N-arylphthalazinium cations: synthons for biphthalazinylidenesviaendocyclic phthalazinium ylide intermediates

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1992 N-Arylphthalazinium Cations: Synthons for Biphthalazinylidenes via Endocyclic Phthalazinium Ylide Intermediates Richard N. Butler" and Carmel S. Pyne Chemistry Department, University College Galwa y, Ireland Treatment of 2-aryl-l -hydroxy-l,2-dihydrophthalazines with HCIO, in MeCN gave 2-N-arylphthalazinium cations as perchlorate salts. These, when heated with NaOAc in MeCN gave good yields of biphthalazinylidenes via an endocyclic 2-arylphthalazin-2-ium-1-ide intermediate. The presence of the ylide intermediate is supported by deuterium protium exchange at C-1 in the phthalazinium cation. At ambient temperature in water some nucleophiles added to the cations to give 1-substituted-2-a ry I-1,2-dihyd rop htha lazi nes. Recently we reported' the first biphthalazinylidenes 4 obtained by heating the 1 -hydroxy-1,2-dihydrophthalazines1with acetic acid in acetonitrile. The ylidenes proved to be particularly interesting because of the pure trans-folded nature of the alkene moiety of the ylidene linkage.' We proposed the mechanism outlined in Scheme 1 as the route to the ylidenes.This involved *-c6w-p I -dr 1 2 2 c----H+ 4 3 Scheme 1 Reagent: i, HOAc in MeCN a phthalazinium cation 2 which was deprotonated to the reactive phthalazinium ylide intermediate 3which reacted with the precursory cation 2 to give the ylidene. The proposed mechanism was supported by reactions with the additives, such as sulfur, dimethyl acetylenedicarboxylate and N-phenyl-maleimide. These gave new ylidene products which were consistent with reactions between the additives and inter- mediates, such as 2 and 3, but they were not conclusive.We present results herein which lend support for the proposed mechanism, because they establish the existence of the species 2 and 3 and show that together they can give rise to high yields of the ylidenes 4. Results and Discussion The cations 2 should be stable since they have the 1h-naphthalene aromatic electronic structure. We isolated these cations in high yields as crystalline solid perchlorate salts 5 (Scheme 2) by treating compounds 1 with perchloric acid in acetonitrile followed by precipitation with ether (Table 1). The salts 5 were identified from microanalysis, 270 MHz proton and carbon-13 NMR spectra which proved their structure.All of the required signals were clearly identifiable and there was no serious overlap. In particular the C=N carbons with their protons HA and H, stood out in the proton and carbon spectra 4 6 7 R = Ac, COCD3 8 R=H /heat 10.2-10.35 5 9 X,CN 1 X.OH Scheme 2 Reagents: i, NaOAc in MeCN; ii, NaOAc-DOAc in MeCN. Y = a Me0 b Me; c H; d Br; e NO,; f C1. Some key proton and carbon NMR shifts shown (Fig. 1) and the related signals were identified by selective proton decoupling during the carbon-1 3 NMR spectral measurements. When the salts 5 were heated with one mol of sodium acetate under anhydrous conditions in acetonitrile the ylidenes 4 were readily obtained in yields which were comparable and, in most cases, better than the yields obtained by heating compounds 1 with acetic acid.' This reaction with the salts 5 provided a cleaner and better route to the ylidenes and side reactions which were encountered with acetic acid did not interfere.For example, the pN02 derivative 4e (Ar = p-NO,C,H,-) could not be made previously because of complicated equilibria involving the acyclic aldehyde form of compound le which gave quite different chemistry on treatment with acid., However, compound 4e was obtained readily by heating compound 5e with NaOAc in acetonitrile (Table 1). When deuterioacetic acid was introduced into the reactions of 5 with NaOAc in acetonitrile and the starting material 5 recovered before the full yield of ylidene 4 built up, significant deuterium exchange at HA in the cation was observed using proton and carbon-13 NMR spectra (Fig.1). This exchange at HA occurred only in presence of NaOAc and on heating. It was most effectively seen with 2 mol of CD,C02D present. The salts 6 recovered from these reactions showed small amounts of contamination (,a,.,.-l'-11 10 9 8 160 150 SH 6c CHB, Fig. 1). Biphthalazinylidenes 4.-Typically a solution of 5c (0.25 g, 0.825 mmol) in dry acetonitrile (10 cm') was treated with anhydrous sodium acetate (70 mg, 0.825 mmol) and the mixture was stirred under reflux for 3 h. On cooling compound 4c (71) separated. Treatment of the acetonitrile mother liquor with diethyl ether resulted in recovery of 5c and no other compounds were encountered.For substrate 5e the mixture was stirred under reflux for 3 h and cooled to give the previously unattainable red coloured derivative 4e,(60) as a mixture with compound le (37). The ylidene 4ewas removed in chloroform in which le is insoluble;4e, m.p. 282-283 "C(from MeCN) (Found: C, 66.7; H, 3.5; N, 16.5. C,gH,gN,O, requires C, 66.9; H, 3.6; N, 16.7). When aqueous solutions of NaOH were treated with equimolar quantities of compounds 5 and the mixtures stirred at ambient temperatures for 30 min, the compounds 1 (d90) separated and were recrystallised from MeCN. Similar treat- ment of aqueous solutions of 5 (0.98 mmol, 10 cm3) with aqueous KCN (0.98 mmol, 10 cm') gave compounds 9 e.g.9c, m.p. 154-155 "C (EtOH) (94) (Found: C, 76.8; H, 4.6; N, 18.0. Cl5Hl1N3requires C, 77.25; H, 4.7; N, 18.05); S,(CD,),-Fig. 1 (a) Lower aromatic region of the proton and carbon-13 (inset) NMR spectra of 5c in (CD,),SO; (b) The same regions for a sample of 5c recovered from being heated with NaOAc and DOAc in MeCN during which a 40 yield of 4c was formed yields of the products 1 and 9 from simple addition of the nucleophile in a reaction that can be synthetically useful. The exchange results (Fig. 1)suggest that the endocyclic ylide 3 is present in anhydrous hot solutions of the cation 5 and sodium acetate and that such solutions containing the species 5 and 3 give good yields of the ylidenes 4.As far as we are aware,' this is the first report of an endocyclic phthalazinium ylide intermediate. Deuterium-hydrogen exchange has been repor- ted3 for substituted amino-pyridazines and pyridazinones and an endocyclic pyridinium ylide is involved in the ready deuterium-hydrogen exchange which occurs at C-2 and C-6 of the pyridinium There are reports of endocyclic quinolinium6 and azolium ylide~'*~ and recently 1,3-di-(1-t The name 'ylide' is widely used (ref. 5 and references therein) for I nitrogen heterocyclic systems containing the moiety +I-.SO 7.2 (s, 1 H, 1 -CH), 7.24-7.26 (m) and 7.54-7.74 (m, 9 H, Ar)These and 8.20 (s, 1 H, 4CH); (with multiplicity for off-resonance systems can also be referred to as ylidenes if a non-octet carbene form decoupling), 45.3 (d, C-1), 115.8 (d, Nph-C-2'), 123.9(s), 126.25 (s, C-4a, C-8a); 116.4 (s, CN), 122.7, 125.8, 129.3, 130.4 Nj:,is drawn.Herein they are referred to as ylides and drawn in the and 131.8 (all ds, ArCHs), 139.5 (d, C-4) and 145.0 (s, N-Ph, octet form. c-1'). J. CHEM. SOC. PERKIN TRANS. 1 1992 References 1 R. N. Butler, A. M. Gillan, F. A. Lysaght, P. McArdle and D. Cunningham, J. Chem. SOC., Perkin Trans. I, 1990,555. 2 R. N. Butler, A. M. Gillan, J. P. James, P. McArdle and D. Cunningham, J. Chem. Res., (S),1989,62; (M), 1990,0523. 3 cf. M. Tisler and B. Stanovnik, in Comprehensive Heterocyclic Chemistry, eds. A. R.Katritzky and C. W. Rees, Pergamon Press, Oxford, 1984, vol. 3, p. 22. 4 J. A. Zoltewicz and C. L. Smith, J. Am. Chem. SOC., 1967,89,3358. 5 T. L. Gilchrist, in Heterocyclic Chemistry, Pitman Publishing Ltd., London, 1985, pp. 252-253. 6 H. Quast and E. Frankenfeld, Angew. Chem., Int. Ed. Engl., 1965, 4, 691; H. Quast and A. Gelleri, Liebigs Ann. Chem., 1975, 929 and 939. 7 H. Quast and S. Hunig, Chem. Ber., 1966,99,2017. 8 A. Takamizawa, H. Harada, H. Sat0 and Y. Hamashima, Heterocycles, 1974,2, 52 1. 9 A. J. Arduengo 111, R.L. Harlow and M. Kli'ne, J. Am. Chem. SOC., 1991,113,361; cf. R.Dagani, Chem. Eng. News, 1991,19. Paper 2/04523K Received 2 1st August 1992 Accepted 17th September 1992