11 Heterocyclic Compounds By A. J. BOULTON and M. J. COOK School of Chemical Sciences University of East Anglia Norwich NR4 7TJ 1 Heterocycles in Transformations of Functional Groups 1,4-Dihydropyridines have received considerable attention as reducing agents in a number of laboratories. The role of metal ions as catalysts has been discussed,’ and the specific effect of zinc ions in the reduction of pyridine-2-carbaldehyde by 1-benzyl- 1,4-dihydronicotinic acid diethylamide has been described.2 A chiral 1,4-dihydropyridine that has been worked into a crown ether system (1) delivers hydride in an asymmetric red~ction.~These reactions are not confined to unsaturated carbon sulphonium salts are also atta~ked.~ Me ,H \ H2NYo2H Me R (4) (2) R=H (3) R=alkyl Me (1) Asymmetric induction using proline derivatives has been described by two Japanese groups.In one approach the basic nitrogen forms the first attachment to the substrate and the carboxy-group delivers the substituent which forms the new asymmetric centre.’ In the other the amino-acid is converted into a range of chiral amine ligands to complex Grignard reagents and organo-lithium compounds during addition to aldehydes6 The lactim ether (2) derived from L-alanine can be lithiated and the C-alkylated product (3) then used to form amino-acids (4) in good optical yield.’ An N-(camphorsulphony1)-oxaziridine has been proposed as a chiral oxidiz- ing ageote8 R. A. Gase and U. K. Pandit J. Amer. Chem. Suc. 1979,101,7059.R. A. Hood and R. H.Prince J.C.S. Chem. Comm. 1979,163. J. G. de Vries and R. M. Kellogg J. Amer. Chem. SUC.,1979,101 2759. T. J. van Bergen D. M. Hedstrand W. H. Kruizinger and R. M. Kellogg J. Org. Chem. 1979,44,4953. ’ S. S. Jew S. Terashima and K. Koga Tetrahedron 1979,35,2337 2345. T. Mukaiyama K. Soai T. Sato H. Shimizu and K. Suzuki J. Amer. Chem. Suc. 1979,101 1455. ’U.Schiillkopf W. Hartwig and U. Groth Angew. Chem. Internat. Edn. 1979,18,863. F. A. Davis R. Jenkins S. Q. A. Rizvi and T. W. Panunto J.C.S. Chem. Cumm. 1979,600. A. J. Boulton and M. J. Cook The use of pyrylium salts for converting primary amines into other functionalities by nucleophilic displacement of a pyridine ring from the derived pyridinium salts [cf. Ann. Reports (B) 1977 74 2511 has led to a number of further preliminary communications and some full papers.Particularly noteworthy transformations not hitherto mentioned in these Reports include the preparation of a wide variety of alkyl aryl and heteroaryl iodides from the corresponding amines,' of aryl" and alkyl" thiocyanates and of alkyl fluorides,'* and the C-alkylation of nitronate anions.I3 Steric acceleration to nucleophilic displacement apparently gives the fused pyrylium salts (5) an advantage over the 2,4,6-triphenyl compounds in these amine-substitution reactions.10 A 'reductive deamination' procedure which had earlier been applied to benzylic pyridinium salts by reduction with borohydride to the 1,2-dihydropyridine (6) and thermal decomposition 14~15was found to proceed more readily and with a wider range of substrates (R = alkyl or aryl) when the 1,4-dihydropyridine (7) was heated.l6 The mechanism of the decomposition of 1,2-dihydropyridine (6) was shown by labelling experiments not to involve a retro-ene reaction (cf ref. 14) and probably to be free-radical in nature.16 Ph &Ph NH Ph NH lrk~~~~,~~~2 Me Me R 0' R' N R2 (9) Isoxazoles have long been employed as protective and directive groups usually with advantage being taken of the ready reductive cleavage of the N-0 bond to generate the reactive enamino-ketone function at an appropriate stage in the sequence. A typical example of this type was reported recently in the synthesis of the 1,2,6-thiadiazine 1,l-dioxide (9) from (8).17 Now 2-isoxazolines are found to be perhaps even more versatile being able to undergo reactions not open to the isoxazoles.'* Metalation of 2,3,4-trimethylisoxazolin-5-one(lo) and its bromina- tion with N-bromosuccinimide followed by reaction with triphenylphosphine both A.R. Katritzky N. F. Eweiss and P.-L. Nie J.C.S. Perkin Z 1979,433. lo A. R. Katritzky and S. S. Thind J.C.S. Chem. Comm. 1979 138. A. R. Katritzky U. Gruntz N. Mongelli and M. C. Rezende J.C.S. Perkin I,1979 1953. l2 A. R. Katritzky A. Chermprapai and R. C. Patel J.C.S.Chem. Comm. 1979,238. l3 A. R. Katritzky. G. De Ville and R. C. Patel J.C.S. Chem. Comm. 1979 602. l4 A. J. Boulton J. Epsztajn A. R. Katritzky and P.-L. Nie Tetrahedron Letters 1976 2689. l5 A. R. Katritzky J.Lewis and P.-L. Nie J.C.S. Perkin Z 1979 442. l6 A. R. Katritzky K. Horvath and B. Plau J.C.S. Chem. Comm. 1979 300. l7 H. A. Albrecht J. F. Blount F. M. Konzelmann and J. T. Plati J. Org. Chem. 1979,44,4191. V. Jager and W. Schwab Tetrahedron Letters 1978,3129;V. Jager H. Grund and W. Schwab Angew. Chem. Znternat. Edn. 1979,18,78. Heterocyclic Compounds activate the methyl group at the 3-position and the intermediates show potential for future construction work.lg The anion derived from 1,3-dihydrobenzo[c]thiophendioxide has been used by two research groups in the synthesis of polycyclic compounds.20-21 The principle is that thermal decomposition of the alkenylated product (1 1) generates an inter- mediate (12) which can undergo an intramolecular Diels-Alder reaction in the same way as that earlier described [Ann.Reports (B) 1974 71,3451 for similar inter- mediates from dihydrobenzocyclobutenes. HO II HO II HO I I Ph,;O I(13) I II OH 'i' I- I I+OPPh I I I- I 'PPh,(13) I- \/ ,c=c Os,OPh N A mixture of imidazole triphenylphosphine and iodine is recommended as a reagent for the reduction of vicinal diols to olefins.22 It is suggested that the intermediate (13) is formed which converts a hydroxy-group into an iodo-group as indicated; the other hydroxy-group is activated and iodide ion completes the reduction. Another heterocyclic reagent which is conveniently prepared in situ is the water-soluble benzoylating agent (14).23 2 General Synthetic Methods Reaction Types and Physicochemical Studies In this Section we discuss some aspects of heterocyclic chemistry which are not conveniently categorized by ring size as in the following Sections.l9 S.A. Tischler and L. Weiler Tetrahedron Lerters 1979,4903. K. C. Nicolaou and W. E. Barnette J.C.S. Chem. Comm. 1979 1119. ''W. Oppolzer D. A. Roberts and T. G. C. Bird Helv. Chim. Acra 1979,62,2017. '* P.J. Garegg and B. Samuelsson Synthesis 1979,469. 23 M. Yamada. Y. Watabe. T. Sakakibara and R. Sudoh J.C.S. Chem. Comm. 1979 179. A. J. Boulton and M. J. Cook Synthesis.-o-Formyl-N-alkyl-anilines (19,important intermediates for the pre- paration of many heterocyclic systems can be prepared by the action of BCI and an isocyanide on the alkyl-aniline; this is an interesting variant on the o-acyl-aniline synthesis using nitriles reported last year [Ann.Reports (B) 1978 75 2411. The intermediate benzoborazoline derivatives (16) can be i~olated.’~ + PhNHOH NaBH,CN ++4 1 CH2CH0 I CH,C=CCO,Et (18) 1 H ?OMe 1 CO,EtQ (17) (21) A number of heterocyclic syntheses were noted which use a hetero-Cope re- arrangement at some stage. The important pyrrolo[l,2-a]indole system (17) was prepared from phenylhydroxylamine and an acetylenic aldehyde (18) in a multi-step sequence in which the 1,2-oxazine (19) was rearranged to the benzazocine (20). None of the intermediates was i~olated.’~ A Diels-Alder addition and Cope rearrangement are concerned in the conversion of a dihydropyridine through an isoquinuclidine into a hexahydroisoquinoline in which the key step is the re- arrangement of the (un-isolated) intermediates (2 1)and (22).26Also relevant here are new syntheses of 3-a~yl-pyrrolidines,’~ of 3,3’-bi(pyrrolidin-2-0ne),’~and of 5,6,7,8-tetrahydroq~inoline.’~ Cyc1oaddition.-A reaction which was at first incorrectly interpreted3’ has now been straightened out and some interesting chemistry of azoalkenes (23) has emerged.24 T. Sugasawa H. Hamana T. Toyoda and M. Adachi Synthesis 1979,99. ” R. M. Coates and C. W. Hutchings,J. Org. Chem. 1979,444742. 26 P. S. Mariano D. Dunaway-Mariano and P. L. Huesmann J. Org. Chem. 1979,44 124. ” L. E. Overman and M. Kakimoto J. Amer. Chem. SOC.,1979,101 1310. ’* Y. Tamaru T. Harada and Z. Yoshida J. Amer. Chem.SOC.,1978,100 1923. 29 T. Kusumi K. Yoneda and H. Kakisawa Synthesis 1979,221. 30 S. Sommer Chem. Letters 1977 583. Heterocyclic Compounds Enamines do not undergo [4+21 but rather [3 +21 cycloaddition giving initial azomethine-imines (24). Proton transfer [to form (25)] and loss of the secondary amine produces N-amino-pyrroles (26). One group31 reports the isolation of the intermediate (24); another3* that of (25) probably both are correct as the sub- tituents chosen by the two sets of workers were quite different. The N-amino- pyrroles were found to undergo cycloadditions to form benzenes with loss of an amino-nitrene when acetylenic esters are used and reversibly to form adducts of type (27) with N-phen~lrnaleimide.~~ Cyclo-adducts of (24) were also prepared.31 On the other hand dimethyl azodicarboxylate forms the six-membered [4 +21 cyclo-adduct (28)with phenylazocyclohexene.34 R'N- R'NH R'NH (24) (25) (26) NNHR' n 0 (27) S II Sulphur trioxide and cyanogen form the 'criss-cross' cyclo-adduct (29).35An interesting cycloaddition mode is shown by ally1 and propargyl dithioesters e.g.(30) which with dimethyl acetylenedicarboxylate forms (3l).36 The reaction between dimethyl diazomalonate and an ynamine is HOMO (ynamine)-/LUMO (dipole)-~ontrolled.~~ The product (32) undergoes an interesting example of a 'conducted tour' migration of one of the methoxycarbonyl 31 S. Sommer Angew. Chem. Internat. Edn. 1979 18 695. 32 A. G. Schultz W. K. Hagmann and Ming Shen Tetrahedron Letters 1979,2965.33 A. G. Schultz and Ming Shen Tetrahedron Letters 1979,2969. 34 S. Sommer and U. Schubert Angew. Chem. Internat. Edn. 1979,18,696. " H. W. Roesky N. Amin G.Remmer A. Gieren U. Riemann and B. Dederer Angew. Chem. Internat. Edn. 1979,18,223. 36 V. Drozd and 0.A. Popova Tetrahedron Letters 1979,4491. 37 R. Huisgen H.-U. Reissig and H. Huber J. Amer. Chem. SOC., 1979,101 3647. A. J. Boulton and M. J. Cook groups guided in this instance by diphenylketen. The intermediate (33) can be i~olated.~’ The same group have published an interesting short note on the [2 +21 and [3 + 21 cyclo-adducts formed from methyl 3,3-dimethyl-3H-pyrazole-5-car-b~xylate.~’ The reactivity of 3,4-dimethoxyfuran in [4 + 21 cycloadditions (Diels- Alder reactions) has been reported extensively in two papers from Eugster’s group.4o I Me02Co \I Et2N Me (33) 1 Nitrogen Extrusion and Other Extrusions.-Interest in the elimination of nitrogen from cyclic azo-compounds has been maintained at a high level.The question of the intermediacy of benzothiirens (35) in the thermal and photochemical de-compositions of 1,2,3-benzothiadiazoles (34) has received further attention [cf. Ann. Reports (B) 1977 74 2531. The earlier work considered evidence from the structures of the thianthrene dimers here4* the decomposition is conducted in tetralin and the authors look at the orientation of the thiols produced. In all cases 6-substituted benzothiadiazoles form the unrearranged (3-substituted) thiols (36) predominantly.However appreciable migration occurred in the photochemical decomposition except when R was OMe and when R was C02Me some re- arrangement was also found in the thermal reaction. The evidence does not require the benzothiiren to occupy an energy minimum on the reaction profile. The de- composition of benzothiadiazole (34; R = H) has also been studied by variable- temperature photoelectron spectroscopy which is claimed to be a useful technique 38 H.-U. Reissig and R. Huisgen J. Amer. Chem. Soc. 1979,101,3648. 39 R. Huisgen and H.-U. Reissig J.C.S. Chem. Comm. 1979,’568. 40 P. X. Iten A. A. Hofmann and C. H. Eugster Helu. Chim. Acru 1979 62 2202; A. A. Hofmann I. Wyrsch-Walraf P. X. Iten and C. H. Eugster ibid. p. 2211. R.C. White J. Scoby and T. D. Roberts Tetrahedron Lerrers 1979 2785. Heterocyclic Compounds for the detection of transient species at elevated temperatures. However here no benzothiiren was observed only the rearrangement product i.e. the thioketen (37).42 Nitrogen is eliminated at high temperatures from the fused cinnoline (38) to give the unstable biphenylene analogue (39).43 Naphth[ 1,8-bc]azete (40) is formed quantitatively on irradiation of (41) and oxidation of (41) with m-chloroperbenzoic acid gives the sulphoxide of (40) directly.44 Stereochemical aspects of the thermal4’ and practical aspects of the photo~hemical~~ decomposition of cyclic azo-compounds have been reported and ab initio calculations on the reaction have been per- formed.47 (42) X=O (45) (43) x=s Elimination of carbon monoxide (at 600 “C) from benzofuran-2,3-dione (42) initially forms the keten (44) but under similar conditions thioisatin (43) gives benzothiet-2-one (49 according to the photoelectron spe~tra.~’ Irradiation of (46) at 77 K forms the monothio-o- quinone (47) which undergoes photo-equilibration with its cyclic isomer (48).Both products proved to be too unstable to be isolated.48 The primary products of thermal elimination of CO,from (49) i.e. the thiocarbonyl ylides cyclized to episulphides before they could be dete~ted.~’ 42 R. Schulz and A. Schweig Tetrahedron Letters 1979,59. 43 J. W. Barton and D. J. Lapham Tetrahedron Letters 1979 3571. 44 J. Nakayama T. Fukushima E. Seki and M.Hoshimo J. Amer. Chem. SOC.,1979,101,7684. 4s P. B. Dervan T. Uyehara and D. S. Santilli J. Amer. Chem. SOC.,1979,101,2069; P. B. Dervan and T. Uyehara ibid. p. 2076; D. S. Santilli and P. B. Dervan ibid. p. 3663. 46 P. S. Engel C. J. Nalepa R. A. Leckonby and W. K. Chae J. Amer. Chem. SOC.,1979,101,6435. 47 P. C. Hiberly and Y. Jean J. Amer. Chem. SOC.,1979 101 2538. 48 P. de Mayo A. C. Weedon and G. S. K. Wong J. Org. Chem. 1979,44,1977. 49 T. B. Cameron and H. W. Pinnick J. Amer. Chem. SOC.,1979,101,4755. A. J. Boulton and M. J. Cook Physicochemical Properties and Structural Studies.-The basicities of bis-annelated pyridines (50)fall regularly with decreasing ring size.” For n =4,the pK is 8.09 but the novel highly strained compound with n = 2 prepared by two groups this year,50*s1 has pKa =4.40.From data for pyridine (pK = 5.3) and compound (51) (pK =4.85) it appears that the effects of the annelated four-membered rings are additive there being a lowering of 0.45 pK units per ring However the quinoline (52) has a pKa of 3.99 which is 1.07 units lower than quinoline itself.s2 The origin of the low basicity of 2,6-di-t-butylpyridine in the aqueous phase has been taken up again by two groups. A study of the rate of protonation by H30+ supports the view that the low basicity is due to steric hindrance of solvation (rather than steric compression of the N-H bond of the conjugate This theory is also supported by a complete analysis of the thermodynamics of hydration which also demonstrates that the hydration properties of both the cation and the free base are at variance with trends in other pyridine~.’~ A systematic study of the proton affinities of some eighteen nitrogen heterocycles shows that in the gas phase the basicity increases progressively on benzoannelation (in contrast with the trend in the solution phase) but decreases with increasing number of nitrogen atoms in the ring.” The basicities of phosphorin and arsenin both in solution and in the gas phase are unexpectedly low a comparison of proton affinities and core ionization data for the two rings with those for phosphines and arsines is consistent with the theory that the low basicities arise from the compounds’ inability to accommodate appropriate changes in geometry on protonation.s6 Studies in a quite different area show that the site of protonation of the fused triazines (53) and (54) is N-6,” and the involvement of the zwitterionic tautomer (55) in isotopic exchange at C-8 of various purines has been verified.s8 n so R.P. Thummel and D. K. Kohli Tetrahedron Letters 1979 143. 51 A. Naimann and K. P. C. Vollhardt Angew. Chem. Znternat. Edn. 1979,18,411. 52 J. H. Markgraf J. H. Antin F. J. Walker and R. A. Blatchly J. Org. Chem. 1979 44 3261. 53 1979,101 2707. C. F. Bernasconi and D. J. CarrC J. Amer. Chem. SOC. 54 E. M. Arnett and B. Chawla J. Amer. Chem. Soc. 1979,101,7141. 55 M. Meot-Ner J. Amer. Chem. SOC., 1979,101,2396. 56 A. J. Ashe M. K. Bahl K. D. Bomben W.-T. Chan J. K. Gimzewski P.G. Sitton and T. D. Thomas J. Amer. Chem. SOC., 1979,101 1764. 57 J. P. Riley F. Heatley I. H. Hillier P. Murray-Rust and J. Murray-Rust J.C.S. Perkin 11 1979 1327. S8 J. R. Jones and S. E. Taylor J.C.S. Perkin ZZ 1979 1253 1587. Heterocyclic Compounds 219 Three examples of the use of nitrogen n.m.r. illustrate its potential value in heterocyclic chemistry. In the imidazole series I5N shifts provide information about the active sites in the molecule demonstrating a degree of charge transfer between the cation and the anion of (56)in CHC13.59 Chemical shifts of 14N are superior to 13C shifts for studying tautomeric equilibria of pyridine-2-thione and various 2-amino- pyridines because of the very large difference in chemical shifts between nitrogen atoms in the alternative environments.60 Coupling constants "N-'H and 15N-13C have been used as a sensitive probe for studying the tautomerism of the uracil anion; the two forms (57) and (58)are very evenly balanced.61 A new mass spectrometric technique has been devised for investigating gas-phase tautomerism.It involves comparison of the collision-induced dissociation-mass- analysed ion kinetic energy (CID-MIKE) spectra of cations formed by ethylation (thermodynamically controlled) of the mobile system with those of the protonated forms of N-and 0-ethyl models. The results confirm that 2-hydroxypyridine predominates over 2-pyridone but that 2-quinolone is favoured over 2-hydr-oxyquinoline under these conditions.62 0 OH R R (59) Ph PhW a phg;h +;uph H Ph N Ph N H H There has been some activity in the hydroxy-pyrrole (pyrrolinone) area recently.A new route to pyrrolin-2-one has been described and the 3H/5H equilibrium investigated the SH-form predominate^.^^ In the 3-series C=O forms are report- ed to prevail in some cases e.g. (59;R = Ph or CH2Ph) but both tautomers (2-H and s9 I. I. Schuster and J. D. Roberts J. Org. Chem. 1979 44 3864; I. I. Schuster C. Dyllick-Brenzinger and J. D. Roberts ibid. p. 1765. 6o L. Stefaniak Org. Magn. Resonance 1979,12 379. 61 R. L. Lipnick and J. D. Fissekis J. Org. Chem. 1979 44 1627. 62 A. Maquestiau Y. van Haverbeke R. Flammang H. Mispreuve A. R. Katritzky J. Ellison J. Frank and Z. Mesziiros J.C.S. Chem. Comm. 1979,888. 63 J.T. Baker and S. Sifniades J. Org. Chem. 1979,44 2798. A. J. Boulton and M. J. Cook OH) are seen in others e.g. (59; R=Me). Various 4-carboxy-substituted 3-hydroxy-pyrroles favour the OH A compound which had earlier been reported to be 3-hydroxy-2,4,5-triphenylpyrrole has been found to have the dimeric structure (60) and to dissociate reversibly on heating to give the pyrrolone (61) and the hydroxy-pyrrole (62) or a tautomer A theoretical study (MIND0/3) of the tautomerism of 3-hydroxypyrrole had very limited success in predicting the experimental results.66 In the field of 'hypervalent' sulphur compounds n.m.r. measurements in the nematic phase add further evidence for the C2"symmetry (or at least fail to provide evidence for anything different) of compounds of type (63).67 However reports of equilibrations involving bond-switching at sulphur have appeared in several journal^.^^-^' Perhaps the simplest example to illustrate here is that between the two amines (64) and (65) which is observed directly by n.m.r.When the sulphur is replaced by oxygen the equilibration does not An X-ray study of the system (66) appears to indicate that there is little or no bonding between the S and X Hypervalent sulphur (or hypovalent nitrogen) is evident in the persistent radicals formed by photolysis of S4N4-olefin adducts to which structures (67) have been assigned. The unsaturated analogue (68) was also prepared.72 R' Ph,N ~ y ~ R 2 L S x (66) Y=NorCH X=OorS (67) 3 (68) 1,4-Dihydro-1-methylpyridine is deprotonated by trimethylsilylmethylpotassium to yield an organometallic 8n-electron system.The species is moderately stable (at -50 "C), and is expected to exist with all the ring atoms except the nitrogen coplanar with the pentadienyl moiety serving as a ligand for the potassium as shown in (69).73 Phosphole anions isoelectronic with thiophens are predicted to possess a de- localized Ir-electron system and evidence for considerable n character in the C-P 64 T. Momose T. Tanaka and T. Yokota Heterocycles 1977,6,1827; T. Momose T. Tanaka T. Yokota N. Nagamoto and K. Yameda Chem. Pharm. Bull. 1979,27,1448. " J. P. Freeman and M. J. Haddadin Tetrahedron Letters 1979,4813. 66 A. Karpfen P. Schuster and H. Berner J. Org. Chem. 1979,44 374.67 J. P. Jacobsen J. Hansen C. T. Pedersen and T. Pedersen J.C.S. Perkin ZZ 1979 1521. 6a K. Akiba S. Arai and F. Iwasaki Tetrahedron Letters 1978,4117. 69 K. Akiba S. Arai T. Tsuchiya Y. Yamamoto and F. Iwasaki Angew. Chem. Internat. Edn. 1979,18 166. 'O K. Akiba T. Kobayashi and S. Arai J. Amer. Chem. SOC. 1979 101 5857. 71 R. J. S. Beer D. McMonagle M. S. S. Siddiqui A. Hordvik and K. Jynge Tetrahedron 1979,35,1199. '* S. Rolfe D. Griller K. U. Ingold and L. H. Sutcliffe J. Org. Chem. 1979,44 3515. 73 M.Schlosser and P. Schneider Angew. Chem. Internat. Edn. 1979,18,489. Heterocyclic Compounds 22 1 bonds has been obtained using 31Pn.m.r. The anions e.g. (70) are formed by cleavage of the P-phenyl derivatives with potassium and are sufficiently stable to be unquenched by added ethanol (contrast dialkyl-phosphines pKca.35).74 The novel bis-1,2,6-selenadiazine (7l),the sulphur analogue of which was reported last year [Ann. Reports (B),1978,75,244]shows its proton chemical shift at S 5.9;cf.4.74for the thiadiazine. The difference in the magnitudes of the induced paramagnetic ring currents is determined by the HOMO-LUMO energy gap.75 K+ N Me (70) In the area of conformational analysis the controversy alluded to last year [Ann. Reports (B) 1978 75 2661 concerning the effect of a second heteroatom on the barrier to inversion of an N-methyl group in six-membered rings is now resolved. Apparently conflicting standpoints have been reconciled with the statement that a p-heteroatom increases the 'ax-ts half-barrier' but decreases the 'eq-ts half-barrier'.76 Another controversial question has been that of the orientation of the N-H bond in piperidines.The weight of evidence is now heavily in favour of the predominance of the NH-equatorial form but some loose ends remain. The difference in chemical shifts of geminal protons a to the nitrogen was used by some as a criterion for assigning an NH-axial preference; now however the chemical shifts of the a-protons in (72)and (73),drawn here as their predominant conformers have been found not to be significantly different.77 An X-ray crystal structure confirms the axial t-butyl group on the chair ring in (72) with a small degree of torsion to relieve the train.'^ A study on bicyclic sulphonium salts has shown that the equilibrium for isomerization of cisltruns ring fusion in (74)favours the trans-fused isomer.However the ring fusion is predominantly cis in the ester (75),and also in Bu' M HH2' 2 aN%H2 H 2' + (72) (73) (74) R=H (75) R=C02Me 74 L. D. Quin and W. L. Orton J.C.S. Chem. Comm. 1979,401. 7s M. L. Kaplan R. C. Haddon F. C. Schilling J. H. Marshall and F. B. Bramwell J. Amer. Chem. Soc. 1979,101,3306. 76 A. R. Katritzky R. C. Patel and F. G. Riddell J.C.S. Chem. Comm. 1979 674. 77 F. W. Vierhapper and E. L. Eliel J. Org. Chem. 1979,44 1081. A. J. Boulton and M. J. Cook the ylide derived from the ion (74).78 Among phosphorus heterocycles twist conformers are adopted by the following (76) in both the solid state and solution (77) in the solid state but not in ~olution,~' and (78)80 and (79),81 both in solution.In 1-methyl-silacyclohexane the methyl group is mainly axial according to the 'H n.m. r . spectrum.82 pf'R' H OAr (76) R' = NMe2 R2 is =O (78) (79) (77) R1is =0,R2 = NMe2 3 Three-memberedRings A novel approach to the synthesis of l-azirines via oxazaphospholines has been described as summarized in Scheme 1. The scheme provides access to azirines not Reagents i Me,C(OMe), H'; ii PPh,; iii H,O'; iv Et,N Scheme 1 readily accessible by the vinyl azide route.83 N-Sulphenyl-aziridines can be pre- pared by oxidation of sulphenamides in the presence of olefins and the sulphenyl groups are readily removed by b~rohydride.~~ The products of two earlier reported ring syntheses have now been shown to be wrongly assigned.Thus alkyl- diazoacetates and NN'-di-isopropylcarbodi-imide,in the presence of copper triflate or rhodium(I1) acetate give (82) rather than (83)85[cf.Ann. Reports (B) 1976,73 2411 and the problems encountered in separating the supposed phosphiren (84) [cf. Ann. Reports (B) 1972 69 4251 from 1,5-diazabicyclo[4.3.0]non-5-enehydro-bromide have now been explained the product is in fact (85)!86 78 D. M. Roush E. M.Price L. K. Templeton D. H. Templeton and C. H. Heathcock J. Amer. Chem. Soc. 1979,101 2971. 79 G. S. Bajwa W. G. Bentrude N. S. Pantaleo M. G. Newton and J. H. Hargis J. Amer. Chem. SOC. 1979,101,1602. R. 0.Hutchins B. E. Maryanoff M. J. Castillo,K.D. Hargrave and A. T. McPhail J.Amer. Chem. SOC. 1979.101.1600. D. G. Gorenstein and R. Rowell J. Amer. Chem. SOC., 1979,101,4925. 82 R. Carleer and M. J. 0.Anteunis Org. Magn. Resonance 1979,12 673. 83 A Hassner and V. Alexanian J. Org. Chem. 1979 44 3861. 84 R. S. Atkinson and B. D. Judkins J.C.S. Chem. Comm. 1979,832,833. J. Drapier A. Feron R. Warin A. J. Hubert and P. TeyssiC Tetrahedron Letters 1979 559. H. Quast and M. Heuschmann J.C.S. Chem. Comm. 1979,390. Heterocyclic Compounds 223 A strong theme in the year’s organic literature has been the investigation of ring-cleavage reactions and a number of theoretical treatments have been reported. The Dewar 12-complex theory was described in detail nearly 30 years ago and now a new series of calculations supports a detailed restatement of the relationship between 12-complexes and three-membered rings containing 0,S NH PH SiH2 OH’ SH’ NH2+,etc.In particular the direction of nucleophilic ring-opening of unsymmetrically substituted compounds which it is argued is a criterion for dis- tinguishing between the 12-complex type and a classical ring species is found to be generally consistent with the MIND0 scale of 12-complex character. According to the theory significant 12-complex character can be attributed to the protonated ring The photochemical ring-opening of oxirang8 and of aziridine diaziridine and ~xaziridine,~~ and the rearrangements of the last have been the subject of ab initio calculations as also have the oxidation of imines to ~xaziridines~~ and the acid-catalysed hydrolysis of benzene An empirical investigation of the mechanism of hydrolysis of oxaziridine has provided evidence for both 0-and N-protonation of this Some new ring-cleavage reactions have been described some of possible synthetic use.The ring-opening of aryl-oxirans under certain conditions (CuS04-C5H5N phosphate buffer at pH 7) gives cis-diols. The stereochemistry of the cleavage is reproduced by nucleophiles other than water which enter at the benzylic po~ition.~’ Ylides are obtained in a novel ring-opening of 2-aryl-3,3-dicyano-oxirans,using pyridine [to give (86)] sulphides or triphenylph~sphine.’~ 1,3-Di-t-butyl- aziridinone a particularly stable a-lactam reacts very readily with m-chloro- perbenzoic acid to give the oxaziridine and CO; N-oxidation is postulated to be the first The oxaziridine (87) with phenylmagnesium bromide gives biphenyl but with phenyl-lithium phenol is produced and also the adduct (88).The analogue (89) follows the latter pathway with both organometallic reagents.98 AryCOCN OPh I 0 (i) PhM iAph% RN-LHPh + RN=CHPh (ii)H30+* RNH-CHPh2 R‘ H (88) (87) R=Bu‘ (86) (89) R=PhS02 (M = Li or MgBr) 87 M. J. S. Dewar and G. P. Ford J. Amer. Chem. SOC.,1979,101 783. B. Bigot A. Sevin and A. Devaquet J. Amer. Chem. SOC.,1979,101 1095 1101. 89 J. Sauer Tetrahedron 1979,35 2109. 90 B.Bigot D. Roux A. Sevin and A Devaquet J. Amer. Chem. Soc. 1979,101,2560. 91 E.Oliveros M. Riviere J. P. Malrieu and C. Teichteil J.Amer. Chem. SOC.,1979 101 318. 92 A. Aiman J. Koller and B. PlesniEar J. Amer. Chem. SOC.,1979 101 1107. 93 J. E.Ferrell and G. H. Loew J. Amer. Chem. SOC.,1979,101,1385. 94 A.R.Butler B. C. Challis and A. M. Lobo J.C.S. Perkin ZI 1979 1035; A. R.Butler J. G. White B. C. Challis and A. M. Lobo ibid. p. 1039. 9s M. Imuta and H. Ziffer J. Amer. Chem. SOC., 1979 101 3990. 96 A. Robert M. T. Thomas and A. Foucaud J.C.S. Chem. Comm. 1979 1048. 97 T. Hata and M. Watanabe J. Amer. Chem. SOC., 1979 101 1323. 98 F. A.Davis P. A. Mancinelli K. Balasubramanian and U. K. Nadir J. Amer. Chem. SOC.,1979 101 1044. A. J. Boulton and M. J. Cook Another burst of papers from Zurich on the apparently inexhaustible chemistry of 3-dimethylamino-2,2-dimethyl-2H-[see Ann.Reports azirine has appea~ed.~~-"~ (B) 1977 74 2551. A feature of its reaction with heterocumulenes is that alter- native pathways are followed as indicated depending upon the nucleophilicity of the atoms or groups X and Y in the intermediates (9O).lo1However among thiocyanates the reaction of the phenyl compound is anomalous giving (91).993-Phenyl-2H-azirines undergo addition of CO with rhodium catalysts to give vinyl i~ocyanafes.~~~ N4cR1R2 Me,N%b (x= O,Y = CR'R~)/ Y S x (90) Thiiran-imines (92) show three different modes of addition to different doubly- or triply-bonded reactants (see Scheme 2). The reactions (a)and (c) find analogies in the chemistry of diaziridine-imines and a-lactams respectively. The successive Me Ph Ph (93) (94) Me N R 1 ArSO,N\I(Ph, Et2N CHZSO~AI Ph2 m QPhNS0,Ar S Nws CHPh Ph (95) Reagents i Et,NCECMe; ii RCHO; iii NMe Scheme 2 99 U.Schmid H. Heimgartner and H. Schmid Helv. Chim. Actu 1979,62 160. loo G. Mukherjee-Miiller S. Chaloupka H. Heimgartner H. Schmid H. Link K. Bernauer P. Schonholzer and J. J. Daly Helv. Chim. Acta 1979,62 768. lo' J. LuklE and H. Heimgartner Helv. Chim. Actu 1979,62 1236. lo2 G. Mukherjee-Miiller H. Heimgartner and H. Schmid Helv. Chim. Actu 1979 62 1429. '03 T. Sakakibara and H. Alper J.C.S. Chem. Comm. 1979,458. Heterocyclic Compounds 225 rearrangements (93) -+ (94)+(95) of the ynamine adduct are note~orthy.'~~ Di-t-butyldiaziridinone (96) does not form the expected thione with the sulphurizing agent (97); instead the five-membered heterocycle (98) is produced which report- edly exists in two stereoisomeric -NBu' 4 Four-membered Rings General.-The sodium salt of dimethyl N-(toluene-p-sulphonyl)sulphoximine a nucleophilic methylene-transfer reagent is known to react with dialkyl ketones to give oxirans.It has now been found that excess of the reagent leads to oxetans so providing a particularly convenient route to this ring system. lo6 Azetidinq-2,4-diones (malonimides) result from the photochemical ring-contraction of suc-cinimides in yields of up to 50% ,lo' and stable four-membered-ring nitrones (azetine 1-oxides) (99) have been obtained from the reaction of nitro-alkenes with ynarnines.'O* A series of reactions involving isocyanides have been reported giving imino-azetidines from N-phthalimido-aziridines bearing electron-withdrawing groups in a (3+ 1) cheletropic reaction with the valence-isomeric azomethine ylides,"' 2,4-bis(imino)thietans from arylsulphonylimino-thiirans (92),ll0 and tris(irnino)thietans (100) from arylsulphonyl isothiocyanates."' The tris-imine (100)reacts at C-2 with methanol diethylamine and ethanethiol to give open-chain products but at C-4 with hydrazoic acid finally forming the tetrazole (101)."* R'kk' 0-R2,*R' H CONR; (99) G.L'abbC J.-P. Dekerk S. Toppet J.-P. Declercq G. Germain and M. Van Meerssche Tetrahedron Letters 1979 1819. lo' G. L'abbC J. Fltmal J.-P.Declercq G. Germain and M. Van Meerssche Buff.SOC. chim. belges 1979 88,737. lo' S. C. Welch and A. S. C. Prakasa Rao J. Amer. Chem. SOC. 1979 101 6135. K. Maruyama T. Ishitoku and Y.Kubo J. Amer. Chem. SOC. 1979,101,3670. lo* A. D. de Wit M. L. M. Pennings W. P. Trompenaars D. N. Reinhoudt S.Harkema and 0.Nevestveit J.C.S. Chem. Comm. 1979,993. J. Charrier H. Person and A. Foucaud Tetrahedron Letters 1979 1381. G. L'abbC and J.-P. Dekerk Tetrahedron Letters 1979 3213. G. L'abbC L. Huybrechts J.-P. Declercq G. Germain and M. Van Meerssche J.C.S. Chem. Comm. 1979,160. 112 G. L'abbC L. Huybrechts S. Toppet J.-P. Declercq G. Germain and M. Van Meerssche Buff. SOC. chim. befges 1979 88 291. A. J. Boulton and M. J. Cook The first authentic stable bisdioxetan (102) has been reported.On thermolysis it forms benzoic anhydride q~antitatively."~ The indole dioxetan (103) has been found to be sufficiently stable to allow its spectroscopic and chemical investigation. '14 A 1,2-disilacyclobutane (104) has been prepared; it undergoes some unusual and interesting thermal and photochemical rearrangements.' l5 A further intriguing reaction is that between phenylbis(trimethylsily1)phosphine and phosgene which gives as a secondary product the tetraphosphabicyclo[2.2.O]hexane (1O5).ll6 Me Ph Me,Si SiMe 0 Me3SiwSiMe3 Ph Ph Me Ph,Si-SiPh PhtN ___) Bu"C 0 I CONHBu' = phthaloyl) (109) P-Lactams.-Routes to p-lactams attract attention because of their application to the synthesis of pharmacologically active materials. Base-catalysed cyclization of y-bromopropionamides suffers from a competing elimination reaction but condi- tions have been described which minimize the latter,"' and an alternative solution to the same problem exploits the acidity of the N-H bond of 0-acyl and 0-alkyl hydroxamic acid derivatives.In this approach cyclization (with base) gives substi- tuted N-hydroxy-compounds and an elegant extension of the method uses diethyl azodiformate and PPh to cyclize hydroxamic derivatives (106) of commercially available N-protected L-serine. This affords the cyclic compound (107)with reten- tion of chirality."' A further P-lactam-forming reaction converts the thiazoline (108) into the penicillin (log) using t-butyl i~ocyanide."~ The first direct introduction of a substituent at C-6 in cephalosporins and at C-5 in penicillins has been reported.The benzoyloxy-group enters the bridgehead position '13 W. Adam C.-C. Cheng 0.Cueto I. Erden and K. Zinner J. Amer. Chem. SOC.,1979,101,4735. '14 I. Saito S. Matsugo andT. Matsuura J. Amer. Chem. SOC.,1979 101,4757,7332. ''' M. Ishikawa T. Fuchikami M. Kumada T. Higuchi and S. Miyamoto J. Amer. Chem. Sac. 1979,101 1348. '16 R. Appel V. Barth M. Halstenberg G. Huttner and J. von Seyerl Angew. Chem. Internat. Edn. 1979. 18 872. H. H. Wasserman D. J. Hlasta A. W. Tremper and J. S. Wu Tetrahedron Letters 1979 549. P. G. Mattingly J. F. Kerwin and M. J. Miller J. Amer. Chem. SOC.,1979,101 3983. '19 A. Schutz and I. Ugi J. Chem. Res. 1979 (S) 157 (M)2064. Heterocyclic Compounds 227 in the a-configuration if one uses t-butyl perbenzoate and catalytic cuprous chloride in refluxing benzene.120 Stereoselective synthesis of 6p- alkyl-penicillanates is achieved by reduction of the known 6a-alkyl-6~-isocyano-derivative with tri-n-but- yltin hydride,12' and the stereocontrolled synthesis of 7a-methoxy-1-oxa-cephems has also been described. In this the methoxy-group is introduced at the 3a-position of the precursor (1lo) obtained from the appropriate 6-epi-peni~i1lin.l~~ There has been a spate of reports on the preparation and properties of further examples in the penem series. The derivatives (111),unsubstituted at the 6-position have dominated the scene with syntheses being described that use clavulanic and 6-aminopenicillanic a~id'~~,'~' as precursors or with structures such as (112)126 and (113)12' as intermediates.A penem sulphoxide is produced on S-oxidation of a thia-analogue of clavulanic acid.128 The acids (111)prove more stable than their 6-acylamino-substituted derivatives and in marked contrast to penicillanic and cephalosporanic acids (which are also unsubstituted on the p-lactam ring) they show antibiotic activity towards a broad spectrum of bacteria. lZ6 RCONH R'CONH 0n-3 m:"' OY (117) 'OZH (118) 'OZH An unusual Cu'-mediated addition process merits special attention. The reaction of (114) with base in the presence of CuI and PBr was claimed to give the 2-alkylthio-penem (115),12'but a report in the early 1980 literature has revised this structure in favour of the unexpected isopenem (116).Details of the preparation of authentic (115) are Other 'non-classical' p-lactam structures include 120 H. Matsumura T. Yano M. Ueyama K. Tori and W. Nagato J.C.S. Chem. Comm. 1979,485. 12' D. I. John E. J. Thomas and N. D. Tyrrell J.C.S. Chem. Comm. 1979 345. S. Uyeo I. Kikkawa Y. Hamashima H. Ona Y. Nishitani K. Okada T. Kubota K. Ishikura Y. Ide K. Nakano and W. Nagata J. Amer. Chem. Spc, 1979,101,4403. lZ3 P. C. Cherry C. E. Newall and N. S. Watson J.C.S. Chem. Comm. 1979,663. 124 C. M. D. Beels M. S. Abu-Rabie P. Murray-Rust and J. Murray-Rust J.C.S. Chem. Comm. 1979,665. 125 I. Ernest J. Gosteli and R. B. Woodward J. Amer. Chem. SOC.,1979 101 6301. 126 M. Lang K. Prasad W. Holick J. Gosteli I.Ernest and R. B. Woodward J. Amer. Chem. SOC.,1979 101,6296. H. R. Pfaendler J. Gosteli and R. B. Woodward J. Amer. Chem. SOC.,1979,101,6306. 12* P. Lombardi G. Franceschi and F. Arcamone Tetrahedron Letters 1979,3777. 129 F. DiNinno E. V. Linek and B. G. Christensen J. Amer. Chem. Soc. 1979,101 2210. 130 S. Oida A. Yoshida T. Hayashi E. Nakayama S. Sato and E. Ohki Tetrahedron Letters 1980,21,619. 228 A. J. Boulton and M. J. Cook the 2-oxocephem system (117). Unfortunately expectations that increased con- jugation to the 2-0x0-group would increase the reactivity of the p-lactam carbonyl thereby enhancing antibacterial activity were not fully realized. 131~132 Compounds based on (118) represent the first examples of p-lactams fused to a saturated six-membered ring that have potent antibacterial a~tivity.'~~ 5 Five-membered Rings Synthetic modifications of five-membered-ring heterocycles using lithiation reac- tions have been extended in scope by several groups.Lithium 3-furoate may be lithiated at the 2-position to give promising intermediate^.'^^ 2-Furyl- 135*136 1-methyl-2-pyrr0lyl-,'~~ react with a trialkylborane and 1-methyl-2-indolyl-lithi~rn'~~ to form the (heterocyc1yl)trialkylborate anions (119) (9-R-9-BBN will serve instead of R3B135.137). The ions (119) may be decomposed (by I2 or N-chlorosuccinimide) to give (120) or first be treated with an electrophilic alkylating agent (e.g. MeI or an &unsaturated ketone) then decomposed (by H202 and NaOH) to give a 2,3- dialkyl derivative e.g.(121).'37 The 1979 literature is replete with indole syntheses including the photochemical formation of the pyrrole ring using o-iodoaniline in an SRNlreaction with an en~late,'~' acid-catalysed cyclization of the pyrrole (122) to the indole (123),13' and too numerous to detail. 3-(Indol-2-yl)pyri- dinium salts with base undergo cleavage of the pyridine ring and subsequent re-cyclization of the chain at the indole 3-position giving 1-formyl-carbazoles (124).14' New syntheses of furans in particular of 3-and 2,4-di-substituted compounds have been reported starting from propargyl tetrahydropyranyl ether in a 'one-pot' sequence which involves the preparation and regiospecific alkylation of the carbanion (125).146A synthesis of 3-acyl-furans using sulphur techniques has been reported.147 13' C. U. Kim P. F. Misco and D. N. McGregor J. Medicin. Chem. 1979,22,743. 13' I. Ernest Helv. Chim. Acta 1979,62,2681. 133 J. G. Gleason T. F. Buckley K. G. Holden D. B. Bryan and P. Siler J.Amer. Chem. SOC.,1979,101 4730. 13' D. W. Knight Tetrahedron Letters 1979 469. 13' E. R. Marinelli and A. B. Levy Tetrahedron Letters 1979 2313. I. Akimoto and A. Suzuki Synthesis 1979 146. 137 A. B. Levy,Tetrahedron Letters 1979,4021. R. Beugelmans and G. Roussi J.C.S. Chem. Cumm. 1979,950. 139 M. Natsume and H. Muratake Tetrahedron Letters 1979 3477. "O I. Fleming and M. Woolias J.C.S. Perkin I 1979,829. "' M. Somei F. Yamada and C. Kaneko Chem. Letters 1979,943. 14' G. S. Ponticello and J. J.Baldwin J. Org. Chem. 1979,44,4003; U. Hengartner D. Valentine K. K. Johnson M. E. Larscheid F. Pigott F. Scheidl J. W. Scott R. C. Sun J. M. Townsend and T. H. Williams ibid. p. 3741. 14' Y. Ito K. Kobayashi N. Seko and T. Saegusa Chem. Letters 1979,1273. 14' R. Beugelmans H. Ginsburg M. Le Goff A. Lecas J. Pusset and G. Roussi Heterocycles 1979 12 811. ldS A. N. Kost T. V. Stupnikova R. S. Sagitullin B. P. Zemskii and A. K. Sheinkman Doklady Akad. NaukS.S.S.R 1979 244 103 [Pruc. Acad. Sci. (U.S.S.R.),1979 244 141. 146 M. Stahle and M. Schlosser. Angew. Chem. Internat. Edn. 1979,18 875. K. Inomata M. Sumita and H. Kotake Chem. Letters 1979,709. Heterocyclic Compounds Work in several laboratories has been directed towards the synthesis of thiophen- 3-acetic and -3-malonic acids one approach to which involves the thiophenium S-ylides [cf.Ann. Reports (B) 1978 75 2541. The dichloro-compound (126) thermally cyclizes with loss of HCl to the thienofuran (127),'48 and with copper catalysis it liberates dicarbomethoxycarbene which can be trapped.'49 A full paper'5o describes a wide range of these ylides and also the preparation of the ester (128) and its rearrangement to (129). Another approach to thiophen-3-acetic esters involves cyclization of the dihalogeno-diene (130). + Me2NYxYNMe2 Me,N N /\ Me Me (133) (131) + Me2NYxTNMe2 RCH2S CH,S RI (134) (132) (X =CH or N; R =H or Me) In an extremely compressed pair of papers Gompper and Schneider15* have described the cyclization of ylides generated by the action of strong base on cations of type (131)and (132).The reaction proceeds with elimination of a molecule of amine lo* R. J. Gillespie J. Murray-Rust P. Murray-Rust and A. E. A. Porter J.C.S. Chem. Comm. 1979,366. lo9 R. J. Gillespie and A. E. A. Porter J.C.S. Chem. Comm. 1979 50. lS0 R. J. Gillespie and A. E. A. Porter J.C.S. Perkin I 1979,2624. P. J. Clayton A. W. Guest A. W. Taylor and R. Ramage J.C.S. Chem. Comm. 1979 500. R. Gompper and C. S. Schneider Synthesis 1979,213,215. A. J. Boulton and M. J. Cook or thiol and results (in some cases) in satisfactory yields of heterocyclic products (133) and (134). An alternative mode of reaction of the compounds where Xis CH is deprotonation from this central position to form allenes.Aza-anti-aromatics such as azete and aza-pentalenes have long been known to be stabilized by dialkylamino- substitution [cf.Ann. Reports (B),1973,70,479,491]. Asimilar effect applies to the highly coloured aza-cyclopentadienium cations (135) and (136) which are made from tetrachloro-2H- imidazole and 1,1,3-trichloro- 1H-isoindole re~pectively.'~~ Techniques for controlling high-temperature reactions which avoid the con- version of the majority of the organic material into unpromising charcoals have been developed to a fine art over the past few years. Flash vacuum pyrolysis (FVP) of 4,5,6,7-tetrahydrobenzofuranat 920-950 "C forms the unstable dimethylenedi- hydrofuran (137)' which can be trapped by dienophiles and the generation of the 'furanoradialene' (138) in a similar reaction is re~0rted.l~~ Pyrolysis of isox- azolinones reported in brief last year [Ann.Reports (B) 1978,75 2581 has been found to produce formonitrile oxide (HCNO) when applied to 4-isonitroso-5- isoxazolinones.'55 Other nitrile oxides are obtained in good yields by FVP of f~roxans.'~~ A series of papers describes in detail the co-pyrolysis of heterocycles with chloroform. Pyrroles and indoles form 2-and 3-chloro-pyridine~'~~ and -quin~lines,'~* while pyrazoles and indazoles give good yields of 2-chloro-pyri- midines and -quinazolines. 15' The reports of recent years on the 'nitrogen-walk' process of photo-rearrange- ment of cyano-pyrroles have been followed up by some equally elegant studies on the cyano-thiophens and one of the episulphide intermediates (139) has been iso- lated.I6' An extension of a well-known isoxazole synthesis provides a useful route to 1,2,4-0xadiazoles (140) from acyl-amidines including the interesting and rather R.Gompper and K. Bichlmayer Angew. Chem. Internat. Edn. 1979,18,156. lS4 J. Jullien J. M. Pechine F. Perez and J. J. Piade Tetrahedron Letters (a) 1979,3079; (6)1980,21,611. lS5 C. Wentrup Angew. Chem. Internat. Edn. 1979 18,467. lS6 W. R. Mitchell and R. M. Paton Tetrahedron Letters 1979 2443. "'R. E.Busby M. Iqbal M. A. Khan J. Parrick and C. J. G. Shaw J.C.S. Perkin I 1979 1958. 15* R. E. Busby S. M. Hussain M. Iqbal M. A. Khan J. Parrick and C. J. G. Shaw J.C.S. Perkin I 1979 2782. R. E. Busby J.Parrick S. M. H. Rizvi and C. J. G. Shaw J.C.S. Perkin I 1979 2786. J. A. Barltrop A. C. Day and E. Irving J.C.S. Chem. Comm. 1979,881,966. Heterocyclic Compounds 231 unstable cases where R=H. Replacing the hydroxylamine in Scheme 3 by a hydrazine leads to 1,2,4-triazole~.~~~ More details have been published of a novel synthesis of imidazoles from N-chloro-amidines and a further study of the chemical behaviour of the imidazoline intermediates has been made.162 4-Methylene-4,s- dihydro-oxazoles (14 l) intermediates in a synthesis of oxazoles from acetylenic imino-ethers have been isolated and can be transformed by electrophilic reagents into oxazoles with a 4-(substituted methyl) group.'63 ArCONH2 A ArCON=CRNMe2 % ArCONHCR=NOH 5 Reagents i (MeO),CRNMe,; ii NH,OH,AcOH Scheme 3 Although the desire to patent it seems to be slackening novel aspects of the evergreen Beirut reaction are still uncovered.Unsubstituted quinoxaline di-N- oxide is from time to time reported as being produced by the diethylamine-catalysed reaction of benzofuroxan with a variety of unlikely compounds; now the Lebanese groups have shown that this is produced amongst other things simply from the amine and the benzof~roxan.~~~ With 1-diethylaminobutadiene the enamine (142) is forrned.l6' 0- I 0' An interesting synthesis of 2-aryl-benzotriazoles has been described. Starting from precursors such as (143) it is suggested that o-nitrophenyl-carbodi-imidesare formed. Subsequent rearrangements involving the nitro-group result in the loss of C02,with formation of the benzotriazole (144).166A nitro-group is again involved in the base-induced cyclization of N-phenacyl-o-nitro-N-tosylaniline(145).The 16' Y.-I. Lin S. A. Lang M. F. Lovell and N. A. Perkinson J. Org. Chem. 1979,44,4160. 162 L. Citerio D. Pocar R. Stradi and B. Gioia J.C.S. Perkin I 1978 309; L. Citerio D. Pocar M. L. Saccarello and R. Stradi Tetrahedron 1979 35 2375 2453. 163 L. E. Overman S. Tsuboi and S. Angle J. Org. Chem. 1979,44,2323. 164 M. Z. Nazer C. H. Issidorides and M. J. Haddadin Tetrahedron 1979.35 681. P. Devi J. S. Sandhu and G. Thyagarajan J.C.S. Chem. Comm. 1979,710. 166 P. G. Houghton D. F. Pipe and C. W. Rees J.C.S. Chem. Comm. 1979,771. A. J. Boulton and M. J.Cook benzoyl and tosyl fragments are lost and 2-ethoxy-1 -hydroxybenzimidazole is formed (Scheme 4).167 I L 0-ti,iii OH Reagents i NaOEt EtOH; ii EtO-; iii H’ Scheme 4 A number of complex azide-tetrazole equilibria have been studied. 3-Azido-5- phenyl-s- triazole (146) is favoured over the cyclized triazolotetrazole forms (147) and (148) but the (slow) equilibrium of the anion is more finely balanced in DMSO the cyclized ion (149) is preferred at low temperatures while the azide [anion of (146)] predominates at high temperatures. An interesting range of isomeric N-methylated derivatives of the ring system was prepared.’68 The preference for cyclization in the anion rather than in the neutral molecule has been supported by theoretical calculations.169 The tautomerism of 3-azido-1,2,4-benzotriazine,which has two alternative ring nitrogens for cyclization has been studied the open-chain and both cyclic forms are ob~erved.”~ The equilibrium between tetrazole and azide in the system (150) S (151) shows a linear dependence between the Hammett substituent constant for R i.e.o,and the equilibrium constant K (rather than (146) (147) 16’ J. Machin and D. M. Smith J.C.S. Perkin I 1979 1371. 16’ R. N. Butler T. McEvoy E. Alcalde R. M. Claramunt and J. Elguero J.C.S. Perkin I 1979 2886. lC9 S. Olivella and J. Vilarrasa J. Heterocyclic Chem. 1979 16 685. A. Messmer G. Hajos J. Tamas and A. Neszmelyi,J. Org. Chern. 1979 44 1823. Heterocyclic Compounds logK).171 This is a curious result and it would be interesting to see whether it is found in other systems or with a wider range ofsubstituents.The structures (152) of the reaction products from S-alkylated thioamides (153) and azide ion have been corrected the acyclic triaza-dienes (154) are formed,17* as was predicted by Variable-temperature photoelectron spectroscopy has been referred to earlier (Section 2). The claim174 to have observed 1,2,3-benzoxadiazole (155) as the major component of the gas-phase equilibrium with the diazo-phenol (156) by this method is particularly interesting and confirmation by other physicochemical techniques would be very welcome. Carbon atoms formed in the decomposition of diazotetrazole (157) insert into furan with ring-cleavage to give the acetylenic aldehyde (158).The fate of the carbon was followed by labelling experiments; both C=C addition and C-2-H insertion seem to occur.175 Ring-cleavage is a common fate of five-membered heterocyclic rings adjacent to which a carbene or nitrene centre is generated and the literature of 1979 contains a number of examples of this. Thermolysis of the oxazolyldiazomethane (159) gives an acyl-imide (160) [with an obvious structural relationship to (158)] which readily rearranges to the acyl-enamine (161). Under N2 (157) A. Konnecke R. Dorre E. Kleinpeter and E. Lippmann Tetrahedron 1979.35 1957. 172 G. L’abbC A. Willocx J.-P. Declercq G. Germain and M. Van Meerssche Bull. SOC. chim. belges 1979 88 107. A. Holm Adv. Heterocyclic Chem. 1976 20 173. 17‘ R.Schulz and A. Schweig Angew. Chem. Internat. Edn. 1979,18,692. ’’’ S. F. Dyer and P. B. Shevlin J. Amer. Chem. SOC.,1979 101 1303. A. J. Boulton and M. J. Cook more vigorous conditions fragmentation occurs to the nitrile R'CN and an acety- lenic ketone and similar products are formed from the isoxazolyldiazomethane (162). For these reactions intermediate dehydro-oxazines are The 4-azido-isoxazole (163) on heating fragments to give the two cyanides (164) and (165) and nit~0gen.l~~ Me N N7CH=CHPh 4 MeCN + N2 + NCCOCH=CHPh (164) (165) (163) Although o-azido-benzanilides do not form either arylamino-anthranils or indazolinones on thermolysis their anions (1 66) form the 2-aryl-indazolin-3 -ones (167) in fair to good ~ie1ds.l~~ With thionyl chloride they give 3-chloro-2-aryl- indaz01es.l~~These two results suggest that cyclization requires a lone pair of electrons in the molecular plane on the nitrogen atom which cyclizes to the azide.However anions of o-azidoacetophenones (168) apparently isoelectronic with the neutral amides do form the C-N bond to give the indoxyls (169).l8' Whatever the mechanisms may be the reactions are useful ones. Photochemical reactions of anthranils,'81*'82 indoxazenes,18* inda~oles,'~~ and 2,l -benzisothiazoles'84 have been reported extensively. Ring-cleavage products are generally observed often with concomitant nucleophilic substitution in the benzene Ph H \Ph (?. H (171) On decomposition in a substituted benzene 2,5-diphenyl-3-diazopyrroleforms either the cyclo-octapyrrole (170) (when R is H CN or NO2) or a 3-aryl-pyrrole 176 S.-I.Hayashi M. Nair D. J. Houser and H. Shechter Tetrahedron Letters 1979 2961. G. Kumar K. Rajagopalan S. Swaminathan and K. K. Balasubramanian Tetrahedron Letters 1979 4685. M. A. Ardakani and R. K. Smalley Tetrahedron Letters 1979,4765. 179 M. A. Ardakani R. K. Smalley and R. H. Smith,.Synthesis 1979 308. '" M. A. Ardakani and R. K. Smalley Tetrahedron Letters 1979,4769. "' E. Giovannini and B. F. S. E. de Sousa Helv. Chim. Acta 1979,62 185 198. T. Doppler H. Schmid and H.-J. Hansen Helv. Chim. Acta 1979,62,271,304,314. E. Georgarakis H. Schmid and H.-J. Hansen Helv. Chim. Actu 1979,62 234. B. Jackson H. Schmid and H.-J. Hansen Helu. Chim. Actu 1979 62 391.Heterocyclic Compounds (171) (when R is Me or OMe). An intermediate spiro-norcaradiene (172) is suggested for the formation of both Cycloaddition reactions of diazo-pyrazoles have been studied widely and recent work in this area has included the reactions of 3-diazo-pyrazoles and -indazoles and of 4-diazo-1,2,3-triazoles with various ylides186" and with isocyanates,'86b to form a wide variety of condensed heterocyclic systems usually in good yield. 1-Chlorobenzotriazole has been reported to be a shelf-stable oxidizing agent but the unfused analogue (173) decomposes very easily. The first step is probably migration of C1 to form the 4H-isomer (174) which can either lose nitrogen to form the chloro-azirene (179 or cleave to benzonitrile and phenylchlorodiazomethane; the observed products are derived from these.187 x-Y Ycp X X,Y The spiro-pyrazolinone (176) has been prepared and in solution it shows an interesting rapid temperature-dependent equilibrium with the isomer (177).188 A synthesis of 4-amino-isothiazoles (178) from a-tosyloximino-nitriles has been reported (Scheme 9 and the products were shown to be flexible synthons for a variety of ring systems containing the fused isothiazole n~c1eus.l~~ NC NC H,N X RCH,SH + ,>x -% ,px% TsO-N RCH,S-N S' Scheme 5 Nucleophilic attack at the sulphur atom of heteroaromatic rings is nothing new but novel aspects continue to be discovered.Isothiazolium and 1,2,5-thiadiazolium M. Nagarajan and H. Shechter J. Amer. Chem. SOC.,1979,101,2198.G. Ege and K. Gilbert Tetrahedron Letters 1979,(a) 1567;(b)4253. 187 T. C.Gallagher M. J. Sasse and R. C. Storr J.C.S. Chem. Comrn. 1979,419. G. Mann L.Hennig H. Wilde S. Hauptmann S. Behrendt and M. Kretschmer Tetrahedron Letters 188 1979,4645. 189 K. Gewald and P. Bellmann Annalen 1979,1534. 236 A. J. Boulton and M. J. Cook salts (179) incorporate cyanide and methylpropiolate anions with ring expansion the product (180; X = CH Z =N) slowly decomposes to the starting material^.'^^ The selenophen (18 1)is ring-cleaved by organolithium reagents. lgl X-X-_Cd,JNHMe F= s' -))-NHMe *s."->,Me cw I N &NMe 111 Me c Me HZ Z 111 (179) Z = N or C-C02Me z (180) X = CH or N MeOOOMe ___* MeOaOMe BuLi Se Li SeBu R'N S ,N Potts continues to reap the fertile field of bicyclic meso-ionic heterocycles.The imidazo[2,1 -b]thiazole and thiazolo[3,2-b][ 1,2,4]triazole systems (182) add dipolarophiles across the sulphur atoms to form adducts which can lose S or H,S to form fused pyridones (183).lg2 The preparation and properties of a number of novel monocyclic meso-ionic systems which were reported in preliminary notes in 1976 [Ann. Reports (B),1976,73,252] are published in full detail in an extensive series of papers from the Sheffield group.'93 Meso-ionic derivatives (184) of the 1,2,5- thiadiazole system have been prepared.lg4 More work on the photochemistry of meso-ionic monocycles (185) has been reported. Two important types of reaction which have been postulated are the ring-opening [to (186)] and the further cyclization [to (187)] with decomposition via an anti-aromatic intermediate (188) (Scheme 6).In the case of the meso-ionic x=c=o 1 (186) 'Y-z (a) R = Me X =CPh Y = CH Z= S (b) R=Ph X = Y =N Z=O (c) R = Ar X = CR' Y = N Z= 0 Scheme 6 J. Rokach P. Hamel Y. Girard and G. Reader TetrahedronLetters 1979 1281. 19' S. Gronowitz A. Hallberg and T. Frejd Tetrahedron 1979,35 2607. lg2 K. T. Potts and S. Kanemasa I. Org. Chem. 1979,44,3803,3808. 193 E. Cawkill R. N. Hanley G. P. Rowson I. S. Smith W. D. OlIis and C. A. Ramsden J.C.S. Perkin I 1979,724 and five succeeding papers. Ig4 K. Masuda J. Adachi and K. Nomura J.C.S. Chem. Comm. 1979 331. Heterocyclic Compounds 237 thiazoles (Ma) the heterocumulene (186a) can be trapped but it has not yet been detected spectroscopically.195 The oxatriazole (185b) on photolysis forms phenyl azide and also phenyl isocyanate. The azide was at one time thought to arise through the ‘cyclic azide’ (188b) but Danish have shown that such a symmetrical intermediate cannot be on the main pathway to the azide by irradiating the labelled compound (185b; Y=15N) the phenyl azide was found to carry the marker practically exclusively on the terminal nitrogen. The formation of the isocyanate also suggests that the phenyl group with or without its attached nitrogen moves closer to the ring carbon atom before cleavage. 196 The cyclization-fragmentation (lower route of Scheme 6) is also found in (185a) as shown by the production of carbonyl sulphide the authors apparently accept the intermediate (188a) here.’95 The thiazole (185a) reacts with singlet oxygen to form (189) presumably uiu the intermediate (190).’95 Sydnones (185c) which hitherto have been reported only to form charge-transfer complexes with tetracyanoethylene react with it under more forcing conditions with loss of C02 giving the open-chain hydrazones (191).19’ Ph \ c=o CR’=C(CN)Z / -B MeN + cos ArN / \ \ c=o N=C(CN)* (192) X = CO R = OH (193) X = CMe2 R = OH z (194) X=CMe,,R=H X = CO Y = NCHZCHzCl Z = C1 X= CMe2 Y = 0,Z = Br X = CMe2 Y = O,Z= ORF Martin Granoth and co-workers have continued their studies on spiro-phos- phoranes and three notes record the synthesis of (192),19’ the pK,+ of (193),’99 and the spectral effects of deprotonation of (194)”’ [cf.Ann. Reports (B),1978 75 2641. The same group have also turned their attention to hypervalent iodine compounds an X-ray structure determination of a benziodazole (195) has been made,201 and the I-bromobenziodoxole (196) was prepared.’” The iodoxole (197) exchanges its perfluoroalkoxy-group very rapidly with a perfluoroalkoxide anion. In these compounds the iodine has approximately trigonal-bipyramidal geometry with two equatorial electron pairs; the exchange intermediate probably has a square-planar arrangement of groups about the iodine atom.202 19’ N. H. Toubro B. Hansen N. Harrit A. Holm and K. T. Potts Tetrahedron 1979,35 229. 196 C. Bjerre C.Christophersen B. Hansen N. Harrit F. M. Nicolaisen and A. Holm Tetrahedron 1979 35,409. 19’ H. C. Berk and J. E. Franz J. Org. Chem. 1979,44 2395. 19’ Y. Segall and I. Granoth J. Amer. Chem. SOC.,1979 101 3687. 199 I. Granoth and J. C. Martin J. Amer. Chem. SOC.,1979 101,4618. ’00 I. Granoth and J. C. Martin J. Amer. Chem. SOC.,1979,101,4623. ’O’ T. M. Balthazor D. E. Godar and B. R. Stults J. Org. Chem. 1979 44 1447. ’O’ R. L. Amey and J. C. Martin J. Org. Chem. 1979 44 1779. 238 A. J. Boulton and M. J. Cook Dico-ordinate phosphorus has also attracted much attention recently. Ketonic hydrazones have been known for some years to form diazaphospholes; e.g. (198) from acetone methylhydrazone and PC13.203 Now it has been found that the isomeric system (199) is also produced in this reaction.It is not known just how this happens and the authors were not able to cause the isomers to inter~onvert.~'~ Russian workers have shown that the diazaphosphole (200) reacts with diphenyl-diazomethane at room temperature in ether to give the fused phosphiran (201) which ring-opens in methanol to form the six-membered ring (202). These results were confirmed by X-ray cry~tallography.~~~ The benzodiazaphospholes (203) prepared as indicated exist as monomer dimer and trimer in solution the propor- tion of monomer being ca. 30% in xylene at 140"C and 100% in nitrobenzene. With BF two species were observed which the authors suggest are the adducts of the monomer in which one or the other nitrogen atom is co-ordinated to the boron.206 Ph \-Me (198) R=Me (200) R=Ph A novel compound containing boron is the very curious species (204) prepared from diphenylbromoborane and di-isopropylcarbamoyl-lithium.207 Metal sandwich compounds are becoming more of a mouthful every year.2o8 Four molecules of the thiadiborolen (205) form the bread of a black centrosymmetric (by X-ray) 'tetra-decker' sandwich complex containing two atoms of cobalt and one of iron between the rings.2o9 6 Six-membered Rings A number of significant advances during the year have added to the heterocyclic chemist's already well-stocked armoury.2-Chloro-3-substituted quinolines and hence the 3-substituted quinolines (by reduction) are easily prepared from acyl- anilides under Vilsmeier formylation conditions.Quinoxalines are produced in the 203 J. Luber and A. Schmidpeter Angew. Chem. Znternat. Edn. 1976,15 111. 204 J. H. Weinmaier J. Luber A. Schmidpeter and S. Pohl Angew. Chem. Internat. Edn. 1979 18,412. *05 B. A. Arbuzov E. N. Dianova and Yu. Yu. Samitov Doklady Akad. Nauk S.S.S.R.,1979 244 1117 [Proc. Acad. Sci.(U.S.S.R.),1979 244,591. 206 C. Malavaud M. T. Boisdon Y. Charbonnel and J. Barrans Tetrahedron Letters 1979,447. '07 A. S. Fletcher W. E. Paget K. Smith K. Swaminathan J. H. Beynon R. P. Morgan M. Bozorgzadeh and M. J. Haley J.C.S. Chem. Comm. 1979 347. cf. W. Shakespeare 'As You Like It' Act 111 Scene 2 line 239. 209 W. Siebert W. Rothermel C. Bohle C. Kruger and D. J. Brauer Angew. Chem. Znternat. Edn. 1979 18.949.Heterocyclic Compounds 239 corresponding reaction using dimethylnitrosamine instead of the formamide.210 Quinoline derivatives are also accessible by photochemical cyclization of thioamides (206); the synthesis is adaptable to a range of 2-and 3-substit~ents.~~~ A general method for c-fused pyridines uses the thermal decomposition of appropriate ortho-methyl vinyl azides e.g. (207) -+(208),212 and a synthesis of pyrimidin-4-ones has been described in which diphenylcyclopropenone reacts with amid~ximes.~~~ The versatility of p-imino-enamines as heterocyclic precursors is demonstrated by their reactions with ethyl chloroformate carbon disulphide aldehydes and ketones to give pyrimidin-2-ones and p~rimidine-2-thiones~~~ and 1,2-dihydropyrimidine~,~~~ while with thionyl chloride they produce the thiadiazine oxides (209) at low temperatures; these lose SO to form the pyrazoles at high temperatures.*16 Two rhodium-catalysed reactions convert aniline into quinaldine; using ethylene under pressure,217 and with acetaldehyde in the presence of nitrobenzene.218 /C02Et -$02Et N N Me (207) A new method for the introduction of substituents at the 4-position of pyridine uses the sequence of Scheme 7.The precursor is prepared from pyridine in two steps. The N-substituent is designed to shield the 2-position and to activate the 4-position towards nucleophilic attack. The conversion is successful with a fairly wide range of Scheme 7 21D B. Narine and 0. Meth-Cohn Tetrahedron Letters 1978 2045; 0.Meth-Cohn B. Narine and B. Tarnowski ibid. 1979 31 11; 0.Meth-Cohn S. Rhouati and B. Tarnowski ibid. p. 4885. 'I' P. de Mayo L. K. Sydnes and G. Wenska J.C.S. Chem. Comm. 1979,499. "'T. L. Gilchrist C. W. Rees and J. A. R. Rodrigues J.C.S. Chem. Comm. 1979,627. 'I3 M. Takahashi and S. Watanabe Chem. Letters 1979 1213. 214 J. Barluenga M. Tomas V. Rubio and V. Gotor J.C.S. Chem. Comm. 1979 675. 'I5 J. Barluenga M. Tomas S. Fustero and V. Gotor Synthesis 1979 346. J. Barluenga J. F. L6pez-Ortiz and V. Gotor J.C.S. Chem. Comm. 1979 891. S. E. Diamond A. Szalkiewicz and F. Mares J. Amer. Chem. SOC.,1979,101,4902. 'la Y. Watanabe M. Yamamoto and S. C. Shim Chem. Letters 1979 1025. A. J. Boulton and M. J. Cook nucleophiles A more familiar route to 4-substituted pyridines is via nitra-tion of the N-oxide.The corresponding bromination has seldom proved satisfactory but in difficult cases the use of thallium(rr1) acetate and bromine may be effective.220 Deoxygenation of nitropyridine oxides with phosphorus reagents can also be temperamental and irradiation of a dilute solution of the N-oxide with trimethyl phosphite is an alternative to the thermal reaction.221 Picoline 1-oxides and N-phenylbenzimidoyl chloride with base give side-chain acyl-aminated (2 10) and acylamino-arylated (21 1)products by rearrangement of the anhydro-bases of type (212).222 In a related series photochemical rearrangement of (213) gives (214) together with the 5-substituted isomer. The corresponding 1-0ctyloxy-pyridone gives the 3-octyloxy-isomer but the 1-phenethoxy-analogue gives the 3-benzyl derivative with loss of CH20.223Rearrangement to the 3-position of pyridine has also been observed in the reaction of N-(ary1oxy)-pyridinium ions with azide (and some other) ions.The products 3-(0- hydroxypheny1)-pyridines,contrast with the 2-substituted isomers obtained by other base-catalysed rearrangement^.^^^ Pentachloropyridine 1-oxide and cyclic enamines afford the expected products (215) and in some cases the far-from-expected ring-contracted compounds (216).225 (210) R = N(Ph)COPh (211) R =C6H4N(H)COPh Ph OCH, I 219 A. R. Katritzky H. Beltrami J. G. Keay D. N. Rogers M. P. Sammes C. W. F. Leung and C. M. Lee Angew. Chem. Internat. Edn. 1979 18 792; A.R. Katritzky H. Beltrami and M. P. Sarnrnes J.C.S. Chem. Comm. 1979 137. 220 H. Saito and M. Hamana Heterocycles 1979,12,475. 221 C. Kaneko A. Yarnamoto and M. Gomi Heterocycles 1979 12,227. 222 R. A. Abramovitch D. A. Abramovitch and P. Tomasik J.C.S. Chem. Comm. 1979,956. 223 A. R. Katritzky A. V. Chapman M. J. Cook and G. H. Millet J.C.S. Chem. Comm. 1979 395. 224 R. A. Abramovitch A. L. Miller T. A. Radzikowska and P. Tornasik J. Org. Chem. 1979,44,464. 225 H. Suschitzky B. J. Wakefield and J. P. Whitten J.C.S. Chem. Comm. 1979 183. Heterocyclic Compounds 241 Novel ring transformations include two conversions of pyrimidine-diones into pyridones. i.e. (217) +(218)226 and (219) +(220).227 In the former the N-C-N unit is replaced by the C-C-N of an a-substituted amide while the latter conversion involves a dianion with rearrangement and extrusion of cyanate ion.Thermolysis of dihydro-triazines (22 1)and -pyrimidines (222) involves ring-open- ing 1,7-hydrogen transfer re-cyclization [cf.Ann. Reports (B),1978,75,267] and loss of ammonia to form pyrimidines (223; X = N) and pyridines (223; X = CH) respectively.228 With alkaline hydrogen peroxide the pyridinium betaine (224) gives (225) and (226) via a 2,3-dihydro-2,3-dihydroxypyridinium betaine intermediate. In contrast 2,4,6-triaryl-pyridinium salts give p-amino- and P-aroylamino-chal- cones.229 0-R’ (i) -2H+ -0I’J-R2 (ii) rearrangement’ N /R3 H (219) Ph CH2R Ph (221) X=N (222) X=CH R A Some interesting pyridinium betaines (227) and (228) are formed reversibly from the pyridines with diethoxycarbonylketen tetraethoxycarbonylallene or their pre- cursors.The allene adducts (228) may be prepared by the reaction of (227) with the free keten.230 226 K. Hirota Y. Kitade S. Senda M. J. Halat K. A. Watanabe and J. J. Fox J. Amer. Chem. SOC.,1979 101,4423. 227 R. N. Comber J. S. Swenton and A. J. Wexler J. Amer. Chem. SOC.,1979,101 5411. 228 L. S. Cook and B. J. Wakefield Tetrahedron Letters 1979 1241. 229 A. R. Katritzky C. A. Ramsden Z. Zakaria R. L. Harlow and S. H. Simonsen J.C.S. Chem. Comm. 1979,363. 230 R. Gompper and U. Wolf Annalen 1979,1388,1406. A. J. Boulton and M. J. Cook An unusual product (229) of reaction between the mesomeric betaine (230) and o-chloranil was verified by X-ray analysis.231 Elimination of C02 from the intramolecular Diels-Alder reaction product of the coumarin esters (23 1)provides the benzo-phthalides (232).232 Other intramolecular cycloaddition reactions to pyrimidine rings [cf.Ann.Reports (B),1977,74,272] have been Loss of C02from the adduct formed between the oxazinone (233) and maleimide gives the pyridine (234). In contrast the reaction of (233) with an ynamine forms (235) and (236) presumably by addition to the valence isomer (237) the former by a [4+2] cycloaddition the latter by a [2+2] cycloaddition to give (238) as an intermediate.234 R 0 NKO -+N Ra:\/ uNR2 Ph Ph (234) 0 c0nr2 1 NEt The Diels-Alder reaction of 4-cyano-1-methyl-2-pyridonewith 2,3-dimethyl- butadiene offers a novel entry into the isocarbostyril series,235 and further investiga- 231 W.Friedrichsen C. Kruger E. Kujath G. Liebezeit and S. Mohr Tetrahedron Letters 1979,237. 232 G. A. Kraus J. 0.Pezzanite and H. Sugimoto Tetrahedron Letters 1979 853. 233 T. Jojima H. Takeshiba and T. Kinoto Heterocycles 1979,12 665. 234 A. E. Baydar G. V. Boyd P. F. Lindley and F. Watson J.C.S. Chem. Comm. 1979 178. 235 H.Kato R. Fujita H. Hongo and H. Tomisawa Heterocycles 1979,12 1. Heterocyclic Compounds 243 tions of 2-pyridones in the role of dienes reveal that the reaction with dimethyl acetylenedicarboxylate is favoured by the presence of a 6-methyl and by high Different types of product arise from Diels-Alder reactions of the triazines (239) and (240).After loss of nitrogen the intermediate (241; X = C1) decomposes via a 1,5-shift and loss of HC1 to a 2,6-dichloropyridine but the fluoro-analogue under- goes a further [4 +21 cycloaddition with another molecule of a1kene.238 X x\L"N +/!HR (ii) -N X XR (239) X=C1 (240) X=F (241) tj/\ But BulQ-.BuIBut (242) But C1 The hitherto unknown 1-arsanaphthalene (242) has been prepared by addition of benzyne to arsenin (arsabenzene) and then removing one of the etheno-bridges by standard tetrazine methods. It is very air-sensiti~e.~~~ Dehydrochlorination of the silacyclohexadiene (243) affords the dimer (244) via the monomeric 1,4-di-t- butylsilabenzene which could be trapped by diene~.~~' 7 Seven-membered and Larger Rings Thiepins are notoriously unstable extruding sulphur via a benzene episulphide intermediate.A remarkably stable example is (245) which has ti 7.1 h at 131 "Cin [2H8]toluene. The t-butyl groups are believed to provide steric hindrance to the cyclization in the decomposition pathway and their effectiveness is well shown by the contrast provided by the di-isopropyl analogue which loses sulphur at -70 0C.241 236 G. P. Gisby S. E. Royall and P. G. Sammes J.C.S. Chem. Comm. 1979,501. 237 K. Matsumoto Y. Ikemi-Kono T. Uchida and R. M. Acheson J.C.S. Chem. Comm. 1979 1091. 238 M. G.Barlow R. N. Haszeldine and D. J. Simpkin J.C.S. Chem. Comm. 1979,658. 239 A.J. Ashe D. J. Bellville and H. S. Friedman J.C.S. Chem. Comm. 1979,880.240 G. Mark1 and P.Hofmeister Angew. Chem. Internat. Edn. 1979,18,789. 241 K. Nishino S. Yano Y. Kohashi K. Yamamoto and I. Murata J. Amer. Chem. SOC., 1979,101,5058. A. J. Boulton and M. J. Cook The thiepin (246) could not be isolated but a sulphur-containing species could be trapped the thiol derivative (247) being amongst the products ___ E (E = C02Me) s >C=CHE E H (249) R = CN or COzMe (248) 1 O-YAc H (252) (E = C02Me) (254) R' =Me R2= H (256) R' =Me R2= H (255) R'= H R2=Me (257) R' = H R2=Me The 1H-and 3H-1,2-benzodiazepines are already known and now the first 5H-compounds (248) have been obtained by oxidation of the 1H-derivatives (249) with lead(1v) acetate. The reaction also forms the indazoles (250) presumably via the unstable 3H-isomers (251).On photolysis (248) gives the indole (252) through a tricyclic valence isomer.243 4H- Benzodiazepines e.g. (253) are valence isomers of cyclopropa-cinnolines (254) and (255) which are formed by cyclization of styryl-nitrilimines obtained by dehydrochlorination of the chloro-hydrazones (256) and "'D. N. Reinhoudt G. Okay W. P. Trompenaars S. Harkema D. M. W. van der Ham and G. J. van Hummel Tetrahedron Letters 1979 1529. 243 T. Tsuchiya and J. Kurita J.C.S. Chem. Comm. 1979 803. Heterocyclic Compounds 245 (257). However (253) is not an intermediate in their formation since it has been found that the cis- and trans-isomers (256) and (257) fo’rm the endo- and exo-isomers (254) and (25 5) stereospecifically.Compound (253) is undoubtedly an intermediate in the thermal interconversion of (254) and (255) which takes place spontaneously in solution and also in their slower transformation into the 1H-isomers (258).244 (259) oCHPr” PhfiPh \ N -N R2 (263) R’ = Bu”,R2= H (269) R = OMe n = 1 (264) R’ = H R2= Bun (270) R=H,n=l (267) R’ = H R2 = Ph (271) R=H,n=3 Photolysis of the N-imide (259) leads to the lH-1,3-benzodiazepine (260) in a reaction which finds analogies in the N-oxide series. Further irradiation of the product gives the indole (261);245 cf. (248) -+(252). In the monocyclic diazepine series it is found that the anions generated by deprotonation of (262) can be used to prepare 4-substituted derivatives of this Thermolysis of the cyclopropanes (263) and (264) gives the (E)-and (2)-isomers of the dihydro-oxepins (265) and (266) respectively.In contrast (267) gives 4-phenylphenol via the unstable compound 4-phenyloxepin. The cyclic allenes (268) have been postulated as intermediates in the two pathwaysz4’ [cf.Ann. Reports (B) 1977 74 2541. The crystal structure of the bicyclic dihydro-oxepin (269) has been reported the double bonds though having normal bond lengths are twisted and the bridgehead carbons approach pyramidal The parent (270) is found not to undergo the Cope rearrangement unlike its homologue (271). The lack of reactivity of (270) has been attributed to its inability to be converted from the structure with transoid oxygen atoms (shown here) into the cisoid isomer.249 244 A.Padwa and S. Nahm J. Org. Chem. 1979,444746. ”’ T. Tsuchiya M. Enkaku J. Kurita and H. Sawanishi J.C.S. Chem. Comm. 1979 534. 246 L. Bemi M. T. Thomas and V. Snieckus Synthesis 1979 130. 247 F. Bourelle-Wargnier M. Vincent and J. Chuche J.C.S. Chem. Comm. 1979,584. 248 W. H. Rastetter T. J. Richard J. Bordner and G. L. A. Hennessee J. Org. Chem. 1979 44 999. 249 W. H. Rastetter and T. J. Richard J. Amer. Chem. Soc. 1979 101 3893. A. J. Boulton and M. J. Cook In the sulphur series the cis- and trans-2,3-divinylthiirans have been thermo- lysed. The cis-isomer gives the product of Cope rearrangement but the trans- isomer forms (272) and (273) presumably via initial C-S bond cleavage and subsequent reactions of the biradi~al.~’~ Two groups have reported the synthesis of the parent 10welectron system 1,4-dihydro- 1,4-diazocine (274) derivatives of which have been reported earlier.The compound is sensitive to air in solution but can be sublimed in uacuo and is stable to acid and basic media. In contrast to derivatives bearing electron-withdraw- ing groups at nitrogen the ring is practically planar and X-ray and spectral data are indicative of aromatic chara~ter.~” The green aza[ 18lannulene (275) the first monocyclic pyridine analogue of this type has been prepared and its n.m.r. spectrun reveals that the N atom occupies an internal position as shown. On protonation the ratio of NH-outside to NH-inside cations is ca. 4 :1.2’2 A correction should be noted to last year’s Report on polycyclic medium rings.3,ll -Dimethy1-1,5,9,13-tetra-azatricyclo[9.5.1.1 3*9]octadecane shown as the (chiral) cis-isomer [Ann. Reports (B),1978 75 274; structure (274)] is in fact the rneso-trans-i~omer.~~~ The diaza-bicyclotetradecane (276) is mono- (pK = 6.5)and di-protonated (pK = -3.25) from the outside but the inside-protonated ion is formed on standing in strong acid for a week. However it appears that this does not arise by simple proton transfer but via an aminium cation radical. Support for this comes from its accelerated production in the presence of a one-electron There are now so many apparently well-funded groups working on crowns and cryptands that it is inevitable that many more interesting and significant papers in this 250 M.P. Schneider and M. Schnaithmann J. Amer. Chem. SOC.,1979 101 255. 251 H.-J. Altenbach H. Stegelmeier M. Wilhelm B. Voss J. Lex and E. Vogel Angew. Chem. Internat. Edn. 1979 18 962; M. Breuninger B. Gallenkamp K.-H. Muller H. Fritz H. Prinzbach J. J. Daly and P. Schonholzer ibid. p. 964. *” W. Gilb and G. Schroder Angew. Chem. Internat. Edn.,1979 18 312. 253 D. S. Kemp R. V. Punzar and J. C. Chabala Tetrahedron Letters 1979,4240. 254 R. W. Alder and R. B. Sessions J. Arner. Chem. Soc. 1979 101 3651; R. W. Alder A. Casson and R. B. Sessions ibid. p. 3652. Heterocyclic Compounds area of feverish publication have to be omitted than can be chosen for mention here. Fortunately detailed reviews of the subject have begun to appear see the following section.The photochemical reduction of the metal in N-crown-complexed silver(1) to the zerovalent and the complexation of alkali metals256 as (M’-crown) M- are two less usual aspects of their chemistry. Multi-looped polyether systems have been developed both ~piro-f~~ed~~~~~~~ and with other arrangement^,^^^ and an amusing exploitation of bullvalene isomerization has led to the production of ‘breathing crown ethers’ i.e. crowns which within limits can adapt their ring size according to wearer. Thus the ring of (277) varies from eleven to thirteen members and similarly the bullvaleno-[20-22]-crown-6 can change within the limits indicated.260 Bis-monoaza-crown ethers (278) form 1 1complexes with the bis-salt (279) each ring acting as host to one cationic moiety,261 and a [27]-crown-9- hexacarboxylate forms complexes with guanidinium and imidazolium ions which are stable and also selective even in aqueous (277) (278) n = 2 X = (CH,) or (CH,) 8 Monographs and Reviews In ‘The Chemistry of Heterocyclic Compounds’ (Weissberger-Taylor series) three volumes on a major ring system (thia~ole),,~~ and one a third on another (ind~le),~~~ covering the condensed py~azines~~~ have been published.A seven-volume mono- graph on the porphyrins has appeared,266 and B. D. Tilak’s 60th birthday is ”’ R. Humphry-Baker M. Gratzel P. Tundo and E. Pelizzetti Angew. Chem. Internat. Edn. 1979 18 630. 2s6 J. L. Dye Angew. Chem. Internat. Edn. 1979 18 587. ”’ E. Weber Angew. Chem. Internat. Edn. 1979 18 219.V. Prelog and D. Bedekovic Helv. Chim. Acta 1979 62 2285. 2s9 R. C. Helgeson T. L. Tarnowski and D. J. Cram J. Org. Chem. 1979 44,2538. 260 G. Schroder and W. Witt Angew. Chem. Internat. Edn. 1979 18,311. 261 M. R. Johnson I. 0.Sutherland and R. J. Newton J.C.S. Chem. Comm. 1979,306. 262 J. M. Lehn P. Vierling and R. C. Hayward J.C.S. Chem. Comm. 1979,296. ‘Thiazole and its Derivatives’ ed. J. V. Metzger (Weissberger and Taylor’s ‘The Chemistry of Hetero-cyclic Compounds’) Wiley-Interscience New York 1979 Vol. 34 Parts 1-3. 264 ‘Chemistryof Indoles’ ed. W. J. Houlihan (Weissberger and Taylor’s ‘The Chemistry of Heterocyclic Compounds’) Wiley-Interscience New York 1979 Vol. 25 Part 3. ‘Condensed Pyrazines’ ed. G. W. H. Cheeseman and R. F. Cookson (Weissberger and Taylor’s ‘The Chemistry of Heterocyclic Compounds’) Wiley-Interscience New York 1979 Vol.35. 266 ‘The Porphyrins’ Vols. I and 11 ‘Structure and Synthesis’; Vols. III-V ‘Physical Chemistry’; Vols. VI and VII ‘Biochemistry’ ed. D. Dolphin Academic Press New York 1978-9. 248 A. J. Boulton and M. J. Cook commemorated in a volume of reviews267 on a variety of interesting short topics 1-hydroxy-indoles,“ naphtho-indolizines,b 3,5-disubstituted pyridines and related pyridinophanes,‘ phospholes and benzophospholes (‘phosphindoles’),d 3-oxido- pyridinium betaines,‘ dibenzoxazepines,’ and benzazetes;R also covered are some aspects of cycloaddition to azoles,h azirine chemistry’ and aziridine stereochemistry,’ pyryliumk and thiiranium salts,’ the reaction of azides with indoles,” synthesis of benzo[b]thiophens the use of thiophens in the synthesis of optically active quater- nary hydrocarbons,” the photochemical construction of heterocyclic compounds,P and quantum-chemical aspects of electrophilic substitution in five-membered rings.4 Crowns cryptands and other multidentate macrocycles are the subject of a monograph,268 and three other reviews deal with certain aspects of this area describes the stabilization of derivatives of alkali-metal anions in which crown ethers play an important role; another269 covers cyclic di- and tetra-esters of polyether systems and a third,270 entitled ‘From Carbohydrates to Enzyme Analo- gues’ covers a lot of ground (including a section extolling the virtues of dreaming271).1,SDipolar cyclizati~ns~~~ are discussed in and 1,3-dipolar cyclo-rever~ions~~~ two long articles that are full of interest. Other reactions to be reviewed include the photo-oxygenation of the cyclotrimerization of cyano-compounds to 1,3,5-triazine~,~~~ condensations of alkyl groups in pyrylium salts 276 acid-catalysed transformations of 1,3-dioxans and 1,3-diox01ans,~~~ the reactions of heterocycles which involve the catalytic use of cyanide and the reactions of nitrones with ketens (including an interesting account of Staudinger’s ‘nitrene~’).~~~ More modern nitrenes are also reviewed,280 and other areas of interest to hetero- cyclic synthesis are the diazenium28’ and 3-chloro-2-propeniminium salts,282 and he~amethylenetetramine.~~~ The ‘imino-Diels-Alder’ synthesis of N-heterocycles (particularly 3-piperideines) has been and also the synthesis of hetero- 267 (a) R.M.. Acheson; (b) N. R. Ayyangar and A. G. Lugade; (c) K. Deuchert and S. Hunig; (d)A. N. Hughes; (e) A. R. Katritzky and N. Dennis; cf) K. Nagaragan; (g)C. W. Rees; (h)R. B. Mitra G. H. Kulkarni G. S. Shirwaikar and R. S. Jagtap; (i)A. Hassner and V. Alexanian; 0’)P. Tarburton C. A. Kingsbury and N. H. Cromwell; (k)A. T. Balaban; (I) V. N. Gogte and H. M. Modak; (m)J. M. Peach and A. S. Bailey; (n)B. Iddon; (0)L. A. Hulshof and H. Wynberg; (p)A. Padwa P. H. J. Carlsen and N. Kamigata; (4)I. A. Abronin L. I. Balen’kii and Ya. L. Gol’dfarb in ‘New Trends in Heterocyclic Chemistry’ ed. R. B. Mitra N. R. Ayyangar V. N. Gogte R.M. Acheson and N. H. Cromwell Elsevier Amsterdam Oxford and New York 1979. 268 ‘Synthetic Multidentate Macrocyclic Compounds’ ed. R. M. Izatt and J. J. Christensen Academic Press New York 1978. 269 J. S. Bradshaw G. E. Maas R. M. Izatt and J. J. Christensen Chem. Rev. 1979 79 37. 270 J. F. Stoddart Chem. SOC.Rev. 1979 8 85. 271 cf. W. Shakespeare ‘Julius Caesar’ Act I Scene 2 line 24. For more on dreams and their place in chemistry see A. KekulC quoted by K. Hafner Angew. Chem. Internat. Edn. 1979,18,641. 272 E. C. Taylor and I. J. Turchi Chem. Rev. 1979 79 181. 273 G. Bianchi C. De Micheli and R. Gandolfi Angew. Chem. Internat. Edn. 1979 18 721. 274 M. V. George and V. Bhat Chem. Rev. 1979,79,447. 27s D. Martin M. Bauer and V. A. Pankratov Russ.Chem. Rev. 1978,47 975. 276 V. V. Mezheritskii A. L. Wasserman and G. N. Dorofeenko Heterocycles 1979,12 51. 277 D. L. Rakhmankulov E. A. Kantor and R. A. Karakanov Heterocycles 1979 12 1039. 278 E. Hayashi and T. Higashino Heterocycles 1979 12,837. 279 M. A. Abou-Gharbia and M. M. Joullie‘ Heterocycles 1979 12 819. 280 B. Iddon 0.Meth-Cohn E. F. V. Scriven H. Suschitzky and P. T. Gallagher Angew. Chem. Internat. Edn. 1979,18,900. M. A Kuznetsov Russ.Chem. Rev. 1979 48 563. 282 L. Liebscher and H. Hartmann Synthesis 1979 241. 283 N. Blazevic D. Kolbah B. Berlin V. Sunjic and F. Kajfez Synthesis 1979 161. 284 S. M. Weinreb and J. I. Levin Heterocycles 1979,12 949. Heterocyclic Compounds 249 cycles using heterocum~lenes.~~~ The uses of isoxazoles in synthesis have been collected.286 Specific ring systems which have been covered during the year include besides those mentioned above the azetidine~,~~’ pyrida~ines,~~~ benzo[c]~innolines,~~~ pyrro10[3,2-c]quinolines;~~~ 1,lO-phenanthroline~~~~ pyrroli~idines,~~’ and other polyaza-phenanthrene~,~~~ 1,4-thia~ines,’~~ quina~olines,~~~ and thiirenium ions.296 Other reviews of special areas deal with Reissert 1,2-azoles (isoxa- zoles pyrazoles and isothia~oles),~~~ selenium-nitrogen heterocycles,299 three- membered rings with two heteroatom~,~~~ physicochemical aspects of purine^,^" the ‘H n.m~.~O* spectroscopy of phytoxanthones and the stereochemistry of and u.v.~’~ quinolizidines indolizidines and pyrrolizidine~.~~~ The application of photoelectron spectroscopy to conformational analysis is illustrated with many heterocyclic exam- ple~,~~~ and a review by Kauffmann on ‘areno-analogy’ while stopping short of a clear definition of the term is certainly packed with plenty of interesting heterocyclic The latest volume of the Specialist Periodical Reports on sulphur selenium and tellurium seems to give excellent value more than half of the chapters deal with heterocyclic ring systems and there is also a section on the p-lactam antibiotic^.^'^ 285 0.Tsuge Heterocycles 1979 12 1067.286 C. Kashima Heterocycles 1979,12 1343. 287 N. H. Cromwell and B. Phillips Chem. Rev, 1979,79 331. 288 J. W. Barton Adu. Heterocyclic Chem. 1979 24 151. 289 M. Tiiler and B. Stanovnik Adv.Heterocyclic Chem. 1979 24 363. 290 M. A. Khan and J. F. da Rocha Heterocycles 1979 12 857. 291 D. J. Robins Adu. Heterocyclic Chem. 1979 24 247. 292 W. Sliwa Heterocycles 1979 12 1207. 293 W. Sliwa and H. Zamarlik Heterocycles 1979 12 529. 294 W. L. F. Armarego Adv. Heterocyclic Chem. 1979 24 1. 295 R. J. Stoodley Adv. Heterocyclic Chem. 1979 24 293. 296 G. Capozzi V. Lucchini and G. Modena Rev. Chem. Intermediates 1979,2 347. 297 F. D. Popp Adv. Heterocyclic Chem. 1979 24 187. 298 S. D. Sokolov Russ. Chem. Rev. 1979,48 289. 299 I. Lalezari A. Shafiee and M. Yalpani Adv. Heterocyclic Chem. 1979 24 109. 300 E. Schmitz Adu. Heterocyclic Chem. 1979 24 63. ”” J. H. Lister Ado. Heterocyclic Chem. 1979 24 215. ’02 M. Afzal and J. M. Al-Hassan Heterocycles 1979 12 421.303 M. Afzal J. M. Al-Hassan and F. N. Al-Masad Heterocycles 1979 12 269. 304 I. M. Skvortsov Russ. Chem. Rev. 1979 48 262. 305 M. Klessinger and P. Rademacher Angew. Chem. Internat. Edn. 1979 18 826. 306 T. Kauffmann Angew. Chem. Internat. Edn. 1979 18 1. 307 L Organic Compounds of Sulphur Selenium and Tellurium’ ed. D. R. Hogg (Specialist Periodical Reports) The Chemical Society London 1979 Vol. 5.