摘要:

2484 J. Chem. SOC. (C), 1970 The Stereochemistry of P-Chlorovinyl-aldghydes By J. M. F. Gagan, Allen G. Lane and Douglas Lloyd," Department of Chemistry, United College of St. Salvator and St. Leonard, University of St. Andrews, St. Andrews, Fife The stereochemistry of P-chlorovinyl-aldehydes, prepared by a Vilsmeier reaction from a-methylene-ketones, has been examined by n.m.r. spectroscopy, including solvent shift studies. A slightly modified method was used for their preparation. P-CHLOROVINYL-ALDEHYDES are readily prepared by the involved the stereospecific preparation of the isomeric action of phosphoryl chloride and NN-dimethylform- p-chloroacraldehydes and a comparison of their i.r. amide on cc-methylene ket0nes.l Although this reaction ~pectra.~ The n.m.r. and i.r.spectra of some p-chloro- is well known2 no comment has been made upon the * Inier alia W. Ziegenbein and W. Lang, Chem. Ber., 1060. 2. -4rnoId and J. ZemliCka, Proc. Chem. SOC., 1958, 227; ~ A. P. Skoldinov, Zhur. o ~ g . Khim., 1965, I., 1748. 3 -4: I. IGanOv, T. V. Protopopova, V. G. Vinokurov, and Coll. Czech. Chem. Conzm., 1959, 24, 2385.Org. 2485 vinyl ketones have been analysed in connexion with their geometrical isomerism,4 and the geometrical isomerism of unhalogenated vinyl carbonyl compounds such as amide~,~ ketones: and carboxylic acids 6 9 7 has been elucidated by a study of the solvent shifts in their n.m.r. spectra. In the present work, a variety of p-chlorovinyl-alde- hydes were made by use of a slight modification of the original method which gave good yields.The products gave normal aldehyde derivatives (2,4-dinitrophenyl- hydrazones and semicarbazones) . The n.m.r. spectra (solutions in CC1,) of samples of 3-chloro-2-methylbut-2-enal (I) and 3-chloro-2-methyl- pent-2-enal (11), prepared, respectively, from butan- 2-one and pentan-2-one, showed clearly that they were mixtures of cis- and traas-isomers (cis and trans refer to the relative positions of the aldehyde and chloro- MexcL Me CHO Me “IMe CHO (r) groups). In the case of (II), signals at T -0.11 (lH, s), 7.35 (2H, q), 8-21 (3H, s), and 8.76 (3H, t) represented one isomer (A), and signals at ‘i 0.05 (lH, s), 7.03 (2H, q), 8.13 (3H, s), and 8.71 (3H, t) were due to the other isomer (B). The assignment of these signals is evident and presumably isomer (A), which has the signal for its aldehyde proton at lower field than isomer (B) is the cis-isomer, the difference being due to the interaction of the adjacent chloro-group.Similarly in the case of (I), it is possible to distinguish between the cis- and tram- isomers. Each isomer shows a methyl signal with chemical shift almost identical with those for the 2-methyl groups in the corresponding isomers of (11). These signals may therefore be assigned to the %methyl groups in (I) and the other methyl signals to the terminal methyl groups. The terminal methyl group in the cis- isomer has its signal at higher field than the terminal methyl group of the trans-isomer, owing to the interaction of the adjacent carbonyl group in the latter case. These assignments were confirmed by a study of the solvent shifts in the n.m.r.spectra which resulted when a benzene-carbon tetrachloride mixture was used as solvent instead of neat carbon tetrachloride. The results are shown in Tables 1 and 2. Benzene appears 5-7 to solvate +-unsaturated com- pounds so that solvent molecules lie above and below 4 W. K. Benson and A. E. Pohland, J. Org. Chem., 1964, 29, 5 J. V. Hatton and R. E. Richards, MoZ. Phys., 1962, 5, 139. 385; J. Dabrowski and J. Terpinski, ibid., 1966, 31, 2159. the plane of the compound in such a way that the benzene rings, although able to interact with the olefinic bond, are kept away from the negative end of the dipolar carbonyl group. In the case of p-chlorovinyl-aldehydes, the benzene TABLE 1 N.m.r. signals (T) of 3-chlor0-2-methylbut-2-enals (I) trans-Isomer cis-Isomer Solvent: ccI4 C,H,-CCl, CCI, C,H&C1& 4-H3 7.59 7.99 7-38 7.80 2-Me 8-19 8.39 8-12 8-17 CHO - 0-22 - 0.20 - 0.07 -t 0.2 1 TABLE 2 N.m.r.signals (7) of 3-chloro-2-methylpent-2-enals (11) cis-Isomer tYans-Isomer Solvent: cc14 C,&-CCl, CCI, C,H(j-CC14 5-H3 8.76 9.00 8.71 8.95 4-H, 7.35 7.64 7.03 7.37 2-Me 8.21 8.36 8.13 8-16 CHO -0.11 -0.11 f0.05 +0*25 rings should also be remote from the chlorine atoms ( c j . ref. 7). The preferred location of the solvating benzene molecules would thus be as shown in (111) and (IV) for the cis- and trans-isomers respectively. Protons on the a-carbon atoms of both alkyl groups will be shielded by the solvating molecules in the case of the cis-isomer (111) , whereas in the trans-isomer (IV) group II cm1 0 II ( N ) 0 R’ and the aldehyde proton should be shielded but group R should not.The results (Tables 1 and 2) are entirely consistent with these modes of solvation and with the attribution of cis- and trans-geometries. The solvent shifts for the 4-protons are greater in each case than those for the %methyl protons. This may reflect the fact that, because of the effect of the carbonyl CHO CHO group, the benzene rings are not symmetrically disposed with respect to the 2,3-bond and may be centrednear& to the 4-carbon atom. Further confirmation of the stereochemistry of acyclic p-chlorovinyl-aldehydes was obtained from the n.m.r. spectra of 2-chlorocyclopent-l-enecarbaldehyde (V) and J. V. Hatton and R. E. Richards, MoZ.Phys., 1962, 5, 153. ’ J. Ronayne and D. H. Williams, J . Chem. SOC. (C), 1967, nnin2486 J. Chem. SOC. (C), 1970 2-chlorocyclol~ex-l-enecarbaldehyde (VI) (see Table 3). For each of these compounds only a cis form is possible. As anticipated, the signals representing the ring protons are shifted to higher field when benzene is a component TABLE 3 N.ni.r. signals ( T) of cyclic chlorovinyl-aldehydes (V) and (VI) Compound (V) Solvent : CCI, C,H,-CCI, CH2 CHO 7.17,' 7-46,* 7.88" 7.31,' 7*57,* 8*16* (2: 2: 2H) (2: 2: 2H) 0.0 0.0 Compound (VI) Solvent : CCl, C,HG-CCl, CH, 7 ~ 4 3 , ~ 7*74,* 8.26' 7.66,* 7.81,* 8-49" CHO -0.11 -0.11 (2 : 2 : 4H) * Centre of multiplet (2 : 2:4H) of the solvent, whereas the positions of the signals due to the aldehyde protons are unaffected.The extent of the solvent shift varies for different methylene groups, presumably again depending on the disposition of the benzene rings. In the case of the ethyl 3-chloro-2-formylbut-2-enoates (VII), the solvation must be similar to that of (I) and (11), as indicated by the solvent shifts (see Table 4). TABLE 4 N.m.r. signals (T) of ethyl 3-chloro-2-formylbut-2-enoates (VII) cis-Isomer tvans-Isomer Solvent : CCI, C,H,-CC14 CCI, C,H,-CCl, 4-H, 6.66 6.84 8-03 8.20 CMO 0.0 0.06 0.20 0.41 The effect of the adjacent ester group on the position of the signal due to the terminal methyl group of the cis- isomer in either solvent is noticeable in these compounds. MeYCL VMe '"Y YPh M / h - i O With phenyl-substituted p-chlorovinyl-aldehydes the pattern is different.For the two P-chloro-cc-methyl- cinnamaldehydes (VIII) , as anticipated, one isomer, presumably the trans, shows no appreciable solvent shift for the signal due to the methyl group [T 7.95 (CCl,), 7.97 (c&&-Cc14)] whereas the other isomer does show a solvent shift for the methyl signal, but smaller than in the previous cases [T 8.19 (CCl,), 8.30 (C,H6-CCl,)]. However the signal due to the aldehyde proton in either isomer shows no appreciable solvent shift [qiS -0.34 (c6H6-cc14)]. Apparently in these cases the presence of the phenyl groups alters the pattern of solvation; the solvating benzene molecules probably tend to associate preferentially with the phenyl groups of the aldehydes. In all cases where two isomeric p-chlorovinyl-aldehydes may be formed, one isomer appears to be formed in pre- ponderant amount. Thus with products (I) and (11) the trans-isomer is the major component (60-70% of the overall yield); in the case of (VIII) the proportion of trans-isomer exceeds 90%.However, for (VII) the major product (ca. 60%) is the cis-isomer and when the corresponding methoxycarbonyl ester was prepared only one isomer (apparently the cis) could be detected. Since the overall mechanism of the reaction has yet to be elucidated no meaningful comments on these results are possible at present. The p-chlorovinyl-aldehydes are not indefinitely st able. After varying periods of time, and even when stored in a refrigerator, they suddenly decompose more or less violently with evolution of hydrogen chloride and form- ation of black tar.Incautious distillation of them can also lead to a similar result. From one sample o€ the tar formed from 3-chloro- 2-methylpent-2-ena1, which had decomposed after several weeks in a refrigerator, colourless needles were separated and recrystallised from aqueous methanol. Their i.r. spectrum showed the presence of carboxy- and chloro-groups ; reversible solubility in aqueous sodium hydroxide also suggested the presence of a carboxy- group. The n.m.r. spectrum indicated that this crystal- line material was 3-chloro-2-methylpent-2-enoic acid, and the very small solvent shift caused by benzene for the signal due to the 2-methyl group further suggests that it may be the trans-isomer (see Table 5). (CCI,), -0.32 (C&&-CCl,) ; 'TtmnS 0.58 (CCIJ, 0.60 TABLE 5 N.1n.r.signals (T) of crystalline material isolated from the decomposition product of 3-chloro-2-methylpent-2-enal Solvent : CC1.1 C,H,-CCI.* l-CO2H -2.48 (s) - 2.14 2-Me 7.91 (s) 7.95 4-H, 7-06 (q, J = 8 Hz) 7-15 5-H3 8.77 (t, J = 8 Hz) 8.85 A large upfield shift of the carboxy-proton signal on addition of benzene to the solvent was also observed. 2-Chlorocyclohex-l-enecarboxylic acid was obtained similarly from the tarry decomposition material from 2-chlorocyclohex-l-enecarbaldehyde. Acid-autocataly- sis may be responsible for these sudden violent decomposi- tions. Hydrolysis of 3-chloro-2-methylbut-2-enal by aqueous potassium carbonate gave a product in poor yield which appeared, from its n.m.r. spectrum (see Experimental section), to be the enol form of 2-methyl-3-oxobutanal (i.e.2-methyl-3-oxobut-l-enol) .Org. The p-chlorovinylaldehydes gave normal aldehyde derivatives, e.g. 2,4-dinitrophenylhydrazones and semi- carbazones. When the dinitrophenylhydrazone of 3-chloro-2-methylbut-2-enal (I) was heated in aniline a t lOQ", the dinitrophenylhydrazone of butan-2-one and aniline hydrochloride were produced. This may be rationalised in terms of nucleophilic substitution of the chlorine atom by aniline, followed by solvolytic cleavage of the product in the manner of a p-dicarbonyl derivative (i.e. a retro-Claisen reaction) together with exchange of the anil moiety for a dinitrophenylhydrazine group, aniline acting both as solvolysis agent and as base. EXPERIMENTAL 3-Chlor0-2-nzethylbut-2-enaZs (I) .-NN-dimethylformam- icle (1 10 ml.) was run slowly into stirred phosphoryl chloride (100 ml.) at 0".Stirring was continued for 0.5 hr. and then butan-2-one (50 ml.) was added slowly during 0.5-1.0 hr. Thc mixture was stirred overnight and allowed to warm to room temperature. The resultant yellow syrup was poured on ice and the whole was stirred until the ice had just melted. The solution was then extracted with ether or methylene chloride ; the extract was washed (saturated aq. Na,CO, and water), and dried (Na,SO,) . Evaporation left a liquid which was distilled in vacuo under nitrogen to give the p-chlorovinyl-aldehyde (51.4 g., 77y0), b.p. 57-59"/21 mm., nD21 1.490, T (neat liquid) cis-isomer -0.14 (lH), 7.59 (3H), and 8.19 (3H); trans isomer -0.04 (lH), 7.35 (3H), and 8.19 (3H) (cis:trans 31 : 69).2,4-Dinitrophenylhydvazones of (I) .-The aldehydes re- acted with 2,4-dinitrophenylhydrazine in ethanolic sul- phuric acid. The precipitate was chromatographed on alumina with benzene and chloroform as eluants, and was thereby separated into stereoisomers which were recrystal- lised from ethanol and acetonitrile. These dinitrophenyl- hydrazones had (a) (first fraction eluted) m.p. 166", Am=. (EtOH) 258, 290, and 377 nm. (E 17,000, 9400, and 32,100), 7 (CDCl,) 0.92 (lH, d), 1.67 (lH, q), 2.08 (lH, d, phenyl protons), 1.58 (lH, s), 7.64 (3H, s), and 7-92 (3H, s) (Found: C, 44.8; H, 3.9; N, 18.8. CllHl1ClN4O, requires C, 44.3; H, 3.7; N, 18.8%); and (b) (second fraction eluted) m.p. 214", (EtOH) 257,289, and 380 nm. (E 12,800,7300, and 22,200) (Found: C, 44.4; H, 3.6; N, 18.6.C,,H,,ClN,O, requires C, 44.3; H, 3.7; N, 18.8%). Other P-chlovoviwyl-aldehydes and their derivatives were pre- pared by the same method. Physical constants of the products and yields are given below. The cis-trans ratios refer in every case to one typical experiment; the ratios varied slightly from one run to another. N.m.r. spectra of some of the chlorovinyl-aldehydes in solution in CCl, or in C,H,-CCI, are given in the earlier part of the paper. 3-Chloro-2-~zethyl~ent-2-enals (II).-The mixture of isomers (58%) (cis: trans ca. 25 : 75) had b.p. 70-74" a t 21 mm. 2-Chlorocyclopezzt- 1-eNecarbaldehyde (V) .-The aldehyde (47%) had b.p. 76-78" a t 17 mm., nD19 1.515, T (neat liquid) 0.04 (lH), 7.2 and 7.5 (4H), and 7.95 (2H); 2,4-di- .I.zitropJzenylhydvazone, 1n.p.184", 7 (CDCl,) 0.86, 1.66 and 2-08 (3H, phenyl), 1.88 (lH, s), and 7.0-7.4 and 7-7-8.3 (6M, m) (Found: C, 46.1; H, 3-4. Cl,HllC1N40, requires C, 46.4; H, 3.6%). 2-Chlorocyclohex- 1-enecarbaldehyde (VI) .-This aldehyde (75%) had b.p. 96" a t 14 mm., nD19 1.520, T (neat liquid) -0.16 (lH), 7.40 (2H), '7.77 (ZH), and 8.25 (4H); 2,4-di- nitro phenylhydrazone, m.p. 175", A,, (EtOH) 259, 291, and 377 nm. (E 15,500, 9000, and 30,700), T (CDCl,) 0.90, 1.68 and 2.10 (3H, phenyl), 1.65 (lH, s), and 7.45br (m) and 8.21br (m) (8H) (Found: C, 48.0; H, 4.0; N, 17.2. C13H13- ClN,O, requires C, 48-1; H, 4.0; N, 17.2%); semicarbazone, m. 216" (decomp.) (Found: C, 47-4; H, 5.8. C,Hl,CIN,O requires C, 47.5; H, 6.0%). 2-Chlorocyclohe~t-l-enecarbaldehyde.-This aldehyde (81%) had b.p.113-114" a t 18 mm., m.p. -4", T (neat liquid) -0.04 (lH), 7.15 (2H), 7.54 (ZH), and 8.0-8-8 (6H); 2,4-dinitrophenylhydrazone, m.p. 155", z (CDC1,) 0.88, 1-64 and 2-06 (3H, phenyl), 1.69 (lH, s), and 7.0-7.4 (m) and 7.9-8-6 (m) (10H) (Found: C, 49.6; H, 4.4; N, 16.8. Cl,H1,ClN,O4 requires C, 49.6; H, 4.5; N, 16.7%). Ethyl 3-chloro-2-for.luylbut-2-enoates (VII) .-The mixture of cis- and trans-chlorovinyl-aldehydes (44%) (cis : trans 59 : 41) had b.p. 106-110" at 17 mm., nDZ0 1.481, T (neat liquid) cis-isomer 0-03 (lH), 5.73 (ZH), 7.55 (3H), and 8.72 (3H), tvans-isomer 0.16 (lH), 5-73 (2H), 7.34 (3H), and 8-72 (3H) ; 2,4-dinitro~henylhydrazones, (a) (first fraction eluted, yellow), m.p. 176", I,,,. (EtOH) 254, 285infl, and 373 nm.(E 14,900, 7600, and 29,200) (Found: C, 44.0; H, 3.8; N, 15.4. Cl,H,,CIN,O, requires C, 43.8; H, 3.7; N, 15.7%) ; (b) (second fraction eluted, orange), m.p. 173", Am=. (EtOH) 259, 294, and 368 nm. (E 16,800, 12,500, and 22,100) (Found: C, 44.3; H, 3-5; N, 15.8. C,,H,,ClN,O, requires C, 43.8; H, 3.7; N, 15.7%). Methyl 3-Chloro-2-for.luylbut-2-enoate.-Only one (cis) isomer was formed (50%). This chlorovinyl-aldehyde had b.p. 102-106" a t 18 mm., T (neat liquid) 0.06 (lH), 6.23 (3H), and 7.56 (3H) ; 2,4-dinitrofihenylhydrazone, m.p. 196" (Found: C, 42.2; H, 3.1; N, 16.4. C,,HllClN,06 requires C, 42-1; H, 3.2; N, 16.4%). Ethyl P-Chlovo-u-formyZcinnamate.-The mixture of cis- and trans-chlorovinyl-aldehydes (52%) (cis : trans 42 : 58) had b.p. 128" a t 0.05 mm., T (neat liquid) cis-isomer -0.13 (lH), 2.54 (5H), 5-95 (2H), and 9-03 (3H), trans-isomer 0.66 (lH), 2.54 (5H), 5-67 (2H), and 8.71 (3H).~-Chloro-u-methylcinna.lualdehyde (VIII) .-The mixture of cis- and trans-chlorovinyl-aldehydes (92%) (cis : trans 7 : 93) had b.p. 82-85' a t 0.2 mm., 7 (neat liquid) trans- isomer 0-50 (lH), 2.61 (5H), and 7-96 (3H); trans-2,4-di- nitrophenylhydrazone, m.p. 188O, T (CDC1,) 0.94, 1.66 and 2.05 (3H, phenyl), 2.24 (lH, s), 2.57 (5H, m), and 7.66 (3H, s) (Found: C, 52.4; H, 3.6; N, 15-25. C,,H1,C1N40, re- quires C, 52.3; H, 3.6; N, 15.25%). 3-Chloro-2-phenylbut-2-enal.-This mixture of chloro- vinyl-aldehydes (56%) (cis : trans 58 : 42) had b.p. 90-96" a t 0.2 mm., T (neat liquid) cis-isomer -0.39 (lH), 2.5-3.2 (5H), and 7.97 (3H), trans-isomer 0.04 (lH), 2-5-3.2 (5H), and 7.57 (3H). Hydrolysis of 3-Ckloro-2-methylbut-2-enal.-The aldehyde (15 ml.) and potassium carbonate (20 g.) in water (150 ml.) and methanol (25 ml.) was heated under reflux for 2 hr. The mixture was cooled, acidified with concentrated hydro- chloric acid, and extracted with ether (1 x 150 ml., 2 x 100 ml.). Removal of solvent from the dried ethereal solution left 2-methyl-3-oxobutanal (2.6 g.), z (CDCl,) -4.66 (lH, s), 2.22 (lH, s), 7.83 (3H, s), and 8-29 (3H, s). Reaction of the Dinitrophenylhydrazone of 3-Chloro- 2-wzethylbut-2-enaZ with Aniline.-A solution of the dinitro- phenylhydrazone (6 g.) in aniline (20 ml.) with a very small amount of ethanol to effect complete solution was heated for 4 hr. a t 100". When the resultant solution was set aside2488 J. Chem. SOC. (C), 1970 orange needles of butan-%one 2,4-dinitrophenylhydrazone We thank Dr. R. K. Mackie for discussions and Miss separated and were filtered off (3.2 g.), m.p. 116" (from K. M. L. Elair for assistance with the practical work. We ethanol) (lit. m.p. 115O), i.r. spectrum identical with that are also grateful for the awards of a Fellowship from the of an authentic specimen. Addition of ether (100 ml.) to Wellcome Foundation Ltd. (to J. F. M. G.) and of a the filtrate precipitated aniline hydrochloride (2-1 g . ) , Leverhulme Visiting Fellowship (to A. G. L.). correct i.r. spectrum. [0/301 Receizred, February 25fh, 19701

ISSN:0022-4952    

DOI:10.1039/J39700002484

出版商:RSC    

年代:1970

数据来源: RSC