摘要:

Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) Red photoluminescence in the synthesis of triphenylmethyl radicals by the Gomberg method Ramil G. Bulgakov,* Sergei P. Kuleshov and Zemfira S. Valiullina Institute of Petrochemistry and Catalysis, Bashkortostan Republic Academy of Sciences and Ufa Scientific Centre of the Russian Academy of Sciences, 450075 Ufa, Russian Federation.Fax: +7 3472 31 2750 DOI: 10.1070/MC2000v010n01ABEH001115 The red photoluminescence (lmax = 580±20 nm) observed in the synthesis of the Ph3C· Gomberg radical is assigned to a luminescence of the (Ph3C–Ph– Ph2)* radical dimer. The discovery of the first radical of the Ph3C· type (generated in a reaction of Ph3CCl with metals) gave impetus to a discussion on the nature of radical and molecular species in the equilibrium system Ph3C dimer.At a later time, NMR spectroscopy was used to disprove certainly a statement on the existence of hexaphenylethane and to show1 that an equilibrium took place in the absence of O2 (Scheme 1), where the maximum equilibrium concentration was [Ph3C·] = 5% at 300 K. The properties and composition of the components of the equilibrium system were studied by various techniques (EPR, NMR and UV spectroscopy and elemental analysis).The photoluminescence (PL) method was never used for these compounds, with one exception, where green PL of Ph3C· was detected at 90 K. At the same time, PL of Ph3C· was observed in studies3–6 where the radical was generated at 77 K as a result of UV and g-irradiation of Ph3CCl and Ph3CH solutions.This PL disappeared when the irradiated solutions were unfrozen. Recently, we have reported that Ph3C· shows a green PL at 300 K in the absence of O2. A green chemiluminescence of redox reactions which generate (Ph3C·)* is also known.7–9 This paper is aimed to investigate the PL method for the equilibrium system (Scheme 1) in the course of the reaction of Ph3CCl with Zn in solutions. Ph3CCl of CP grade was used after triple recrystallization from hexane. The purity was monitored by PL (lmax = 435 nm) and HPLC.The solvents (THF, CCl4 and Et2O of CP grade, benzene, toluene and hexane of reagent grade and rectified EtOH) and argon purified and dried according to refs. 10 and 7, respectively, were used. The reactions proceeded in a thermostatted cell of a spectrometer under stirring, the mixture was centrifuged before spectral measurements. PL and absorption spectra were recorded in sealed quartz vessels (l = 10 mm, 300 K) or cells (l = 5 mm, 77 K) on a Specord-M40 spectrophotometer and an Aminko-Bowman fluorimeter, respectively.A decrease in the PL intensity of Ph3CCl (lmax = 435 nm) and the appearance of the PL of Ph3C· (lmax = 525, 550 nm) were observed after mixing Ph3CCl (0.18 mmol) with Zn powder (1.56 mmol) at 300 K in Ar (Figure 1).Within 5–10 min, a red PL (lmax = 580±20 nm) was observed together with a rise in the intensity of the green PL of Ph3C·. An absorption spectrum of the solution consists of bands of the radical Ph3C· (lmax = 334, 516 nm) and lmax = 440 nm.In the PL excitation spectra of the solution, for the bands at lmax(PL) = 525, 550 nm, lmax = 334, 516 nm were detected, caused by the Ph3C· absorption, and for a band at l(PL) 580 nm, lmax = 435 nm. These data allowed us to assign a band at lmax = 435 nm to the absorption of a product responsible for the red PL. Note that the position of the maximum does not correspond to Ph3C· or its molecular dimer having lmax = 313 nm.Previously, an absorption band at lmax = 430 nm was found in an analogous reaction alongside with the bands of Ph3C· though it was not identified. As the reaction proceeded for 30–40 min, the intensities of the bands at lmax = 525 and 550 nm were redistributed and the intensity of the red PL increased. At longer reaction times (> 2 h), the green PL disappeared, and the red PL was retained.However, in this case, Ph3C· was detected in the solution by its characteristic PL at 77 K. Two reasons for the disappearance of green PL are possible: the quenching of (Ph3C·)* with energy transfer to a product responsible for the red PL (Ered) and a chemical transformation of Ph3C· to this product. We cannot explain now this PL disappearance.The presence of a red PL depends on the nature of the solvent. It does not appear in THF (77, 300 K). In benzene, toluene, CCl4, EtOH or Et2O, a red PL was detected at lmax = 580±20 nm. The addition of THF to a toluene solution (having red and green PL) causes selective quenching of the red PL. The red PL was quenched completely at the THF:toluene volume ratio 1:1.A decrease in the intensity and disappearance of the red PL during the addition of THF can be caused by two reasons: radiationless energy transfer from (Ered)* to THF and a chemical reaction of the red PL emitter with THF. The fact that red PL is not reduced in a frozen solution evidences a chemical interaction. (Ered)* is more stable to O2 than (Ph3C·)*. When an aliquot portion of air is added to the reaction mixture exhibiting green and red PL, the green PL of Ph3C· disappears immediately, and the red PL is detected for more than 2 h.However, after passing an air flow for more than 2 h, the red PL also disappears. When O2 is added to a Ph3CCl solution before the contact with Zn and C · 2 Ph3C CPh2 H Ph3C 1 Scheme 1 40 30 20 10 0 60 50 40 30 20 10 0 120 100 80 40 0 IPL (arbitrary units) l/nm 420 440 460 480 500 520 540 560 580 1 2 3 4 5 6 7 8 9 10 11 1 2 3 4 5 7 6 4 7 5 7 7 Figure 1 PL spectra in the reaction Ph3CCl + Zn: (1) and (2) THF, 300 K, after 0 and 10 min; (3), (4) and (6) toluene, 300 K after 20, 40 and 60 min; (5) and (7) toluene, 77 K, after 40 and 60 min; (8), (9), (10) and (11) toluene, 77 K, after thawing (7) and a single O2 injection (10 ml) and exposure at 300 K for 1, 30, 40 and 30 min, respectively.Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) then it is bubbled during the reaction, green and red PL are not detected at all, as Ph3C· is consumed completely11 to react with O2 [Scheme 2(a)]: Thus, a trityl radical is transformed according to Scheme 2(b) in the absence of O2.In the presence of O2 a dimer is not observed, and path 2(a) is the case. Hence, (Ered)* is not generated in a reaction of Ph3C· with O2; this fact allows us to exclude the set of reaction products [Scheme 2(a)] as (Ered)*. First of all, Ered is a product of the interaction of two radicals Ph3C·. Molecular dimer 1 was found1 to be a product of this interaction. Intermediate 1 generated in reactions of phenyl radicals with tert-butyl sulfide and phenyl tert-butyl sulfide is highly reactive and transforms into 2 according to Scheme 2(b).12 A choice between 1 and radical dimer 2 falls on 2 as Ered.First, molecular dimer species are stable to O2 and exhibit luminescence at shorter waves. Second, the replacement of an H atom in the phenyl ring of Ph3C· is known to cause a shift of the PL maximum to the red region of a spectrum.The results obtained and the absence of a red PL in initial and final reaction products (molecular dimer species) and in all of the solvents allowed us to propose that 2, an excited radical dimer, is the emitter of the red PL. References 1 H. Hankamp, W. Nanta and C. Machean, Tetrahedron Lett., 1968, 11, 249. 2 L. N. Levis, D. Lipkin and T. T. Magei, J. Am. Chem. Soc., 1944, 66, 1579. 3 D. N. Shigorin and Yu. I. Kozlov, Opt. Spektrosk., 1961, 10, 600 (in Russian). 4 Yu. I. Kozlov, D. N. Shigorin and G. A. Ozerov, Zh. Fiz. Khim., 1966, 40, 700 (Russ. J. Phys. Chem., 1966, 40, 372). 5 T. Izumida, Y. Tanabe, T. Ichikawa and H. Yoshida, Bull. Chem. Soc. Jpn., 1979, 52, 235. 6 M. A. Pak, D. N.Shigorin and G. A. Ozerov, Izv. Akad. Nauk, Ser. Fiz., 1968, 32, 1443 (in Russian). 7 R. G. Bulgakov, G. Ya. Maistrenko, B. A. Tishin, G. A. Tolstikov and V. P. Kazakov, Dokl. Akad. Nauk SSSR, 1989, 304, 1166 (in Russian). 8 R. G. Bulgakov, G. Ya. Maistrenko, G. A. Tolstikov and V. P. Kazakov, Izv. Akad. Nauk, Ser. Khim., 1990, 2658 (Bull. Acad. Sci, Div. Chem. Sci., 1990, 39, 2411). 9 S. P. Kuleshov, R. G. Bulgakov, G. Ya. Maistrenko, G. A. Tolstikov and V. P. Kazakov Izv. Akad. Nauk., Ser. Khim., 1992, 762 (Russ. Chem. Bull., 1992, 41, 597). 10 A.Weissberger, E. S. Proskauer, J. A. Riddick and E. E. Toops, Technique of Organic Chemistry. Organic Solvents, Interscience Publishers, New York, 1955, vol. 7, p. 519. 11 K. J. Skinner, H. S. Hochster and J. M. McBride, J. Am. Chem. Soc., 1974, 96, 4301. 12 J. A. Kampmeier, R. P. Geer, A. J. Meskin and Rose Marie D’Silva, J. Am. Chem. Soc., 1966, 88, 1257. 13 V. A. Smirnov and V. G. Plotnikov, Usp. Khim., 1986, 55, 1633 (Russ. Chem. Rev., 1986, 55, 929). Ph3C Ph3C O2 Ph3COOCPh3, Ph3COOH, CPh2 H Ph3C OOH Ph3COH, Ph2C=O, Ph3CH, Ph3COO 1 Ph3C Ph3C CPh2 + Ph3CH (a) (b) Scheme 2 2 Received: 17th February 1999; Com. 99/1444

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年代:2000

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Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) A new procedure for estimating the enthalpies of formation for RCH2 · free radicals Yurii D. Orlov*a and Vyacheslav V. Takhistovb a Department of Physics and Technology, Tver State University, 170000 Tver, Russian Federation. Fax: +7 0822 33 1274; e-mail: s000771@tversu.ru b St. Petersburg Scientific Centre of Ecological Safety, Russian Academy of Sciences, 197042 St.Petersburg, Russian Federation. Fax: +7 812 235 4361 DOI: 10.1070/MC2000v010n01ABEH001122 From the observed regularity that for certain substituents the DDHf 0 values for Me· ® RCH2 · free radicals and CH2=CH2 ® ® RCH=CH2 molecules are nearly identical, new or corrected values for the enthalpies of formation were estimated for about 30 gaseous free radicals and molecules.It is known that the H ® Me replacement in hydrocarbon molecules gives different DDHf 0 (DHf 0 shift) values: ca. –20.9 kJ mol–1 in alkanes, –33.5 for CH2=CH2 ® MeCH=CH2 or –43.3 kJ mol–1 for HCºCH ® MeCºCH replacement.1,2 The observed tendencies could be explained by the increasing electronegativity (EN) value of the carbon atom in sp3 ® sp2 ® sp hybridization accompanied by a stabilization effect of the Me group.We observed that for certain substituents the DDHf 0 values for Me· ® ® RCH2 · free radicals and CH2=CH2 ® RCH=CH2 molecules are very close with minor deviations < 6.5 kJ mol–1 which is in the range of mean accuracy of DHf 0(R·) determination (Table 1). This fact can be indicative of nearly identical charges at C-atoms of both the Me· free radical and the ethylene molecule or of their nearly identical EN values.Let us comment data presented in Table 1. The experimental DHf 0 (ClCH=CH2) = 37.2 kJ mol–1 was criticised,5,6 and the new value 21.7 kJ mol–1 (ref. 5) was computed [the brief form of DHf 0 instead of the full form of DHf 0 (gas; 298.15 K) is used in the text]. An analysis of the thermochemistry of ROH and their fluorinated analogues RF2,9 displayed the DDHf 0 (ROH ® ® RF) of ca.–(20–25) kJ mol–1 and thus DHf 0 (FCH2CH=CH2) = = –148.5 was taken from DHf 0 = –122.0 kJ mol–1 (ref. 1) for HOCH2–CH=CH2 instead of the estimated values –155 (ref. 7) or –172 kJ mol–1 (ref. 8). For checking the known and finding the new values of the enthalpies of formation for free radicals we widely used isodesmic reactions2,3,6,9 originally suggested by Benson.12 For example: An isodesmic ‘reaction’ is a hypothetical reaction, but like any reaction, its enthalpy is related to the enthalpies of formation of reactants and products. We define Q as –DHreaction for convenience; –Q measures the deviation from bond additivity.If Q > 0, the free radical in the right-hand side of an isodesmic reaction is more stable than that in the left-hand side, and at Q < 0 the free radical in the right-hand side (·CH2F) is less stable than the free radical (·CH2OH) in the left-hand side of equation (1).Equations (2) demonstrate the most important regularity in the stabilities of free radicals: a less stable free radical extracts a larger stabilising effect from the same substituent (here Me) than a more stable one (DHf 0 and Q values in kJ mol–1): The isodesmic reactions in (2) are given in the brief form ·SH ® MeS· instead of the full form ·SH +MeSH® H2S +MeS· + + Q because the structures of the molecules taking part in isodesmic reactions are obvious.We represent the application of isodesmic reactions to deduce the correct value of DHf 0 for ·CH2SH.If we involve a currently used value of 151.9 kJ mol–1 (refs. 10, 13) in isodesmic reactions (3), we see the inconsistency of Q values with thermochemical properties of free radicals: ·CH2OH free radical being slightly more stable than ·CH2F (Q < 0 for ·CH2OH ® ·CH2F) should give the Q' value more negative than Q'' [compare with equation (2)] but not a positive one (the DHf 0 values were taken from refs. 1 and 2): In general, the electron-donor properties (which stabilise free radicals centres) of the substituents comprising the elements of the third row of the Periodic Table are smaller than those for the elements of the second row: Cl < F, S < O and P < N. For example, the sp + and R (resonance) constants are more positive (destabilization) for the elements of the third row.14 Therefore, the DHf 0 value 175.7 kJ mol–1 for ·CH2SH fits better the above properties of the elements (equations 4).We also obtain Q ~ –20 kJ mol–1 by extrapolation for the ·CH2NH2 ® ·CH2PH2 isodesmic reaction and taking DHf 0 (·CH2PH2) = –20.9 kJ mol–1 (ref. 2) we obtain DHf 0 (·CH2PH2) = 194.6 kJ mol–1.Next, calculating DDHf 0 (Me· ® ·CH2PH2) = 49.0 kJ mol–1, we get the previously unknown value of DHf 0(CH2=CHPH2) = DHf 0(CH2=CH2) (52.5) + + 48.9 = 101.4 kJ mol–1. The enthalpies of formation for some of the free radicals collected in Table 1 or discussed in the text were also estimated using the group additivity with non-linear correction (GANLC) method.15–18 The method was successfully used for verifying, correcting or getting new values for about 350 free radicals and carbene-like species from diverse classes of hydrocarbons and heteroatomic compounds.19 The GANLC method is represented by three versions in which three different levels of approximation are used.The method is based on the introduction of the variable group contribution to free radical thermochemistry as compared with earlier suggested constant group contributions.12 For example, in the XC4H2C3H2C2H2C1H2 · free radical the group contributions of –CH2– (2), –CH2– (3) or –CH2– (4) differ from those in neutral molecules reflecting the effect of the free radical centre on the thermochemical properties of these groups.The GANLC method was detailed in refs. 15–18.The reliability of the method is further confirmed in this work. Thus, the value 177.4 kJ mol–1 was obtained for the ·CH2SH free radical supporting the suggested value 175.7 kJ mol–1 (Table 1). For the ClCH2CH2 · and HOCH2CH2 · free radicals, the values 92.9 and ·CH2OH + MeF MeOH + ·CH2F + Q DHf 0/kJ mol–1: –17.63 –228.02,9 –201.51 –32.03,13 –12.1 (1) ·SH Me· ·NH2 ·OH 144.32,3 145.62,3 192.52,3 39.32,3 MeS· MeCH2 · MeNH· MeO· 129.72,3 110.92,3 177.42,3 17.62,3 (2) –56.1 –18.0 –48.7 +12.5 +25.1 +39.7 +62.3 ·CH2OH ·CH2F –17.63,13 –31.83,13 ·CH2SH ·CH2Cl 151.910,13 121.33,13 (3) –12.1 Q' +8.9 Q'' –9.6 ·CH2NH2 ·CH2OH ·CH2F 149.42,10 17.6 –31.8 ·CH2PH2 ·CH2SH ·CH2Cl [194.6] 175.72,3 121.33,13 (4) –11.3 –12.1 [–21] –14.6 –9.6 QMendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) –33.9 kJ mol–1, respectively, were calculated, which are very close to the data in Table 1. The value of DHf 0 estimated by the GANLC method for 3-cyanocyclobutyl free radicals is 338.9 or 343.0 kJ mol–1 which was derived from either 251 or 255 kJ mol–1, respectively, for NCCH2CH2 · free radicals. We used the regularities represented in Table 1 for either getting new values of the enthalpies of formation for RCH2 · free radicals from the known or estimated values of the enthalpies of formation for RCH=CH2 molecules or vise versa.For estimation of DHf 0 (RCH=CH2), we used the earlier found observation2,7,9 that DDHf 0(RPh ® RCH=CH2) replacement gives the more or less permanent value –30 kJ mol–1. Since the DHf 0 values for RPh molecules are widely represented in the literature,1 those for DHf 0(RCH=CH2) can be reliably estimated. For example, taking DHf 0 values for PhNH2, PhSH and PhBr to be 87.0, 112.4 and 105.41 kJ mol–1, respectively, and DDHf 0(RPh ® RCH=CH2) –30 kJ mol–1, we get 57.0, 82.4 and 75.4 kJ mol–1 for the enthalpies of formation for CH2=CHNH2, CH2=CHSH and CH2= =CHBr molecules, respectively.Using the found regularity that the DDHf 0 values for radicals and molecules are identical and the known data on DHf 0 of RCH=CH2 molecules, either experimental1 or estimated from known data on RPh,1 EH4, EMe4 and EPh4 molecules20–24 (E = = Si, Ge, Sn, Pb) and DDHf 0 (RCH=CH2 ® RPh) ~ 30 kJ mol–1 (refs. 2, 7 and 22), the following new values for the enthalpies of formation for free radicals were obtained (kJ mol–1): CH2= =CHCH2CH2 · 198.7; PhCH2CH2 · 228.0; 2-bicyclo[2,2,2]octyl radical 83.7; BrCH2CH2 · 138.1; ICH2CH2 · 190.4; CH2=CHOCH2 · 79.5; ·CH2OAc –221.7; ·CH2CH2C(O)OEt –261.5; ·CH2OC(O)Ph –98.3; ·CH2OPh 115.1; H2NNHCH2 · 265.7; NCCH2CH2 · 255.2; 3-cyanocyclobutyl radical 347.3; HSCH2CH2 · 154.8; EtS(O)– CH2CH2 · –10.5; p-MeC6H4SO2CH2CH2 · 108.8; ·CH2PH2 194.6; ·CH2At 284.5; H3ECH2 · 165.3, 240.6, 324.3, 405.8 (E = Si, Ge, Sn or Pb, respectively).A new estimation procedure for the enthalpies of formation of RCH2 · free radicals can be applied to RR'CH· (Table 1) and other organoelement free radicals. This work was supported by INTAS (grant no. 96-1990). References 1 J. B. Pedley, R. D. Naylor and S. P. Kirby, Thermochemical Data of Organic Compounds, 2nd edn., Chapman and Hall, New York, 1986. 2 V. V. Takhistov, Organicheskaya mass-spektrometriya (Organic Mass Spectrometry), Nauka, Leningrad, 1990 (in Russian). 3 D. Ponomarev and V. Takhistov, J. Mol. Struct., 1997, 435, 259. 4 L. A. Curtis, D. L. Lucas and J. A. Pople, J. Chem. Phys., 1995, 102, 3292. 5 L. A. Curtis, K. Radhavachari, P. C. Redfern and J. A. Pople, J.Chem. Phys., 1997, 106, 106. 6 D. Ponomarev and V. Takhistov, J. Chem. Educ., 1997, 74, 201. 7 Y.-R. Luo and J. L. Holmes, J. Phys. Chem., 1992, 96, 9568. 8 Y.-R. Luo and J. L. Holmes, J. Phys. Chem., 1994, 98, 303. 9 V. V. Takhistov, T. A. Pashina, N. G. Ismagilov, V. M. Orlov, A. A. Rodin and V. G. Barabanov, Zh. Org. Khim., 1995, 31, 1786 (Russ. J. Org. Chem., 1995, 31, 1582). 10 CRC Handbook of Chemistry and Physics, ed. D. R. Lide, CRC Press, Boca Raton, 1996–1997. 11 K. Miyokawa and E. Tschuikow-Roux, J. Phys. Chem., 1990, 94, 715. 12 S. W. Benson, J. Chem. Educ., 1965, 42, 502. 13 D. F. McMillen and D. M. Golden, Ann. Rev. Phys. Chem., 1982, 33, 493. 14 C. Hansch, A. Leo and R. W. Taft, Chem. Rev., 1991, 91, 165. 15 (a) Yu. D. Orlov and Yu. A. Lebedev, Izv.Akad. Nauk SSSR, Ser. Khim., 1984, 1074 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1984, 33, 897); (b) Yu. D. Orlov and Yu. A. Lebedev, Izv. Akad. Nauk SSSR, Ser. Khim., 1984, 1335 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1984, 33, 1227); (c) Yu. D. Orlov, Yu. A. Lebedev and B. L. Korsunskii, Izv. Akad. Nauk SSSR, Ser. Khim., 1984, 1550 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1984, 33, 1424); (d) Yu.D. Orlov and Yu. A. Lebedev, Izv. Akad. Nauk SSSR, Ser. Khim., 1986, 1121 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1986, 35, 1016). 16 (a) Yu. D. Orlov and Yu. A. Lebedev, Zh. Fiz. Khim., 1991, 65, 289 (Russ. J. Phys. Chem., 1991, 65, 163); (b) Yu. D. Orlov and Yu. A. Lebedev, Zh. Fiz. Khim., 1993, 67, 925 (in Russian) 17 Yu. D. Orlov, Yu. A. Lebedev and G.A. Krestov, Dokl. Ross. Akad. Nauk, 1994, 338, 776 (in Russian). 18 Yu. D. Orlov, Yu. A. Lebedev, L. G. Menchikov and O. M. Nefedov, Izv. Akad. Nauk, Ser. Khim., 1997, 57 (Russ. Chem. Bull., 1997, 46, 52). 19 Yu. D. Orlov, Dr. Sci. Thesis, Tver, 1996. 20 D. A. Ponomarev and V. V. Takhistov, J. Mol. Struct., in press. 21 W. V. Steele, J. Chem. Thermodyn., 1983, 15, 395. 22 V.V. Takhistov, Dr. Sci. Thesis, Leningrad, 1989. 23 W. V. Steele, J. Chem. Thermodyn., 1978, 10, 445. 24 R. Walsh, in The Chemistry of Organic Silicon Compounds, eds. S. Patai and Z. Rappoport, Wiley, New York, 1989, p. 371. Table 1 DDHf 0(g) values for Me· ® RCH2 · free radicals and CH2=CH2 ® RCH=CH2 molecules (DHf 0 and DDHf 0 in kJ mol–1). RCH2 · DHf 0 (RCH2 · ) DDHf 0(A) Me· ® RCH2 RCH=CH2 DHf 0(RCH=CH2) DDHf 0(B) C2H4 ® RCH=CH2 D A ® B Me· 145.61 CH2=CH2 52.51 MeCH2 · 110.92,3 –34.7 MeCH=CH2 20.01 –32.5 +2.2 HOCH2CH2 · –29.32 –31.03,4 –174.9 –176.6 HOCH2CH=CH2 –124.51 –177.0 –2.1 –0.4 ClCH2 · 121.32,3 –24.3 ClCH=CH2 21.85,6 –30.7 +6.4 FCH2CH2 · –56.53 –202.1 FCH2CH=CH2 –172.08 –154.87 [–148.5]9 –224.5 –207.3 –201 –22.4 –5.2 +1.1 BrCH2 · 169.43 +23.8 BrCH=CH2 79.21 [75.4] +26.7 +22.9 +2.9 –0.9 ICH2 · 228.03 +82.4 ICH=CH2 134.72,7 +82.2 –0.2 H2NCH2 · 149.43 +3.8 H2NCH=CH2 [57.0]2,7 +4.5 +0.7 HSCH2 · 151.910 175.72,3 +6.3 +30.1 HSCH=CH2 [82.4] +29.9 +23.6 –0.2 ClCH2CH2 · 91.211 –54.4 ClCH2CH=CH2 [1.2] –51.3 +3.1 Me2CH· 77.82,3 –67.8 Me2C=CH2 –16.91 –69.4 –1.6 MeCHCl· 72.010 –73.6 MeC(Cl)=CH2 –20.91 –73.4 +0.2 Cyclobutyl radical 214.610 +69.0 Methylidenecyclobutane 121.31 +68.8 –0.2 Cyclopentyl radical 105.010 –40.6 Methylidenecyclopentane 12.11 –40.4 –0.2 Received: 25th February 1999; Com. 99/1450

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年代:2000

数据来源: RSC

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Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) Reaction of 2,2,3,3-tetracyanocyclopropyl ketones with ammonia Vladimir P. Sheverdov,*a Oleg V. Ershov,a Oleg E. Nasakin,a Evgenia V. Selunina,a Irina G. Tikhonovaa and Victor N. Khrustalevb a Department of Chemistry, Chuvash State University, 428015 Cheboksary, Russian Federation. Fax: +7 8352 42 8090; e-mail: ershov@chuvsu.ru b A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 117813 Moscow, Russian Federation. Fax: + 7 095 135 5085 DOI: 10.1070/MC2000v010n01ABEH001204 A single-step synthesis of 2,4-diamino-1,6-dicyano-3-azabicyclo[3.1.0]hex-2-en-6-carboxamides from 2,2,3,3-tetracyanocyclopropyl ketones and ammonia has been performed. H. Hart and F. Freeman1 were the first to use 3,3-dimethyl- 1,1,2,2-tetracyanocyclopropane in the synthesis of nitrogencontaining heterocyclic compounds.The reaction time varied from 1 to 3 h. More recently, Yashkanova et al.2,3 prepared oxygen-containing heterocycles from b-cyanocyclopropyl ketones. The reaction time varied from 1 h to a day, and the yields were 8–54%. We have recently found that tetracyano-substituted alkanones exhibit high reactivity towards ammonia.We have synthesised 3-amino-1,2-dicyano-4,6-diazabicyclo[3.2.1]oct-2-en-7-ones4 and 3-amidinio-2-aminopyridine-4-carboxylates5 from b,b,g,g- tetracyanoalkanones and ammonia. Based on these data, we assumed that 2,2,3,3-tetracyanocyclopropyl ketones will also be highly reactive towards ammonia. As a result of the reaction of 2,2,3,3-tetracyanocyclopropyl ketones 1 with ammonia, we found a new property of tetracyanocyclopropanes, namely, the formation of a pyrroline ring, the transformation of only one of the cyano groups to a carboxamide group, and the addition of two ammonia molecules to a molecule of 1.The mixing of compounds 1 with aqueous ammonia (at room temperature) gives bicyclic compounds 4a,b.† The reaction proceeds very rapidly in 30–40 s with 72–82% yields.Moreover, complicated multistage processes correspond to this rapid reaction. We synthesised compounds 1 from a-chloro ketones and tetracyanoethylene.6 The structure of compounds 4a,b was determined by X-ray diffraction analysis using single crystals of 4b‡ and by IR and 13C NMR spectroscopy.† The formation of a single carboxamide functional group in † Experimental procedure: 0.01 mol of 2,2,3,3-tetracyanocyclopropyl ketones 1a,b was mixed with 10 ml of aqueous ammonia (10–20%).The reaction was complete in 30–40 s. The formed precipitate was filtered off and washed with propan-2-ol. 13C NMR spectra were recorded on a Geminee-300 (Varian) instrument in [2H6]DMSO. For 4a: yield 72%, mp 131–132 °C. 13C NMR, d: 31.83 [C(6)], 35.25 [C(1)], 53.75 [C(5)], 87.05 [C(4)], 112.88 (CN), 112.99 (CN), 154.66 [C(2)], 162.54 (CONH2). IR (Vaseline oil, n/cm–1): 3500–3220 (nNH), 3085 (nC–H) 1640 (dNH), 2270 (nCºN), 1690 (nC=O), 1580 (nC=C). For 4b: yield 82%, mp 134–135 °C. 13C NMR, d: 34.72 [C(6)], 35.36 [C(1)], 54.26 [C(5)], 91.39 [C(4)], 113.51 (CN), 114.50 (CN), 151.65 [C(2)], 160.36 (CONH2).IR (Vaseline oil, n/cm–1): 3490–3190 (nNH), 1650 (dNH), 2270 (nCºN), 1700 (nC=O), 1590 (nC=C). The carbon atoms C(1)–C(6) are numbered in accordance with the name 2,4-diamino-1,6-dicyano-3-azabicyclo[3.1.0]hex-2-en-6-carboxamide. ‡ Crystal data for 4b: C11H16N6O3, M = 280.30, triclinic crystals, at 25 °C a = 8.228(3), b = 8.682(3), c = 10.895(4) Å, a = 82.51(3)°, b = = 86.22(3)°, g = 62.85(3)°, V = 687(1) Å3, dcalc = 1.356 g cm–3, Z = 2, space group P1.The cell parameters and intensities of 2796 independent reflections were measured on a Siemens P3/PC automatic four-circle diffractometer (lMoKa radiation, graphite monochromator, q/2q-scan to q = 25°). The terminal discrepancy factors are R1(F) = 0.057, wR2(F2) = = 0.150. The whole calculation was carried out according to the SHELXTL PLUS program.Atomic coordinates, bond lengths, bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2000. Any request to the CCDC for data should quote the full literature citation and the reference number 1135/59.this reaction apparently occurs by an intramolecular process. Based on the fact that only the cyano groups disposed at the same side of the cyclopropane ring towards the C®O direction of the C=O bond6 enter the reaction, we suppose that an ammonia molecule adds, and the HO···CN interaction leads to intermediate 2. Analogous intramolecular processes of the formation of the carboxamide group were described earlier for the transformation of 6-hydroxy-3,3,4,4-tetracarbonitriles into 3,3,4-tricyano- 2,3,4,5-tetrahydropyridine-4-carboxamides7 and for the reaction of b-cyanoalkanones with ammonia.8 Next, probably, the second ammonia molecule adds to form intermediate 3.The formation of the pyrroline ring and compounds 4a,b results from the interaction between amino and cyano groups in intermediate 3.R2 O R1 CN NC CN NC R2 OH R1 CN NC CN NC NH2 R2 CN NC NC O HN R1 NH2 NH3 NH3 R2 NH2 R1 CN NC NC NH2 O NH2 R2 NC NC O NH2 NH HN NH2 R1 R2 NC NC O NH2 N H2N NH2 R1 1 2 4 3 a R1 = Me, R2 = H b R1 + R2 = (CH2)3 N(10) N(1) C(9) C(8) C(7) C(6) N(13) C(12) C(3) C(5) C(2) O(15) N(16) C(14) C(4) C(17) N(18) O(1) O(2) N(11) Figure 1 Molecular structure of 4b.Bond lengths (Å): O(15)–C(14) 1.219(2), N(1)–C(9) 1.479(2), N(11)–C(2) 1.345, N(16)–C(14) 1.317(3), C(2)–C(3) 1.509(2), C(3)–C(5) 1.519(2), C(4)–C(17) 1.444(2), C(4)–C(14) 1.546(2), C(5)–C(9) 1.536(2), N(1)–C(2) 1.284(2), N(10)–C(9) 1.450(2), N(13)–C(12) 1.136(3), N(18)–C(17) 1.141(2), C(3)–C(12) 1.438(2), C(3)– C(12) 1.438(2), C(3)–C(4) 1.550(2), C(4)–C(5) 1.507(2), C(5)–C(6) 1.507(2), C(6)–C(7) 1.531(3), C(7)–C(8) 1.501(3), C(8)–C(9) 1.555(3).Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) The one-pot synthesis of compounds 4 is a new method for the annelation of a pyrroline ring to tetracyanocyclopropanes and for the preparation of new condensed compounds, in which a moiety contains several electron-acceptor substituents, and the other, several electron-donating substituents.As compared with the heterocycle syntheses described in refs. 1–3, the method based on b-cyanocyclopropyl ketones is much easier to perform. The reaction proceeds more rapidly, and the yields are higher. References 1 H. Hart and F. Freeman, J. Am. Chem. Soc., 1963, 85, 1161. 2 O. V. Yashkanova, P. M. Lukin, O. E. Nasakin, Yu.G. Urman, V. N. Khrustalev, V. N. Nesterov and M. Yu. Antipin, Zh. Org. Khim., 1997, 33, 943 (Russ. J. Org. Chem., 1997, 33, 877). 3 O. V. Yashkanova, O. E. Nasakin, Yu. G. Urman, V. N. Khrustalev, V. N. Nesterov, M. Yu. Antipin, P. M. Lukin and E. V. Vershinin, Zh. Org. Khim., 1997, 33, 542 (Russ. J. Org. Chem., 1997, 33, 484). 4 O. E. Nasakin, V. P. Sheverdov, O. V. Ershov, I.V. Moiseeva, A. N. Lyshchikov, V. N. Khrustalev and M. Yu. Antipin, Mendeleev Commun., 1997, 112. 5 O. E. Nasakin, V. P. Sheverdov, I. V. Moiseeva, A. N. Lyshchikov, O. V. Ershov and V. N. Nesterov, Tetrahedron Lett., 1997, 4455. 6 V. P. Sheverdov, O. V. Ershov, O. E. Nasakin, A. N. Chernushkin, E. V. Selunina, I. G. Tikhonova and V. N. Khrustalev, Zh. Obshch. Khim., in press. 7 Ya. S. Kayukov, O. E. Nasakin, Ya. G. Urman, V. N. Khrustalev, V. N. Nesterov, M. Yu. Antipin, A. N. Lyshchikov and P. M. Lukin, Khim. Geterotsikl. Soedin., 1996, 1395 [Chem. Heterocycl. Compd. (Engl. Transl.), 1996, 1200]. 8 O. E. Nasakin, V. P. Sheverdov, I. V. Moiseeva, O. V. Ershov, A. N. Chernushkin and V. A. Tafeenko, Zh. Obshch. Khim., 1999, 69, 302 (Russ. J. Gen. Chem., 1999, 69, 291). Received: 3rd September 1999; Com. 99/1532

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Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) New condensation methods in the synthesis of bicyclic bisureas Angelina N. Kravchenko,* Oleg V. Lebedev and Elena Yu. Maksareva N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow, Russian Federation. Fax: +7 095 135 5328 DOI: 10.1070/MC2000v010n01ABEH001186 For the first time, synthetic approaches to bicyclic bisureas of the octane series bearing three alkyl substituents at nitrogen atoms have been developed.Bicyclic bisureas of the octane series, 2,4,6,8-tetraazabicyclo- [3.3.0]octane-3,7-diones (TABOD) are a new class of promising physiologically active substances.1 Calculations performed by the QSAR method demonstrated that N-alkylated TABOD with methyl and ethyl substituents are most promising.2 Published data concerning condensation methods for preparing TABOD indicate that changes in the position and number of substituents at nitrogen atoms creates some synthetic difficulties.Only mono-, di- and tetra-N-methyl(ethyl)-substituted TABOD (cis- and trans-) can be prepared by known synthetic methods. Tri-N-methyl(ethyl)- substituted TABOD derivatives were not described in the literature.For the first time, we examined the interaction of N-methyl- (ethyl)ureas with glyoxal at pH 4–5 using 1H NMR spectroscopy and TLC control. We found that it results in corresponding mono-N-alkyl-4,5-dihydroxyimidazolidin-2-ones 1, 2 (Scheme 1) which were further condensed with N,N'-dialkylureas 5, 6. The condensation of 1 with 5 or 6 results in 9 (yield 47–49%) or 10 (yield 40–42%), respectively, and the condensation of 2 with 5 or 6 gives 11 (yield 44–46%) or 12 (yield 37–39%), respectively. This synthetic approach (method A) allowed us to obtain the following tri-N-alkyl-substituted TABOD: 2,4,6-trimethyl- 2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione 9, 2,4-diethyl-6- methyl-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione 10, 2,4- dimethyl-6-ethyl-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione 11 and 2,4,6-triethyl-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7- dione 12.To confirm the structure of the compounds obtained, an independent synthesis was performed. 1,3-Dimethyl(diethyl)-4,5-dihydroxyimidazolidin- 2-ones 3, 4 were synthesised according to published procedures.4,5 These compounds (Scheme 1) reacted with N-monomethyl(monoethyl)ureas 7, 8 to form 9–12 (method B).The reaction of 3 with 7 or 8 results in 9 (yield 32–35%) or 11 (yield 50–52%), respectively, and the reaction of 4 with 7 or 8 gives 10 (yield 60–61%) or 12 (yield 37–39%), respectively. Both of the above approaches can be used for the synthesis of target products 9–12. However, method A seems to be more suitable for the synthesis of 9 and 12, and method B is better for the synthesis of 10 and 11. In addition, known tetra-N-alkyl- TABOD 13, 14 (20–25%) were formed simultaneously as a result of the interaction of dimethyl- and diethylureas with glyoxal. The physico-chemical properties of tri- and tetra-alkyl-TABOD are very similar, and therefore column chromatography was used to separate individual compounds 9–12.Tri-N-alkyl-TABOD 9–12 are of both theoretical and practical interest. This is evident not only from the structure of 9–12, but also from their NMR spectra.† The geometrical rigidity and nonplanar structure of the molecular sceleton are characteristic of bicyclic bisureas. Therefore, a chiral environment is created for any pair of geminal protons or N-substituent groups (for example, for CH2 of the ethyl group) to result in diastereotopy displayed in chemical nonequivalence of the above pairs of magnetic nuclei.For compounds 10–12, these are diastereotopic methylene protons of the N-ethyl groups. The 1H NMR spectrum of compound 10 exhibits a singlet of N–Me protons with d 3.03 ppm. The AB system of CH–CH protons exhibits signals with dA 5.23 and dB 5.37 ppm (JAB 8.3 Hz); the former is due to HA located between N-ethyl and N-methyl groups, and the latter, due to the HB proton located between N-ethyl and NH groups because it is additionally split into a doublet with J 2.3 Hz as a result of vicinal spin–spin interaction with the NH proton.According to the structure of compound 10, two N-ethyl groups exhibit the AMX3 and A'M'X'3 systems with the following parameters: dA 3.66, dM 3.33 and dX 1.29 ppm (JAM = 2JAX = 2JMX = 14.0 Hz) and dA' 3.51, dM' 3.31 and dX' 1.25 ppm (JA'M' = 2JA'X' = 2JM'X' = 14.2 Hz), respectively.The signals due to the NH group are represented by a singlet at d 7.18 ppm. The 1H NMR spectrum of compound 11 exhibits two singlets from N–Me groups with the chemical shifts d1 2.89 and d2 2.98 ppm and the AMX3 system with the chemical shifts dA 3.52, dM 3.23 and dX 1.19 ppm and the spin–spin coupling constants JAM = 2JAX = 2JMX = 16.0 Hz.The X-part is a triplet, and the AM-part is a doublet of sextets. The CH–CH protons manifest themselves as the AB system with the very close chemical shifts dA 5.16 and dB 5.17 ppm (JAB 8.2 Hz).The NH group exhibits a singlet at d 7.20 ppm. The 1H NMR spectrum of compound 12 includes the AB system of methine protons with dA 5.28 and dB 5.29 ppm (JAB 8.2 Hz) and a singlet from the NH group with the chemical shift d 7.2 Hz. All ethyl groups in compound 12 are structurally nonequivalent; this fact manifests itself as three AMX3 systems in the spectrum. Two of these systems exhibit similar spectrum charac- † 1H NMR spectra were recorded on a Bruker spectrometer at 250 MHz in CDCl3.Mass spectra were measured on a Varian MAT-311A (EI, 70 eV). Column chromatography was performed using Silica Gel L (100/160 mm) and CHCl3–MeOH (10:1) as an eluent. 9: mp 126–128 °C, Rf 0.26. 1H NMR, d: 2.83 (s, 3H, N–Me), 2.95 (s, 3H, N–Me), 2.99 (s, 3H, N–Me), 5.02 and 5.18 (2H, AB system, CHCH, JAB 8.20 Hz), 7.15 (s, 1H, NH).IR (KBr, n/cm–1): 1700 (C=O), 3320 (NH). MS, m/z: 184 (M+). 10: mp 118–121 °C, Rf 0.34. IR (KBr, n/cm–1): 1685, 1700 (C=O), 3250 (NH). MS, m/z: 212 (M+). 11: mp 148–149 °C, Rf 0.32. IR (KBr, n/cm–1): 1720 (C=O), 3230 (NH). MS, m/z: 198 (M+). 12: mp 130–131 °C, Rf 0.41. IR (KBr, n/cm–1): 1700, 1720 (C=O), 3270 (NH).MS, m/z: 226 (M+). The structures of 9–12 were also confirmed by elemental analysis. 1 R1 = H, R2 = Me 2 R1 = H, R2 = Et 3 R1 = R2 = Me 4 R1 = R2 = Et 5 R3 = R4 = Me 6 R3 = R4 = Et 7 R3 = H, R4 = Me 8 R3 = H, R4 = Et 9 R1 = H, R2 = R3 = R4 = Me 10 R1 = H, R2 = Me, R3 = R4 = Et 11 R1 = H, R2 = Et, R3 = R4 = Me 12 R1 = H, R2 = R3 = R4 = Et 13 R1 = R2 = R3 = R4 = Me 14 R1 = R2 = R3 = R4 = Et N N O R2 R1 N N R3 R4 O NHR1 NHR2 O i, glyoxal N N O R2 R1 OH OH NHR4 NHR3 ii, O 5–8 1–4 9–14 R1, R2 = H, Me, Et Scheme 1 Reagents and conditions: i, H2O, pH 4–5, 45–50 °C, 2 h; ii, H2O, pH 1–2, 90 °C, 1 h.Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) teristics as follows: dA = dA' = 3.69, dB = dB' = 3.72 and dX = dX' = = 1.18 ppm (JAM = JA'M' = 2JAX = 2JA'X' = 2JMX = 2JM'X' = 14.4 Hz).The A''M''X'' system has the following parameters: dA'' 3.42, dB'' 3.23 and dX'' 1.14 ppm (JA''M'' = 2JA''X'' = 2JM''X'' = 14.2 Hz). References 1 O. V. Lebedev, L. I. Khmel’nitskii, L. V. Epishina, L. I. Suvorova, I. V. Zaikonnikova, I. E. Zimakova, S. V. Kirshin, A. M. Karpov, V. S. Chudnovskii, M. V. Povstyanoi and V. A. Eres’ko, in Tselenapravlennyi poisk novykh neirotropnykh preparatov (Directed search for novel neurotropic drugs), Zinatne, Riga, 1983, p. 81 (in Russian). 2 I. V. Svitan’ko, I. L. Zyryanov, M. I. Kumskov, L. I. Khmel’nitskii, L. I. Suvorova, A. N. Kravchenko, T. B. Markova, O. V. Lebedev, G. A. Orekhova and S. V. Belova, Mendeleev Commun., 1995, 49. 3 H.Petersen, Liebigs Ann. Chem., 1969, 726, 89. 4 G. A. Orekhova, O. V. Lebedev, Y. A. Strelenko and A. N. Kravchenko, Mendeleev Commun., 1996, 68. 5 H.Petersen, Synthesis, 1973, 243. Received: 8th July 1999; Com. 99/1514

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Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) Synthesis of new heterocyclic sulfamides Galina A. Gazieva,* Angelina N. Kravchenko, Konstantin Yu. Chegaev, Yuri A. Strelenko and Oleg V. Lebedev N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow, Russian Federation. Fax: +7 095 135 5328 DOI: 10.1070/MC2000v010n01ABEH001188 The synthetic approaches to novel N- and SO2-containing bi-, tri- and tetracyclic systems, 6,8-di- and 2,4,6,8-tetraalkyl-7-oxo-3- thia-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,3-dioxides, 8,12-dioxo-9,11-dimethyl-4-thia-1,3,5,7,9,11-hexaazatricyclo[5.5.1.010,13]- tridecane-4,4-dioxide and 8,16-dioxo-3,5,11,13-tetramethyl-4,12-dithia-1,3,5,7,9,11,13,15-octaazatetracyclo[7.7.2.07,17.015,18]octadecane- 4,4,12,12-tetraoxide, have been developed.Sulfamides constitute a class of compounds among which are biologically active substances.1–3 Here, we studied the condensation of sulfamides with 1,3-dialkyl-4,5-dihydroxyimidazolidin- 2-ones, 2,8-dihydroxymethyl-4,6-dimethyl- and 2,4,6,8-tetrahydroxymethyl- 2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-diones. It was found previously that the interaction of 1,3-dialkyl- 4,5-dihydroxyimidazolidin-2-ones 1 with unsubstituted sulfamide 2a at pH 1 leads to 4,4'-sulfonyldiiminobis(1,3-dialkylimidazolidine- 2-ones)4 3 (Scheme 1).A study of the effect of acidity on the course of this reaction demonstrated that the yield of 3b at pH < 1 increased from 5% reported earlier4(b) to 40%. A shift of pH towards the weakly acidic region resulted in the formation of a mixture of 3b and 6,8-diethyl-7-oxo-3-thia- 2,4,6,8-tetraazabicyclo[3.3.0]octane-3,3-dioxide 4a; however, only 4a was formed at pH 5 (Scheme 1).Aran et al.5 noted that most attention was focused on unsubstituted and monosubstituted sulfamides, whereas the reactivity of 1,3-disubstituted sulfamides is less well understood. The condensation of 1,3-dimethylsulfamide 2b with 1 was found to form 2,4,6,8-tetraalkyl-7-oxo-3-thia-2,4,6,8-tetraazabicyclo[3.3.0]- octane-3,3-dioxides 4b,c (Scheme 2).The combination of urea and sulfamide moieties allows us to suppose that these compounds exhibit high biological activity. This was supported by primary tests of the acute toxicity and the effect on the motional activity and orientation behaviour in mice (the results will be published elsewhere).Recently, data on the inhibition of HIV-1 protease by sevenand eight-membered cyclic sulfamides and ureas were published. 2,3,6 Here, we developed the synthetic approaches to polycyclic systems including eight-membered rings with sulfamide and urea units. Thus, the condensation of 2a with 2,8-dihydroxymethyl- 4,6-dimethyl-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7- dione 5 in an acidic medium leads to 8,12-dioxo-9,11-dimethyl- 4-thia-1,3,5,7,9,11-hexaazatricyclo[5.5.1.010,13]tridecan-4,4-dioxide 6 (Scheme 3).Analogously, the reaction of 1,3-dimethylsulfamide with 2,4,6,8- tetrahydroxymethyl-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione 7 resulted in 8,16-dioxo-3,5,11,13-tetramethyl-4,12-dithia- 1,3,5,7,9,11,13,15-octaazatetracyclo[7.7.2.07,17.015,18]octadecane- 4,4,12,12-tetraoxide 8 (Scheme 4).We intend to prepare compounds like 6 and 8 bearing aryl substituents at a later time. The structure shown in Scheme 4 was attributed to compound 8. Using NMR spectroscopy, it is impossible to validate or disprove the alternative structure 8'.† Scheme 1 Reagents and conditions: i, H2O, conc.HCl, 80 °C, 0.5–1.5 h; ii, H2O, pH 5, 60 °C, 0.5 h. N N HO HO O R1 R1 H2N SO2 H2N N N O R1 R1 N N NSO2N O R1 R1 N N O R1 R1 N SO2 N H H i ii 3a R1 = Me 3b R1 = Et 4a R1 = Et 2a 1a R1 = Me 1b R1 = Et Scheme 2 Reagents and conditions: i, H2O, pH 1 (HCl), 80–90 °C, 1–2 h. HN SO2 HN N N O R1 R1 N SO2 N R2 R2 4b R1 = R2 = Me 2b R2 = Me R2 R2 4c R1 = Et, R2 = Me 1a R1 = Me 1b R1 = Et i N N HO HO O R1 R1 N N O H Me N N H Me O N N O Me N N Me O N N O Me N N Me O OH HO HN NH S O O i ii 5 6 Scheme 3 Reagents and conditions: i, MeOH, paraform, NaHCO3, pH 8, 80 °C, 1 h; ii, MeOH, pH 1 (HCl), 2a, boiling with stirring.N N O H H N N H H O N O N O N O N O OH HO N N S O O i ii 7 8 N N OH HO Me Me N N N N S O O Me Me Scheme 4 Reagents and conditions: i, aqueous CH2O solution, NaHCO3, pH 8, 80 °C, 1 h; ii, H2O, pH 1 (HCl), 80 °C, 2b, stirring for 2 h.N O N O 8' N N N N S O O Me Me N N S O O Me MeMendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) We decided on the structure of 8 based on calculations of the conformational energies for two possible isomers using the MM2 program (107 and 349 kcal mol–1 for 8 and 8', respectively).† NMR spectra were measured on AM 300 (300.13 MHz) and WM 250 (250.13 MHz) spectrometers (Bruker). Chemical shifts were measured with reference to residual protons of the deuterated solvents [2H6]DMSO (2.50 ppm) and D2O (4.80 ppm). 4a: yield 58–60%, mp 198–199.5 °C. 1H NMR ([2H6]DMSO) d: 1.05 (6H, Me), 3.05, 3.30 (4H, CH2), 5.37 (2H, CH). IR (KBr, n/cm–1): 3448, 3144 (NH), 1656 (C=O), 1360, 1324, 1168 (SO2).MS, m/z: 234 (M+). Found (%): C, 36.02; H, 6.19; N, 24.01; S, 13.62. Calc. for C7H14N4O3S (%): C, 35.89; H, 6.02; N, 23.91; S, 13.69. 4b: yield 51–53%, mp 177–179 °C. 1H NMR (D2O) d: 2.90 (6H, Me), 2.96 (6H, Me), 5.31 (2H, CH). IR (KBr, n/cm–1): 1730 (C=O), 1345, 1140 (SO2). MS, m/z: 234 (M+). Found (%): C, 35.98; H, 6.13; N, 24.00; S, 13.74.Calc. for C7H14N4O3S (%): C, 35.89; H, 6.02; N, 23.91; S, 13.69. 4c: yield 7–9%, mp 85–87 °C. 1H NMR ([2H6]DMSO) d: 1.10 (6H, Me), 3.15, 3.35 (4H, CH2), 5.25 (2H, CH). IR (KBr, n/cm–1): 1710 (C=O), 1345, 1150 (SO2). MS, m/z: 262 (M+). Found (%): C, 41.36; H, 7.02; N, 21.44; S, 12.35. Calc. for C9H18N4O3S (%): C, 41.20; H, 6.92; N, 21.36; S, 12.22. 6: yield 58–60%, mp 237–239 °C (decomp.). 1H NMR ([2H6]DMSO) d: 2.82 (6H, Me), 4.30, 4.83 (4H, CH2), 5.15 (2H, CH), 7.60 (2H, NH). IR (KBr, n/cm–1): 3336, 3272 (NH), 1704 (C=O), 1320, 1156 (SO2). MS, m/z: 290 (M+). Found (%): C, 32.93; H, 4.99; N, 29.10; S, 10.87. Calc. for C8H14N6O4S (%): C, 33.10; H, 4.86; N, 28.95; S, 11.04. 8: yield 69–71%, mp > 300 °C (decomp.). 1H NMR ([2H6]DMSO) d: 2.92 (12H, Me), 4.80 (8H, CH2), 5.50 (2H, CH).IR (KBr, n/cm–1): 1730 (C=O), 1355, 1160 (SO2). MS, m/z: 374 (M+ – mSO2). Found (%): C, 32.75; H, 4.95; N, 25.32; S, 14.87. Calc. for C12H22N8O6S2 (%): C, 32.87; H, 5.06; N, 25.55; S, 14.63. References 1 P. Ahuja, J. Singh, M. B. Asthana, V. Sardana and N. Anand, Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem., 1989, 28, 1034. 2 P. K. Jadhav and F. G. Woerner, Tetrahedron Lett., 1995, 36, 6383. 3 P. K. Jadhav, W. F. Daneker and F. G. Woerner, US Patent, 5506355, CO7D, 1996 (Chem. Abstr., 1996, 125, 34038h). 4 (a) G. A. Orechova, O. V. Lebedev, Yu. A. Strelenko and A. N. Kravchenko, Mendeleev Commun., 1996, 68; (b) G. A. Gazieva, A. N. Kravchenko, O. V. Lebedev, Yu. A. Strelenko and K. Yu. Chegaev, Izv. Akad. Nauk, Ser. Khim., 1998, 1604 (Russ. Chem. Bull., 1998, 47, 1561). 5 V. J. Aran, P. Goya and C. Ochoa, Adv. Heterocycl. Chem., 1988, 44, 81. 6 P. Y. S. Lam, P. K. Jadhav, C. J. Eyermann, C. N. Hodge, Y. Ru, L. T. Bacheler, J. L. Meek, M. J. Otto, M. L. Rayner, N. Y. Wong, C. H. Chang, P. C.Weber, D. A. Jackson, T. R. Sharpe and S. Erickson-Viitanen, Science, 1994, 263, 380. Received: 8th July 1999; Com. 99/1516

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Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) An unusually fast nucleophilic addition of amidoximes to acetylene Boris A. Trofimov, Elena Yu. Schmidt,* Al’bina I. Mikhaleva, Alexander M. Vasil’tsov and Andrey V. Afonin Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk, Russian Federation. Fax: +7 3952 39 6046; e-mail: lschmidt@irioch.irk.ru DOI: 10.1070/MC2000v010n01ABEH001217 The addition of amidoximes to acetylene in the presence of the KOH–DMSO superbase system afforded O-vinylamidoximes in 26–59% yields.The oxime function is capable of adding to the carbon–carbon triple bond at its either oxygen or nitrogen site depending on the structure of the reactant and on the reaction conditions.1–4 In the presence of superbases such as the KOH–DMSO system, ketoximes react with acetylene to form O-vinylketoximes which are further rearranged to pyrroles (the Trofimov reaction),1,2,5,6 whereas aldoximes are dehydrated to nitriles under the same conditions.1,2 However, the nucleophilic addition of amidoximes to acetylenes has not been adequately studied.Thus, amidoximes react with propiolates to form imidazole derivatives via O-adducts.7 Diacetylene, in the presence of KOH in aqueous DMSO, adds amidoximes at 22–36 °C to give unstable O-1-but-1-en-3-ynyl ethers in 21–24.5% yields.8 Consequently, only very reactive (‘activated’) acetylenes are able to add amidoximes.At the same time, the reaction of amidoxime multident anions with simpler acetylenes might contribute both to a better understanding of nucleophilic addition at triple bonds and to the chemistry of building blocks.Our study of these compounds has shown that amidoximes 1a,b are able to readily add to acetylene in a short contact (5–7 min) at about 75 °C under a pressure of 12–14 atm in the KOH–DMSO superbase system to afford O-vinylamidoximes 3a,b in 26 and 59% yields, respectively.† The structure of adducts 3a,b unambiguously follows from an excellent agreement between the 1H and 13C NMR and IR spectra of these adducts and O-vinylketoximes.3,4 The 1H and 13C NMR spectra of 1a and 3a show only a signal due to methyl groups, whereas there is a set of signals corresponding to a phenyl ring in the spectra of 1b and 3b.This suggests the presence of only one configurational isomer. In order to identify the isomers of amidoximes 1a,b, the direct 13C–13C coupling constants involving the oxime group carbon (53.0 and 67.2 Hz, respectively) were measured and compared to the coupling constants in acetamides and benzamides (49.5 and 62.4 Hz, respectively).In amidoximes 1a,b, an increase in † 1H NMR (400.13 MHz), 13C NMR (101.61 MHz) in CDCl3, TMS as a standard.O-Vinylacetamidoxime 3a: nD 20 1.5682. A mixture of 3.7 g (50 mmol) of amidoxime 1a and 2.7 g (48 mmol) of KOH in 100 ml of DMSO was saturated with acetylene (12–14 atm), heated to 75 °C and immediately cooled to room temperature. The mixture was diluted with 200 ml of water and extracted with diethyl ether (4×20 ml). The extract was washed with water (4×5 ml) and dried over MgSO4.After the removal of diethyl ether and purification of the residue by column chromatography (SiO2, diethyl ether:pentane, 1:3), 1.3 g (26%) of O-vinylamidoxime 3a was obtained. 1H NMR, d: 6.72 (dd, 1H, Ha, 3Ja–b 14.0 Hz, 3Ja–b' 6.8 Hz), 4.62 (br. s, 2H, NH2), 4.55 (dd, 1H, Hb, 3Ja–b 14.0 Hz, 2Jb–b' 1.6 Hz), 4.01 (dd, 1H, Hb' , 3Ja–b' 6.8 Hz, 2Jb–b' 1.6 Hz), 1.85 (s, 3H, Me). 13C NMR, d: 153.44 [C(1), 1J1–Me 52.6 Hz], 153.23 [C(2), 1J2–3 80.2 Hz], 85.70 [C(3), 1J2–3 80.2 Hz], 16.55 (Me). IR (neat, n/cm–1): 3475, 3340 (NH2), 3085 (=CH2), 1655 (C=N), 1630, 1615 (C=C), 1190 (C–O), 1170 (C=C), 960 (CH=CH), 835 (C=CH). O-Vinylbenzamidoxime 3b was prepared analogously in 59% yield, nD 20 1.5806. 1H NMR, d: 7.65, 7.39 (m, 5H, Ph), 6.88 (dd, 1H, Ha, 3Ja–b 14.0 Hz, 3Ja–b' 6.8 Hz), 4.95 (br. s, 2H, NH2), 4.66 (dd, 1H, Hb, 3Ja–b 14.0 Hz, 2Jb–b' 1.6 Hz), 4.13 (dd, 1H, Hb' , 3Ja–b' 6.8 Hz, 2Jb–b' 1.6 Hz). 13C NMR, d: 154.37 [C(1), 1J1–ipso 65.7 Hz], 153.23 [C(2), 1J2–3 80.2 Hz], 133.08 (Cipso, 1J1–ipso 65.7 Hz), 130.70 (Cpara, 1Jpara–meta 55.4 Hz), 129.07 (Cmeta, 1Jmeta–ortho 56.4 Hz), 126.91 (Corto, 1Jortho–ipso 58.8 Hz), 87.36 [C(3), 1J2–3 80.2 Hz].IR (neat, n/cm–1): 3490, 3390 (NH2), 1645 (C=N), 1620 (NH2), 1600 (C=C), 1185 (C–O), 1160 (C=C), 960 (CH=CH), 845 (C=CH). the 13C–13C coupling constant by 3.5 and 4.8 Hz, respectively, with respect to the isostructural amides was observed. This result is in good agreement with the Z-form of compounds 1a,b.9 To support this conclusion, a 1H NMR spectrum of acetamidoxime 1a was recorded in the presence of the broadening paramagnetic reagent Gd(fod)3.An additive of Gd(fod)3 causes an abrupt broadening of the Me group signal due to paramagnetic relaxation proportional to r–6 (where r is the distance from the paramagnetic centre to the proton observed) and due to Gd(fod)3 coordination to the iminic nitrogen in the cis-arrangement of the paramagnetic centre with respect to the Me group (Z-isomer);10 the NH2 group signal remained unaffected.In the spectra of O-vinylamidoximes, the methyl group chemical shift and the 13C–13C coupling constants 1J1-Me in 3a, as well as the chemical shift of the phenyl ring ipso-carbon and the 13C–13C coupling constants 1J1-ipso in 3b, changed only slightly. This indicates that O-vinylamidoximes 3a,b exhibit the same configuration as the initial amidoximes 1a,b.9,11 Therefore, neither nitrogen-centred anionic species of the starting amidoximes, nor those of their apparent tautomers 2 are able to successfully compete with the oxygen-centred anions during the nucleophilic addition to acetylene under the above conditions.Heterocycles 4–6, which were expected from cyclizations of adducts 3, were not detected in the reaction mixture, probably, because of a relatively low temperature (as compared N H2N R OH NHOH HN R HC CH 1a,b 2 N H2 N R O Ha Hb Hb ' HN N R HN O N R Me N NH O R 3a,b 4 5 6 a R = Me b R = Ph 1 2 3 N H2N R O 7 1 OH– + H2O N HO R O 7 OH– H2O O O R + H2NOHMendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) with other nucleophilic additions to acetylene) and a short contact time.The latter are also supposed to be the factors that allow the O-vinylation to compete with the anticipated nucleophilic substitution of the amino group in amidoximes 1 (hydrolysis of anion 7) or deoximation. At the same time, the moderate yields of adducts 3 can also result from the above hydrolytic processes.References 1 B. A. Trofimov and A. I. Mikhaleva, N-Vinilpirroly (N-Vinylpyrroles), Nauka, Novosibirsk, 1984, p. 90 (in Russian). 2 B. A. Trofimov, in Adv. Heterocycl. Chem., ed. A. R. Katritzky, Academic Press, San Diego, 1990, vol. 51, p. 280. 3 B. A. Trofimov, S. E. Korostova, A. I. Mikhaleva, L. N. Sobenina and R. N. Nesterenko, USSR Patent SU 1095593, C 07 C, 1982, Byull.Izobret., 1994, no. 6, 196 (Chem. Abstr., 1995, 123, 285266j). 4 O. A. Tarasova, S. E. Korostova, A. I. Mikhaleva, L. N. Sobenina, R. N. Nesterenko, S. G. Shevchenko and B. A. Trofimov, Zh. Org. Khim., 1994, 30, 810 (Russ. J. Org. Chem., 1994, 30, 863). 5 G. P. Bean, in The Chemistry of Heterocyclic Compounds. 48. Pyrroles. Part 1, ed. R. A. Jones, Wiley, New York, 1990, p. 153. 6 B. A. Trofimov, in The Chemisty of Heterocyclic Compounds. 48. Pyrroles. Part 2, ed. R. A. Jones, Wiley, New York, 1992, p. 131. 7 N. D. Heindel and M. C. Chun, Tetrahedron Lett., 1971, 1439. 8 A. N. Volkov, L. V. Sokolyanskaya and B. A. Trofimov, Izv. Akad. Nauk SSSR, Ser. Khim., 1976, 1430 (in Russian). 9 L. B. Krivdin and G. A. Kalabin, Progr. Nucl. Magn. Reson. Spectrosc., 1989, 21, 293. 10 V. K. Voronov, V. V. Keiko and T. E. Moskovskaya, Zh. Strukt. Khim., 1977, 18, 917 [J. Struct. Chem. (Engl. Transl.), 1977, 18, 726]. 11 G. E. Hawkes, K. Herwig and J. D. Roberts, J. Org. Chem., 1974, 39, 1017. Received: 27th October 1999; Com. 99/1545

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Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) Synthesis of N-(5-oxo-2,5-dihydro-1H-pyrrol-2-yl)acetamides using the Ritter reaction Kirill V. Nikitin* and Nonna P. Andryukhova Department of Chemistry, M. V. Lomonosov Moscow State University, 119899 Moscow, Russian Federation. Fax: +7 095 939 0798; e-mail: newscientist@mtu-net.ru DOI: 10.1070/MC2000v010n01ABEH001197 Aromatic tert-alkylamines and N-(5-oxo-2,5-dihydro-1H-pyrrol-2-yl)acetamides were successfully prepared using the Ritter reaction under mild dilute conditions. Aliphatic tertiary alkyl amines are extensively used in constructing biologically active molecules.1 The Ritter reaction2 with hydrogen cyanide in acidic media followed by hydrolysis of the resulting amide is a useful and practical way to obtain alkylamines3 from more readily available alcohols.Nevertheless, the synthesis of tert-alkylamines under classical Ritter conditions (acetic acid, sulfuric acid, 50 °C) is restricted due to competitive elimination and requires the use of milder conditions.4 Moreover, the use of highly toxic alkali metal cyanides in an acidic medium requires careful handling.We used the Ritter reaction with acetonitrile under dilute conditions followed by amide methylation and hydrolysis5 (Scheme 1) for the synthesis of tert-alkylamines which cannot be prepared under classical Ritter conditions. We also applied the dilute conditions to the synthesis of previously unknown N-[1-(tert-butyl)- 3,4-dimethyl-5-oxo-2,5-dihydro-1H-pyrrol-2-yl]acetamides expected to be potent herbicides.6 The key factors affecting the amide yield are the initial alcohol concentration and the acidity.The greater is the excess of acetonitrile, the higher is the amide yield provided that the initial quantity of sulfuric acid is low and constant (Table 1). Under classical conditions, the reaction of 2-(3-chlorophenyl)- propan-2-ol 1a (R1 = R2 = Me, R3 = 3-ClC6H4) with acetonitrile does not lead to 2-(3-chlorophenyl)-2-acetamidopropane 2a at all (Table 1, run 1); the products were substituted indans and chain styrene dimers easily formed from 1a under acidic conditions. 7 The dilution of the initial reaction mixture with MeCN in the absence of AcOH drastically enhanced the formation of 2a (run 2), and it became predominant at a 0.2 mol dm–3 initial concentration of 1a.If the concentration of 1a was 0.1 mol dm–3 or lower (runs 4 and 5), 2a became the only product in the form of sulfate 4a, which can be easily isolated by filtration. Examples of the preparation of N-alkylamides 2 from alcohols 1 are summarised in Table 2. Under dilute conditions (0.1 M solutions of starting alcohols), N-tert-alkylamides 2a–c,e were prepared in high yields (runs 1–3 and 5), but primary alkylamides (runs 6 and 7) could not be obtained.We found that phenylacetonitrile (run 2) can be employed as a nitrogen nucleophile under dilute conditions. Unfortunately, 2-phenyl-2-acetamidopropane 2d (run 4) was not obtained preparatively even under dilute conditions because of elimination and irreversible formation of a-methylstyrene dimers.7 The difference may be accounted for a lower electrophilic activity of the carbocation formed from 2d.The reaction under dilute conditions appeared to be indispensable for the preparation of potentially biologically active N-(5-oxo-2,5-dihydro-1H-pyrrol-2-yl)acetamides 5 (Scheme 2). The syntheses of previously unavailable compounds 5 in high yields are summarised in Table 3.R1 R3 R2 OH R1 R3 R2 NHCOR4 R1 R3 R2 NH2 R4CN, i, Me2SO4 ii, H2O, NaOH H2SO4 1 2 3 Scheme 1 aRitter conditions: 1a (5 mmol), acetic acid (2 ml), sulfuric acid (1 ml), MeCN (10 mmol, 0.5 ml), 60 °C. Dilute conditions: 1a (5 mmol), sulfuric acid (15 mmol), MeCN (according to Table 1), 20–25 °C. b3-Chloro-a-methylstyrene dimers are formed. cProcedure: to a solution of 1a (0.85 g, 5 mmol) in acetonitrile (50 ml, 1 mol) sulfuric acid (1.47 g, 15 mmol) was added, and the reaction mixture was stirred for 2 h at ambient temperature.Salt 4a (0.94 g, yield 61%) was filtered off as a solid;6 water (10 ml) was added, and the mixture was extracted with ethyl acetate; 2a (0.64 g, 61%) was isolated. The acetonitrile filtrate was neutralised with triethylamine (3 g, 30 mmol), concentrated and extracted with ethyl acetate; additional amide 2a (0.20 g, yield 19%) was isolated as a solid: mp 114 °C, 1H NMR (CDCl3) d: 1.63 (s, 6H), 1.94 (s, 3H), 5.98 (br.s, 1H), 7.1–7.4 (m, 4H). Table 1 Reaction of 1a with MeCN under Ritter (run 1) and dilute conditions. a Run Initial concentration of 1a/ mol dm–3 Yield of 4a (%) Total yield of 2a (%) 1 1.25 — 0b 2 0.625 19 20 3 0.42 33 38 4 0.2 50 60 5c 0.1 61 80 Table 2 Preparation of amides 2 from alcohol 1 under dilute conditions (Scheme 1).Run R1 R2 R3 R4 Time/h Product Yield (%) 1 3-ClC6H4 Me Me Me 24 2a 86 2 3-ClC6H4 Me Me PhCH2 96 2b 60 3 3,5-Cl2C6H3 Me Me Me 24 2c 84 4 Ph Me Me Me 24 2d 6 5 Me Me Me Me 24 2e 68 6 Me H H Me 24 — 0 7 H H H Me 24 — 0 N O OH R1 R2 R3 N O NHCOMe R1 R2 R3 MeCN, H2SO4 Scheme 2 5 aTo a solution of 1-(tert-butyl)-5-hydroxy-3,4-dimethyl-1,5-dihydro-2Hpyrrol- 2-one (0.376 g, 2 mmol) in MeCN (25 ml) sulfuric acid (0.6 g, 6 mmol) was added, the mixture was stirred at room temperature for 24 h, triethylamine (2 ml) was added, the mixture was evaporated, extracted with ethyl acetate, washed with water and aqueous NaHCO3 and dried.N-[1-(tert- Butyl)-3,4-dimethyl-5-oxo-2,5-dihydro-1H-pyrrol-2-yl]acetamide (0.41 g, 91%) was isolated as a solid: mp 169 °C; 1H NMR (CDCl3) d: 1.38 (s, 9H), 1.64 (s, 3H), 1.79 (s, 3H), 2.02 (s, 3H), 5.89 (d, 1H, 9.5 Hz), 6.35 (d, 1H, 9.5 Hz, exchangeable); IR (KBr, n/cm–1): 1223, 1256, 1375, 1526, 1665, 3294; MS, m/z: 225 (M + 1). ba,a-Dimethyl-3,5-dichlorobenzyl. Table 3 Preparation of 5 from corresponding 5-hydroxy-1,5-dihydro-2Hpyrrol- 2-ones (MeCN, 0.1 M solution of the starting compound, 0.3 M H2SO4, 24 h, ambient temperature). Run R1 R2 R3 Yield of 5 (%) 1 But Me Me 91a 2 PhCH2 R2 + R3 = –CH=CH–CH=CH– 88 3 DDBb Me Me 98 4 DDB 2-FC6H4 Me 93 5 DDB Ph Me 95Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) N-tert-Alkylamines 3a–d were prepared by methylation and hydrolysis of amides 2a in high yields (Table 4). Since 2c was not available, corresponding amine 3d was obtained via the catalytic (Raney nickel) reduction of 3a with hydrazine (Scheme 3).Thus, the Ritter reaction in the presence of a 200-fold excess of a nitrile proceeds selectively under mild conditions and can be useful for the synthesis of branched alkylamines and N-pyrrolylacetamides.References 1 (a) K. Moriyasu, H. Akieda, H. Aoki, M. Suzuki, S. Matsuto, Y. Iwasaki, S. Koda and K. Tomiya, US Patent 5409886, 1995 (Chem. Abstr., 1995, 124, P86808c); (b) N. Ohba, A. Ikeda, K. Matsunari, Y. Yamada, M. Hirata, Y. Nakamura, A. Takeuchi and H. Karino, US Patent 5006157, 1991 (Chem. Abstr., 1991, 114, 247145). 2 (a) J.J. Ritter and P. P. Minieri, J. Am. Chem. Soc., 1948, 70, 4045; (b) J. J. Ritter and J. Kalish, J. Am. Chem. Soc., 1948, 70, 4048; (c) L. W. Hartzel and J. J. Ritter, J. Am. Chem. Soc., 1949, 71, 4130; (d) S. R. Bus, J. Am. Chem. Soc., 1947, 69, 254. 3 R. C. Larock and W. W. Leong, in Comprehensive Organic Synthesis, ed. B. M. Trost, Pergamon, Oxford, 1991, vol. 4, p. 292. 4 H.G. Chen, O. P. Goel, S. Kesten and J. Knobelsdorf, Tetrahedron Lett., 1996, 37, 8129. 5 E. Tanayama, S. Imada and K. Okama, Jpn. Pat. 07 206783, 1995 (Chem. Abstr., 1996, 124, 55539s). 6 B. Bohner and M. Baumann, CH Patent 633678, 1982 (Chem. Abstr., 1983, 98, 121386n). 7 K. V. Nikitin and N. P. Andryukhova, Mendeleev Commun., 1998, 195. aHydrolysis: to 2a (1.055 g, 5 mmol) dimethyl sulfate (4 g, 32 mmol) was added, and the mixture was stirred for 1 h at 80 °C.Next, the excess of dimethyl sulfate was distilled at a reduced pressure. Water (3 ml) was added, the mixture was filtered, extracted with toluene (50 ml), basified to pH 12 with solid sodium hydroxide and extracted with hexane (3×5 ml). The extract was dried with NaOH and distilled at 75–80 °C (1 mmHg) to give 3a (0.61 g, yield 72%). 1H NMR (CDCl3) d: 1.50 (s, 6H), 1.60 (s, 2H), 7.1–7.5 (m, 4H). bPrepared by reduction of 3a with the hydrazine: 3a (0.5 g, 2.9 mmol), MeOH (3 ml), hydrazine hydrate (1 ml, 30 mmol) and potassium hydroxide (0.5 g, 9 mmol) were stirred with Raney Ni (0.10 g) for 4 h; the mixture was concentrated, extracted with hexane, dried with NaOH and evaporated to give 3d (0.30 g, yield 77%). 1H NMR (CDCl3) d: 1.51 (s, 6H), 1.62 (s, 2H), 7.2–7.4 (m, 3H), 7.5–7.7 (m, 2H). Table 4 Preparation of tert-alkylamines 3a,c–e from amides 2 (Scheme 1).a Run R1 R2 R3 Product Yield of 3 (%) 1 3-ClC6 H4 Me Me 3a 72 2 3,5-Cl2 C6 H3 Me Me 3c 70 3 Ph Me Me 3d 77b 4 Me Me Me 3e 71 NH2 Cl NH2 N2H4, Raney Ni Scheme 3 3a 3d Received: 9th August 1999; Com. 99/1525

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Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) Cleavage of the N–O bond in substituted hydroxylamines under basic conditions Kirill V. Nikitin* and Nonna P. Andryukhova Department of Chemistry, M. V. Lomonosov Moscow State University, 119899 Moscow, Russian Federation. Fax: +7 095 939 0798; e-mail: newscientist@mtu-net.ru DOI: 10.1070/MC2000v010n01ABEH001206 The cleavage of the N–O bond in hydroxylamines R1NR–OR2 accompanied by oxidation of the adjacent carbon is directed by the CH acidity of R1 and R2 groups.Oxidation by organic amine oxides has been effectively employed1 –3 to convert organic halides (Scheme 1) into corresponding aldehydes. In these methods, the aldehyde oxygen comes from the amine oxide used as an oxidant1 so that, in the intermediate, the carbon atom adjacent to the oxygen atom is oxidised.Similarly, the oxidation at carbon atom in the 3-position of isoxazoles4 and the oxidative rearrangement of isoxazol- 3-ones5 have been reported. To our knowledge, the tendencies for N–O cleavage in hydroxylamines R1NR–OR2 1 have not been studied under basic conditions although similar N–O bond reductive cleavage can be expected via an intermediate carbanion.We studied the behaviour of 1 under basic conditions (Et3N, NaOMe, NaH or LDA in THF). In a series of substrates we tried to arrange the substituents around the N–O moiety in order to favour the formation of a carbanion adjacent to oxygen or nitrogen. The results are summarised in Table 1. We observed differences in the behaviour of mono- (1a), di- (1b) and tribenzylhydroxylamine (1c).While 1a (Table 1, run 1) is apparently converted by sodium hydride to benzaldehyde (Scheme 2), and the latter is condensed with an excess of unreacted 1a into the final product O-benzylbenzaldoxime, 1b and 1c unexpectedly do not undergo any transformations under the same conditions (runs 2 and 3). The difference may be accounted for by the lower CH acidity of methylene in 1b and 1c.Benzoyloxyphthalimide 1d does not react with weak bases such as triethylamine (Table 1, run 4) or strong bases (sodium hydride, run 5). With sodium ethoxide (run 7) or lithium diisopropylamide (run 6), ring opening takes place. Thus, the acidity of the benzylic methylene in 1b–d is insufficient to provide a carbanion for further transformations though the nitrogen is involved into the electron-withdrawing phthalimide system.N-Benzoyloxy-a-phenylethylamine 1e benzoylated at the oxygen atom has only one possibility to form a carbanion capable of N–O cleavage. Under basic conditions, 1e is slowly converted (Table 1, run 8) into acetophenone and acetophenone oxime (after treatment with water). Since the introduction of a carbonyl group should increase drastically the acidity of the a-methylene adjacent to the oxygen atom, we tested the behaviour of N-benzoylmethoxyphthalimide 1f.We found that 1f can be easily converted into phthalimide with a catalytic amount of sodium hydride (Table 1, run 9); the products of benzoylmethoxy group degradation were not identified. Similarly, N-benzoylmethoxy-N-(1-phenylethyl)phenylacetamide 1g and N-benzoylmethoxy-N-tert-butylphenylacetamide 1h undergo transformations leading to the corresponding amides in high yields (runs 10 and 11).The possible base catalysed mechanism involves the formation of a methylene carbanion followed by N–O bond cleavage (Scheme 3). In the last example, 1-benzyl-5-benzyloxyamino-3,4-dimethylpyrrolin- 2-one 1i, the carbon atom adjacent to the N atom of the N–O system is a member of a pyrrolin-2-one ring.Apparently, the CH acidity at this atom is enough to allow intermediate carbanion formation6 (Scheme 4) leading quantitatively to N–O cleavage products (Table 1, run 12). Thus, the cleavage of the N–O bond in 1 under basic conditions is directed by the formation of a carbanion centre adjacent to either nitrogen or oxygen atom. The structures in which a carbanion can be formed near nitrogen undergo reduction of the N–O with the release of R2O– as a leaving group and formation of an imine.Similarly, if a carbanion is situated near oxygen, the cleavage leads to RR1N– and an aldehyde. References 1 A. G. Godfrey and B. Ganem, Tetrahedron Lett., 1990, 31, 4825. 2 V. Franzen and S. Otto, Chem. Ber., 1961, 1363. 3 D. Barby and P. Champagne, Tetrahedron Lett., 1996, 37, 7725. 4 E. Dominiguez, E. Ibeas, E. Martines, J. K. Palacios and R. San Martin J. Org. Chem., 1996, 61, 5435. 5 H. Uno and M. Kurokawa, Chem. Pharm. Bull., 1978, 26, 549. 6 K. V. Nikitin and N. P. Andryukhova, Mendeleev Commun., 1999, 168. RCH2X RCH2 ONMe3 RCHO Me3NO Scheme 1 PhCH2ONH2 PhCHO PhCHNOCH2Ph NaH Scheme 2 1a 1a N O Ph O O Ph N O Ph O HC O Ph N Ph O NaH 1g Ph Ph Ph Scheme 3 N O HN O CH2Ph Ph 1i C N O HN O CH2Ph Ph N O NH Ph NaH Scheme 4 Received: 21st September 1999; Com. 99/1534Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) a88 °C. b10 mol%. cProcedure: to 1i (0.200 g, 0.62 mmol) in THF (5 ml), NaH (0.004 g dispersion in oil, 0.1 mmol) was added.The mixture was stirred for 24 h, quenched with 1 M HCl, evaporated and extracted with ethyl acetate. Column chromatography (40% ethyl acetate–hexane) afforded benzyl alcohol (61 mg, 95% yield) and 1-benzyl-3,4-dimethyl-5-imino-1,5-dihydro-2H-pyrrol-2-one (0.130 g, 98% yield) as a solid, mp 83 °C. MS, m/z: 215 (M + 1). FTIR (KBr, n/cm–1): 3282 , 1710, 1640, 1446, 1072.Table 1 The cleavage of 1 by bases in THF (20 °C, 0.1 M substrate solution, 2 equiv. of the base). Run Substrate Base Time/h Product 1H NMR (CDCl3), d/ppm Yield (%) 1 PhCH2 ONH2 1a NaH 40 PhCH=NOCH2Ph 5.21 (s, 2H), 7.3–7.6 (m, 10H), 8.13 (s, 1H) 70 2 PhCH2 O NHCH2Ph 1b NaH 60 — — 3 PhCH2 O NH(CH2Ph)2 1c NaH 60 — — 4 Et3 Na16 — — 5 1d NaH 96 — — 6 1d LDA 2 1.06 (d, 6H, J 6.1 Hz), 1.49 (d, 6H, J 7 Hz), 3.5 (m, 2H), 4.97 (s, 2H), 7.2–7.7 (m, 9H) 32 7 1d NaOEt 48 1.35 (t, 3H, J 7.1 Hz), 4.32 (q, 2H, J 7.1 Hz), 5.07 (s, 2H), 7.2–7.5 (m, 9H), 8.63 (br.s, 1H) 20 8 NaHb72 PhCOMe PhC(Me)NOH 2.22 (s, 3H), 7.3 (m, 3H), 7.5 (m, 2H), 9.03 (s, 1H) 56 25 9 NaHb16 95 10 NaOEtb 1 PhCH2CONHCHPhMe 1.62 (d, 3H, J 7 Hz), 3.83 (d, 1H, J 16 Hz), 3.94 (d, 1H, J 16 Hz), 5.6 (br. s, 1H), 6.55 (q, 1H, J 7 Hz), 7.1–7.5 (m, 10H, Ph) 93 11 NaOEtb 1 PhCH2CONHBut 1.27 (s, 9H), 3.46 (s, 2H), 5.3 (br. s, 1H, NH), 7.2–7.4 (m, 5H) 97 12c NaHb 12 PhCH2OH 1.94 (s, 3H), 1.95 (s, 3H), 4.80 (s, 2H), 7.2–7.4 (m, 5H), 8.2 (br. s, 1H) 98 95 N O O O Ph 1d NHOCH2Ph O NPr2 O i NHOCH2Ph O OEt O Ph HN O Ph O 1e N O O O COPh 1f NH O O N O Ph O O Ph 1g Ph N O O O Ph 1h Ph N O HN O CH2Ph Ph 1i N O NH Ph

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Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) Pyridazine ring opening in phthalazines induced by electron transfer Boris I. Buzykin, Vitalii V. Yanilkin,* Vladimir I. Morozov, Nataliya I. Maksimyuk, Rimma M. Eliseenkova and Nataliya V. Nastapova A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy of Sciences, 420088 Kazan, Russian Federation.Fax: +7 8432 75 2253; e-mail: buz@iopc.kcn.ru DOI: 10.1070/MC2000v010n01ABEH001142 The formation of phthalonitrile from 1-Cl-4-X-phthalazines possessing a substituent capable of anionic elimination in the 4-position (X = Cl, OPh or OMe) was found to be induced by electron transfer. The processes of electron transfer to halogen-containing organic molecules, in particular, compounds containing the C(Cl)=N group (imidoyl halides, a-halogenated aza cycles, etc.), as a rule, result in the rupture of the C–Hal bond.1,2 The substitution of hydrogen for the halogen atom is the most frequent case, but other reactions can take place depending on the nature of the compound. Thus, electron transfer to the molecules of benzoyl chloride arylhydrazones was accompanied by the cleavage of both the C–Cl bond and the N–N bond with the formation of benzonitrile and the corresponding amines.3 We assumed that this electrochemical reduction of heterocyclic compounds can result in heterocyclic ring opening.In this connection, we have studied the electrochemical reduction of 1,4-dichlorophthalazine 12 in more detail and of 1-chloro-4-RO-phthalazines [R = Ph (2) or Me (3)] for the first time.Voltammetry and electrolysis–EPR in DMF in the presence of 0.1 M Bu4NI were used. The polarograms of 1,4-dichlorophtalazine 1 in DMF and of compounds 2, 3 exhibit three or two waves of reduction, respectively. Table 1 summarises the polarography data. The first wave of compound 1 is irreversible (Figure 1), and its limiting current corresponds to the transfer of two electrons per molecule.At the potentials of the second one-electron wave and the third twoelectron wave, intermediates oxidised in the same potential range were detected by commutative polarography. The concentrations of the intermediates were no high as judged from the relative anodic currents (Table 1). The reversibility of the second stage was also confirmed by cyclic voltammetry (CV) (Figure 1).At potentials of the second waves, the electrolysis was accompanied by the formation of a paramagnetic product [aH(6,7) 0.417, aN 0.173 and aH(5,7) 0.42 mT] detected directly in the cell of the EPR spectrometer and unambiguously identified as the phthalonitrile radical anion.7 The formation of the phthalonitrile radical anion during the electrochemical reduction of compound 1 indicates that, in aprotic media, the electron transfer to the molecule of 1,4-dichlorophthalazine induces a new reaction, which was not described earlier in the literature, involving the anionic elimination of chloride ions, the cleavage of the pyridazine ring and the formation of phthalonitrile 4 (Scheme 1).The overall process involves the transfer of two electrons, the cleavage of three s-bonds (two C–Cl bonds and an N–N bond) and the formation of two new p-bonds.The diffusion nature of the limiting current of the first wave (the ip–u1/2 relationship is linear) indicates that all stages proceed rapidly. The subsequent two waves, the characteristics of which are identical to our data and the published data for phthalonitrile,7 correspond to the further reduction to phthalonitrile radical anions at the potentials of the second wave and to benzonitrile radical anions at the potentials of the third wave.It is the benzonitrile radical anions, detected by EPR [aH(2,6) 0.363, aN 0.215, aH(3,5) 0.03 and aH(4) 0.842 mT], that result in the appearance of the anodic current in the commutative curves at the potentials of the third wave.The low values of the anodic oxidation current of the phthalonitrile and benzonitrile radical anions are explained by the consumption of the radical anions in the homogeneous reduction of initial compound 1. The overall five-electron transfer of the reduction of 1,4-dichlorophthalazine can be represented by Scheme 1.The electrochemical reduction of 1-Cl-4-RO-phthalazines 2, 3 proceeds according to a similar scheme. In this case, the corresponding anodic currents were also observed in the voltammograms (Figure 1) and in the commutative curves. The phthalonitrile and benzonitrile radical anions were detected by EPR during electrolysis at the potentials of the first and second waves, respectively.The potentials E1/2 of the first wave of the reduction of 1-Cl- 4-X-phthalazines 1, 3 increased with increasing electron-donor properties of the X group (Table 1). Compound 1 is reduced more easily than phthalonitrile; therefore, in this case, the separate reduction of the above compounds was observed. Compounds 2 and 3 are reduced in the same potential range as phthalonitrile; because of this, only a three-electron wave of reduction was detected.It is well known that the radical anions of organic compounds are effective electron-transfer agents in the processes of reduction of halogen-containing organic compounds. The potential differences of the reduction of phthalonitrile and compounds 1–3 are N N Cl Cl C C N N + 2e – 2Cl– E1/2 1 4 + e 4 C C N N 5 E1/2 2 5 + 2e C N E1/2 3 hydrogen donor – CN – Scheme 1 aPhthalazines 1 and 3 were synthesised according to the known procedures. 4,5 bBoutius heat apparatus; Lit., mp/°C: 1, 164;4 3, 108;5 4, 139–141.6 cAt a Hg electrode vs. Hg/I–. dThe number of electrons determined by comparison with the one-electron wave of the benzophenone reduction. eThe ratio of the anodic commutative current to the cathodic current for reversible processes under the given conditions (f = 10 Hz) is equal 0.78.fData from ref. 6. Table 1 The characteristics of the reduction waves of substituted phthalazines 1–3 and phthalonitrile 4 in DMF in the presence of 0.1 M Bu4NI. Compounda mp/°Cb –Ec 1/2/V DE[Dlg i/(id – i)]–1/mV nd ia/ic e 1 163–164 0.93 1.14 2.05 63 58 128 2.0 1.0 2.4 0.0 0.59 0.41 2 120–122 1.07 2.02 52 125 3.0 2.4 0.24 0.18 3 105–108 1.16 2.03 68 115 3.0 2.4 0.24 0.18 4 138–140 1.12f 2.03 60 130 1.0 2.0 0.78 0.60Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) very low or even have a negative value. This is indicative of a high rate of homogeneous reduction of the initial compounds by the phthalonitrile radical anions generated at the electrode. The appearance of low concentrations of these radical anions leads to, on the one hand, a dramatic increase in the contribution of the homogeneous reaction to the overall reduction process and, on the other, an increase in the overall rate of reduction.In fact, an autocatalysis phenomenon takes place. This can affect the slope and the wave symmetry, as we have observed in the case of compounds 2, 3 (Table 1).The slope for compound 2 is somewhat lower (52 mV at 25 °C), and the wave for compound 3 is much steeper in the initial portion. Thus, the simultaneous heterogeneous and homogeneous reduction of compounds 2 and 3 according to Scheme 2 takes place during the electrochemical reduction. The one-electron level of the limiting current of the second wave for 1,4-dichlorophthalazine, which corresponds to the reduction of phthalonitrile, and the three-electron level of that for compounds 2 and 3 indicate that in DMF pyridazine ring opening in the phthalazine system proceeds quantitatively with the formation of phthalonitrile under conditions of voltammetry.This conclusion was indirectly confirmed by EPR spectroscopy: for all of the compounds under identical conditions, signals of the phthalonitrile radical anion with almost equal intensities were observed.Thus, we found that pyridazine ring opening in phthalazines is the main reaction path in the electrochemical reduction in aprotic media for not only 1,4-dichlorophthalazine but also other 1,4-disubstituted phthalazines having two groups capable of anionic elimination.This reaction is specific not only for the electrochemical reduction but also for chemical reduction of the above compounds by potassium metal in DMF. In the latter case, the phthalonitrile radical anions were also detected by EPR. References 1 L. G. Feoktistov, in Organicheskaya elektrokhimiya (Organic Electrochemistry), eds. M. M. Baiser and H. Lund, Moscow, Khimiya, 1988, p. 270 (in Russian). 2 V. Kh. Ivanova, B. I. Buzykin and N. N. Bystrykh, Khim. Geterotsikl. Soedin., 1979, 541 [Chem. Heterocycl. Compd. (Engl. Transl.), 1979, 443]. 3 L. A. Taran, B. I. Buzykin, O. Yu. Mironova, N. G. Gasetdinova and Yu. P. Kitaev, Izv. Akad. Nauk SSSR, Ser. Khim., 1983, 166 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1983, 32, 142). 4 J. Druey and B. H. Ringer, Helv. Chim. Acta, 1951, 34, 197. 5 F. M. Rowe and A. T. Peters, J. Chem. Soc., 1933, 1331. 6 C. K. Mann and K. K. Barnes, Electrochemical Reactions in Nonaqueous Systems, Marcel Dekker, New York, 1970, 338. 7 P. H. Rieger, J. Bernal, W. H. Reinmuth and G. K. Fraenkel, J. Am. Chem. Soc., 1963, 85, 683. (a) (b) 1 2 3 1 2 10.0 0.0 –10.0 5.0 0.0 –5.0 I/mA E/V (vs. Hg/I–) 0 –0.4 –0.8 –1.2 I/mA Figure 1 Cyclic voltammograms of (a) 1,4-dichlorophthalazine and (b) 1-chloro-4-methoxyphthalazine (c = 1×10–3 mol dm–3) in 0.1 M Bu4NI–DMF at a glassy carbon electrode for the potential sweep rates u = (1) 20, (2) 50 and (3) 100 mV s–1; T = 25 °C. N N Cl X + 2e – Cl–, – X– E1/2 1 4 + e 5 E1/2 1 2 5 + 2 or 3 E1/2 1 – CN –, – X– Scheme 2 2 X = OPh 3 X = OMe 3 4 4 Received: 9th June 1999; Com. 99/1498

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Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) An unusual 3,4-dihydroisoquinoline ring enlargement with the annulation of pyrazole Yurii V. Shklyaev,*a Vladimir A. Glushkov,a Viktor V. Davidov,b Valentina I. Sokolc and Vladimir S. Sergienkoc a Institute of Technical Chemistry, Urals Branch of the Russian Academy of Sciences, 614600 Perm, Russian Federation. Fax +7 3422 124 375; e-mail:cheminst@mpm.ru b Peoples’ Friendship University of Russia, 117198 Moscow, Russian Federation.Fax: +7 095 952 1186; e-mail: vdavidov@mx.pfu.edu.ru c N. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, 117907 Moscow, Russian Federation. Fax: +7 095 954 1279; e-mail: sokol@ionchran.msk.ru DOI: 10.1070/MC2000v010n01ABEH001167 The treatment of substituted ethyl 1-(3',4'-dihydro-3',3'-dimethylisoquinolyl)-1-oximinoacetates with hydrazine hydrate leads to a 3,4-dihydroisoquinoline ring enlargement with the annulation of a pyrazole ring to form substituted 5,5-dimethyl-2,3,5,6-tetrahydro- 3-oxopyrazolo[3,4-b]benzo-3-azepines.Alkyl 1-(3',4'-dihydroisoquinolyl)-1-oximinoacetates exhibit biological activity.1 Studying chemical properties of ethyl 1-(3',3'- dimethyl-3',4'-dihydroisoquinolyl)-1-oximinoacetates 1a,b,2 we found an unusual transformation of these compounds by the reaction with hydrazine hydrate.The treatment of compounds 1a,b with 3–6 equivalents of hydrazine in propan-2-ol leads to the slow evolution of N2 from the reaction mixture. The subsequent refluxing (3–5 min) and exposure to air for 1–3 days resulted in the formation of substituted 5,5-dimethyl-2,3,5,6- tetrahydro-3-oxopyrazolo[3,4-b]benzo-3-azepines 2a,b in good yields (47–74%).† The mechanism of this reaction is not clear.Possible reaction paths for the conversion of 1a,b into 2a,b, are depicted in Scheme 1. Path A involves oxidation of the initially formed hydrazone to a diazo compound, decomposition of this latter with a ring enlargement to form benzo-3-azepine, addition of hydrazine to electrophilic intermediate C, intramolecular cyclization and oxidation with air to form substituted 5,5-dimethyl- 2,3,5,6-tetrahydro-3-oxopyrazolo[3,4-b]benzo-3-azepines 2a,b.Path B involves the base-induced tautomeric conversion of the oxime into a nitrozo form (pH of the reaction mixture was ~8), the elimination of NO+ and the insertion into the C=N bond to form electrophilic intermediate C; the subsequent transformations are similar to path A.† Oxime 1b was synthesised from ethyl 1-(3',3'-dimethyl-3',4'-dihydroisoquinolyl) acetate10 by the known method.2 Oxime 1b (0.31 g, 0.93 mmol) was dissolved in 30 ml of propan-2-ol (50 °C); next 0.3 g (6 mmol) of hydrazine hydrate was added; the mixture was refluxed for 3 min and allowed to stand in air for 1–3 days.Next, a small amount of a polymeric substance was filtered off, and the red solution was evaporated. The residue was twice treated with cool water (2×3 ml) for removing hydrazine, dried and recrystallised to result in 2b. Compound 2a was purified by chromatography on a silica gel column (eluent: benzene–CHCl3, 5:1). N Me Me R R N OEt O OH Path B (NH2)2 N Me Me R R N OEt O O H N2 (NH2)2 – NO+ R R N H O OEt Me Me N Me Me R R H2NN OEt O 1a,b C Path A (NH2)2 [O] N Me Me R R N2 OEt O + H+ – N2 + H+ R R NH NH EtO O Me Me (NH2)2 H2N – EtOH R R NH Me Me HN N O H [O] R R N Me Me N N O H 2a,b a R = H b R = OMe Scheme 1 C(1) C(2) C(3) C(4) C(5) C(6) C(7) C(8) C(9) C(10) C(11) C(12) C(13) C(14) C(15) O(1) O(2) O(3) N(1) N(2) N(3) Figure 1 The structure of compound 2b.Selected bond lengths (Å): N(1)– C(12) 1.252(5), N(1)–C(9) 1.475(5), N(2)–C(1) 1.304(4), N(2)–N(3) 1.386(4), N(3)–C(13) 1.348(5), O(1)–C(13) 1.205(5).Mendeleev Communications Electronic Version, Issue 1, 2000 (pp. 1–42) The role of the tautomeric nitrozo form was supported by the fact that corresponding O-methylated ethyl 1-(3',3'-dimethyl-3',4'- dihydroisoquinolyl)-1-oximinoacetates treated by hydrazine in the same manner did not form compounds 2a,b.Note that the ring enlargement of 3,4-dihydroisoquinolines to benzo-3-azepines is well known,3–7 but these reactions frequently give a variety of products.8 Moreover, the simultaneous annulation of a pyrazole ring to benzoazepine is of synthetic importance. Compounds 2a,b are the diaza analogues of the recently discovered alkaloids nordeoxyharringtonine and homodeoxyharringtonine9 of Cephalotaxus from Cephalotaxus harringtonia var.drupacea. The structure of compounds 2a,b was confirmed by elemental analysis, 1H NMR and IR spectroscopy,‡ and compound 2b was additionally examined by 13C NMR spectroscopy, mass spectrometry‡ and X-ray diffraction analysis.§ The general view of molecule 2b is given in Figure 1.This study was supported by the Russian Foundation for Basic Research (grant no. 98-03-32689a), and the Special Federal Programme ‘Integratsiya’ (grant no. A0129). ‡ 1b: mp 196–197 °C (ethanol). 1H NMR (80 MHz, CDCl3) d: 1.17 (t, 3H, CH2Me), 1.23 (s, 6H, 3-Me), 2.68 (s, 2H, 4-CH2), 3.75 (s, 3H, OMe), 3.85 (s, 3H, OMe), 4.19 (q, 2H, OCH2), 6.60 (s, 2H, 5,8-H), 9.56 (br.s, 1H, N–OH). IR (Nujol, n/cm–1): 3100 (br.), 1720 (O–C=O), 1600, 1565, 1520, 1270, 1240, 1215, 1170, 1160 (sh.), 1100, 1035, 960, 920, 900, 865, 845, 825. 2a: mp 199–202 °C (decomp.) (benzene–hexane). 1H NMR (250 MHz, [2H6]DMSO) d: 1.32 (s, 6H, 5-Me), 3.10 (s, 2H, 6-CH2), 7.15–7.40 (m, 3H, 7,8,9-H), 7.90 (d, 1H, 10-H), 11.95 (s, 1H, NH). IR (Nujol, n/cm–1): 3245 (NH), 1730 (C=O), 1620 (C=N), 1325, 1260, 1240, 1173, 1105, 1040, 965, 925, 895, 770. 2b: mp 206–210 °C (decomp.) (ethanol). 1H NMR (250MHz, [2H6]DMSO) d: 1.31 (s, 6H, 5-Me), 3.02 (s, 2H, 6-CH2), 3.83 (s, 6H, 8,9-OMe), 6.74 (s, 1H, 7-H), 7.36 (s, 1H, 10-H), 11.80 (br. s, 1H, NH). 13CNMR ([2H6]DMSO) d: 161.38 (C=O), 151.54 [C(3a)], 150.61 [C(10b)], 147.52 [C(8)], 140.18 [C(9)], 130.27 [C(6a)], 121.70 [C(10a)], 114.08 [C(10)], 107.62 [C(7)], 60.63 [C(5)], 55.51 and 55.38 [8,9-(MeO)2], 45.25 [C(6)]; signals of 5,5-Me2 are overlapped by [2H6]DMSO. IR (Nujol, n/cm–1): 3290 (NH), 1720 (C=O), 1680 (sh.), 1600 (C=N), 1530, 1500, 1260, 1215, 1165, 1100, 1050, 1030, 1000, 860. MS, m/z (%): M+ 287 (100), 272 (28), 256 (9), 243 (27), 229 (32), 203 (99), 188 (19), 176 (20), 160 (12), 144 (11), 129 (20), 115 (20).References 1 K. Harsanyi, K. Takacs, E. Benedek and A. Neszmelyi, Liebigs Ann. Chem., 1973, 1606. 2 V. S. Schklyaev, B. B. Aleksandrov and M. S. Gavrilov, Izv. Akad. Nauk SSSR, Ser. Khim., 1986, 959 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1986, 35, 877). 3 T.Kametani, S. Hirata, S. Shibuya and K. Fukumoto, J. Chem. Soc., C, 1971, 1927. 4 M. Natsume and M. Wada, Chem. Pharm. Bull., 1972, 20, 1837. 5 I. Takeuchi, K. Masuda and Y. Hamada, Chem. Pharm. Bull., 1992, 40, 2602. 6 S. V. Kessar, P. Singh, N. P. Kaur, U. Chawla, K. Shukla, P. Aggarwal and D. Venugopal, J. Org. Chem., 1991, 56, 3908. 7 A. F. Khlebnikov, T.Yu. Nikiforova, M. S. Novikov and R. R. Kostikov, Synthesis., 1997, 677. 8 Y. Sato, N. Shirai, Y. Machida, E. Ito, T. Yasui, Y. Kinoro and K. Hatano, J. Org. Chem., 1992, 57, 6711. 9 T. Ichiro, I. Yasuda, M. Nishijima, Y. Hitotsuynagi, K. Takeya and H. Itokawa, J. Nat. Prod., 1996, 59, 965. 10 V. A. Glushkov and Yu. V. Shklyaev, Mendeleev Commun., 1998, 17. 11 G. M. Sheldrick, Acta Crystallogr., 1990, 46A, 467. 12 G.M. Sheldrick, SHELXL-93, Program for the Refinement of Crystal Structures, University of Göttingen, Germany. § Crystallographic data for 2b: C15H17N3O3, monoclinic, space group P21/n, a = 8.733(2), b = 10.646(2), c = 16.093(3) Å, b = 104.40(3)°, V = = 1449.2(5) Å3, Z = 4, dc = 1.317 g cm–3, l(MoKa) = 0.7107 Å, m(MoKa) = = 0.90 cm–1, F(000) = 608, T = 294 K.Intensity data were collected on an Enraf-Nonius CAD-4 diffractometer using the w scan method (2qmax = = 56.9°). The structure was solved by the direct method (SHELXS-8811) and refined by a full-matrix least-squares procedure (SHELXL-9312) in an anisotropic approximation for all non-hydrogen atoms. The coordinates and thermal parameters of the hydrogen atoms were fixed (UH 0.08 Å2, C–H 0.096 Å). Final R1 = 0.054, wR2 = 0.120 and S = 1.115 for 1384 observed reflections with I > 2s(I). Atomic coordinates, bond lengths, bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2000. Any request to the CCDC for data should quote the full literature citation and the reference number 1135/57. Received: 1st June 1999; Com. 99/1494

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数据来源: RSC