13 Heterocyclic Chemistry ~~~~~~~~ ~ By B. C. UFF Department of Chemistry Loughborough University of Technology. Leicestershire Threemembered Rings.-Mare examples of slow nitrogen inversion in hetero- cycles have appeared. In general there is a marked increase in inversion barrier caused by the presence of electronegative substituents (Cl Br N 0)on nitrogen and by the inclusion of nitrogen in a strained cyclic system.’,’ For example N-alkoxyaziridines (l),formed from alkoxynitrene insertion into olefins reveal the expected slow inversion at the nitrogen atom.3 ff N Thermal C-C cleavage of the 3-aroylaziridine system to permit [2 + 3]cyclo-addition reactions has been put to further good use in synthesis4 For example addition of (2) to activated imino-compounds provides a new general route to imidazolidines (4),uia the intermediate ylide (3).’ Addition of activated aromatic aldehydes to aroylaziridines gives 4-aroyloxazolidines in good yield.6 ’ Ann.Reports (B) 1969,66,423; 1968,65 441. E.g. J. M. Lehn and J. Wagner Tetrahedron 1970 26 4227; H. Kessler and D. Leib-fritz Tetrahedron Letters 1970 4289 4293 4297; G. W. Gribble N. R. Easton and J. T. Eaton ihid. 1970 1075; P. Rademacher and W. Luttke Angew. Chem. inrernat. Edn. 1970,9,245; J. M. Lehn and J. Wagner Chem. Comm. 1970,414. ’ S. J. Brois J. Amer. Chem. SOC.,1970 92 1079. Ann. Reports (B) 1969 66 423; 1968,65 443. J. W. Lown J. P. Moser and R. Westwood Canad. J. Chem. 1969 47 4335; 1970 48 1682. ti G. Dallas J. W. Lown and J. P.Moser Chem. Comm. 1970,278; J. Chem. SOC.(C) 1970 2383. 434 %. c. ug Treatment of 2,3-diaryl-1-azirine-3-carboxamides (5) with hydrazine results in ring expansion to give 172,4-triazin-6-onederivatives (6):' reactions of aziridines involving ring expansion have been reviewed.* N-Cyanoaziridines (8) have been prepared by treatment of olefins with cyanamide and a source H CONH Ar Ar N Ar Ar H tf X-C-C-NHCN -+ N X-L-A-NHCN -+ I II CN (7) (8) of positive halogen via a vicinal halogenocyanoamine (7).9 The stereochemistry of the oxidation of cis-and trans-1-amino-2,3-diphenylaziridines has been studied," as also has the solvolysis of 3-phenyl-l-azabicyclo[l,l,0]butane.' Good support for the existence of the azepine-benzeneimine equilibrium (9 S10) has been provided by the isolation of adduct (11 R = tosyl) from N-R + Me0,C N (9) (10) addition of diazomethane to (9).The observed orientation of addition rules out direct attack on (9) and subsequent isomerisation. Adducts from attack on (9) were however also isolated.I2 PhyHC0.NH-CMe3-+ N I I CF3 CMe (12) (13) ' T. Nishiwaki and T. Saito Chem. Comm. 1970 1479. F. N. Gladysheva A. P. Sineokov and V. S. Etlis Russ. Chem. Rev. 1970 39 118; and see J. W. Lown and K. Matsumoto Chem. Comm. 1970 692. K. Ponsold and W. Ihn Tetrahedron Letters 1970 1125. lo L. A. Carpino and R. K. Kirkley J. Amer. Chem. Sue. 1970 92 1784. I ' J. L. Kurtz J. Arner. Chem. SOC.,1970,92 5008. '' H. Prinzbach D.Stusche and R. Kitzing Angew. Chem. Internat. Edn. 1970 9 377. Heterocyclic Chemist r.y 435 An unusually stable trisubstituted a-lactam (13)has been reported formed from (12)by treatment with t-butyl hypochlorite and potassium t-butoxide.I3 Although a-lactams have been known for some years attempts to prepare the correspond- ing aziridine imines have been less successful. Now however they have been prepared from 1,3-elimination of a-bromo-amidines. For example (14) yields about equal amounts of (15) and (16). Valence isomerisation between (15) and Me,CCH-C=NCMe -+ CMe3 N + Me N $r AHMe Me3C -I(NMe Me3C AN CMe (14) (15) (16) (16) has not been detected. l4 The related three-membered ring amidine system 2-arnino-l-azirine has also been reported for the first time.Treatment of a-chloroenamine (17) with sodium azide yields ( 18)presumably via an a-azido-ena- mine.’’ (17) (18) (19) A high-yield route to the formation of epoxides is reported using the novel reagent peroxyacetyl nitrate (19) of potential value as a non-acidic epoxidising agent. The iodohydrination of double bonds followed by base treatment has also been shown to provide an efficient route to the oxiran ring.I7 The novel epoxyketen ketal(21) has been synthesised from (20). As can be anticipated the epoxy ortho-ester readily breaks down in acid but proves very inert to basic Me2CBrCO2CH2C(Me),CH20H% Meq>Me Me Me (20) CMe CMe 0 I’ E. R. Talaty and C. M. Utermoehlen Tetrahedron Letters 1970 3321 l4 H.Quast and E. Schmitt Angew. Chem. Internat. Edn. 1970,9 381. ‘’ M. Rens and L. Ghosez Tetrahedron Letters 1970 3765. l6 K. R. Darnall and J. N. Pitts Chem. Comm. 1970 130. ” J. W. Cornforth and D. T. Green J. Chem. SOC.,(0,1970 846. 436 B. C. Ufl reagents.18 Addition of excess diazomethane to diepoxide (22) results in an unusual rearrangement to give ketone (23) together with the anticipated tetra- epoxide.' A review has appeared on cyclisation reactions involving participation of epoxy-compounds.20 Persuasive evidence exists that a-lactones occur as intermediates in certain displacement and free-radical reactions.21 Now an a-lactone (24) has been prepared in solution by ozonolysis of di-t-butylketen at -78 "C on warming to -20 "C it begins to polymerise presumably by participation of the dipolar form (25).The analogous reaction with diphenylketen did not give a stable Me3Cy~~ 0 + (Me3C),C-C!/* -Me3C \ 0 (24) (25) a-lactone polyester being formed immediately at -78 0C.22A cyclobutadiene epoxide (28; R = alkyl X = halogen) is claimed to have been isolated from treatment of (26) by alkoxide possibly via the anion (27).23 The preparation of 1,2-naphthalene oxide (29) was reported previously24 and no isomeric benzoxepin could be detected spectroscopically. In such cir- cumstances (29) should be isolable in optically active forms and use of an optically active precursor has now resulted in production of (29) with an optical purity of ca. Isolation of the epoxide (30) of acenaphthylene is reported as resulting from treatment of acenaphthylene with rn-chloroperbenzoic acid.The M. S. Newmann and E. Kilbourn J. Org. Chem. 1970,35 3186. l9 H. W. Moore and M. W. Grayston J. Org. Chem. 1970,35 2832. 2o V. N. Yandovskii V. S. Karavan and T. I. Temnikova Run. Chem. Rev. 1970 39 265. 21 E.g. J. E. Leffler and R. G. Zepp J. Amer. Chem. SOC.,1970 92 3713. 22 R. Wheland and P. D. Bartlett J. Amer. Chem. SOC.,1970 92 6057. 23 F. Toda and K. Akagi Chem. Comm. 1970 764. 24 Ann. Reports (B) 1968 65 371. 25 D. R. Boyd D. M. Jerina and J. W. Daly J. Org. Chem. 1970 35. 3171. Heterocyclic Chemistry product (30) is readily converted to acenaphthenone which probably accounts for previous difficulties in isolating this compound.26 The I9F n.m.r.shielding parameters have been determined for a series of trans-p-fluor0-m’- and $-substituted stilbene epoxides and show that the oxiran ring transmits conjugation to the same extent as does the cyclopropane ring i.e. ca. 26% as effective as a double bond.” An example of cis-opening of an oxiran ring is provided by the conversion of (31)into the diacetate (32). Rearward c1 approach of acetate is hindered and possibly o-participation is involved.28 The epoxide-allylic alcohol rearrangement of cis-and trans-4-t-butylcyclo-hexene oxide by lithium diethylamide is shown through appropriate deuterium substitution to occur by a syn-elimination process.29 The mechanism of oxida- tion ofSchiff bases to oxaziranes by peroxy-acids reported last year3’ has been further studied in aprotic solvent^.^ Four-membered Rings.-Pyrolysis of the p-lactams (33) and (35) gives the olefins (34)and (36)stereospecifically.The process involved is a reverse [,2 + x2a]cyclo-addition in which the cyanuric acid acts as the ,2 component. The high tempera- ture necessary is considered an indication of a high energy of activation asso- ciated with the severe ring distortion required for adoption of the antarafacial mode.32 (33) (34) (35) (36) The conditions for the C-6epimerisation of the penicillin nucleus by a p-elimina- tion mechanism have been di~cussed,~ and a new non-basic reversible method of epimerising penicillin sulphoxides at C-6 by exposure to NO-bis(trimethy1- sily1)acetamide is reported.The equilibrium occurs regardless of the nature of the amide ~ide-chain.~~ The trans-p-lactam (37) is epimerised on heating with 26 T. H. Kinstle and P. J. Ihrig J. Org. Chem. 1970,35,257. ” R. G. Pews and N. D. Ojha Chem. Comm. 1970 1033. 28 A. S. Y.Chua and W. P. Cochrane Chem. and Ind. 1970 1569. ’’ R. P. Thummel and B. Rickborn J. Amer. Chem. SOC.,1970,92 2064. 30 Ann. Reports (B) 1969 66 425. V. Madan and L. B. Clapp J. Amer. Chem. SOC.,1970,92,4902. 32 L. A. Paquette M. J. Wyvratt and G. R. Allen J. Amer. Chem. Sac. 1970 92 1763. 33 S. Wolfe W. S. Lee and R. Misra Chem. Comm. 1970 1067. 34 G. E. Gutowski Tetrahedron Letters 1970 1779. 438 B. C. Uf the base 1,5-diazabicyclo[4,3,0]non-5-eneto give an equilibrium mixture con- taining 30% of the cis-isomer.No reaction occurred when the weaker base HH Br -_{-f Ph triethylamine was An efficient non-enzymic conversion of benzyl-penicillin (38)to 6-aminopenicillanic acid (39)has been accomplished by treating (38) (39) the silyl ester of benzylpenicillin consecutively with phosphorus pentachloride n-butanol and water at low temperature^.^^ The chemical conversion of penicillin to the cephalosporin system was dis- cussed last year37 and a further report involving a double sulphoxide rearrange- ment has appeared.38 Two other novel rearrangements of penicillin derivatives p-NO,. C,H4C H =N t> 'CO,CH,OMe p-NO,.C,H,CH=N zc3 /. 0 'C02CH ,OMe (42) ~-No,.c,H,cH=N% 'NKCO,Me (4)MeAMe 35 A. K. Bose C. S.Narayanan and M. S. Manhas Chem. Comm. 1970,975. " H. W. 0.Weissenberger and M. G.van der Hoeven Rec. Trau. chim. 1970,89 1081 3' Ann. Reports (B) 1969 66 429. '' D. 0.Spry J. Amer. Chem. SOC.,1970,92 5006. Heterocyclic Chemistry 439 have appeared. The penicillin sulphoxide ester (40) on treatment with trimethyl phosphite rearranged to (41) probably via a sulphenic acid inte~mediate.~' Secondly the 6-P-aminopenicillanic acid derivative (42) on treatment with base followed by diazomethane has been shown to give the 1,3-thiazine (44).40 The rearrangement is considered to proceed via the 1,4-thiazepine (43) an analogue of which was formed in competition with the epimerisation of methyl 64-phthalimidopenicilliate on treatment with base.41 Relatively few azetines are known and the formation of the 1-azetine (48) is now reported it results from nucleophilic addition of trichloromethyl-lithium Me I to azirine (45) followed by treatment with base via (46) and presumably the azabicyclobutane (47) as intermediate.42 PhCH,CH2C0.Me -+ PhCH (49) (50) (51) 3-Thietanones have been prepared by reaction of ketones with thionyl chloride [e.g.(49)+(SO)].An a-chloro-a-sulphenyl chloride is considered a likely inter- mediate.43 The parent compound (51)of a new skeleton in the strained sulphur- bridged polycyclics series has been prepared by base treatment of 3-chloro- cyclopentyl thi~acetate.~~ The previously unknown 2-thiabicyclo[2,2,0]hexane system has been formed by cycloaddition of the reactive thiete 1,l-dioxide with enamines and ynamines [e.g.to give (53)]."' 39 R.D. G. Cooper and F. L. Jose J. Amer. Chem. Soc. 1970,92,2575 and see R. D G. Cooper ibid. p. 5010. 40 J. R. Jackson and R. J. Stoodley Chem. Comm. 1970 14. 41 0.K'. J. Kovacs B. Ekstom and B. Sjoberg Tetrahedron Letters 1969 1863. 42 A. Hassner J. 0.Currie A. S. Steinfeld and R. F. Atkinson Angew. Chem. Internat. Edn. 1970 9 731. 43 A. J. Krubsack,T. Higa and W. E. Slack J. Amer. Chem. SOC.,1970,92,5258. 44 I. Tabushi Y. Tamura and Z. Yoshida Tetrahedron Letters 1970 2931. 45 L. A. Paquette R. W. Houser and M. Rosen J. Org. Chem. 1970,35 905. 440 B. C.U’ The first preparations of 1,2-dioxetans by photo-oxygenation are For example cis-and trans-diethoxyethylenes on reaction with singlet oxygen give stereospecifically cis-and trans-diethoxy-l,2-dioxetansrespectively [e.g.OEt EtO OEt (54) (54)]. If the process is concerted then the singlet oxygen must undergo antara- facial addition to the alkene. Five-membered Rings with One Hetero-atom.-Reviews have appeared on the physicochemical properties of pyrr~les,~’ the reduction of in dole^,^^ the elec- trolysis of N-hetero~ycles,~~ and on the reactions and properties of cyclic mono- hides particularly of the succinimide and phthalimide type.50 A new synthesis of substituted pyrroles is reported resulting from the rearrangement of O-vinyl-oximes. For example on heating (55)(the adduct from acetophenone oxime and dimethyl acetylenedicarboxylate) the pyrrole (57)is produced probably via the CO Me CO,Me PhyMro2Me NLO C0,Me H (55) (56) (57) OS02R Et 0 Et 9-Meff&Me CHO CHO dH ,CI -(58) (59) (60) iminoketone (56)? Also reported is a synthesis of 7-azabicyclo[2,2,l]heptane (59) by treatment of the sulphonate (58) with aqueous base.52 Recent chemistry and biochemistry of the bile pigments have been reviewed,53 as has the structure of porphyrins and metall~porphyrins~~ and the synthesis55 46 P.D. Bartlett and A. P. Schaaf J. Amer. Chem. Soc. 1970 92 3223; S. Mazur and C. S. Foote ibid. 1970 92 3225. 47 R. A. Jones Adv. Heterocyclic Chem. 1970 11 383. 48 B. Robinson Chem. Rev. 1969,69 785. 49 H. Lund Adu. Heterocyclic Chem. 1970 12 213. ’O M. K. Hargreaves J.G. Pritchard and H. R. Dave Chem. Rev. 970 70 439. T. Sheradsky Tetrahedron Letters 1970 25. 52 R. R. Fraser and R. B. Swingle Canad. J. Chem. 1970 48 2065. ” W. Rudiger Angew. Chem. Internat. Edn. 1970 9 473. ” E. B. Fleischer Accounts Chem. Res. 1970 3 105. ” A. Eschenmoser Quart. Rev. 1969 24 366. Heterocyclic Chemistry 441 and chemistry56 of the corrin system. An improved route to 5,S-diformyl- dipyrrylketones [e.g. (60)] is reported by oxidation of 5,S-diformyldipyrryl- methanes with bromine followed by sulphuryl chloride:57 a range of oxypor-phyrins were then synthesised by condensation with appropriate dipyrryl- me thane^.^^ A methyl group has been introduced into the 1-position of the octaethyl- porphin derivative (61) via a chloroform adduct to give (62).59The synthesis of some NN’-dimethylporphyrins has been reported by direct methylation of the Et ?+ Et Et Et 20H-i CHCI,-AICI A ii NaBH iii HCl Et Et .Et Et (62) parent porphyrins.60 The reaction of benzoyl peroxide with octaethylpor- phyrin leads to side-chain and meso-substituted benzoyloxy-derivatives.61 Electrophilic substitution reactions of a wide range of metalloporphins have been examined and contrasted with the behaviour of metal-free porphins.62 The conformation of a number of metalloporphyrins in solution has been calculated by use of the high-field shift of the co-ordinated extra-planar ligand in the H n.m.r. spectrum.63 An appraisal of bond strain in the porphin skeleton r Ph 12+ Ph + 2c104 --Ph -B Ph -,Ph CIO -Ph 2 56 T.A. Melent’eva N. D. Pekel’ and V. M. Berezovskii Russ. Chem. Rev. 1969 38 926. ’’ P. S. Clezy A. J. Liepa A. W. Nichol and G. A. Srnythe AustruI. J. Chem. 1970,23 589. 58 P. S. Clezy A. J. Liepa and G. A. Smythe AustraI. J. Chem. 1970,23,603. ’’ J.-H. Fuhrhop T. Lumbantobing and J. Ullrich Tetrahedron Letters 1970 3771. 6o G. R. Dearden and A. H. Jackson Chem. Comm. 1970 205; M. J. Broadhurst R. Grigg and G. Shelton ibid. 1970 231; R. Grigg A. Sweeney G. R. Dearden A. H. Jackson and A. W. Johnson ibid. 1970 1273. 6‘ R. Bonnett and A. F. McDonagh Chem. Comm. 1970 337. 62 R. Grigg A. Sweeney and A. W. Johnson Chem. Comm. 1970 1237. ‘’ C. B. Storm J. Amer. Chem. Soc. 1970,92 1423. 442 B.C. UJY. has also appeared.64 A metalloisoporphyrin (64) has been synthesised by nucleophilic addition of methanol to dication (63).65 The disruption of the aro- matic system and consequent loss of ring current is reflected in the n.m.r. spectrum of (64).66 The part structure of heme A of cytochrome c oxidase has been shown to be (65) in which the group X is a labile substituent lost during the isolation.67 xo A new potentially general method for the synthesis of semicorrins has been described based on the use of isoxazoles as intermediates. The latter result from a nitrile oxide-alkyne cycloaddition. Reduction of (66)and treatment with Ncfl 3-OCj HN N-O (66) (67) base gives (67) as a mixture of double-bond isomers.68 Methylation of nickel(rr) corrole was formerly thought to occur at the metal atom.69 However an X-ray structure determination of the methylation product of copper 8,12-diethyl- 2,3,7,13,17,18-hexamethylcorrole has shown that substitution takes place on the nitrogen atom of ring A giving (68)." Nickel 1-substituted octa-p-alkyltetrade- hydrocorrins (69)on heating rearrange to nickel corroles (70)containing geminal 64 D.M. Collins and J. L. Hoard J. Amer. Chem. Soc. 1970,92 3761. 65 D. Dolphin R. H. Felton D. C. Borg and J. Fajer J. Amer. Chem. Soc. 1970 92 743. " J. Fajer D. C. Borg A. Forman D. Dolphin and R. H. Felton J. Amer. Chem. SOC. 1970 92 345 1. 6' G. A. Smythe and W. S. Caughey Chem. Comm. 1970 809. " R. V. Stevens L. E. DuPree and M. P. Wentland Chem.Comm. 1970 821. 69 Ann. Reports (B) 1968 65 453. '' R. Grigg T. J. King and G. Shelton Chem. Comm. 1970 56. Heterocyclic Chemistry substituents at C-3 rather than at C-2 as previously thought. The rearrangement proceeds in a two-stage process involving C-2 and probably occurs by a sigma- tropic mechani~m.~ ' Me Me Me Me I Me Me Et Me Et Me (69) (70) 3H-Indol-3-01s [e.g. (7111 result from a novel ring-contraction of 4H-3,l-benzoxazines on treatment with potassium amide in liquid ammonia. In methanolic sodium hydroxide (71) rearranged further to the indoxyl (72).'' The structure (73) which incorporates a cyc1[4,2,2]azine system is one of the cyclazines which has been obtained starting from 3H-pyrrolizine. It represents a 14 r-electron analogue of a~ulene.~~ " R.Grigg A. W. Johnson K. Richardson and M. J. Smith J. Chem. SOC.(C),1970 1289; R. Grigg A. W. Johnson and K. W. Shelton ibid. 1968 1291. 72 D. Lednicer and D. E. Emmert J. Heterocyclic Chem. 1970 7 575. 73 M. A. Jessop and D. Leaver Chem. Comm. 1970 791. 444 B. c. u-Tetrachlorobenzyne has been shown to react with simple carbonyl compounds to form benzo-1,3-dioxan derivatives [e.g.(74)from acetone and butane-2,3-dione]. These rearrange on cleavage with sulphuric acid in acetic anhydride to give CI CI (74) (75) Me02C@ C02Me Me02C -+ & C0,Me (76) (77) benzofurans of type (75).74The oxygen-bridged system (77) a potential precursor of fully unsaturated C ,-hydrocarbons has been synthesised from photoproduct (76) by reduction dehydration and oxidative decarboxylation of the correspond- ing A review of macrocycles involving the thiophen ring system has appeared76 and one of recent advances in the chemistry of benzo[b]thiophen~.~~ A further route to thiophens utilising 2-thiocarbonylenamines and a-bromocarbonyl compounds is reported.78 The ring system has also been synthesised from base condensation of a-bromocarbonyl compounds with (a-thiobenzoy1)acetophe-none.79 Thiophens have been shown to react with singlet oxygen forming sulphines as oxidation products or intermediates.80 The non-symmetrical N MeOyJJJ -+ Me0ds Me0 Me0 (78) (79) 74 H.Heaney and C. T. McCarty Chem. Comm. 1970 123. 7s N. E. Rowland F. Sondheimer G.A. Bullock E. LeGoff and K. Graham Tetrahe-dron Letters 1970 4769. 76 0.Meth-Cohn Quart. Reports Sulfur Chem. 1970 5 129. 77 B. Iddon and R. M. Scrowston Adv. Heterocyclic Chem. 1970,11 178. 78 S. Rajappa and B. G. Advani Tetrahedron Letters 1969 5067; cf. Ann. Reports (B) 1969 66 438. 79 M. Takaku Y. Hayasi and H. Nozaki Bull. Chem. SOC. Japan 1970,43 1917. ao C. N. Skold and R. H. Schlessinger Tetrahedron Letters 1970 791 ;H. H. Wasserman and W. Strehlow ibid. 1970 795. Heterocyclic Chemistry 445 isothianaphthene (79) results from pyrolysis of the isothiachromanone enamine (78) possibly through the intermediacy of a thiiranium ion.* Condensation reactions of 1,3-dimethyl-6H-cyclohepta[c]thiophen-6-one(80) have been carried out to yield potentially 6n-10n:dipolar systems for example with (81) the heterosesquifulvalene (82) is obtained.Examination of the electronic CI CI qcl c1 0 A Ac,O Me Q+ + s Me spectra however indicates a high occupancy of the apolar limiting formula in the ground state.82 The first example of a heterocyclic analogue of biphenylene is reported. 1,2-Benzocyclobutadienoquinone(83) with (84)gave 2-thianorbi- phenylene (85). Comparison of the n.m.r. spectra of (85) and the corresponding Ph,P-\ S-W -t Ph,P=/ /' (83) (84) (85) 2,2-dioxide clearly demonstrates the presence of a paramagnetic ring-current shielding effect of the 4n cyclobutadienyl ring in (85).83 The synthesis of a hepta- heterohelicene was reported last year.84 Now the heptaheterohelicene has been employed in the formation of the optically active undecaheterohelicene (86).85 " F.H. M. Deckers W. N. Speckamp and H. 0.Huisman Chem. Comm. 1970 1521. 82 G. Seitz and H. Monnighoff Angew. Chem.Internat. Edn. 1970,9,907;cf. G. V. Boyd, A. W. Ellis and M. D. Harms J. Chem. SOC.(C),1970 800; G. V. Boyd and M. D. Harms ibid. 1970 807. 83 P. J. Garratt and K. P. C. Vollhardt Chem. Comm. 1970 109. 84 Ann. Reports (B) 1969 66 438. 85 H. Wynberg and M. B. Groen J. Amer. Chem. SOC.,1970,92,6664. 446 B. C. Ufl Five-membered Rings with Two or More Hetero-atoms.-Advances in imidazole chemistry have been reviewed.86 The utility of dipolar cycloaddition reactions for the synthesis of five-membered ring heterocycles continue^.^' For example intramolecular nitrone-allene cycloaddition has resulted in the formation of bicyclic isoxazolidines.88 The novel diazatetracycloundecane system (88) results from a double 1,3-cycloaddition of sydnone (87) with cis,cis-cyclo-octa- l,5-diene.89 The use of 1$dipolar cycloaddition in heterocyclic synthesis has R' (87) been discussed.g0 For example u-triazoles (90) are obtained from vinyl azides (89) in strongly basic media whereas thermolysis in neutral or protic solvents leads to azirine formation (91).9 Examples of syntheses of condensed s-triazoles are also pre~ented.'~ Protonation of the mesoionic 3-phenylsydnone and 1,l-disydnonylethylene in FS03H-SbF solution has been shown to occur on the carbonyl oxygen atom by analogy with protonation of regular carbonyl groups.93 Oxidation of the bis(benzoy1hydrazone) (92) with potassium hexacyanoferrate(rI1) has been N -COPh / Me N-NH*CO.Ph Me + x$.-..Ph x Me N-NH-CO-Ph Me (92) (93) 8b M.G. Grimmett Ado. Heterocyclic Chem. 1970 12 104. '' Ann. Reports (B) 1969 66 439. " N. A. LeBel and E. Banucci J. Amer. Chem. SOC.,1970,92 5278. 89 P. M. Weintraub Chem. Comm. 1970 760. 'O H. Reimlinger Chem. Ber. 1970 103 1900. 9' F. P. Woerner and H. Reimlinger. Chem. Ber. 1970,103. 1908; also see H. Reimlinger. J. J. M. Vandewalle G. S. D. King W. R. F. Lingier and R. Merenyi ibid. p. 1918; A. J. Hubert and H. Reimlinger ibid. p. 381 I. pz H. Reimlinger. J. J. M. Vandewalle and W. R. F. Lingier Chem. Ber.. 1970.103. 1960; H. Reimlinger and M. A. Peiren ibid. p. 3266; H. Reimlinger ibid. p. 3278; H. Reimlinger Chem. and Ind, 1970 1082. 9J G.A. Olah D. P. Kelly and N. Suciu J. Amer. Chem. Soc. 1970,92 3133. Heterocyclic Chemistry 447 shown to give the mesoionic triazole (93) and not a dihydrotetrazine as previously The water-soluble 5-tetrazolyl ylide (94) has been obtained from reaction of 5-dimethylaminotetrazole with benzyl chloride in base together with the expected 1- and 2-benzyl derivative^.^^ NMe PhCH,NMe2 (94) Benz[cd]indazole 1-oxide (95) and 1,2-dioxide (96)have been prepared and the latter is considered to have the structure shown (96)rather than that of l,&dinitro- ~onaphthalene.~~ Reduction of the 1-oxide bypasses the unknown benz[cd]inda- (95) (96) (97) zole itself giving di- and tetra-hydro-derivatives two of which were reported last year.97 4-Phenyl- 1,2,4-triazoline-3,5-dione is well known as a very powerful dienophile :98 now the parent compound (97) has been prepared though not isolated and trapped by a series of dienes.” 0-and N-Acylated derivatives of 3-hydroxy-1,2-benzisoxazole(98) and (99) have been shown to undergo a thermal rearrangement to the isomeric acylated benzoxazol-2-ones (100).With the N-acyl derivatives (99) the rearrangement can also be achieved photochemically. It is thought to proceed by initial cleavage Rx *q:-0Jo \ / \ CO R OCO R 0 I CO R (98) (99) (100) II R R’ Ph-C-CH-CH-NR Me1 -+ Ph*R N N ‘0 H 1 (101) OH (102) 94 S.Peterson and H. Heitzer Angew. Chem. Internat. Edn. 1970,9 67. 95 L. Huff D. M. Forkey D. W. Moore and R. A. Henry J. Org. Chem. 1970,35,2074. 96 R. W. Alder G. A. Niazi and M. C. Whiting J. Chem.SOC.(C),1970 1693. 9’ Ann. Reports (B) 1969 66 441. z Ann. Reports 1962 59 331; 1967 (B)64 205. M. G. de Amezua M. Lora-Tamayo and J. L. Soto Tetrahedron Letters 1970 2407. 448 B. C. Ufl of the 0-N bond in (99).loo The stereochemical consequences of the known'" involvement of the oximate anion as a powerful neighbouring group in the synthesis of A2-isoxazolines (102) by base-induced cyclisation of (101) has been used to provide the first synthesis of optically active A2-isoxazolines.'02 A number of mechanistic pathways have been reported for the thermal decomposition of cyclic azo-compounds.'03 Now the first example of a car- bonium ion mechanism is provided in the acetolyses of azo-p-bromobenzene- sulphonates (103; R' = H R2= OBs and R' = OBs R2= H).Evidence for neighbouring-group participation by the -N=N-group is also presented.lo4 The novel bridged heterocyclic system (104) has been isolated from the pyrolysis of N-(2-hydroxyethyl)trifluoroacetamide.'05 A review has appeared on five-membered cyclic disulphides,'06 on thiadiazole and thiadiazine 5-oxides,'07 and on 5-aryl-1,2,4-dithiazole-3-thiones. The thermal reaction of carbon disulphide with acetylenes having at least one elec- tron-attracting substituent has been shown to generate 1,3-dithiolium carbenes (e.g.105) which have been captured by electrophilic reagents and have effected c1 alkylations and acylations. Chlorinated benzothiazoles (e.g. 106) have been formed by thermal cyclisation of o-chloroaryl isothiocyanates. 'lo Unsubstituted thiazolo[5,4-d]thiazole (107) has been obtained from an acid derivative the loo H. Boshagen and W. Geiger Chem. Ber. 1970,103 123. lo' Ann. Reports 1963 60 259. Ioz R. J. MacConaill and F. L. Scott Tetrahedron Letters 1970 2993. lo3 Ann. Reports (B) 1969 66 455. Io4 E. L. Allred and C. R. Flynn J. Amer. Chem. Soc. 1970,92 1064. Io5 G. M. J. Shusarczuk and M. M. Joullie Chem. Comm. 1970 469. A. Hordvik Quart. Reports Sulfur Chem. 1970 5 21. lo' A. Lawson and R. B. Tinkler Chem. Rev. 1970 70 593.J. Vialle Quart. Reports Sulfur Chem. 1970 5 15 1. Io9 H. D. Hartzler J. Amer. Chem. SOC.,1970 92 1412 1413. 'lo E. Degener G. Beck and H. Holtschmidt Angew. Chem. Infernat. Edn. 1970,9,65. Heterocyclic Chemistry compound proves remarkably stable and does not undergo electrophilic sub- stitution. ''' Further studies' l2 on the thiathiophthene' l3 no-bond resonance system and related structures have appeared.'I4 The first X-ray structure of an extended Ph &CMe2 s-s s-s no-bond resonance system uiz. (108) has shown the row of five sulphur atoms to be linear. Bond distances suggest there probably exists partial bonding between all the sulphur atoms.' ' Six-membered Rings with One Hetero-atom.-Nitrogen derivatives. The synthesis of pyridines via Diels-Alder addition of oxazoles has been reviewed,' l6 as also has the chemistry of lactim ethers"' and 3-piperideines."' A synthesis of the pyridine system is provided by reaction of unsaturated y-cyanocarbox- ylic acid chlorides with hydrogen chloride in an ether (e.g.109-llO).'I9 Me Ph (109) (110) (111) 4-Amino-2-pyridones have been formed from cycloaddition of ynamines to styrylisocyanates.' 2o The acetylation product of 4-pyridone formerly thought to be 4-acetoxypyridine has been shown to be wholly N-acetyl-Spyridone in the solid state although an equilibrium exists in The first example in the heteroaromatic series of a stable aroxyl radical (111) has been generated 'I1 J. R. Johnson D. H. Rotenberg and R. Ketcham J. Amer.Chem. Soc. 1970 92 4047. Ann. Reports (B) 1969 66 443. 'I3 L. K. Hansen and A. Hordvik Acta Chem. Scand.. 1970 24 2246; A. Hordvik and L. J. Saethre ibid. p. 2261. '14 E.g. D. Festal and Y. Mollier Tetrahedron Letters 1970 1259; K. I. G. Reid and I. C. Paul Chem. Comm. 1970 329; F. Leung and S. C. Nyburg ibid. 1970 707; R. J. S. Beer D. Frew P. L. Johnson and I. C. Paul ibid. 1970 154. ' J. Sletten Acta Chem. Scand. 1970 24 1464. M. Ya. Karpeiskii and V. L. Florent'ev Russ. Chem. Rev. 1969,38 540. l'' R. G. Glushkov and V. G. Granik Adv. Heterocyclic Chem. 1970 12 185; Russ. Chem. Rev. 1969 38 91 3. 'I' M. Ferles and J. Pliml Ado. Heterocyclic Chem. 1970,12,43. ' l9 G. Simchen Chem. Ber. 1970 103 389. R. Fuks Tetrahedron 1970 26 2161. I.Fleming and D. Philippides J. Chem. SOC. (0,1970 2426; F. Arndt and A. Kalischek Ber. 1930 63 587. 450 B. C. Ufl by dehydrogenation of 3-hydroxy-2,4,6-triphenylpyridine.The pyridoxyl proves stable towards oxygen and reacts preferentially as a dehydrogenating agent. 22 A new heterocyclic system 2H-thiapyrano[2,3-b]pyridine (1 12) has been prepared from ethyl 2-thioethylnicotinate as shown. 123 By a similar procedure (1 12) (113) (114) the 2H-pyrano[2,3-b]pyridine system (1 13) has been formed from 2-ethoxy-3- (1',3'-dihydroxypropy1)pyridine. 24 Synthesis of the new furo[2,3-b]pyridine structure (114) has resulted from a route commencing with 3-bromoacetyl- pyridone. ' 3-Azabicyclo[3,3 llnonanes have been synthesised for example (115; R' = CO,Et R2R3= 0)from the pyrrolidine enamine of N-toluene-p-sulphonylpiperidone and or-bromomethylacrylate.The diol (I 15;R' = CH,OH, 95 H R' OH (1 15) (116) RZ = OH R3 = H) underwent smooth detosylation to give 4hydroxyaza- adamantane (1 16).' 26 A number of syntheses of the 1-azatwistane system (119) H have been rep~rted.'~' For example on heating the mesylate (1 17)the salt (1 18) was obtained which formed (1 19)in quantitative yield on hydr~genolysis.'~~' Interest in some branches of heterocyclic chemistry has now risen to the level of duplicate publication. Reviews concerning the naphthyridine~'~' and the benzoisoquinolines and azafluorenes' 30 have appeared. Most syntheses of tetra- or di-hydroisoquinolines require an activating substituent in the carbo- lZ2 H.-J.Teuber G. Schutz and H.-J. Gross Angew. Chem. Internat. Edn. 1970 9 519. H. Sliwa Bull. SOC. chim. France 1970 642. '14 H. Sliwa Bull. SOC. chim. France 1970 631. 25 H. Sliwa Bull. Sac. chim. France 1970 646. W. N. Speckamp J. Dijkink and H. 0.Huisman Chem. Comm. 1970 196 197. (a)K. Heusler Tetrahedron Letters 1970,97; (b)D. Perelman S. Sicsic and Z. Welvart ibid. 1970 103; (c) S. Dube and P. Deslongchamps ibid. 1970 101. E.g. Tetrahedron Letters 1969 5143 5287. 12' W. W. Paudler and T. J. Kress Adu. Heterocyclic Chem. 1970,11 124. I3O N. S. Prostakov Russ. Chem. Rev. 1969 38 774. Heterocyclic Chemistry 45 1 cyclic ring. A general synthesis of 4-aryltetrahydroisoquinolinesis reported in which this condition is not necessary involving the cyclisation of 2-vinylbenzyl-amines under basic conditions.' ' Base-catalysed elimination of hydrogen chloride from the isoquinoline Reissert compound chlorohydrin (120) results in rearrangement probably via (121) to an isochromene (122).This product can be further attacked by ethoxide to ring-open again and re-form a new isoquinoline (123).132 A two-carbon ring-expansion of heterocycles can be achieved by NC NHCOPh]+wo @:h-[a NC EtOe NCOPh CHO (123) OEt ynamine addition to a cyclic imine. For example 3,4-dihydroisoquinoline with (124) gives the 3-benzazocine (126). The primary cycloadduct (125) can be isolated as its hydrolysis product (127) without ring opening. By a similar proce- dure indolenines can be expanded to benzazepines.l3 1,2,3,4-Tetrahydroiso-quinolines of the type (1 28) have been prepared by a-aminoalkylation of styrenes -NMe + PhC =CNMel-+ (124) ' ' Ph Ph Ph Ph Ph G ,CHR' H+ PhCH=CH /CH,O -9 Ph R=R'=H 'NH O' R' R (129) 13' K. Freter E. Dubois and A. Thomas J. Heterocyclic Chem. 1970,7 159. '32 G. W. Kirby S. L. Tan and B. C. Uff,Chem. Comm. 1970 1 138. 133 R. Fuks and H. G. Viehe Chem. Ber. 1970 103 573. 452 B. C. Ufl with an aldehyde and aromatic amine. If formaldehyde is used with primary amines 1H,SH-benzo[ij]quinolizines are the principal products (e.g. 129).'34 Oxygen and Sulphur Derivatiues. Reviews have appeared on unsaturated sugars ' nitro-sugars,' 36 branched-chain amino-sugars,' 1,6-anhydroaldo-hexopyranoses,' 38 mutarotation of sugars in solution,' 39 mechanistic aspects of carbohydrate ~hemistry,'~' sulphonic esters of carbohydrate^,'^' the synthesis of O-glyc~sides,'~~ gums and mucilages '43 and the formation of polysaccharide gels and net~0rks.I~~ A simple procedure has been developed for the stereo- specific synthesis of some 2-chloro-2-deoxypentoses.For example treatment of H #H -.OR% OR OR H ci H (130) (131) (130; R = S0,CI) with aluminium chloride resulted in (131) via anomeric chlorine migration to the extent of almost loO%.145A high-yield synthesis of 2,3-isopropylidene-~-~-ribofuranosylamine is reported from reaction of D-ribo- pyranosylamine with acetone 2,2-dimethoxypropane and toluene-p-sulphonic acid.The product is of value as an intermediate in nucleoside ~yntheses.'~~ The synthesis of two tetra-amino-sugars has been reported 2,3,4,6-tetra- tetrahydr~chloride'~~ amino-2,3,4,6-tetradeoxy-~-galactose and the glucose analogue.'48 The route to the latter compound for example is from the galacto- dimesylate derivative (1 32) which on conversion to the diazide (1 33) gives (1 34) 134 K.-D. Hesse Annalen. 1970,741 117. 135 R. J. Ferrier Adv. Carbohydrate Chem. 1969 24 199. 136 H. H. Baer Adv. Carbohydrate Chem. 1969,24 67. 13' F. W. Lichtenthaler Fortschr. Chem. Forsch. 1970 14 556. 138 M. Cerny and J. Stangk Fortschr. Chem. Forsch. 1970 14 526. 139 H. S. Isbell and W. Pigman Adv. Carbohydrate Chem. 1969 24 14. J. S. Brimacombe Fortschr.Chem. Forsch. 1970 14 367; H. Simon and A. Kraus ibid. p. 430; H. Paulsen H. Behre and C.-P. Herold ibid. p. 472. 141 D. H:Ball and F. W. Parrish Adu. Carbohydrate Chem. 1969 24 139. 142 R. J. Ferrier Fortschr. Chem. Forsch. 1970 14 389. G. 0.Aspinall Adv. Carbohydrate Chem. 1969 24 333. 144 D. A. Rees Adv. Carbohydrate Chem. 1969,24 267. 145 H. J. Jennings Canad. J. Chem. 1970,48 1834. 146 N. J. Cusack and G. Shaw Chem. Comm. 1970 11 14. 14' W. Meyer zu Reckendorf Chimia (Switz) 1970,24 16. W. Meyer zu Reckendorf Tetrahedron Letters 1970 287. Heterocyclic Chemistry 453 in good yield by hydrogenation and hydrolysis. A one-step procedure for protecting trans-diequatorial amino- and hydroxy-groups in amino-sugars is reported utilising p-nitrophenoxycarbonyl chloride.For example methyl CH,OH "Ox+) \fH OMe 0 (135) 2-amino-2-deoxy-a-~-glucopyranoside gives the 2,3-carbamate derivative (135) in good yield.'49 Glycosides have been obtained in good yields by the use of silver salts of 2- 3- or 4-hydroxyalkanoic acids or of 1,3- or 1,4-dicarboxylic acids with alcohols and 2,3,4,6-tetra-0-acetyl-a-~-ghcopyranosy1bromide in ether the method proves simple and mild.' so A crystal structure of a seven-membered-ring sugar 1,2 :3,4-d~-O-isopropylidene-5-O-chloroacetyl-or-~-glucoheptanose,shown has the heptanose ring to adopt a conformation which lies between the chair and twist-chair forms.' s1 A new route to or-pyrones (137) is reported from P-diketones and the phos- phorane (1 36).52 Pyrolytic decarboxylation of 5-methyl-6-carboxy-2-pyrone affords 3-methyl-2-pyrone. The rearrangement occurs for other similar pyrones PO HZC + k-O R and it is suggested that following decarboxylation a 1,5-sigmatropic hydrogen shift is involved accompanying reversible electrocyclic ring opening (138) +(1 39)' 2-Alkoxy-3,4-dihydro-2H-pyrans (140) have been found to undergo an oxidative rearrangement to substituted tetrahydrofuran derivatives (141) in the presence of peracid possibly via ring-opening of the intermediate epoxide.' s4 fixGcqX= flX e nx OOH IIH 0 0 H II HOO (138) 0 0 (139) lQ9 S. Umezawa T. Tsuchiya and Y.Takagi Bull. Chem. SOC. Japan 1970,43 1602. 150 G. Wulff G. Rohle and W. Kruger Angew. Chem.Internat. Edn. 1970,9,455. 51 J. Jackobs and M. Sandaralingam Chem. Comm. 1970 157. A. K. Sorensen and N. A. Klitgaard Acta Chem. Scand. 1970,24 343. W. H. Pirkle H. Seto and W. V. Turner J. Amer. Chem. SOC. 1970,92,6984. 154 S. S. Hall and H. C. Chernoff Chem. andfnd. 1970 896. 454 B. C.U! A number of syntheses of 2-oxabicyclo[2,2,2]octane(143) have been reported ; the most efficient involves a l&transannular elimination from the cis-tosylate (142) proceeding in over 95 yield. " The 2,7-dioxaisotwistane (145 ;R = H) and 2,7-dioxatwistane (146; R = H) ring systems have been obtained via the acetoxy-compounds (145 and 146; R = OAc). The twistane skeleton results from a molecular rearrangement of the iodoisotwistane compounds (144) on treatment with silver acetate.156 The first synthesis of loganin (150),the key iridoid glucoside involved in indole alkaloid biogenesis has been achieved involving as main step the formation of (149) by photocycloaddition of the P-tricarbonyl compound (147) to the protected lS5 T. A. Giudici and T. C. Bruice J. Org. Chem. 1970 35 2386; W. Schneider and K. Lehman Tetrahedron Letters 1970 428 I. C. Ganter and K. Wicker Helv. Chim.Acta 1970 53,1693. Heterocyclic Chemistry 455 olefin (148).lS7 A useful route to azachromones is reported employing hetero- cyclic enamines. Treatment of (151) with diketen gives (152) which on dehydro- genation gives (153).' '* Me Halfordinin (154) a linear furanocoumarin has been isolated from the bark of Ha2fordia kendak and shown to possess the novel feature of an aa-dimethylallyl side-chain joined to the ring through an ether linkage.'" A review has appeared on the chemistry of the aflatoxins,16' and a book on flavanoid identification.16' Two optically active flavans (155 R = H and Me) have been isolated from two Me0 OMe 0 Me 9 (154) (1 55) species of Dianellinae and have an uncommon feature of no oxygen atom attached to the heterocyclic ring.162 Eight new members of the small family of homoiso-flavones' 63 have been isolated e.g.punctatin (1 56). 164 Treatment of flavylium OMe salts with hydroxylamine has been shown to give A3-isoxazolines [e.g. (157)+ (158)]'65 and not a chalcone oxime as thought earlier although the latter may be an intermediate.15' G. Buchi J. A. Carlson J. E. Powell and L.-F. Tietze J. Amer. Chem. SOC.,1970,92 2165. I 58 I. Belskey Tetrahedron Letters 1970 4597. I 5y J. K. MacLeod Tetrahedron Letters 1970 361 1. I6O C. P. Mathew Chem. andInd. 1970 913. 16' T. J. Mabry K. R. Markham and M. B. Thomas 'The Systematic Identification of Flavanoids' Springer-Verlag New York 1970. 162 R. G. Cooke and J. G. Down Tetrahedron Letters 1970 1037. Ann. Reports (B) 1967 64 414. 164 W. T. L. Sidwell and Ch. Tamm Tetrahedron Letters. 1970. 475; R. E. Finckh and Ch. Tamm Experientia 1970 26 472. L. Jurd Chem. and Ind. 1970 624. 456 B. C. Ufl MW / O -Me \ woMe \ 0-NH (157) (158) Interest in quadrivalent-type sulphur heterocycles continues.' For example thiabenzene (160) has been generated from the fluoroborate (159) with base. The spectral and chemical properties of (160) are consistent with an ylide-type C 1 CH (161) Me (162) 1 1 Me (163) bonding description for thiabenzenes. ' ' Thermolysis of prop-2-ynyl phenyl sulphide (161) can produce (162) (163) and (164) the first being the result of a thiopropynylic rearrangement (by analogy with the thioallylic shift in ally1 phenyl sulphides). Both (161) and (162) then undergo a thio-Claisen rearrange- ment followed by cyclisation to give the 2H-thiachromene (163)and benzo[b]thio- phen (1 64).'68 Six-membered Rings Containing Two or More Hetero-atoms.-The conforma-tional analysis of saturated heterocylic compounds containing two hetero-atoms has been re~iewed.'~' A book has appeared on the pyrirnidine~'~' and a review 166 Ann.Reports (B) 1969 66 455; 1968 65 476. 167 A. G. Hortmann and R. L. Harris J. Amer. Chem. Soc. 1970,92 1803. 16' H. Kwart and T. J. George Chem. Comm. 1970,433. 16' E. Eliel Accounts Chem. Res. 1970 3 1 ; Bull. SOC. chim. France 1970 517. I7O D. J. Brown 'The Pyrimidines' Supplement 1 of 'Chemistry of Heterocyclic Com- pounds' Volume 16 Wiley-Interscience New York 1970. Heterocyclic Chemistry on progress in 1,3,4-thiadiazine chemistry has been published. l7 The synthesis of adenine from formamide and phosphorus oxychloride was reported pre- viou~ly.'~~ The method has now been modified by addition of other amides to give a one-step route to pyrimidines (165) and condensed pyrimidine^.'^^ (165) The isomerisation of 2-pyridylcarbene to phenylnitrene was discussed last year' 74 and the work has been extended to a study of nitrene~diazines.'~~ Whereas displacement with potassium amide in liquid ammonia of 6-bromo-4-t-butyl-pyrimidine (1 66) gives the 6-amino-derivative probably via a 56-heteroaryne CMe3 N5 _____) C,HIoNLi IkHCN d Br H,,C,N H ( 166) (1 67) intermediate,17' treatment of the system with a different nucleophile lithium piperidide in ether causes ring-opening.The product (167) is considered to arise by addition of the nucleophile to the azomethine bond in (166) followed by opening of the 1,Zdihydro-compound. N H H. Beyer Quart. Reports Sulfur Chem.1970 5 177. Ann. Reports (B) 1968 65 479. K. Morita S. Kobayashi H. Shimadzu and M. Ochiai Tetrahedron Letters 1970 861. 'l4 Ann. Reports (B). 1969. 66. 444. 175 C. Wentrup and W. D. Crow Tetrahedron 1970,26,4915; C. Wentrup ibid. p. 4969. 176 Ann. Reports (B) 1968 65 480. H. C. van der Plas and A. Koudijs Rec. Trav. chim. 1970 89 129. 458 B. c. ufl An unusual rearrangement of a pyrimidine derivative (168) is reported on' treatment with aqueous hydrazine or water alone at 210 "Cthe 1,2,4-triazole (169) is produced. A possible mechanism initiated by nucleophilic attack at position 2 with ultimate loss of the C6-N1 fragment is indicated."' A new synthesis of the quinazoline system results from cyclisation of o-cyano-phenyl isocyanates (170) in the presence of hydrogen halide giving 4-halogeno-2- quinazolones (171).17' The triazolo[4,3-a]pyrazines (172) have been shown to ,aCN sRelo N=C=O H R' R2$TNH R3 NH2 R3 Nf 0 R1 (172) (173) rearrange in acid to the hitherto unreported 1H-imidazo[2,l-c]-s-triazoles (173)"' and not to triazolo[2,3-a]pyrazinesas reported previously.l8 The dihydro-1,3-oxazine system (1 74) was reported last yearLs2 as a building block for the synthesis of aldehydes ketones and carboxylic acids. Other aspects 0 (178) 178 H. C. van der Plas and H. Jongejan Rec. Trau. chim. 1970,89,680. 179 G. Simchen G. Entenmann and R. Zondler Angew. Chem. Internat. Edn. 1970 9 523. I80 F. L. Rose G. J. Stacey P. J. Taylor and T. W. Thompson Chem.Comm. 1970 1524. I81 Ann Reports 1966 63 479. 182 Ann Reports (B),1969,66 458. Heterocyclic Chemistry of the aldehyde synthesis sequence have been e~amined,'~~.'~~ and a further route to ketones (177) is now recorded via Grignard or alkyl-lithium addition to the cation (175 ;R = alkyl or aryl) followed by acid-catalysed ring-cleavage of (176).18' The synthetic utility of the oxazine approach has also been comple- mented by use of the 2-oxazoline ring system in application to the synthesis and alkylation of acids,' 86 and the formylation of Grignard reagents. ' The structure of mitiromycin has been elucidated as (178) and represents the first mitomycin antibiotic to contain an oxazinone ring in place of the usual open-chain carbamate ester grouping.88 A new synthesis of the 1,2,4-oxadiazine system is provided by condensation of chloroacetylisocyanate (179) with N-monosubstituted hydroxylamines. The intermediate (180) cyclises in base to give (181).'89 A poisonous compound (1821 found in the Daphne genus has the structure (182) daphnetoxin. The structure is similar in its high degree of oxygen-bridging to a number of other toxic nitro- genous and non-nitrogenous compounds. ''' An attempted Bischler-Napieralski reaction on the thioketal (183) gave instead of the expected isoquinoline the 183 A. I. Meyers G. R. Malone and H. W. Adickes Tetrahedron Letters 1970. 3715. A. I. Meyers and E. M. Smith Tetrahedron Letters 1970,4355. A. I. Meyers and E. M. Smith J. Amer. Chem. SOC.,1970,92 1084.A. I. Meyers and D. L. Temple J. Amer. Chem. Soc. 1970,92,6644 6646. 18' A. I. Meyers and E. W. Collington J. Amer. Chem. SOC.,1970 92 6676. G. 0. Morton G. E. Van Lear and W. Fulmor J. Amer. ChCm. SOC.,1970,92,2588. P. Rajagopalan and B. G. Advani Chem. Comm. 1970 167. I9O G. H. Stout W. G. Balkenhol M. Poling and G. L. Hickernell J. Amer. Chem. SOC. 1970 92 1070. 460 B. C. Ufl dihydro-p-dithiin structure (184) with loss of the amide group. Other dihydro-p- dithiins have been prepared similarly and the method extended to give a dihydro- dithiepin from a propylene thioketal.lgl Seven-membered and Larger Rings.-A novel transannular ring contraction is reported as resulting from the attempted Wolff-Kishner reduction of 2,7-di-phenylhexahydro-4-azepinone (185) the product being the pyrrole (186).Several (1851 (186) mechanisms for the transformation have been suggested which must involve cleavage of the W,bond of the intermediate hydrazone.Ig2 Although cis-azo- dienophiles were found to add in a (4 + 2)n manner to N-ethoxycarbonylazepine [e.g. to give (187)] reaction of diethyl azodicarboxylate (trans-configuration) 0 proceeded very slowly to give the (6 + 2)n product (188) suggesting steric factors are inhibiting concerted attack in this case.Ig3 Compound (190) an aza- analogue of homocyclohexadienone is afforded by the thermal [3,3)sigmatropic (189) (190) (191) (192) rearrangement (the Cope rearrangement) of the cyclopropylisocyanate (189) the process is reversed photo~hemically.'~~ Ring-expansion of the azahomo- adamantane (191) to the diaza-homologue (192) is reported via Beckmann rearrangement of the corresponding oxime.95 19* J. L. Massingill M. G. Reinecke and J. E. Hodgkins J. Org. Chem. 1970,35 823. 192 C. G. Overberger J. Reichenthal and J.-P. Anselme J. Org. Chem. 1970 35 138. 193 W. S. Murphy and J. P. McCarthy Chem. Comm. 1970 1129. 19' T. Sasaki S. Eguchi and M. Ohno J. Amer. Chem. Soc. 1970,92 3192. 19s V. G. Keizer J. Q. Korsloot F. W. v. Deursen and M. E. v. d. Heeden Tetrahedron Letters 1970 2059. Heterocyclic Chemistry 46 1 An example of the 4-am-azulene system viz. (194) results from treatment of (193) with pyrrolidine in the presence of an acid cata1y~t.l’~ Whereas azulene (193) (194) does not appear to undergo cycloaddition reactions the 5-aza-azulene system is reported to add to alkynes.6-Phenyl-5-am-azulene (195) gives products (196) (197) and (198) derived from the two initial adducts as sh~wn.’’~ Ph Ph RC sCR (€95) (198) The activity of annulated thiepins towards dienophiles was reported last year.’98 The adducts normally reveal loss of sulphur but by use of bulky sub- stituents a stable 8n-electron thiepin system (199) has been prepared.lgg This is of particular interest since calculations have predicted the thiepin system to be antiaromatic.200 Thermal decomposition of the azide (200)leads to the thiazepin (201) via a rearrangement involving nitrene participation.201 In the case of the 0 OH M&OH (199) 196 M.K. Conner and E. LeGoff Tetrahedron Letters 1970 2687. 19’ K. Hafner J. Haring and W. Jakel Angew. Chem. Internat. Edn. 1970 9 159. 19’ Ann. Reports (B) 1969 66 462. 199 J. M. Hoffmann and R. H. Schlessinger J. Amer. Chem. Soc. 1970,92,5263. M. J. S. Dewar and N. Trinajstic J. Amer. Chem. Soc. 1970,92 1453. 201 J. I. G. Cadogan and S. Kulik Chem. Comm. 1970 233. 462 B. C. Ufl dimethoxy-analogue a nitrene-induced 1,4-rnethoxy shift occurs to give (202) as one product.202 A compound (203) in which a triple bond is present in a seven-membered ring has been isolated for the first time from the bis-hydrazone shown.203 Me -? H Me Me A new route to azocines [e.g. (204)] is reported using a sequence of cyclo-addition/retro-Diels-Alder reactions as indicated.204 It is known that the four double bonds in simple azocines lack appreciable conjugative interaction due Ph N+N C02Me Ph'N~ C02R C02Me C02Me I (204) COzMe to the preferred tub conformation of these heterocycles.205 However it has now been shown that the azocine ring readily undergoes two-electron reductions to give like cyclo-octatetraene,z06 a planar 1%-electron dianion [e.g.(ZOS)] (206) J. 1. G. Cadogan and S. Kulik Chem. Comm. 1970,792. '03 A. Krebs and H. Kimling Tetrahedron Letters 1970 761. lo4 J. A. Elix W. S. Wilson and R. N. Warrener Tetrahedron Letters 1970 1837. Ann. Reports (B) 1968 65 485. 'Ob Ann. Reports 1960 57 230. Heterocyclic Chemistry with a high degree of n-electron delo~alisation.'~~ l-Azabicyclo[3,3,3]undecane (207) has been prepared by sodium in liquid ammonia treatment of the tricyclic salt (206) synthesis of the carbocyclic analogue is also described.208 We reported last year the synthesis of N-ethoxycarbonylazonine.209Brief low-temperature contact with potassium t-butoxide has now been shown to lead to the parent 1H-azonine (208) itself."' There has been disagreement over the (208) interpretation of the temperature-dependent n.m.r.spectra of N-ethoxycar- bonylazonine.21 l2 A c omparative study of oxonin and N-substituted azonines 'p2 indicates there is a gradual transition from polyenic to aromatic character on increasing the availability of the electron pair on the heter~atom.~'~ There is good evidence supporting the concertedness of the majority of 1,3-dipolar cycloaddition reactions,' l4 thus addition of 1,3-dipoles to trienes is a symmetry- allowed [,6 + .4,] thermal process and some reactions of this type have been pr0vided.l s*21h For example the bridged dihydrodiazonine (209) results from generation of diphenylnitrileimine in the presence of tropone.2 ' Thermal cycloaddition of 4-phenyl- 1,2,4-triazoline-3,5-dioneto oxonin gives adduct (210) which could result from a direct [2 + 2 + 21 cycloaddition or a two-step process involving initial [2 + 81 intera~tion.~'~ Two isomers (211) and (212) of an analogue of biphenylene in which one of the benzene rings has been Ph Ph I -N O O + + ;I -C 1 Ph '07 L.A.Paquette T. Kakihana and J. F. Hansen Tetrahedron Letters 1970 529; L. A. Paquette J. F. Hansen T. Kakihana and L. B. Anderson Tetrahedron Letters 1970 533. N. J. Leonard and J. C. Coll J. Amer. Chem. Soc. 1970,92 6685. '09 Ann. Reports (B) 1969 66 465. 'lo A. G. Anastassiou and J. H. Gebrian Tetrahedron Letters 1970 825. A. G. Anastassiou R. P. Cellura and J. H. Gebrian Chem. Comm. 1970,375. ''' K. Hojo and S. Masamune J. Amer. Chem. SOC.,1970,92,6690. 'I3 A. G. Anastassiou S. W. Eachus R. P. Cellura and J. H. Gebrian Chem. Comm. 1970 1133. Ann. Reports (B),1968,65 457. K. N. Houk and C. R. Watts Tetrahedron Letters 1970 4025. 'I6 K. N. Houk and L. J. Luskus Tetrahedron Letters 1970 4029. 'I7 A. G. Anastassiou and R. P. Cellura Chem. Comm.1970 485. 464 B. c. ufl replaced by an alkylated potentially aromatic thionin ring are reported. Isomer (212) represents the first isolated case of a fully unsaturated nine-membered ring containing a trans-double bond.’ l8 Formation of NN’-dimethyl[2,2] (2,5)pyrrolophane (213) has been achieved from the corresponding difurano-cyclophane.2 l9 The nitrogen-bridged [12]- annulene derivative (214) has been synthesised :n.m.r. studies suggest it is not in pJ \I equilibrium with the diaza-annulene structure (215) although no definite con- clusion has yet been drawn.220 In interesting juxtaposition to this however is the report of the synthesis of [2,2](2,6)pyridinophane-1,9-diene(216).22 (216) (217) The product contrary to earlier predictions,’22 does not undergo spontaneous valence tautomerisation to 15,16-dihydro-15,16-diazapyrene (217).221 The synthesis of some fully unsaturated 11- 12- and 13-membered sulphur heterocycles has been reported including the trans,trans 13-membered ring *18 P.J. Garratt A. B. Holmes F. Sondheimer and K. P. C. Vollhardt J. Amer. Chem. Soc. 1970 92,4492. 219 H. H. Wasserman and D. T. Bailey Chem. Comm. 1970 107. 120 W. W. Paudler and E. A. Stephan J. Amer. Chem. SOC., 1970,92,4468. 221 V. Boekelheide and J. A. Lawson Chem. Comm. 1970 1558; cf. V. Boekelheide and W. Pepperdine J. Amer. Chem. SOC.,1970,92 3684. 222 Ann. Reports 1958 55 268. Heterocyclic Chemistry structure (218). The n.m.r. spectra of the macrocycles indicate no appreciable ring-current effects and they are presumably non-planar molecules.223 The Me Me Me I I I N-NH N-N=N-N 1 (N-NH2 -+( N-N=N-N I I I Me Me Me (219) (220) cyclic bis-2-tetrazene (220) has been formed by potassium bromate oxidation of (219)224 and a number of dihydro-octa-aza[l4]annulenes(221 n =0 1 2) have been prepared from the corresponding bishydrazones as (223) (224) Further hetero-bridged cyclophanes have appeared.226 For example the triaza-cyclophanes (222; X = NS02C6H,Me)227 and (222; X = S and X = have been synthesised.Interest continues229 in heteromacrocycles and their use as complexing agents for metal ions.230 The macrocycle (223) has been used to solubilize potassium metal in ether solvents231 and to give the familiar deep blue solution and the thioether macrocycle (224) is able to complex two nickel ions at 223 A.B. Holmes and F. Sondheimer J. Amer. Chem. SOC.,1970,92 5284. 224 M. Iwamura P. J. Hintz and S. F. Nelson J. Amer. Chem. Soc. 1970,92,3496. 225 H. Neunhoeffer and L. Motitschke Tetrahedron Letters 1970 655. 226 Ann. Reports (B) 1969 66 466. 227 F. Vogtle and P. Neumann Chem. Comm. 1970 1464; and see F. Vogtle and P. Neu- mann Tetrahedron Letters 1970 115. 228 F. Vogtle Annafen 1970 735 193. 229 C. J. Pedersen J.Amer. Chem. Sac. 1970,92,386,391;J. M. Lehn J. P. Sauvage and B. Dietrich ibid. p. 2916. "O Ann. Reports (B) 1969 66 467. 231 J. L. Dye M. G. DeBacker and V. A. Nicely J. Amer. Chem. Soc.. 1970,92. 5226. 232 K. Travis and D.H. Busch Chem. Comm. 1970 1041.