摘要:
1002 J. Chern. SOC. (C), 1970 Reaction of t-Butylamine with Cyclohexane-1.3-dione By J. V. Greenhill, School of Studies in Pharmaceutical Chemistry, University of Bradford, Bradford 7 When t-butylamine reacts with cyclohexane-I ,3-dione in refluxing xylene the first product is a dehydrated dirner of the diketone which then reacts with the base. The nature of the yellow final product is discussed on the basis of u.v., pK, and n.rn.r. data. ENAMINONES are formed when a number of primary and secondary amines react with cyclohexane-l,3-dione (I) .l When the dione was treated with t-butylamine in re- fluxing benzene only a very small yield (3%) of the ex- pected product (11) was obtained. The bulk of the product was a crystalline t-butylammonium salt of the acidic 1,3-diketone. In refluxing xylene, with con- tinuous collection of water, this salt was converted into a yellow compound, C16H23N02.It seemed likely that this compound had either structure (111) or (V) and this was confirmed when the same material was obtained by treatment of the trione (IV) with t- butylamine. Prolonged refluxing of the enaminone (11) in xylene with or without the addition of the dione (I) (1 equiv.) failed to produce any yellow colour and the starting material was recovered unchanged. However, when the dione (I) was refluxed in xylene in the presence of a tertiary base (triethylamine; 1 equiv.) a sample of the dehydrated dimer (IV) was obtained. The dione (I) must undergo a base-catalysed dimerisation followed by dehydration and reaction with the t-butylamine to 1 J.,V.Greenhill, J . Chem. SOC. (B), 1969, 299. a H. Lutz Heh. Chim. Aclu., 1940, 23, 1147. produce the yellow compound. U.V. data for this compound (111) and some similar materials, the cor- responding normal enaminones, and the parent dione and trione are presented in the Table. U.V. data at 25' In 0 . 1 ~ - In water In O.~N-HCI NaOH In CHC1, r------7 r L - 7 r--7 & Corn- A,,,. L a x . Amax. L a x . pound (nm.) E (nm.) E (nm.) E (nm.) E (I) 263 13,800 256 17,000 281 26,000 253 8700 (11) 292 31,500 282 25,400 294 32,200 284 26,600 (X) 295 29,900 284 24,300 296 30,500 286 26,500 (VIII) 305 34,300 287 25,100 305 36,000 301 30,400 283 16,300 259 20,900 287 21,800 259 10,400 237 11.500 422 45,400 286 14,200 261 19,700 291 19,400 261 9700 { 410 26,100 237 9900 424 48,900 281 19,800 261 24,100 287 21,200 265 2200 (Ix) { 401 14,800 237 10,900 433 52,300 (Iv) { 284 19,800 264 21,500 288 26,700 256 12,100 239 13,400 (I1') { 405 19,000 The yellow compound (111) showed a broad peak in the 250-290 nm. region and a sharp peak at 405 nm.In increasing strengths of acid, a sharp peak at 259 nm. developed and in increasing strengths of alkali a sharp peak at 287 nm. appeared. The peak at 405 nm. was depressed in both acid and alkali and absent in both 0-Oh-hydrochloric acid and -sodium hydroxide. (pK, 5.26 at 25") and has been shown to give a broad U.V. absorption in the range 250-290 nm. due to the presence of a mixture of the ionised and un-ionised forms in aqueous solution, the wavelength of maximum absorption varying with concentration.3 As shown in the Table, sharp peaks occur in acid (256 nm.) and in alkali (281 nm.).The Chem. SOL. 1946, 68, 666. Cyclohexane-1,3-dione (I) is acidic E. R. Blout, V. W. Eager, and D. C. Silverman, J . Amer.Org. 1003 trione (IV) has been shown to exist with the planes of the two rings at an angle to each other owing to over- crowdingJ4 a situation analogous to that of the ortko- substituted biphenyls. This structure is confirmed by molecular models. The major U.V. absorption of this coinpound in water, acid, and alkali, is very similar t o that of the dione (I) , and is due to the cyclohexanedione ring. In addition, absorption due to the cyclohexenone ring is seen as a shoulder at 239 nm. in 0-1N-hydrochloric acid and as a peak in this position in 0-1N-sodium hydroxide. This indicates that the new compound has a cyclohexanedione ring, and therefore has structure Enaminones have been shown to be protonated on oxygen,ss6 which in this case would give structure (VI).(111). NHEJ ti*/ \OH- (VII ( Y I I l Similarly, treatment with base would lead to structure (VII). Molecular models show that although (111) can be accommodated as a flat structure, both (VI) and (VII) would have to exist with the planes of the two rings at an angle to each other. Thus the main absorption in acid and base is due to the cyclohexanedione ring, although the alkaline solution shows a peak at 237 nm. correspond- ing to the second ring. If the new compound had structure (V) it would probably exist with the twisted conformation and not show the long-wavelength absorption.More important, however , the short-wavelength absorption would be closer to that for the enaminone (11). As shown in the Table, this occurs at longer wavelength and shows a much sharper peak in water and no ionisation in base. In order to obtain a similar compound containing a tertiary nitrogen, the trione (IV) was treated with piperidine. The derivative (IX) shows absorption very similar to that of the compound containing secondary nitrogen, including the small peak at 237 nm. in alkali. This suggests that the proton lost is that from the C-4’ ring carbon atom rather than that from NH (VII). This compound is compared in the Table with the enaminone derived from piperidine (VIII) . For correlation with the following n.m.r.data, the U.V. absorptions in chloroform are also given (Table). As expected there is an increase in the extinction co- efficient for the long-wavelength peak at the expense of K. Conrow, J . Org. Chew., 1966, 31, 1050. the short-wavelength absorption. This is because the broad peak at short wavelength represents protonation and deprotonation of the amphoteric species (111) which is favoured in the more polar solvent. 0 0 The new compound was found to be a stronger base (pK, 3.45) than the enaminone (11) (pK, 2.96).l If it had had structure (V) the cyclohexenone ring would have exerted a base-weakening effect . This conclusion is confirmed by a comparison of the acid strengths of the dione (I) (pK, 5.26) and the trione (IV) (pK, 4.32). The trione is a considerably stronger acid owing to the electron-withdrawal effect of the cyclohexenone ring.A substituent which is acid-strengthening is base- weakening, so compound (V) would be a weaker base than the enaminone (11). The new compound also ionises as an acid (pK, 11.55). It is weak because of the necessity of removing either the NH proton or the ring C-4’ proton [(111) -+ (VII)]. In order to help in the ehcidation of the n.m.r. spectrum, the related compound (XI) derived from dimedone. was prepared. Reaction of t-butylamine with dimedone in refluxing xylene gave a mixture of the required compound (XI) and the enaminone (X), separated by fractional crystallisation. The U.V. data show the dimedone derivatives (X) and (XI) to be structurally similar to the cyclohexanedione derivatives (11) and (111) (see Table).The dimedone derivative (XI) gave n.m.r. signals as follows: T 8.95-9.00 (12H, d, 4 x Me), 8-48 (9H, s, But), 7-60 (4H, s, 4- and 6-H,), 7-07 (2H, s, 6’-H,), 7-81 (2H, s, 4’-H,) , 1.81 (lH, s, 2’-H) , deshielded by a carbonyl oxygen in the flat structure, and 3-4 (NH, shifted on dilution). In the spectrum of the cyclohexanedione derivative (111) the C-6’ protons gave a triplet at z 6.97 and the C-2’ proton a singlet at ‘c 1.80. Only broad 0 N H B ~ peaks were recorded for the rest of the ring protons, owing to splitting and overlapping of the signals. No signals were seen in either spectrum to indicate the presence of another tautomer. It is concluded that t-butylamine reacts with cyclo- hexane-lJ3-dione in benzene to give the enaminone (11) G.H:Alt and A. J. Speziale, J . Org. Chem., 1965, SO, 1407. 0 N. J. Leonard and J. A. Adamcik, J . Amer. Chem. SOL. 1959, 81, 595.1004 J. Chem. SOC. (C), 1970 in poor yield, but in the higher-boiling xylene, di- merisation of the dione followed by dehydration and reaction with the base takes place to give 2-(3-t-butyl- aminocyclohex-2-enylidene)cyclohexane-l,3-dione (111). EXPERIMENTAL t-Butylarnine salt of Cyclohexane-l,3-dione.-A solution of cyclohexane-1,3-dione (2.25 g.) and t-butylamine (8.4 g.) in benzene (300 ml) was heated under reflux in a Dean-Stark apparatus for 2 hr. The solvent was evaporated off and the residue was shaken with dilute hydrochloric acid (10 ml.) and chloroform (20 ml.). The acid layer was basified and extracted with chloroform (3 x 10 ml.).The total chloro- form extract was dried (MgSO,) and evaporated to give 3-t-butylaminocyclohex-2-enone (0.1 g., 3%), m.p. and mixed m.p.l 173". Alternatively, if after evaporation of the benzene, the residue was recrystallised from ethanol- ether the t-butylamine salt of cyclohexane-1,3-dione (3 g., 80y0), m.p. 137-138' (decomp.) was obtained (Found: C, 64.8; H, 10.0; N, 7.6. C,,H,,N02 requires C, 64.9; H, 10.3; N, 7.6%). 2-( 3-t-Butylavninocyclohex-2-enylidene) cyclohexane- 1,3-di- one.-A solution of the t-butylamine salt of cyclohexane- l13-dione (42 g.) in xylene (200 ml.) was refluxed in a Dean- Stark apparatus for 4 hr., during which time 8 ml. of a solution of t-butylamine in water was collected. The xylene solution was allowed to cool to yield the $Yoduct (10 g., 34y0), m.p.249-250' (from ethanol-ether) (Found: C, 73.6; H, 8.9; N, 5.6. C,,H23N0, requires C, 73.6; H, 8.8; N, 5.4%) ; hydrochloride, m.p. 210-211" (decomp.) (from ethanol-ether) (Found: C, 64.5; H, 8.2; C1, 11.8; N, 4.6. C16H2,ClN0, requires C, 64.6; H, 8-1; C1, 11-9; N, 4.7%). 5,5-Dimethyl-2- (5,5-dimethyl-3-t-butylaminocycZohex- 2-ertylidene)cycEohexane-l, 3-dione.-A solution of dimedone (14 g.) and t-butylamine (7.2 g.) in xylene (100 ml.) was boiled under reflux for 1 hr. Boiling was continued under a Dean-Stark head for a further 3 hr. during which time water (1.5 ml.) was collected. The solution was allowed to cool and the product was collected to yield 5,5-dimethyl-3-t- butylauninocyclohex-2-enone (5 g., 26y0), m.p.218-219" (from ethanol-ether) (Found: C, 74.1; H, 10.4; N, 7.0. C,,H,,NO requires C, 73.8;. H, 10.8; N, 7.2%). The xylene solution was evaporated and the residual gum was triturated with ether to give the title compound (1.8 g., 5-7%), m.p. 248-249' (from methanol) (Found: C, 76.0; H, 9-6; N, 4.6. C20H,1N0, requires C , 75.7; H, 9.8; N, 4.4%). 2- (3-Piperidinocyclohex-2-enylidene) cyclohexane- 1,3-dione. -A solution of 2- (3-oxocyclohex- l-enyl) cyclohexane- 1,3-dione (1.03 g.) and piperidine (0.85 g.) in benzene (50 ml.) was refluxed for 0.75 hr. The solvent was evaporated off, the residue was dissolved in refluxing benzene, and the solution was filtered through aluminium oxide. Light petroleum (b.p. 40-60") was added to yield the product (1 g., 73%), m.p. 127-128" (from benzene-light petroleum) (Found: C, 74.8; H, 8.3; N, 5.0. C,,H,,N02 requires C, 74.7; H, 8.4; N, 5.1%). 3-Piperidinocyclohex-2-enone.-A solution of cyclohexane- 1,3-dione (22.4 g.) and piperidine (17 g.) in benzene (200 ml.) was refluxed under a Dean-Stark head for 2.5 hr. The solvent was evaporated off and the residue was distilled to give 3-piperidinocyclohex-2-enone (22 g., 62%), b.p. 164'/ 1.0 mm., nD20 1,5780 (Found: C, 73.7; H, 9.3; N, 7.5. C,,H,,NO requires C, 73.7; H, 9.5; N, 7.8%) ; hydrochloride, m.p. 160-161" (from ethanol-ether) (Found: C, 61.3; H, 8.5; C1, 16-7; N, 6.5. C,,H,,ClNO requires C, 61.3; H, 8.4; C1, 16.5; N, 6.5%). The potentiometric titrations were carried out as pre- viously described., The U.V. spectra were determined for ca. 3 x 1 0 - 6 ~ solutions with a Unicam SP 800 spectro- photometer (1 cm. cells). The n.m.r. spectra were deter- mined with a Perkin-Elmer R12 spectrometer. [9/1832 Received. October 28th1 19691
ISSN:0022-4952
DOI:10.1039/J39700001002
出版商:RSC
年代:1970
数据来源: RSC