1434 J.C.S. Perkin I Carbon-I3 and Proton Magnetic Resonance Spectra of 2,2-Dialkyl-5,5-dimethylcyclohexane-1,3-diones (2,2-Dialkyldimedones) By Jaswant R. Mahajan, Universidade de Brasilia, Departamento de Qulmica, 70000 Brasilia-DF, Brazil Proton and natural abundance carbon-13 Fourier transform n.m.r. spectra of ten 2.2-dialkyldimedones have been examined at 100 and 20 MHz respectively. Chemical shifts have been assigned in each case. In contrast to the significant long-range anisotropic shielding observed in the lH n.m.r. spectra of 2-benzyl compounds, there was a slight deshielding of the corresponding carbon nuclei in the 13C spectra. The preparation of several new dialkyl- dimedones is also described. IN connection with a recent 13C n.m.r. study of some 6-alkyl-3,3-dimethyl-5-oxodec-8-enolides(1) and several 29.1 0 (1) lSC N.ni.r.chemical shifts (6)for (1). R = Me gives 6 16.8 other medium-ring and macrocyclic oxo-lactones,2 we have examined the 13C spectra of the title compounds (2) to evaluate the effect of conformational mobility as well as that of the two y-carbonyl functions on the chemical J. R. Mahajan, Abstracts, 29th Annual Meeting of ' SBPC,'Cikncia e Cultuva, 1977,29 (supplement), 403. J. R. Mahajan and H. C. Aralijo, Canad. J. Chem.,1977,55, 3261. shifts of the gem-dimethyl group. Moreover, as appreci- able long-range shielding effects have been observed in the lH n.m.r. spectra of 2,2-dibenzylcyclohexane-l,3-diones, as well as the related spirotriketones (3)carrying aromatic group^,^ we have compared the 13C and 1H n.m.r.spectra of these compounds. RESULTS AND DISCUSSION 13C N.m.r. Spectra (Table l).-All the carbon reson- ances in compounds (2a-j) could be assigned unambigu- ously on the basis of proton noise-decoupled and single frequency off -resonance decoupled (SFORD) spectra. As dimedone (5,5-dimethylcyclohexane-1,3-dione)and its monoalkylated derivatives are present mainly in the enolic form and have poor solubility in most organic solvents, it is not possible to obtain the shielding para- meters for the mono- or di-alkylated dimedones relative * H. A. P. De Jongh and H. Wynberg, Telrahedvon, 1966, 21, 616. to the replacement of a hydrogen atom. However, shielding values for the replacement of one or two methyl groups, with the new substituents are given as a difference of chemical shift with respect to 2,2-dimethyldimedone (2a). Table 1 shows that the effect of substitution on the most affected C-2 is fairly additive for all the substituents examined.Although variations in the chemical shifts of other carbon atoms are small, the additive relation- ship seems to hold. The gem-dimethyl group becomes equivalent in com- pounds carrying two identical substituents at C-2, thus shieldings observed in compounds (1).2 In a frozen conformation the geminal axial and equatorial methyl groups have shifts usually separated by ca. 8 p.p.m., as exemplified by 1,1,3-trimethylcyclohexane(CHh,,, 25.5; CHamp;, 34.3 p.p.m.) 4a and 3,3,5-trimethylcyclohexanol (CHamp;z,25.7 ; CH,,,33.1p.p.m.) .5 The observed small difference in the present series is probably due to the conformational equilibrium, as in the case of sym-metrically substituted compounds.The other possible cause for lowering the difference between the axial and equatorial methyl groups may be the lack of syn-axial TABLE1 13C Chemical shifts of 2,2-dialkyl-5,5-dimethylcyclohexane-1,3-diones (Sa-j) C-1-3 c-2 C-4-6 C-5 C-7 C-8 210.0(4 60.3(s) (t)51.0 (s) (9) (430.5 28.3 R1 R2 R' = RB= CH,: 22.1 (4) 208.9 64.2 51.5 30.6 29.1 27.9 CAH~CBH:CcH2CHS: 18.5 (9) -1.1 208.2 3.9 67.9 0.5 51.9 0.1 0.8 -0.4 30.6 28.6 CA, 41.3 (t); C,, 132.3 (d) cc, 119.1 (t)R' = R2 = CAH~*CBH:C~H~ -1.8 7.6 0.9 0.1 0.3 CA,38.7 (t); CB, 132.6 (d); Cc, 119.3 (t) 208.6 -1.4 207.0 63.3 3.0 66.4 50.8 -0.2 51.1 30.6 29.1 27.1 0.1 1.3 -1.2 30.8 28.5 CH3: 23.6 (9) CAH~CBH~C~N Cdl 29.2 (t); Cg, 12.9 (t)Cc, 119.4 (s)R' = R2 = CAH2CBH2CCN -3.0 6.1 0.1 0.3 0.2 CA, 29.1 (t); CB, 12.7 (t);Cc, 118.6 (s) 210.1 0.1 64.7 4.4 52.5 1.5 30.1 28.9 28.0 -0.4 0.6 -0.3 CH,: 20.5 (9) CAH~P~ CA, 43.8 (t);C,, 136.1 (s);C,, 130.3; C,, 128.2; 211.2 70.2 54.3 29.2 28.6 C,, 127.0 R' = R2 = CAH2Ph CA,44.5 (t); C,, 136.4 (s); C,, 130.9;C,,,, 128.3; C,, 127.1 1.2 9.9 3.3 -1.3 0.3 209.7 68.8 53.2 30.1 29.0 28.5 CAH~P~CAH~C~H:C~H, -0.3 (-1.0)207.9 8.5 68.5(8.3) 2.2 51.9(2.0) -0.4 0.7 0.2 30.7 30.2 27.0 CA, 40.9 (t); CB, 132.7 (d); CA,42.3 (t); C,, 136.3 (s); Cc, 119.6 (t) C,, 130.9; C,, 128.2; C,, 127.0 CAH, *CBH~*C~N CA HzPh -2.1 8.2 0.9 0.2 1.9 -1.3 CA, 27.3 (t); CB, 12.9 (t) C,, 44.7 (t); C,, 133.8 (s);Ccl 119.4 (s) C,, 130.1; C,, 128.6; C,, 127.8 (-1.3) (7.4) (1.3) 207.4 67.6 6.12 30.7 30.2 26.9 C.4H~*CBH:CCHZ CAH~CBH~C~N -2.6 ( -2.5) 7.3 (6.9) 0.2 (0.3) 0.2 1.9 -1.4 Cc, 120.6 (t) Cc, 119.5 (s) CA,42.3 (5); CB, 130.1 (d) CA,26.4 (t); Cg.12.8 (t) s = Singlet; d = doublet; t = triplet; q = quartet, as observed in the SFORD spectra. For simplicity only the multiplicity of the quaternary carbon is marked in the aromatic nucleus. C,, C,, C,, and C, refer to the chemical shifts for the quaternary, ortho-, meta-, and para-C-atoms, respectively. A Indicates the difference with respect to compound (2a). The values in parentheses are the sum of the shielding parameters for the corresponding single substituents, as observed in this Table for the replacement of one of the 2-Me groups by the new substituent.revealing a rapid conformational equilibrium in these compounds, as has already been shown by De Jongh and Wynberg on the basis of lH n.m.r. spectra for (2a and g).39 t However, in the case of asymmetrical substitution at C-2, the two methyls are separated by 0.9-3.3 p.p.m., their chemical shifts being very close to the gem-dimethyl t However, these authors were unable to draw a definite con- clusion regarding the presence of a rapid chair-chair equilibrium or that of an intermediate flexible form (e.g., a twist-boat or flattened chair) on the basis of a variable temperature (-80 to 140 "C) study conducted with the spirotriketone (3; R' = Ph; R2 = Me);, although our data do not resolve this matter, the arguments here presented remain valid.hydrogen atoms at the y-positions, which are assumed to be responsible for lowering the chemical shift of the axial methyl gro~p.~~,~ However, the reported shieldings for the axial (25.7)and equatorial (32.0)methyl carbons in 3,3,5-trimethylcyclohexanoneare almost identical with the corresponding values in the previous two examples, thus belying any effect of the removal of the syn-axial hydrogen atom in the present case. On the other hand, * J. B. Stothers, ' Carbon-13 NMR Spectroscopy,' Academic Press, New York, 1972, (a) p.64; (b)p. 66. L. F. Johnson and W. C. Jankowski, 'Carbon-13 NMR Spectra,' Wiley-Interscience, New York, 1972. J. B. Stothers and C. T. Tan, Canad. J. Chem., 1974,52,308. 1436 J.C.S. Perkin I these three examples demonstrate that there is almost no Finally, we point out that, in sharp contrast to the lH change in the chemical shift of the axial methyl group on n.m.r. spectra where appreciable long-range shielding introducing an equatorial hydroxy or an oxo-group at the has been observed for the protons of the gem-dimethyl y-position, while the same transformations produce a group and the 4,6-methylenes in compounds carrying one R1 R2 = H or Me successive shielding of 1.1 p.p.m. for the equatorial methyl carbon.Although distinction between an axial and an equa- torial substituent is not very clear in a conformationally flexible molecule, the conformer with the larger sub- stituent in the equatorial position is f, h-j) reflect thisto predominate. Structures (2b, d, evidently expected +I= bsol;+p2 + .amp;*;; I*:: R2bias and the lower chemical shift has been assigned to the 0 0 0axial methyl group in this conformation or that cis to in the twist boat form. Re-and especially two benzyl substituents (vide infra),therethe larger substituent (R2) placement of a single methyl group by a new substituent is no such effect observed in the 13C spectra, in accord- at C-2 affects the two methyls at C-5 to a different degree ance with the previous observation^.^ On the contrary, TABLE2 'H Chemical shifts (100 MHz) of 2,2-dialkyl-5,5-dimethylcyclohexane-1,3-diones (2a-j) R1 R2 CH2-4-6 R' = R2= CH,: 1.30 (s) 2.61 (s)R' = R2= CH2CZH3 CH,, 2.50 (d, J 7 Hz) : C2H3 4.96-5.80 (m) 2.59 (s) 0.99 R1 = R2 5 CH,*CH,CN: 2.20 (m, A,B,) 2.67 (s) 1.00 R' = R2= CH2Ph CH,, 3.20 (s); Ph, 7.17 (m) 1.98 (s) 0.26 CH,: 1.24 (s) CH2*C,H3 2.60 (ABq, J 15 Hz) CH,, 2.50 (d, J 7 Hz); VAB = 16 HZ 1.08 0.93 C2H3, 4.96-5.82 (m) CH,: 1.39 (s) CH,*CH,*CN: 2.20 (m, A,B,) 2.65 (ABq, J 15 Hz) VAB = 33 HZ 1.12 0.87 CH,: 1.26 (s) CH,Ph 2-41 (ABq, J 16 Hz) ..CH,, 3.07 (s); PK, 6.96-7.36 (m) VAB = 8 HZ 0.87 0.79 CH,C,H, CHzPh 2.34 (ABq, J 16 Hz) CH,, 2.53 (d, J 7 Hz) ; CH,, 3.08 (s); Ph, 6.94-7.35 (m) VAB = 15 HZ 0.89 0.54 C2H,, 4.95-5.88 (m) CH,*CH,*CN: 2.11 (m, A,B,) CH2Ph 2.62 (ABq, J 14 Hz) CH,, 3.05 (s); Ph, 6.82-7.40 (m) VAB = 31 HZ 1.06 0.80 CH,C,H3 CH,.CH,.CN : 2.18 (m, A,B,) 2.61 (ABq, J 15 Hz) CH,, 2.50 (d, J 6 Hz) ; VAB = 36 HZ 1.16 0.82 C,H3, 5.00-5.74 (m) m,A,B, = A,B, type multiplet; ABq = AB-type quartet; VAB = d(1-4) (2 -3) and in the opposite direction.In the case of two identical in the most affected 2,2-dibenzyldimedone (Zg),there is a substituents these opposing effects cancel to leave a slight deshielding of both the gem-dimethyl group (0.3 small (0.3p.p.m.) deshielding of the gem-dimethyl group. p.p.m.) as well as the 4,6-methylenes (3.3 p.p.m.). However, when the two substituents at C-2 are different, G.C. Levy and G. L. Nelson, ' Carbon-13 Nuclear Magnetic the opposing influences are reinforced in a Resonance for Organic Chemists,' Wiley-Interscience, New Yoamp;,larger separation (3.3 p.p.m.). 1972, p. 24. IH N.m.r. Spectra. (Table 2).-Chemical shifts for two of these compounds (2a and g) have already been reported and the long-range shielding effects of the aryl substituents have been reationalized in these, as well as in the related spirotriketones (3), by De Jongh and W~nberg.~In dimedones carrying identical sub-stituents at C-2, the gem-dimethyls as well as the C-4 and C-6 methylene protons are equivalent, due to conform- ational mobility, and show a single peak for each group. On the other hand, when the substituents are different, the two methyls at C-5 are not equivalent and the methylene hydrogens show an AB pattern.In the asymetrically substituted dialkyl derivatives of dimedone, the lower chemical shift has been assigned to the methyl group cis to the larger substituent (R2). on a rotary evaporator, the residue was dissolved in ether and washed with 0.5~-sodium hydroxide and water. Usual work-up afforded the dialkyldimedone, which was purified as described for individual compounds. Yields of the purified products were 60-75y0. 2-AlZyE-2-methyldimedone (Zb), prepared as above from 2-allyldimedone and methyl iodide gave needles from petrol- eum ether (b.p. 40-60"), m.p. 41O; vmaX 1724, 1695, and 1639 cm-l (Found: C, 74.0; H, 9.2. C,,H,,O, requires C, 74.2, H, 9.3). 2-A llyl-2-benzyldimedone (2h), prepared as above from 2- benzyldimedone and ally1 bromide gave rods from petroleum ether (b.p.40-60"), m.p. 66-67"; vmx. 1 724, 1692, and 1 645 cm-l (Found: C, 80.1; H, 8.3. C1,H2,0, requires C, 80.0; H, 8.2). 2-Benzyl-2-methyldimedone(2f), prepared as above from Although this assignment is consistent with the calcul- ated anisotropic effect of the aromatic ring and possibly that of the double bond, the choice is arbitrary in the case of a p-cyanoethyl group. EXPERIMENTAL Proton noise-decoupled and single-frequency off-resonance decoupled (SFORD) natural abundance l3C Fourier trans- form n.m.r. spectra of 1.0-2.0~ solutions in deuteriochloro- form, containing 10 (v/v) tetramethylsilane, were recorded on a Varian CFT-20 (20 MHz) spectrometer using standard parameters, with pulse angle of 30-37.5" (8-10 ps), aquisition time of 0.75-0.91 s, and without any pulse delay.The line positions and intensities were obtained relative to internal tetramethylsilane. Line positions (6 p.p.m.) are quoted to the nearest first decimal place. The lH n.m.r. spectra were recorded at 100 MHz on a Varian HA-100 spectrometer for 0.2-0.3~ solutions in the above solvent- standard system. Melting points were determined on a Kofler block. lnfrared spectra were recorded for KBr discs on a Perkin-Elmer 137 Infracord spectrophotometer. The dimethyl (Za), diallyl (Zc), and dibenzyl (2g) deriv-atives of diniedone were obtained as by-products in the corresponding monoalkylations, conducted according to the general procedure described by Stetter.8 These three products have already been characterized by De~ai.~ The remaining dialkyldimedones were prepared by the following modifications of the described methods8 Dialkyldimedones.l0-To a solution of 2-alkyldimedone (10 mmol) in potassium t-butoxide-t-butyl alcohol (1~; 11 ml) was added alkyl halide (11 mmol) and potassium iodide (1 mmol). The mixture was gently refluxed on a water- bath for 14-20 h, when the reaction mixture was cooled and extracted with ether. The extracts were washed with 0.5~-sodium hydroxide and water and dried. Evaporation of solvent gave 80-100~0 yield of crude product, contain- ing some O-alkylated compound (t.l.c., i.r.), which was refluxed (ca.4 h) in aqueous ethanol (50) containing 0.5- 1.Oyohydrochloric acid. After removing the excess ethanol * H. Stetter, in ' Newer Methods of Preparative Organic Chemistry,' ed. W. Foerst, Academic Press, New York, 1963, vol. 2, ch. 3. 2-benzyldimedone and methyl iodide gave crystals from hexane, m.p. 49-50"; vmx. 1 730 and 1 695 cm-l (Found: C, 78.8; H, 8.4. C,,H,,O, requires C, 78.7; H, 8.3). 2-(2-Cyanoethyl)-Z-methyldimedone (2d). Methyl-dimedone (1.85 g, 12 mmol), acrylonitrile (0.95 g, 18 mmol), and potassium t-butoxide (N; 1 ml) in t-butyl alcohol (15 ml) was gently refluxed for 15 h. The reaction mixture was cooled, diluted with benzene, and washed with water, O.B~-sodiumhydroxide, and water again.Drying, evapor- ation, and crystallization from 95 ethanol gave shiny plates (2.0g, 82); m.p. 100-101"; vmx. 2 268, 1 730, and 1698 cm-l (Found: C, 69.7; H, 8.4; N, 6.9. Cl,H1,N0, requires C, 69.5; H, S.3; N, 6.8). 2-A ZZyZ-2-(2-cyanoethyl)ninzedone (2j), prepared from 2-allyldimedone as for (2d) and crystallized from 95 ethanol gave rods (83), m.p. 89-90'; vmx. 2 278, 1 730, and 1 698 cm-l (Found: C, 72.2; H, 8.4; N, 5.9. C1,HlgNO2 requires C, 72.1; H, 8.2; N, 6.0). 2-BenzyZ-2- (2-cyanoethyZ)dimedone (2i), prepared from 2-benzyldimedone as for (2d) and crystallized from 95 ethanol gave rods (64), m.p. 13O-135OJ with softening at ca. 125"; vmx. 2 257, 1 721, and 1 689 cm-l (Found: C, 76.5; H, 7.4; N, 4.8. C18HzlN02 requires C, 76.3; H, 7.5; N, 4.9). 2,2-Bis-( 2-cyanoethyZ)dimedone (2e), prepared from dimedone as for (Zd), with double the proportion of solvent, basic catalyst, and acrylonitrile, gave rods from 950/, ethanol (40y0),m.p. 139-140"; vmx. 2 268, 1 727, and 1 692 (Found: C, 68.5; H, 7.2; N, 11.5. C14H,8N,0, requires C, 68.3; H, 7.4; N, 11.4). This work was carried out at the Division of Biological Sciences of the National Research Council (N.R.C.), Ottawa, Canada. The author thanks Drs. 0. E. Edwards and I. C. P. Smith for research facilities, Dr. H. Shguin for elemental analyses, and Dr. R. R. Fraser of Ottawa Univer- sity for 100 MHz lH n.m.r. spectra. Special thanks are recorded to the N.R.C., Canada, and the Conselho Nacional de Pesquisas (CNPq), Brazil, for the award of a visiting fellowship. 7/1911 Received, 1st November, 19771 R. D. Desai, J. Chern. SOC.,1932, 1079. lo J. R. Mahajan, Synthesis, 1976, 110.
展开▼
