone (143) (R = R' = H) is reported to exist in the CH form in tetrahydrofuran but as an enol in sulphuric acid,"' and to be an even stronger acid (pK <-1) than the disic acids."' N-NH L (143) (142) A modification of an earlier procedure for acylating dilithiated oximes which uses NN-dimethyl amides instead of esters provides a regiospecific synthesis of isox- azoles in generally good yields. The amide carbonyl becomes the isoxazole C-5."' Flash vacuum pyrolysis of isoxazolin-5-one derivatives has led to some interesting systems. The stable molecules CO and Me-(or Ph)CN are lost leaving an unsaturated carbene [from (144)] which rearranges to an acetylene (R'CECH).* l3 The imines (145) produce isonitriles and a wide range of these were formed,'14 while the readily-available hydrazones (146) give fulminic amide derivatives (ArNH.NC)."' (144) R =Me X = CHR' (145) R =Ph X = NR' (146) R =Me X = NNHAr The A1CI3-catalysed addition of a-diazoketones to nitriles results in an efficient oxazole synthesis."6 The oxazole (147) on heating undergoes intramolecular cyclo- addition of the acetylene to the ring followed by loss of acetonitrile. The furan (148) is hydrolysed to the butenolide (149) by acid."7 E. M. Kosower B. Pazhenchevsky and E. Herschkowitz J. Amer. Chem. Soc. 1978,100,6516. D. S.Kemp J.C. Chabala and S. A. Marson Tetrahedron Letters 1978 543. G. Zvilichovsky Trtrahedron 1975,31 1861;cf.Ann. Reports (B),1975 72 261. 'I2 G. N. Barber and R. A. Olofson J. Org. Chem. 1978,43,3015. C. Wentrup and H. W. Winter Angew. Chem. Internat.-Edn. 1978 17,609. 114 C. Wentrup U.Stutz and H. J. Wollweber Angew. Chem. Internal. Edn. 1978,17,688. 115 W. Reichen and C. Wentrup Helv. Chim. Actu 1976,59,2618. M. P. Doyle M. Oppenhuizen R. C. Elliott and M. R. Boelkins Tetrahedron Letters 1978 2247; T. Ibata and R. Sato Chem. Letters 1978 1129. P.A.Jacobi and T. Craig J. Amer. Chem. Soc. 1978,100,7748. Heterocyclic Chemistry M~OCH,-C~C-~H-OM~ L (147) J-M~CN Benzoxazoles are reduced by diborane in glyme followed by acid work-up to o-aminophenols.The reaction has been followed by "B n.m.r. and three inter- mediates were detected. One was the benzoxazaborole (150) which could be isolated in excellent yield by omitting the hydrolysis step. Another was assigned the tricyclic structure (151) on account of the boron signal splitting (a triplet) and chemical shift. The earliest detectable intermediate is the borane adduct (152). Similar reactions were observed for benzothiazole 2-methylbenzothiazole and 2-methylbenzoselenazole.1 l8 (150) The zoanthoxanthins remarkable coral pigments containing two imidazole rings fused to a seven-membered ring have yielded to a neat synthesis the key step of which is a [4 +6lcycloaddition of two moieties formed by dehydration of 4-hydr-oxyethylimidazoles thus the two precursors as shown in (153) eventually form pseudozoanthoxanthin.Inthe course of this work an unprecedented rearrangement was discovered. The imidazoles were produced by a known rearrangement from 1,2,4-0xadiazoles (Scheme 10,Path a). However in addition a pyrazole by-product (154) was found for the formation of which the very strange mechanism of Path b was suggested. Path b operates when R = H and steric effects involving R and the "* K. K. Knapp P. C. Keller and J. V. Rund J.C.S. Chem. Comm. 1978 971. 260 A. J. Boulton Me 1 J Scheme 10 N-Na group (or ion-pair) are invoked to explain the preference for Path a otherwise.' l9 Mesoionic heterocycles have as usual received a considerable amount of attention. The electric dipole moments of derivatives of fourteen classes of mesoionic compound (32 compounds altogether) have been measured.The values found are usually quite large (some <40,but most >5 and some >9D),which the authors state is consistent with their assigned mesoionic structures (drawn as 155).lZ0 It was not altogether clear how low a moment would have to be before it would be regarded as inconsistent with such a structure. An extensive paper describes the photochemistry of sydnones (156) and 1,3,4-oxadiazolin-2-ones (157).I2l The unusual sydnone (158)on irradiation forms a photoisomer which was shown by X-ray crystallography to have the interesting structure (159).lZ2 The unstable 1,3,4-oxadiazolines (160) are formed by cycloaddition of aryl-diazomethanes to perfluoroketones.This addition is in the opposite sense to that found in reactions between diazomethane and normal ketones (in which a new C-C M. Braun G. Biichi and D. F. Bushey J. Amer. Chem. Soc. 1978,100,4208. R. N. Hanley W. D. Ollis C. A. Ramsden G. Rowlands and L. E. Sutton J.C.S. Perkin I 1978,600. lZ1 M. MGky H. Meier A.'Wunderli H. Heimgartner H. Schmid and H. J. Hansen Helu. Chim. Acra 1978,61 1477. 12* H. Gotthardt F. Reiter A. Gieren and V. Lamm Tetrahedron Letters 1978 2331. Heterocyclic Chemistry 26 1 bond is formed) but is in accord with its reactions with C=S and C=N It is however not necessary to postulate that diazomethane (or its substituted derivatives) adopts any particular one of its resonance canonical forms in order to react as appears to be suggested to account for the formation of (161)from (162).'24 N-N RJ=p N-\ CH,N, [p-];=s -N_\ b-(J Ar 0 RF (160) (162) (161) R = Ar or Me RF= CF3 or CF2H The azidoquinoxaline dioxide (163)on heating gives two products both with o-quinonoid benzene rings.The first is a violet solid (164),which on further heating rearranges to an amber oil (165).'25 Benzyne and 2,1,3-benzoselenadiazoleform the benzisoselenazole (166) by addition of the two reactants in the sense as indicated.lZ6 Furoxans are thermally 0-0-[ak:e] 05;:0-a;x: I I 0-0-(163) (164) (166) (165) cleaved to nitrile oxides. Unless the ring is strained as for instance by fusion to a five-membered ring this reaction requires high temperatures when the nitrile oxide groups are isomerised to isocyanates.This potentially useful isocyanate-forming lZ3 N. Shimizu and P. D. Bartlett J. Amer. Chem. Soc. 1978,100,4260. lZ4 A.Martvon L. Floch and S. Sekretar Tetrahedron 1978,34 453. J. P. Dirlam B. W. Cue and K. J. Gombatz J. Org. Chem. 1978,43 76. '*' C. D. Campbell C. W. Rees M. R. Boyce M. I).Cooke P. Hanson and J. M. Vernon J.C.S. Perkin I 1978,1006. 262 A. J. Boulton reaction can be brought about at lower temperatures by sulphur dioxide catalysis when cycloaddition of SOz,and its elimination creates a more favourable pathway for the group ~earrangernent.~~’ Thioketone S-imides react with 1,3-dienes to give [2 + 4]cycloadducts (167) but with enol ethers [3 + 2]cycloadducts (168) are formed.The precise location of the substituents in the products is not known with certainty.128 Thioketene S-oxides form [3 + 2]cycloadducts (169) with imines which in some cases thermally rearrange to oxazolidinethiones (170).12’ Bistrifluoromethylthioketene reacts with mesityl azide to form the thiatriazoline (171). This loses nitrogen on heating perhaps transiently forming a thioketene S-imine but the product which is isolated is the 2,1-benzisothiazole (172); the fate of the lost methyl group was not determined.13’ (171) ( 172) When the dithiazole (173) is oxidised with rn-chloroperbenzoic acid (MCPBA) two products (174) and (175) are obtained in approximately equal amounts one of which has lost a t-butyl group. In this case it is suggested that the departing residue deposits 0 N-S HN-S; // 0’1MCPBA .Ic;.To + e’ / / / t t t (173) (174) (175) 12’ J.F. Barnes R. M. Paton P. L. Ashcroft R. Bradbury J. Crosby C. J. Joyce D. R. Homes and J. A. Milner J.C.S. Chem. Comm.. 1978 113. 12* T. Saito and S. Motoki Chem. Letters 1978 591. E. Schaumann J. Ehlers and U. Behrens Angew. Chem. Znternat. Edn. 1978,17,455. 130 M. S. Raasch J. Org. Chem. 1978,43,2500. Heterocyclic Chemistry a proton on the nitrogen atom as it 1ea~es.l~' The system of (175) is that formed on partial hydrolysis of Herz Another alkyl leaving group whose fate was determined is that in the aromatisation of the pyrazoline (176). On heating in xylene with triethylamine catalysis methane was evolved while the lithium salt [from (176) with BuLi] on heating eliminates methyl lithium.A similar dealkylation was involved in the aromatisation of the spiro-pyrazolidines (177).75 Me0,C H MeO,? - HUX (176) h177) X =H or CO2Me Many interesting developments were noted in the field of five-membered phos- phorus heterocycles. The phosphacymantrene (178)133 and pho~phaferrocene'~~ are claimed to be 'the first carbon-phosphorus 5eterocycles with a true aromatic chemistry'; certainly (178) undergoes conventional Friedel-Crafts acylation. 133 1,3-Benzazaphospholes (179) are formed from o-aminophenylphosphine and imin- oether hydrochlorides. Oddly P-phenyl and P-ethyl derivatives of the phosphine also produce the same compounds by loss of ROMe from the intermediate benz- azap hospholines.135 + R (178) (179) A series of tri- and tetra-azacycloalkanes with bridges of two and three CH groups between the N atoms has been prepared and reaction with hexamethyl phosphorous triamide studied. Whether or not compounds of type (180) or (181) are formed or whether in the case of the tetra-aza rings compoun.? (182) predominates depends on the sizes of the rings formed.'36 A hydroxyphosphorane with a P-H 13' Y. Inagaki R. Okazaki and N. Inamoto Chem. Letters 1978 1095. "* L. D. Huestis M. L. Walsh and N. Hahn J. Org. Chem. 1965,30,2763. 133 F. Mathey. A. Mitschler and R. Weiss J. Amer. Chem. SOC. 1978,100 5748; F. Mathey Tetrahedron Letters 1976,4155. 134 F. Mathey A. Mitschler and R.Weiss J. Amer. Chem. Soc. 1977 99 3537; F. Mathey J. Organo-metallic Chem. 1977,139 77. K. Isslieb R. Vollmer H. Oehme and H. Meyer Terruhedron Lerters 1978,441. (a) T.J. Atkins Tetrahedron Letters 1978,4331; (6)J. E. Richman and T.J. Atkins ibid.,p. 4333; (c)T. J. Atkins and J. E. Richman ibid. p. 5149. 264 A. J. Boulton bond -the covalent hydrate (183)-has been rep~rted.'~' A 'phosphoranoxide anion' (184)'38and a 'phosphoranide anion' (185)'39 have been described. Both tautomers (186)and (187)of the neutral molecule are observed by 31Pn.m.r. but the anion (184)is ~ymmetrical.'~~ With CF3S03H the phosphonium salt (188)is formed; this can be reduced (LiAlH4) to the anion (185) probably viu the intermediate phosphorane (189) which is also formed on protonation of (185).139 P3S03H The optically active spirosulphurane (190)was found to be configurationally very stable to racemisation not losing its activity even after 1hr at 210 "C.On oxidation it gave the corresponding sulphurane oxide which was reported to racemise very readily (AG' 46 kJ m~l-').'~~ Sulphuranes of type (191) have been prepared by cyclisation of 2-arylsulphinylisophthalic acids. The compounds with CH20H instead of COOH do not ~yclise.'~' Sulphurane anions (192)14*and (193)'43have been made. Methylation of (193)produces both 0-and S-alkylated products (194; R = Me) and (195).143 13' D. Houalla M. Sanchez R. Wolf and F. H. Osman Tetrahedron Letters 1978,4675. 138 1. Granoth and J. C. Martin J.Amer. Chem. SOC.,19?8,100 5229. 139 I. Granoth and J. C. Martin J. Amer. Chem. Soc. 1978,100 7434. P. Huszthy I. Kapovitz A. Kucsman and L. Radics Tetrahedron Letters 1978 1853. W. Walter B. Krische and J. Voss J. Chem. Res. 1978 (S) 332; (M) 4101. 14* W. Walter B. Krische G. Adiwijaja and J. Voss Chem. Ber. 1978,111 1685. P. H. W. Lau and J. C. Martin J. Amer. Chem. Soc. 1978,100,7077. Heterocyclic Chemistry +q;z +o ql-K0 + (194) (193) (195) Phenylene orthosulphite (196; R = H) has been looked at again,144 by "C and 'H n.m.r. At low temperatures the apparent symmetry is lost (below -80 "Cfor the 13C spectrum) an activation energy of ca. 38 kJ mol-' was estimated for the inversion process and ca. 46 kJ mol-' for a similar process in the 3-methylcatechol derivative (196; R=Me) (an 'unusually pure sample'!) which seems to exist in two isomeric forms (cis and trans),each undergoing fluxional processes.A trigonal bipyramidal geometry about the sulphur atom was suggested to explain the A related S'" heterocycle is the sulphurane (197).146The fused dithiolium salt (198) on (196) (197) (198) reduction formed a very stable and persistent free radical which showed no tendency to dimerise in The iodine heterocycles (199) and (200) have been as have the silicon and phosphorus compounds (201)149 and (202).''' Finally in this Section we have this year's Puzzle Corner. Maleic anhydride is refluxed in acetic acid with 2-aminopyridine followed by hydrolysis (reflux in 2M H2S04),to produce dimethyl-maleic anhydride in good yield.The imide (203) is the intermediate which is hydrolysed giving the anhydride according to the 144 cf Ann. Reports (B),1977,74 262. 145 B. A.Belkind D. B. Denney D. Z.Denney Y. F. Hsu and G. E. Wilson J. Amer. Chem. SOC.,1978 100,6327. 146 T.Kitazume and J. M. Schreeve J. Amer. Chem. SOC.,1978,100 985. 147 R.C. Haddon F. Wudl M. L. Kaplan J. H. Marshall R. E. Cais and F. B. Bramwell J.C.S. Chem. Comm. 1978,429;J. Amer. Chem. SOC.,1978,100,7629. 148 R.L.Amey and J. C. Martin J. Amer. Chem. Soc. 1978,100,300. 149 H.Watanabe K. Higuchi M. Kobayashi and Y. Nagai J.C.S. Chem. Comm. 1978,1029. 150 M.Baudler and E. Tolls 2. Narurforsch. 1978,33b 691. 266 A. J. Boulton (199) X=ICl (201) R =Ph X = SiMez (200) X=IFg (202) R =H X =PMe 0 0 0 (203) stoicheiometry required by the equation and regenerating the amine.The curious but impatient reader may find an elegant explanation for these results in ref. 151. 6 Six-membered Rings The kinetics of conformational inversion processes in saturated heterocyclic six- membered rings has been the subject of numerous reports and enlivened by occasional controversy. Ring-inversion and nitrogen-inversion commonly occur together and when an inverting nitrogen is adjacent to an oxygen atom its barrier is increased so that it is comparable with that of the ring-inversion. Compounds of this type e.g. 2-methyl-perhydro- 1,4,2-dioxazine (204) have been studied pre- vi~usly;’~~ however the conclusion that the Winversion barrier is lower than the ring-inversion is now challenged by another group.153 Nitrogen barriers comparable with or even higher than ring barriers are found for the novel perhydro-1,2,4- and 1,2,5-oxadiazine derivatives (205)’54 and (206).ls5 13C n.m.r. is now probably the M~N-X M~N? I 0-NMe (204) X=O (206) (205) X=NMe most powerful tool for conformational study being particularly useful when low barriers are involved as in the perhydro-l,2,5-oxadiazinesand -tria~ines,’~~ and a detailed account of its application to bridgehead diazadecalins has appeared. 157 Information on hexahydropyridazines from a more unusual source has been pro- vided by low-temperature cyclic voltammetry which is suggested to be a probe for M.E. Baumann and H. Bosshard Helv. Chim. Acra 1978,61 2751. R. A.Y.Jones A. R. Katritzky A. R. Martin and S. Saba J.C.S. Perkin ZI 1974 1561. F.G.Riddell M. H. Berry and E. S. Turner Tetrahedron 1978,34 1415. F.G.Riddell and E. S. Turner J. Chem. Research 1978,(S)476. Is’ A. R. Katritzky and R. C. Patel Heterocycles 1978,9,263;F. G. Riddell and E. S. Turner ibid. p. 267. V.J. Baker I. J. Ferguson A. R. Katritzky R. C. Patel and S. Rahimi-Rastgoo J.C.S. Perkin TI 1978 377. Is’ S. F. Nelsen and E. L.Clennan J. Amer. Chem. Soc. 1978,100,4004. Heterocyclic Chemistry 267 conformational measurements since the various conformers behave differently on electron-removal.15* From conformational equilibrium studies on the dithioacetals (207) and (208) (X=SMe and OMe) it has been concluded that there is a repulsive interaction between S and 0,and between S and S.In (209) however there is a net 0-0 attra~tion."~ The inversion at phosphorus is well known to be many orders of magnitude slower than that at nitrogen. The kinetics of the isomerisation of the cis and trans isomers of (210) have been followed the reaction parameters show an X .? Ph (210) unexpectedly large entropy of activation (AG* 147 kJ mol-' AS*193 J K-'mol-' at 164"C) with a modest preference for the Ph-equatorial (trans) isomer (AGO 1.2 kJ mol-') as expected.16* Although experimental evidence has shown that in non-polar solvents the 2- hydroxypyridine-2-pyridonetautomeric equilibrium swings somewhat towards the hydroxy-form comparison with results in the vapour phase (in which the hydroxy- form heavily predominates) suggested that the pyridone proportion is still anomalously high.It now appears that this is due to the effect of self-association of the pyridone in the condensed phase. Even in very dilute chloroform solutions the pyridone is very heavily self -associated. "' It seems likely that other equilibrium constants determined by apparently direct and reliable spectral methods may bear little relation to the simple monomer-monomer equilibria which they were thought to represent. In another study of 2- and 3-hydroxypyridines in acetonitrile-water mixtures the lactam or zwitterion proportions were found to increase with the water concentration which was attributed to preferential stabilisation of these tautomers by hydration.'62 Cope rearrangements in dihydropyran systems have been investigated.The thione (211) produces (212),'63 but the imines (213) on heatingappear to react in the enamine forms because the rearrangement products are the cyclohexenes (214).'64 Thermal rearrangement of 1-alkyl- 1,2-dihydropyridines generated from their azabicyclohexene valence bond isomers proceeds by electrocyclic ring-opening and 1,7-H-shift followed by recyclisation as illustrated for the 1-ethyl compound (215).16' S. F. Nelsen E. L. Clennan. and D. H. Evans J. Amer. Chem. Soc. 1978,100,4012. E. L. Eliel and E. Juaristi J. Amer. Chem. SOC.,1978,100,6114. I6O G. D. Macdonell K. D. Berlin J. R. Baker S. E. Ealick D. van der Helm and K.L. Marsi J. Amer. Chem. SOC.,1978,100,4535. '" P. Beak J. B. Covington and J. M. Zeigler J. Org. Chem. 1978,43 177. 0.B ensaude M. Chewier and J. E. Dubois Tetrahedron Letters 1978 2221. K. B. Lipkowitz and B. P. Mundy Tetrahedron Letters 1977 3417. lWB. P. Mundy and W. G. Bormann Tetraheifron Letters 1978,957. 165 I. Hasan and F. W. Fowler J. Amer. Chem. SOC.,1978 100 6696. Mecoo A. J. Boulton Mea M e aC,Hs Me NHR X I A 200°C 1 The 1,3-dipolar activity of 3-oxidopyridinium betaines has featured in these Reports on an earlier occasion.'66 The 5-methoxy analogues (216)have proved to be particularly reactive examples of this class of compound and they form adducts (across the 2,6-positions)with a wide variety of dipolarophiles.Singlet oxygen for instance gives the primary adduct (217) with (216; R = Ph) but with (216; R =H) the quinone (218) is obtained.167Flash vacuum pyrolysis allows valence isomers of 6-dialkylamino-1,3-0xazin-2-ones (219) to be isolated. These isocyanates (220) slowly revert to the heterocycles at room temperature.'68 A convenieot synthesis of 3-hydroxyisoquinolines and 2-substituted isoquinolin-3-ones (221) is by the cyclisation (H2S04)of N-benzyl-diethoxyacetarnide~.'~~ The bridged peroxide (222)decomposes on refluxingin oxygen-free benzene to generate the yellow unstable species (223) which can be trapped by maleic anhydride; otherwise it collapses to odibenzoylbenzene.I7' A new synthesis of 2,3,1-diazaborines has been reported by cyclising aldehyde tosylhydrazones with boron trichloride or tribromide (at 50-80 OC in CCl,) 166 Ann.Reports (B),1976,73 261.Y. Tamura M. Akita H. Kiyokawa L. C. Chen and H. Ishibashi TetrahedronLetters 1978 1751. P. W. Manley R. C. Storr A. E. Baydar and G. V. Boyd J.C.S. Chem. Comm. 1978,902. H. Fukumi and H. Kurihara Heterocycles 1978,9 1197. ''O 3. P. Smith and G. B. Schuster,J. Amer. Chem. Soc. 1978 100 2564. Heterocyclic Chemistry followed by hydrolysis. The example illustrated (224) is produced from 0-naph- thaldehyde with cyclisation in an unexpected dire~tion.'~' a-Lithiated nitrosamines if allowed to stand for some days form interesting tetrazine structures e.g. (225) from lithio-dirnethylnitro~amine.'~~ Diphenylthi-irene dioxide and azide ion react to form the thiatriazine dioxide (226).'73 The structures of these last two products were established by X-ray analysis and the molecular dimensions of the compounds (227) and (228) have been determined ~imi1arly.l~~ Me COMeMeQ*\ I Me PIl% Ph Me (226) (227) X=CH (228) X=N Cyclic sulphimides (229) have been prepared by reaction of amidines (230) with sulphenyl halides and N-chlorosuccinimide (NCS).With 4,4'-thiobismorpholine instead of the sulphenyl halide the product is (229; R=morpholino) which on heating gives the benzothiadiazine (23 1).'75 (230) (229) (231) Some interesting new cyclazines were reported from the bispyridinium salts (232) and (233). Dimethyl acetylenedicarboxylate (DMAD) when in excess condenses with (232) in the presence of sodium hydride to form (234) while acetic anhydride and (233) form (235).When (232) DMAD and NaH react in a 1 1:1 ratio a mixture of the red quinolizine (236) and its colourless valence isomer (237) are produced. 176 17' B. W. Miiller Helv. Chim. Acta 1978,61 325. D. Seebach R. Dach D. Enders B. Renger M. Jansen and G. Brachtel Helv. Chim. Acta 1978,61 1622. 173 B. B. Jarvis G. P. Stahly and H. L. Ammon Tetrahedron Letters 1978,3781. 174 T. Fujiwara T. Hombo K. Tomita Y. Tamura and M. Ikeda J.C.S. Chem. Comm. 1978 197. T. L. Gilchrist C. W. Rees and D. Vaughan J.C.S. Chem. Comm. 1978,1049. 176 G. G. Abbot D. Leaver and K. C. Mathur J. Chem. Res. 1978 (S)224; (MI 2850. 270 A. J. Boulton (232) R=H (234) R =R'= C02Me (233) R=Me (235) R =Me R1=H The diene (238)has been prepared as part of an attempt to produce the phosphorus analogue (239)of a nitro-compound.A Diels-Alder adduct was formed between (238)and an acetylenic ester but on pyrolysis the hoped-for fragment proved too unstable and polymerised at once.177 Another unsuccessful try was one to force a C=P bond into existence by Diels-Alder addition of (CF&C2 to 3-methyl-2-phosphanaphthalene;however the product (240)was too labile and lost MeCP which polymerised. 17' (238) (239) (240) There have been further interesting developments in arsenin (asabenzene) chem- istry. The rearrangement of 1-phenylarsenin-4-one noted kt year,'79 when ap- plied to the corresponding oxime (241)proceeds with an unexpected reduction to form the diacetylamine (242).18*Radical substitution (Ph2Hg heat) into 2-aryl-4- hydroxyarsenin gave the 1-phenyl derivative.This rearranges (Ac20/H') to the 2,6-diaryl-4-acetoxy-compound,hydrolysis of which gives a product which appears NOH fi3 H+ As I Ph (241) (242) 177 I. Segal and L. hew J. Amer. Chem. SOC.,1978,100,6394. T.C.Klebach L. A. M. Turkenburg and F. Bickelhaupt Tetrahedron Letters 1978 1099. 179 Ann.Reports (B),1977,74,277. G. Mark1 and J. B. Rampal Tetrahedron Letters 1978 1175. 17' Heterocyclic Chemistry 27 1 to contain both tautomers (243) and (244) in EtOH and CHCI,.'" Friedel-Crafts acylation (AcC1/AlCl3 -70 "C in CH2C12) of arsenin gave a 4 1mixture of the 4-and 2-acetyl derivatives.This is in striking contrast to the behaviour of pyridine in that the heteroatom here behaves effectively as a powerful activating opdirecting substituent.'82 n H (243) (244) Silabenzenes continue to evade isolation but the evidence for their transient formation must now convince all but the most sceptical. The method of thermal elimination of an ally1 group68 has been applied to compound (245) providing an intermediate which is in all probability (246) since it could be trapped by acetylenes to form (247).'83 7 Seven-membered and Larger Rings Matrix isolation experiments (in Ar at 8 K) have shown that on ultraviolet irradia- tion of various phenylnitrene and 2-pyridylcarbene precursors the aza- 1,2,4,6- cycloheptatetraene structure (248) is to be preferred to the aza-norcaratriene (249) in the schemes involving reactions of these species.184 Similarly 4-pyridyl- diazomethane forms 5-aza-l,2,4,6-~ycloheptatetraene(250).18' The evidence is based mainly on strong i.r. bands near 1895cm-'. Azatropolones (251) and (252) have been prepared from the photo-adduct (253) of phenylacetylene and 3-ethoxycarbonyl-2-phenyl-2-pyrroline-4,5-dione, by heating with or without prior photoisomerisation. Diazomethane produces a single 0-methyl ether from (25l),which has been examined by X-ray crystallography; (252) forms two isomeric ethers. The compounds readily rearrange in methanol to pyridine-2-carboxylic acid derivatives. 186 G. Mark1 and J. B. Rampal Tetruhedron Leffers 1978 1471."* A. J. Ashe W. T. Chan and T. W. Smith Tetrahedron Letfers 1978,2537. T.J. Barton and G. T. Burns J. Amer. Chem. SOC. 1978,100 5246. 0.L.Chapman and J. P.LeRowt J. Amer. Chem. SOC. 1978,100,282. ''' 0.L.Chapman R. S.Sheridan and J. P. LeRoux J. Amer. Chem. SOC.,1978,100,6245. lab T.Sano Y. Horiguchi and Y. Tsuda Heterocycles 1978.9,731. 272 A. J. Boulton (251) R=Ph,R=CO,Et (253) (252) R=CO,Et R=Ph The thienodiazepine (254) on heating forms the thienylpyrazole (255) probably via an initial 1,5-H-shift and rearrangement. On irradiation (254) forms a thieno- pyrazole (256) by biradical cleavage (of the 2,3-bond) and recombination. The mechanisms were studied by deuterium-labelling.'87 (255) (254) (256) The Cope rearrangement of the isomeric oxepin oxides (257) and (258) has been studied.The azo-compound (259) forms (257) specifically and this can be detected although it rapidly rearranges to the more stabie (258). In the presence of a catalytic trace of acid (257) forms the pyran (260) faster than it rearranges to (258) which with acid gives (261).lS8 The relief of strain which occurs on forming the azepine (262) from the cyclo- propane (263) is almost completely counterbalanced by the loss of imidate resonance at equilibrium ca. 75% of (262) is pre~ent."~ Imidate resonance is also important in determining the site of cyclopropanation (by CH2C12) of 2-methoxy- azocine dianions [e.g. (264)l:190.191 the products (265) and (266) all retain this structural element which is also present in the compounds (267) and (268) which T.Tsuchiya M. Enkaku and H. Sawanishi J.C.S. Chem. Comm. 1978,568. 18' W. H. Raststetter and T. J. Richard Tetrahedron Letters 1978 2995. lS9 L. A. Paquette and G. D. Ewing J. Amer. Chem. SOC.,1978,100 2908. 190 L. A. Paquette G. D. Ewing S. V. Ley H. C. Berk and S. G. Traynor J. Org. Chem. 1978,43,4712. 19' G. D. Ewing S.V. Ley and L. A. Paquette J. Amer. Chem. SOC.,1978,100,2909. 18' Heterocyclic Chemistry + Me MeQ M e OMe N-OMe (264) (265) (266) 1. 1 Me &e N-OMe MQMe OMe (267) (268) they form on thermal rearrangement although transiently lost in the monocyclic azonine intermediate^."^ The optical and kinetics of racemi~ation'~~ of the (non-planar) dibenzodiazocine (269) have been reported.The kinetics were followed by an (269) unusual method applicable to very small quantities of material involving periodic measurements on the pitch of spiral optical phenomena observed in cholesteric liquid crystal droplets. Several groups have reported the preparation of ma-analogues of the 1,5-methano-bridged cyclodecapentaenes. The key step in the synthesis of (270) is the cyclisation of (271) to (272).'94The isomeric system (273) has also been made with an alkoxy-group (OMe or OEt) present as indi~ated.'~~-''~ A variety of new synthetic techniques have been applied to the preparation of medium- and large-ring polyamines. Diborane reduction of the tetraketopyrazolo- pyrazoles (143) leads to cleavage of the N-N bond and formation of perhydro-diazocines.'" With suitable substituents R in (143) further aza-bridging could be J.M. Ruxer and G. SolladiC J. Chem. Res. 1978 (S)409; (M)4944. 193 J. M. Ruxer G. SolladiC and S. Candau J. Chem. Res. 1978 (S)82. 194 M. Schafer-Ridder A. Wagner M. Schwamborn H. Schreiner E. Devrout and E. Vogel Angew. Chem. Internat. Edn. 1978,17 853. 19' H.-J. Golz J. M. Muchowski and M. L. Maddox Angew. Chem. Internat. Edn. 1978,17,855. 196 W. J. Lipa H. T. Crawford P. J. Radlick and G. K. Helmkamp J. Org. Chem. 1978 43 3813. 274 A. J. Boulton -[ao] H (273) (272) introduced to form for instance (274)with three mutually bridged eight-membered rings.19' A rather spectacular macrocycle formation is the so-called 'zip reaction' in which the nitrogen of a lactam group is exchanged for another four atoms further along a chain under the influence of a strong base.198 When the amide carbonyl group of (275) fiinally reaches the terminal NH2 group the salt of the amide (276) is produced so the reaction stops at the bottom of its thermodynamic energy trough.'99 n (274) (275) Having displayed considerable versatility with cations crown ethers and cryptates have now turned their attention to anions.The bicyclic compound (277) when hexaprotonated forms stable complexes with linear triatomic anions such as N3-.200 Other anion receptors include macrocyclic guanidium salts with two and three cationic units.20* The polyamine cryptand (278) has a particular interest in heavy metal cations (Hg2+ Cd2+ and Pb2') which has led to the suggestion that compounds of this type may become of importance in therapeutic and environmental nn (277) (278) lg7 D.S. Kemp R. V. Punzar and J. C. Chabala Tetrahedron Letters 1978 547. 19* U. Kramer A. Guggisberg,M. Hesse a.nd H. Schmid Helo. Chim. Acta 1978,61 1342. 199 U. Kramer A. Guggisberg M. Hesse and H. Schmid Angew. Chem. Internat. Edn. 1978,17 200. J. M. Lehn E. Sonveaux and A. K. Willard. J. Amer. Chem. Soc. 1978,100,4914. '01 B. Dietrich T. M. Fyles J. M. Lehn L. G. Pease and D. L. Fyles J.C.S. Chem. Comm. 1978,934. Heterocyclic Chemistry 275 detoxification.202 The ability of tri- and tetra-aza-cycloalkanes with rings of 9-16 members to encircle a P"' atom has beeh referred to earlier136 (Section 5) and the synthesisof N-substituted derivatives of this type of compound has been The introduction of elements of dissymmetry and the question of 'chiral recog- nition' in crown ether complexes have been studied in several laboratorie~.~~-~~~ Polyether-bridged compounds have been prepared with chiral 1,l'-binaphthyl components.206 The importance of conformation in the association of crown ether (18-crown-6) derivatives with t-butylamine thiocyanate and with alkali metal chlorides has been An ion-selective crown ether azo-dye has been described.208 The porphyrin N-oxide (279) has been made by oxidation of octaethylporphyrin with hypofluorous acid.The oxygen atom is rather labile.209 The 'stretched porphy- rin' (280) has been synthesised.210 An interesting quinquedentate ligand (281) forms complexes of unusual geometry with transition metal ions.211 Me N \ N-N-3 N' Me (281) 'O' J.M. Lehn and F. Montavon Helv. Chim. Acra 1978,61 67. '03 M. Hediger and T. A. Kaden J.C.S. Chem. Comm. 1978,14. 2cu J. M.Lehn and C. Sirlin J.C.S. Chem. Comm. 1978 949. 'OS S. C. Peacock L. A. Domeier F. C. A. Gaeta R. G. Helgeson J. M. Timko and D. J. Cram J. Amer. Chem. Soc. 1978,100,8190. 206 E. P. Kyba G. W. Gokel F. de Jong K. Koga L. R. Sousa M. G. Siegel L. Kaplan G. D. Y.Sogah and D. J. Cram J. Org. Chem. 1977.42,4173. 'O' A. C. Coxon D. A. Laidler R. B. Pettman and J. F. Stoddart J. Amer. Gem. Soc. 1978,100,8260. '08 J. P. Dix and F. Vogtle Angew.Chem. Internat. Edn. 1978,17 857. '09 R. Bonnett R. J. Ridge and E. H. Appelman J.C.S. Chem. Comm. 1978,310. 'lo R. A. Berger and E. LeGoff Tetrahedron Letters 1978.4225. 211 M. M. Bishop J. Lewis T. D. O'Donoghue and P. R. Raithby J.C.S. Chem. Comm. 1978,476; M. M. Bishop J. Lewis T. D. O'Donoghue P. R. Raithby. and J. N. Ramsden. ibid. p. 828. 276 A. J. Boulton 8 Reviews Several valuable monographs have recently been published. Studies on 1-benzo-pyran systems,’12 on six-membered rings with three or more nitrogen atorn~,’’~ and the first part of a multi-volume work on quin01ines”~ are new additions to a well-known series. A volume on heterocyclic photochemistry has appeared,215 and also three more volumes on six-membered ring heterocycles.216 Specific ring systems which have been reviewed generally include the iso- benzofuran~,~’ pyrrol0[3,4-b]quinolines,”~ the indolizines,21 the 1,3-oxazine~,’’~ phenanthrolines,221 the quinoxalines,”’ and P-lactam~.’’~ Of interest to indole chemists is a review on ‘the spiroindolenine intermediate’ (in the Pictet-Spengler condensation and one on isatogens and in do lone^,"^ and one on the synthesis of pyrrolo[ 1,2-~]indoles.’’~ Other special aspects of specific ring systems include the 13Cn.m.r.of quinoli~idines,~’~ and ‘ring-modifying reactions of pyridines containing a quaternary nitrogen’,228 the latter including some interesting hitherto unpublished work of the Wageningen group. Personal accounts of studies on the conformation of hexahydropyrida~ines,’’~and on asymmetric C-C bond formation from chiral oxazoline~,~~~ have appeared.Reviews in which several ring systems are treated under a general heading include one on eight-membered rings with ten or more tr-electrons (‘tr-excessive heteroan- n~lenes’),~~’ and one which another concerned with the ‘aromatic a~apentalenes’,~~’ deals with cyclazines and related N-bridged ann~lenes.~~~ Heterocycles containing P-N-N linkages,234 and the Group V heterobenzene~,~~’ have been covered as have heterocyclic v-complexes of the transition metals.236 Further accounts of ”’ ‘Chromenes Chromanones and Chromones’ ed. G. P. Ellis (Weissberger and Taylor’s ‘The Chemistry of Heterocyclic Compounds’) J. Wiley and Sons,London 1977,vol. 31.’13 H. Neunhoeffer and P. F. Wiley ‘The Chemistry of 1,2,3-Triazines 1,2,4-Triazines Tetrazines and Pentazines’ (Weissberger and Taylor’s ‘The Chemistry of Heterocyclic Compounds’) Wiley -Inter-science New York 1978,vol. 33. 214 ‘Quinolines’ Part I ed. G. Jones (Weissberger and Taylor’s ‘The Chemistry of Heterocyclic Compounds’) Wiley -Interscience New York 1977,vol. 32. ‘15 ‘Photochemistry of Heterocyclic Compounds’ ed. 0.Buchardt J. Wiley and Sons,New York 1976. ‘16 ‘Rodd’s Chemistry of Carbon Compounds’ 2nd Ed. ed. S.Coffey Elsevier Amsterdam and New York 1977,vol. IV part E; 1978,vol. IV part G part H. ’17 M. J. Haddadin Heterocycles 1978,9,865. ”* F.J. Swinbourne J. H. Hunt and G. Klinkert Adu. Heterocyclic Chem. 1978,23 103. 219 Z.Eckstein and T.Urbanski Ado. Heterocyclic Chem. 1978,23,1. 220 M. A. Khan and J. F. da Rocha Heterocycles 1978 9 1059. 221 L.A. Summers Adu. Heterocyclic Chem. 1978 22 1. 222 G.W. H. Cheeseman and E. S. G. Werstiuk Adv. Heterocyclic Chem. 1978 22 367. 223 A. K. Mukerjee and A. K. Singh Tetrahedron 1978,34 1731. 224 F.Ungemach and J. M. Cook Heterocycles 1978,9 1089. 225 S.P.Hiremath and M. Hooper Adu. Heterocyclic Chem. 1978,22,123. 226 T.Kametani and K.Takahashi Heterocycles 1978,9,293. 227 D.Tourw6 and G. Van Binst Heterocycles 1978,9,507. ’” H.C. van der Plas Heterocycles 1978 9 33. 229 S.F.Nelsen Accounts Chem. Res. 1978 11 14. 230 A. I. Meyers Accounts Chem. Res. 1978,11 375. 231 A. G.Anastassiou and H. S. Kasmai Adu. Heterocyclic Chem. 1978 23 55. 232 J.Elguero R. M. CIaramunt and A. J. H. Summers Ado. Heterocyclic Chem. 1978 22 183. 233 W. Flitsch and U. Kramer Ado. Heterocyclic Chem. 1978 22 321. 234 J. P. Majoral Synthesis 1978 557. 235 A. J. Ashe Accounts Chem. Res. 1978,11,153. 236 K.H. Pannell B. L. Kalsotra and C. Parkanyi J. Heterocyclic Chem. 1978 15 1057. Heterocyclic Chemistry personal research treat the chemistry of cryptate ligand~,’~~ and the design of macrocycles in the study of host-guest complexes.238 Reviews on aspects of heterocyclic reactivity include a very extensive account of the reactions of acetylenic esters with nitrogen-containing a consi- deration of quantitative aspects of the quaternisation of heteroaromatic and a study on the S,(ANRORC) me~hanism.~~’ There is also a detailed account of the ‘anil reaction’ whereby olefins are prepared by condensation of aldimines with heterocyclic (and other) methyl A review on the synthetic applications of malononitrile is of considerable interest to heterocyclic An obituary review of the chemical work of H.Schmid who died in 1976 takes pride of place in the Helvetica Chimica His posthumous papers still enrich the pages of that journal contributing largely to its heterocyclic content. 237 J. M. Lehn Accounts Chem. Res. 1978,11,49. 238 D. J. Cram and J. M. Cram Accounts Chem. Res. 1978,11,446. 239 R. M.Acheson and N. F. Elmore Ado. Heterocyclic Chem. 1978,23,263. 240 J. A. Zoltewicz and L. W. Deady Ado. Heterocyclic Chem. 1978 22 71. 241 H. C. van der Plas Accounts Chem.Res. 1978,11,462. 242 I. J. Fletcher and A. E. Siegrist Adv. Heterocyclic Chem. 1978 23 171. A. Fatiadi Synthesis 1978 165 241. 244 H. J. Hansen M. Hesse and W. von Philipsborn Helv. Chim. Actu 1978,61 1.