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1975 2479Syntheses of Heterocyclic Compounds. Part XXXII.l Intramolecular1.3- Dipolar Cycloadditions of 2-Allyloxy- and 2-Prop-2-ynyloxy-aromaticAldehyde AzinesBy Suchet S. Mathur and Hans Suschitzky," The Ramage Laboratories, Department of Chemistry and AppliedThermolysis of 2-prop-2-ynyloxy-benzaldehyde and -1 -naphthaldehyde azines as well as 2-allyloxy-1 -naphth-aldehyde azines in NN-diethylaniline causes intramolecular cycloaddition in a bis- [3 + 21 or ' criss-cross ' fashionof the prop-2-ynyl or ally1 group to the azine side-chain.Chemistry, University of Salford, Salford M5 4WT, LancashireFEW intramolecular 1,3-dipolar cycloadditions have sofar been reported although they would be expected to bea thermodynamically favourable pathway to hetero-cycles. Nitrones have been found to add intramole-cularly to an olefinic bond to give various isoxazoles,2and azomethineimines with internal double bonds givepyrazolidines ; more recently nitrilimines have beenshown to combine intramolecularly with an acetylenicgroup to afford pyrazole~.~it wasthought that aromatic aldehyde azines might undergointramolecular bis-[3 + 21 or ' criss-cross ' cycloadditionwith a suitably positioned internal dipolarophile. Wethought that an o-allyloxy-group in an azine [as (1;R = H)] might undergo internal cycloaddition with theazine grouping (:CH:N-N:CH*) to give the fused six-ringsystem (2) in preference to a [3,3] sigmatropic (Claken) re-arrangement to the hydroxy-compound (3).However,heating a solution of (1 ; R = R' = H) in diethylanilinefor 4 h gave the Claisen product (3; R = H).The ortho-blocked 6-methoxy-compound (1 ; R = OMe, R' = H)produced the rearranged phenol (4; R = H), and theortho,para-blocked allyloxy-ether (4 ; R = CH,*CH:CH,) and the but-2-enyl derivative (1; R = OMe,R' = Me) gave intractable mixtures. The failure toproduce internal cycloadducts in the benzene series ledus to study the analogous naphthaldehyde azine ( 5 ;R = Me, R' = H) under similar conditions. Chromato-graphy of the reaction mixture gave a white solid whichdid not show an allylic pattern in the lH n.m.r. spectrum,thus excluding any [3,3] sigmatropic rearrangement.Its spectral and analytical data were fully compatiblewith the diazabicyclo[3.3.0]octane structure (6) arisingfrom intramolecular ' criss-cross ' cycloaddition betweenthe *CH:N*N:CH* chain and the two *CH:CH,* groupsacting as 1,3-dipole and dipolarophile, respectively.ThelH n.m.r. spectrum (in CDC1,) indicated a symmetricalstructure. Protons a (T 5.9) and b (7 6.05) coupled toH, formed an ABX system which appeared as an eight-line pattern (Jab 12, JBc 6, Jbc 9 Hz). Proton c, beingcoupled to Hd (Jca 9 Hz), Hf ( J c f 6 Hz), Ha, and Hb,appeared as a nine-line multiplet (overlapping triplet oftriplets) at T 7.7 with intensities roughly in the ratio1 : 2 : 2 : 1 : 4 : 1 : 2 : 2 : 1. The Hf resonance is initiallyPart XXXI, S. S. Mathur and H. Suschitzky, precedingpaper.(a) N. A. LeBel, M. E. Post, and J. J. Whang, J .Amer.Chem. SOL, 1964, 86, 3759; (b) W. C. Lumma, jun., ibid., 1969,91,2820; (c) W. Oppolzer and K. Keller, Tetrahedron Letters, 1970,1117, 1121, 4313.Since azines are known to act as l,&dipolessplit by four interactions (Jef 6, and Jcf 6 Hz) leading toa quintet at T 6.8 (ca. 1 : 4: 6 : 4 : 1). The methylsignal appeared as a doublet at T 9.65, and that of & atT 4.8 coupled to H, (d, Jcd 9 Hz). The aromatic protonsH, and Hh gave rise to doublets at 7 3.0 and 2.4, respect-ively (Jgh 9 Hz) and the rest of the naphthalene protonsH2:c H-c HR 6 cH=f( 3 )appeared as multiplet atfragmentation was also2aT 1.5-2.8. The mass spectral.consistent with the structure(6):showing a peak at 448(M+) with sequential losses asindicated in Scheme 1 (R = Me).A prominent peak atW. Oppolzer, Tetrahedron Letters, 1970, 3091; 1972, 1707.R. Fusco, L. Garanti, and G. Zecchi, Tetrahedron Letters,T. Wagner-Jauregg, Ber., 1930, 3213; M. Haring and T.1974, 269.Wagner- Jauregg, Helv. Chim. Ada, 1957, 40(99), 8522480 J.C.S. Perkin Ireported for the isosteric heterocyclic part in benzo-pyran0[4,3-c]isoxazole.~~ The slightly high-field methylresonance (7 9.65) suggests shielding, presumably owingto the alkyl group lying over the plane of the aromaticrings which is only possible if both naphthopyran unitsare in an endo-position relative to the two folded pyra-zolidine rings (B).Thermolysis of the 2-methylbut-2-enyl ether (5;R' = R = Me) gave only the dealkylated product, inhigh yield (82%).We extended our studies to the azine (11 ; R = OMe)with an ort?zo-prop-2-ynyloxy-group.Its thermolysis inNN-diethylaniline at 200 "C for 1-2 h gave, on cooling,a solid (50%) which on the basis of its spectra is identi-fied as the diazabicyclo-octadiene (12; R = OMe),rather than an internal Diels-Alder product as obtainedfrom some 2,6-disubstituted aryl prop-2-ynyl etherswhen treated in a similar way.' Its significant lHn.m.r. signals (in CF,*CO,D) were at 2.5 (s, Ha), 1.5 (s,Hb), and 4.8 (s, 2 H,) with the methyl signal at 76.15 (s).The low-field position of the Ha signal as compared withHd in (6) may be regarded as due to the combined de-shielding effect of the double bond and the adjacentnitrogen atom (quaternised by the solvent).The massspectrum showed peaks which can be rationalised as setout in Scheme 2. The adduct undergoes fission to givethe azine (14) which suffers N-N cleavage.8 Loss ofHCN gives the fragment ion (16) which by a symmetry-allowed suprafacial 1,2 H-shift affords the chromenylcation (17). Further changes are due to loss of CO (18)and acetylene to give fragment ion (19) (m/e 107).m/e 182 is assigned to benzorflchromen (7), converted byloss of a hydrogen atom into the chromenyl cation (€9,7.R = H , r n / e 4 2 OR = M e , m / e 4 4 8R C H=N-N=C H R + mo+*( 7 ) m / e 1 8 21 t( 1 0 1 m / e 1 2 7129, and 106 were observed for these fragmentationsSCHEME 1 m,,* m2*, and m3*: metastable peaks at m/e 180,appearing as the base peak at mle 181.The fragmention at m/e 127 corresponds to the naphthyl cation (10).2H-Chromen6 itself is known to give the chromenylcation by a similar fragmentation pattern leading to theanalogous phenyl cation.Thermolysis of the azine (5; R = R' = H) undersimilar conditions gave the corresponding diazabicyclo-octane (6; H for Me) (12%) with lH n.m.r. and massspectral data analogous to those of its methyl homo-logue. Each cycloadduct (6) was isolated in one formonly, indicating stereospecificity of the cycloaddition,but the spectral data did not enable us to distinguish withcertainly between several possible conformations.Models (Dreiding) suggest cis-fusion between A and B[see (6)] on the basis of least strain, which is also com-patible with the observed coupling (J& 9 Hz) and that6 B.Willhdm, A. F. Thomas, and F. Gautschi, Tetrahedron,1964, 20, 1186.H( 1 3 )Prolonged heating (6-7 h) of the adduct (12; R =MeO) in diethylaniline gave a new adduct with a complexlH n.m.r. spectrum possibly formed by migration of thedouble bond. However, no conclusive evidence for analternative structure was obtained.7 I. Iwai and H. Ide, Chem. and Pharm. Bull. (Japan), 1963,11, 1042; J. Zsindely and H. Schmid, Helv. Chim. Acta, 1968, 51,1610.8 R. G. Cooks and S. W. Tam, Org. Mass Spectrometry. 1968, 1,583; B. Zeeh and R. Beutler, ibzd., p. 7911975 24831Thermolysis of the o-prop-2-ynyloxy-azine (1 1 ; R =H) gave the criss-cross cycloadduct (12; R = H) asexpected and not a chromens as is usual with prop-2-ynyl ethers under Claisen conditions. The structure isconsistent with the lH n.m.r.and i.r. data (see Experi-mental section) as well as with its mass spectrum, whichshowed a peak at 316 (M+) and a fragmentation patternanalogous to that of its methoxy-derivative (cf. Scheme2). Thermolysis of the naphthaldehyde azine (13) inNN-diethylaniline gave the cycloadduct analogous toWe presume that the observed intramolecular cyclo-additions follow a pathway analogous to that postulatedfor the usual intermolecular ‘ criss-cross ’ additions ofazines with dipolar~philes.~ A zwitterionic intermediate(20) is formed arising from the intramolecular cyclo-addition of one of the double or triple bonds of the un-saturated ether side-chain onto the azine group.This(12).M em1+-*M e/ n( 1 5 ) m / e 1 8 8 ( 1 6 ) m / e 1 6 10 *m3* I + + m p *Me0 Me0 Me0\ . \ + / - 4( 1 9 ) m / e 1 0 7 ( 1 8 1 m / e 133 ( 1 7 l m / e 1 6 1SCHEME 2 m,*, m,*, and m3*: metastable peaks a t nz/e 137,109, and 86 were observed for these fragmentationsis followed by a second intramolecular cycloadditionleading to the described adduct [(6) or (12)]. Theintermediacy of the dipolethe recent isolation of the(20) is given some credence bydipolar cornpound lo (21).“a - NC F 3 C F 31 2 1 )Thermolysis of o-allylamino- or o-allylthio-benzalde-hyde azine gave only intractable mixtures.EXPERIMENTAL1.r. spectra were recorded with a Perltin-Elmer 257instrument, 1K n.m.r.spectra with a Varian A60 or A100instrument (Me,Si as standard), and mass spectra with anA.E.I. MS 12 or MS 9 (for high resolution work) instrument.Preparation of 2-Alkoxy-aroinatic Aldehydes.-In a typicalprocedure a mixture of the 2-hydroxy-aldehyde (0.1 mol)and allyl, but-2-enyl, or prop-2-ynyl bromide (0.1 mol) andfinely powdered anhydrous potassium carbonate (0.1 mol)in dry acetone was heated under reflux for 12-24 h. Aftercooling, water was added and the mixture extracted withethyl acetate. The extract was washed with aqueoussodium hydroxide (10%) followed by water, dried (MgSO,) ,and evaporated, leaving the aldehyde which was purifiedby distillation or recrystallisation (Table 1).Preparation of Aromatic Aldehyde Azines .-By a con-ventional method the aldehyde (0.1 mol) in ethanol (20ml) was treated with hydrazine hydrate (0.05 mol) and theresulting solution was kept on a water-bath for 0.5-1 h.The solution was cooled and the product filtered off andrecrystallised from ethanol or chloroform as yellow needles.Some physical data are listed in Table 2.1H N.m.r.spectra were in accord with the proposed structures.3-Methoxy-5- (Prop-2-enyZ) -2- (prop- 2-enyloxy ) benzaldehydeAzine (4; R = CH,:CH*CH,).-A mixture of the hydroxy-azine (1.0 g) obtained from the Claisen rearrangement of( 1 ; R = MeO, R’ = H) (see below), prop-2-enyl bromide(2.4 g) and finely powdered anhydrous potassium carbonate(3 g> in dry acetone was heated under reflux for 20 h. Themixture was cooled, diluted with water (60 ml), and ex-tracted with ethyl acetate (2 x 20 ml).The extract waswashed with aqueous sodium hydroxide (lo%), dried, andevaporated. Chroniatography of the residue over aluminawith light petroleum-ethyl acetate (1 : 4) gave the yellowazine (4; R = CH,:CH*CH,) (1.0 g, SOYo), m.p. 90’ (Found:C, 72.8; H, 7.1; N, 5.8. C,,H,,N,O, requires C, 73.1; H,7.0; N, 6.0%). Thermolysis in NN-diethylaniline gavetars.2-(Prop-2-enyZamino) benzaldehyde Azine.-A mixture oflo K. Burger, W. Thenn, and A. Gieren, Angew. Chem. Internat.R. Huisgen, Angew. Chem. Internat. Edn., 1963, 2, 565.Edn., 1974. 7 , 474J.C.S. Perkin I2-aminobenzaldehyde azinell ( 1.6 g) , ally1 bromide (4.0 g),and anhydrous potassium carbonate (2.0 g) in dry butanolwas heated under reflux for 24 h.Work-up as describedabove gave the azine as yellow needles (0.4 g, 26y0), m.p.145" (Found: C, 75.2; H, 6.7; N, 17.5. C,,H,,N, requiresC, 75.5; H, 6.9; N, 17.6%). Thermolysis in diethylanilinegave only tars.andRm.p. 70' (Found: C , 68.7; H, 5.4; N, 7.4. C,,,H,,N,S,requires C, 68.2; H, 5 . 7 ; N, 7.9%). Thermolysis in diethyl-aniline gave intractable tars.Thermolysis of the Azines in NN-Diethylani1ine.-Asuspension of the finely powdered azine [(111) or (IV) ; seeTable 21 (ca. 3.0 g) in diethylaniline (15 ml) was heated underreflux for 3 h. After cooling, the mixture was poured ontoTABLE 12-Alkoxy-benzaldehydes and - 1 -naphthaldehydesR I O C H O W O ROR CHO( 1 1 (4:)Found (%) Required (yo)Yield Mp.("C) c - 7 - R' (%) [B.p. ("C); mmHg1 C H Formula C H(1)CH,:CH:CH, H 75 [135; 101" ClOH1002CHIC-CH, H 66 64 75.4 5.2 C10H802 75.0 6.0CH,:CH:CH, Me0 55 [165; 123" C11H1203 CHMe:CHCH, Me0 65 b 69.5 6.3 C12H1403 69.9 6.8CHICCH, Me0 60 b 69.0 4.9 C11H1003 69.5 6.3(11)CH,:CHCH,CHMe:CHCH,CMe,:CHCH,CHIC-CH,C14H12026.0 C15H140277 77 =79.7 6.2 70 49 79.382 64 79.6 6.5 C16H1602 80.0 6.776 116 80.5 5.0 C14H1002 80.0 4.8Ref. 7. The aldehyde was obtained as an oil by chromatography [AI,O,; light petroleum-ethyl acetate (1 : 2)]. L. Claisen0. Eisleb, ..lnnaZen, 1913, 401, 21.TABLE 22-Alkoxy-benzaldehyde and -1-naphthaldehyde azinesFound (%) Required (yo)r-------7R R' (%) ("C) c H N Formula C H Na; CH,:CH*CH, H 84 108 75.5 6.5 8.9 C2,H,,N,0, 75.0 6.3 8.7b; CH,:CH*CH, Me0 62 100 69.2 6.8 7.5 C,,H,,N,O, 69.5 6.3 7.3c; CHMe:CHCH, Me0 80 164 70.2 6.7 6.8 C24H28N204 70.6 6.9 6.8e ; CHICCH, Me0 52 210 69.8 6.6 7.4 C2,H,,N,04 70.2 5.3 7.4a; CH,:CH.CH, 83 160 79.9 5.9 6.6 C2,H,,N,0, 80.0 5.7 6.6b; CHMe:CHCH, 88 131 80.3 6.2 6.5 C,,H,,N,O, 80.4 6.3 6.2c; CMe,:CHCH, 66 135 80.8 6.7 6.8 C3,H3,N20, 80.7 6.7 5.8d; CHICCH, 76 186 80.5 5.0 7.0 C,,H,,N,O, 80.8 4.8 6.7a E.G. Brain, F. P. Doyle, M. D. Mehta, D. Miller, J. H. C. Nayler, and E. R. Stove, J . Chem. Soc., 1963, 491.Yield M.p. p-,-.-.---,(111)d ; CHiCCH, H 84 174" C20H16N202(Iv)2-(Prop-2-enylthio)benzaldehyde Azine.-A mixture ofo-fluorobenzaldehyde (12.0 g), prop-2-ene-1-thiol (10 g),powdered potassium carbonate, and butanol (50 ml) waskept under reflux for 24 h.Dilution with water wasfollowed by extraction with chloroform. The extract wasdried (MgSO,) and evaporated in vacuo. The resultingoil was purified on silica with light petroleum-ethyl acetate(1 : 1) as eluant. The resulting oily 2-(prop-2-enylthio)-benzaldehyde was converted into the azine (6.5 g, 73 yo) withhydrazine as described above for the preparation of azines;an alumina column and the solvent was eluted with lightpetroleum. The products obtained by further elution withother solvents (in parentheses) and recrystallised fromethanol were as follows. (a) The azine (IIIa) rearranged togive 2-hydroxy-3-(prop-2-e~zyl) benzaldehyde azine (chloro-form) (3; R' = H), m.p.124" (46%) (Found: C, 75.2;H, 6.7; N, 8.2. C,oH2,N,02 requires C, 75.0; H, 6.3; N,8.7%). (b) The azine (IIIb) rearranged to 2-hydroxy-3-methoxy-5-(prop-2-enyZ)benzaZdehyde azine (4; R = H),l1 C. E. Pawloski, U.S.P. 3,236,6951975m.p. 182" (55%) (Found: C, 69.8; H, 6.7; N, 7.8. CZ2-H,,N,O, requires C, 69.5; H, 6.3; N, 7.3%), z [(CD,),SO-CDCl,)] 6.6 (4 H, s), 6.1 (2 MeO, s), 4.6 (4 H, m), 3.8 (2 H,m), 3.1 (4 H, s), 1.25 (2 H, s), and - 1.3 (OH, s, collapsedon addition of D,O). (c) Thermolysis of the azine (IIIc)gave tarry material. (d) The azine (IVa) gave 8a,9b,-17a, 18b-tetrahydro-8H, 9H, 17H, 18H-7,16-dioxa-9a, 18a-diaza-pentaleno[2,1-~:5,4-~']diphenanthrene (6; H for Me) (fromethyl acetate) as white needles (12%), m.p. 275-276"(Found: C, 79.6; H, 5.7; N, 6.4.C2,H2,N,0, requires C,80.0; H, 5.7; N, 6.6%), T (CF,*CO,D) 6.15 (4 H, m), 5.65(8 H, m), 4.25 (2 H, d, Jcd 8 Hz), 3.1 (2 H, d), and 2.2-2.8(10 H, m). (e) The azine ( I n ) gave the 9,18-dinzethylderivative (6) of the foregoing compound (from diethylether), m.p. 243-245" (17%) (Found: C, 80.2; H, 6.0;N, 6.1. C,,H,,N,O, requires C, 80.4; H, 6.3; N, 6.2%);for 1H n.m.r. data see Discussion section. (f) When theazine (IIId) was heated, 6H,7bH, 13H,14bH-5,12-dioxa-7a, 14a-diaza~entaZeno[2,1-~:5,4-c']dina~hthaZene (1 2 ; R =H) separated on cooling; m.p. 254" (from dimethylforma-mide) (33%) (Found: C, 76.2; H, 5.2; N, 8.5. C,,H,,N,02requires C, 76.0; H, 5.1; N, 8.8%), z (CF,*CO,D) 4.65(2H, s), 2.35-2.95 (8H, m), 2.25 (2H, s), and 1.4 (2 H, s).(9) The azine (IIIe) gave the 4,ll-dimethoxy-derivative(12; R = OMe) in a similar manner; m.p. 252-253"(50%) (Found: C, 70.2; H, 5.4; N, 7.2. C,,H,,N,O,requires C, 70.2; H, 5.3; N, 7.4%) (see Discussion sectionfor 1H n.m.r. spectrum). (h) From the aldazine (IVd) 8H,-9H, 17H, 18H-7,16-dioxa-9a, 18a-diazafientaleno[2,l-c: 5,4-c']-diphenanthrene separated on cooling (35%) ; m.p. 285-287"(from dimethylformamide) (Found: C, 80.7; H, 4.8;N, 6.6. C,,H,,N,O, requires C, 80.8; H, 4.8; N, 6.7%).(i) When the aldazine (IVc) was heated, 2-hydroxy-l-naphth-aldehyde azine (IV; R = H) (82%), m.p. 290" (decomp.)(lit.,l2 290°), was deposited on cooling.We thank Allen and Hanbury for a studentship ( t oS. S. M.), Dr. D. Bishop for discussions, and Mr. T. McC.Paterson for experimental assistance.[5/680 Received, 10th April, 19751l2 I. H e i l p n and H. M. Bunbury, 'Dictionary of OrganicCompounds, Eyre and Spottiswoode, London, 1966

ISSN:1472-7781    

DOI:10.1039/P19750002479

出版商:RSC    

年代:1975

数据来源: RSC