Alain
Crépin
a,
Nicolas
Wattier
b,
Sylvain
Petit
b,
Laurent
Bischoff
*c,
Corinne
Fruit
c and
Francis
Marsais
d
aCurrent adress: Val-de-Pharm, Parc industriel d'Incarville, BP 606, 27106, Val-de-Reuil Cedex, France. Fax: +33 02 32 25 79 15
bCNRS UMR 6014 COBRA B.P., 08 76131, Mont-Saint-Aignan Cedex, France. Fax: +33 02 35 52 29 62
cUniversité de Rouen, place Emile Blondel, 76130, Mont-Saint-Aignan, France. E-mail: laurent.bischoff@univ-rouen.fr
dLCOFH, IRCOF-INSA Rouen, B.P., 08 76131, Mont-Saint-Aignan Cedex, France
First published on 31st October 2008
Starting from suitably protected aminoacids, mercaptoimidazoles were synthesized either from the acid or including the amine nitrogen itself. A preliminary optimisation study led to efficient conditions for the obtention of the imidazole ring. These conditions are compatible with the presence of aminoacid or dipeptide scaffolds.
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Fig. 1 N - or C-terminus aminoacid-derived mercaptoimidazoles. |
In the past thirty years,5thiol inhibitors have been widely developed. The imidazole ring which is found in histidine often accounts for the chelation of the zinc cation in the binding site of the enzyme.6 In addition, mercaptoimidazoles are appealing targets for their antioxidant properties. This moiety is present in natural compounds such as ergothioneine or ovothiol.7 In this paper, we wish to report a validation of a general method for the conversion of aminoacids into their mercaptoimidazole analogs.
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Fig. 2 Strategies described in the literature. |
In the case of aminoacids and peptides, we chose (Fig. 3) the method described in ref. 9, believing that those mild conditions would be suitable with highly-functionalized aminoacid derivatives. Preliminary results, however, called for further optimisation of the cyclisation step and the introduction of a subsequent protection step.
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Fig. 3 Retrosynthetic analysis. |
Unraveling the reactivity of this system was initially conducted with N-acetyl-N-benzylaminothioacetamide 1 as a model substrate before being applied to aminoacids. As shown in Scheme 1, several parameters were examined to reach an efficient one-pot process. Preparation of the reagent was accomplished by treating N-benzyl aminoacetonitrile with excess thioacetic acid in pyridine12 followed by acetylation. Dehydration of this compound with TMSOTf/Et3N following the literature conditions led to a modest yield of 4-mercaptoimidazole.
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Scheme 1 Reagents and conditions: i, TMSOTf, Et3N, CH2Cl2, −78 °C to RT, 6.5 h; ii, see conditions in Table 1. |
In addition, the imidazole thiol may be isolated as a thiol or disulfide but characterisation of this compound is facilitated by protecting the thiol moiety. On the one hand, pKa values13 indicate that 4-mercaptoimidazoles predominantly exist under a zwitterionic form, since 1,5-dimethyl-4-mercaptoimidazole exhibited a pKa of 2.3 for the thiol and 10.3 for the imidazole itself. On the other hand, as free thiols, mercaptoimidazoles in particular are very potent anti-oxidants, and they have a high propensity to undergo oxidative dimerisation. Their corresponding disulfides were more commonly isolated. Thus, in situ electrophilic trapping was used as a mean to facilitate the isolation of the products. As listed in Table 1, in situ protection of the thiol was performed with benzylic halides or di-tert-butyl dicarbonate Boc2O, though the reaction seemed rather slow in this case. We also noticed that treatment with NaBH4 prior to S-protection was unnecessary if the reaction is conducted under inert atmosphere (entries 3 and 4). The optimal conditions consisted in treating the crude reaction medium with methanol before protection of the thiol moiety with Boc2O (Table 1, entry 6). We suggest that S-desilylation occurs with methanol, the free thiol being further protected. Having this result in hand, we examined whether the method was applicable to aminoacid substrates. Aminoacids in which the carboxyl group was replaced with the heterocycle were obtained according to Scheme 2.
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Scheme 2 Reagents and conditions: i, CH3–NH–CH2CN, dioxane; ii, EDCI, DMAP in dry MeOH, 56% overall; iii, 8 equiv CH3COSH, pyridine, 65%; iv, TMSOTf, Et3N, CH2Cl2, −78 °C to RT; v, MeOH, 15 min; vi, Boc2O, Et3N, DMAP, CH2Cl2, 53%; vii, 1.5 M HCl, 50% aq dioxane, 40 °C, 100% |
For instance, with glutamic acid, opening of the anhydride with a N-cyanomethyl amine such as sarcosine nitrile afforded the amide 4 with a good regioselectivity in favour of the α-carbonyl.14 To facilitate the purification step, the crude reaction mixture was treated with EDCI/DMAP in anhydrous methanol, leading to the amidoester 4. Thioacetic acid-mediated addition of H2S on the nitrile afforded thioamide 5 in a 65% yield. NMR spectra of most cyanomethyl amides and aminothiocarbonyl amides in CDCl3 revealed two rotamers (see experimental section).
It is worth noticing that the use of TMSOTf under our optimized conditions successfully led to compound 6 (53% yield) from a more sensitive functionalized substrate such as 5. Final deprotection under standard acidic hydrolysis conditions of the thiol, side-chain acid and amine afforded the pure compound 7 as its hydrochloride salt. 1H NMR in D2O exhibited a rapid exchange of the proton at C5 of the imidazole ring, due to an easy thiol/thione tautomerism.
As far as the “N-terminus” mimetic was concerned, the cyanomethylamine was prepared directly from the amino group of the aminoacid, as depicted in Scheme 3.
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Scheme 3 Reagents and conditions: i, RCOOAc, 50% (9a), 95% (9b); ii, 8 equiv CH3COSH, pyridine, 78% (10a), 71% (10b); iii, TMSOTf, Et3N, CH2Cl2, −78 °C to RT; iv, MeOH, 15 min; v, Boc2O, Et3N, DMAP, CH2Cl2, 60% (11a), 66% (11b); vi, 1.5 M HCl, 50% aq dioxane, 40 °C, 100% |
Cyanomethylation of aminoacid methyl esters is a known reaction that can be performed smoothly either by direct alkylation with chloroacetonitrile,15 or via aminomethylation in presence of benzotriazole derivatives.16 The free cyanomethylamine 8 can be readily purified by flash chromatography on silica gel without noticeable degradation. Subsequent acetylation or formylation was carried out with acetic anhydride or mixed formic acetic anhydride. Compounds 10 were cyclized in good yields with TMSOTf and S-Boc protected as described above, to produce the 4-mercaptoimidazole 12 after final acidic hydrolysis. This new isoleucine derivative 12 bears a potential zinc ligand as a surrogate of the amine moiety.
Further applications of this work were devoted to the evaluation of a dipeptidic substrate. We were interested in knowing whether the formation of the imidazole ring was compatible with the presence of the secondary amide bond. Examination of the reactivity of the dipeptide-derived compound 13 proved that our conditions are amenable to starting materials which contain peptidic linkages. In addition, quenching with methyl iodide instead of Boc2O at the end of the cyclisation process afforded the S-methyl derivative 15b. This allowed an efficient synthesis of both dipeptides 15b and 16a (Scheme 4).
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Scheme 4 Reagents and conditions: i, HCOOH, Ac2O, 57%; ii, 8 equiv CH3COSH, pyridine; iii, TMSOTf, Et3N, CH2Cl2, −78 °C to RT; iv, MeOH, 15 min; v, Boc2O, Et3N, DMAP, CH2Cl2, 42%; vi, CH3I, Et3N, 26%; vii, 1.5 M HCl, 50% aq dioxane, 40 °C, 100%. |
Recently, 2-substituted 1-benzyl-4-methyl imidazoles were described as acid mimics in aminoacid series. Their preparations used palladium-catalyzed cyclisation of N-allyl oxime aminoacid derivatives17 or electrocyclization of azomethine ylides.18 We were interested in examining whether our mercaptoimidazoles could serve as precursors of similar, unsubstituted imidazoles. Initial attempts at desulfurisation of S-Boc derivatives with Raney nickel were unsuccessful. We could, however, overcome this poor reactivity by using the methylsulfanyl imidazole 17. The latter was readily converted to the unsubstituted imidazole by treatment with Raney nickel19 in refluxing ethanol overnight as shown in Scheme 5.
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Scheme 5 Reagents and conditions: i, Raney nickel, EtOH, reflux, 95% |
Compound 1 (2.14 g, 77%) was obtained as a stench, pale yellow oil. (Found: C, 57.29; H 8.02; N 12.38. C11H14N2OS requires C, 57.39; H, 8.21; N, 12.41); 1H NMR ratio of rotamers 4:1, major compound : δH(300 MHz; CDCl3) 2.15 (3H, s), 4.29 (2H, s), 4.64 (2H, s), 7.11–7.33 (5H, m), 7.77 (1H, br s), 8.27 (1H, br s); δC(75 MHz; CDCl3) 21.9, 53.4, 57.4, 127.0, 128.4, 129.5, 135.8, 173.2, 204.2
A solution of N-(2-amino-2-thioxoethyl)-N-benzylacetamide 1 (489 mg, 2.2 mmol) and Et3N (1.26 cm3, 9.0 mmol) in anhydrous CH2Cl2 (15 cm3) was cooled to −78 °C and trimethylsilyl triflate (1.27 cm3, 6.6 mmol) was added dropwise. After stirring 15 min at −78 °C and 6.5 h at RT, methanol was added and stirring continued during 15 min. The solvents were evaporated and a solution of DMAP (27 mg, 0.22 mmol) and anhydrous Et3N (2 cm3, 14.4 mmol) in CH2Cl2 (15 cm3) was added to the residue. To this solution was added dropwise a solution of Boc2O (1.9 g, 8.8 mmol) in anhydrous CH2Cl2 (5 cm3). After stirring overnight and concentration in vacuo, the residue was purified by flash chromatography through silica gel, eluent [EtOAc:cyclohexane:Et3N= 6:4:0.01], Rf 0.35, yielding 2c (400 mg, 60%) as a colourless oil.
(Found: C, 62.93; H, 6.61; N, 9.19; S, 10.69. C16H20N2O2S requires C, 63.13; H, 6.62; N, 9.20; S, 10.53); δH(300 MHz; CDCl3) 1.40 (9H, s), 2.26 (3H, s), 4.95 (2H, s), 6.99–7.02 (2H, m), 7.22–7.29 (3H, m); δC(75 MHz; CDCl3) 13.7, 28.6, 50.5, 85.6, 125.1, 127.1, 127.2, 128.6, 129.5, 135.8, 146.9, 168.3
(Found: C, 73.28, H, 6.14, N, 9.25, S, 10.7. C18H18N2S requires C, 73.43; H, 6.16; N, 9.51; S, 10.89); δH(300 MHz; CDCl3) 2.22 (3H, s), 3.90 (2H, s), 4.83 (2H, s), 6.53 (1H, s), 6.86–6.88 (2H, m), 7.08–7.25 (8H, m); δC(75 MHz; CDCl3) 13.6, 40.3, 50.1, 124.3, 127.0, 127.1, 128.4, 128.6, 129.36, 129.39, 130.3, 136.2, 138.9, 146.3; [EtOAc:cyclohexane= 3:2, 1% Et3N]: Rf 0.38; m/z (DCI) 295 (100%), 189 (90%).
δ H(300 MHz; CDCl3) 1.45 (9H, s), 1.85–2.0 (1H, m), 2.42–2.46 (1H, dd, J 12.8, 6.2), 3.01 (1H, dd, J 5.5, 2.4), 4.39–4.43 (1H, m), 5.34 (1H, br s); δC(75 MHz; CDCl3) 23.6, 28.3, 29.8, 50.9, 81.1, 155.4, 165.3, 167.2; [α]D20−21 (c 1 in CH2Cl2)
δ H(300 MHz; CDCl3), major rotamer: 1.39 (9H, s), 2.31–2.50 (4H, m), 3.30 (3H, s), 3.71 (3H, s), 4.20–4.41 (3H, m), 5.26–5.34 (1H, m); δC(75 MHz; CDCl3) 27.7, 27.9, 28.3, 35.2, 35.3, 35.7, 52.5, 80.1, 115.4, 155.6, 172.3, 172.8
(Found: C, 48.32, H, 7.39, N, 12.35, S, 9.16. C14H25N3O5S requires C, 48.40; H, 7.25; N, 12.09; S, 9.23); δH(300 MHz; CDCl3): 1.38 (9H, s), 1.57–1.65 (1H, m), 2.26–2.61 (3H, m), 2.98 (3H, s), 3.78 (3H, s), 3.96 (1H, d, J 17.1), 4.38–4.45 (1H, m), 5.03 (1H, d, J 17.0), 5.43 (1H, d, J 8.1), 7.98 (1H, br s), 8.63 (1H, br s); δC(75 MHz; CDCl3) 28.2, 28.3, 29.0, 36.0, 52.1, 52.7, 59.0, 80.4, 156.1, 172.4, 173.1, 203.5; [α]D20 +20.61 (c 0.97 in CH2Cl2); m/z (DCI) 348 (100%).
δ H(300 MHz; D2O) 2.32–2.39 (2H, m), 3.06–3.24 (2H, m), 3.75 (3H, s), 4.11 (1H, t, J 6.0), 7.51 (1H, br s); δC(75 MHz; D2O) 21.4, 26.8, 34.8, 52.8, 123.3, 149.1, 172.1; [α]D20 +24.3 (c 1 in abs EtOH).
(Found: C, 58.36; H 8.81; N 15.94. C9H16N2O2 requires C, 58.67; H, 8.75; N, 15.31); δH(300 MHz; CDCl3) 0.92 (6H, d, J 6.6), 1.41–1.58 (2H, m), 1.67–1.82 (2H, m), 3.39 (1H, dd, J 8.1, 6.2), 3.54 (1H, d, J 17.4), 3.64 (1H, d, J 17.4), 3.75 (3H, s); δC(75 MHz; CDCl3) 21.8, 22.7, 24.6, 35.9, 42.1, 52.0, 58.7, 117.5, 174.8; [α]D= −32.0 (c 1, CH2Cl2).
(Found: C, 58.43; H 8.29; N 12.55. C11H18N2O3 requires C, 58.39; H, 8.02; N, 12.38); δH(300 MHz; CDCl3): two rotamers, ratio 3:2 in this solvent: major: 0.95–1.02 (6H, m), 1.64–1.89 (3H, m), 2.30 (3H, s), 3.72 (3H, s), 4.09 (1H, d, J 15.0), 4.36 (1H, d, J 15.0), 4.45 (1H, dd, J 9.1, 6.0); minor: 0.95–1.02 (6H, m), 1.64–1.89 (3H, m), 2.20 (3H, s), 3.77 (3H, s), 4.28 (2H, s), 5.41 (1H, dd, J 9.9, 5.4); δC(75 MHz; CDCl3) 24.7, 30.4, 38.2, 52.6, 54.0, 115.7, 171.0, 171.1; [α]D20−28.4 (c 1.09 in CH2Cl2).
(Found: C, 56.51; H, 7.55; N, 13.69. C10H16N2O3 requires C, 56.59; H, 7.60; N, 13.20); δH(300 MHz; CDCl3) two rotamers, ratio 4:1 in this solvent: major: 0.95–1.02 (6H, m), 1.59–1.69 (1H, m), 1.76–1.87 (2H, s), 3.78 (3H, s), 4.19–4.39 (3H, m), 8.15 (1H, s); δC(75 MHz; CDCl3) 21.0, 22.7, 29.2, 37.9, 52.8, 58.2, 114.9, 162.8, 170.9; [α]D20−24.4 (c 0.53 in CH2Cl2).
(Found: C, 45.66; H, 7.21; N, 8.71; S, 8.20. C11H20N2O3S requires C, 50.75; H, 7.74; N, 10.76; S, 12.32); δH(300 MHz; CDCl3): two rotamers, ratio 6.7:1 in this solvent: major: 0.93–0.99 (6H, m), 1.41–1.58 (1H, m), 1.80 (2H, t, J 7.4), 2.08 (3H, s), 3.8 (3H, s), 4.27 (1H, t, J 7.0), 4.36 (1H, d, J 19.4), 4.52 (1H, d, J 19.4), 7.83 (1H, br s), 10.1 (1H, br s); δC(75 MHz; CDCl3) 22.0, 22.1, 23.2, 25.2, 38.0, 53.3, 59.4, 172.2, 175.0, 203.5; [α]D20−63.8 (c 0.8 in CH2Cl2).
(Found: C, 48.68; H, 7.39; N, 11.33; S, 12.67. C11H14N2OS requires C, 48.76; H, 7.37; N, 11.37; S, 13.02; δH(300 MHz; CDCl3): two rotamers, ratio 1.25:1 in this solvent: major: 0.82–0.92 (6H, m), 1.55–1.65 (3H, m), 3.60 (3H, s), 3.98–4.34 (2H, m), 4.78 (1H, m), 8.14 (1H, s), 9.37 (1H, br s), 9.80 (1H, br s); minor: 0.82–0.92 (6H, m), 1.55–1.65 (3H, m), 3.65 (3H, s), 3.98–4.34 (2H, m), 4.43 (1H, m), 8.24 (1H, s), 8.91 (1H, br s), 9.70 (1H, br s).
(Found: C, 55.49; H, 7.78; N, 7.76; S, 9.25. C16H26N2O4S requires C, 56.12; H, 7.65; N, 8.18; S, 9.36); δH(300 MHz; CDCl3): 0.92 (6H, m), 1.47 (9H, s), 1.47 (1H, m), 1.84–2.03 (2H, m), 2.39 (3H, s), 3.73 (3H, m), 4.67 (1H, dd, J 9.0, 6.6), 7.23 (1H, s); δC(75 MHz; CDCl3) 13.6, 21.8, 22.7, 24.6, 28.3, 41.2, 53.1, 56.9, 85.3, 123.7, 125.6, 146.3, 167.6, 170.2; [α]D20−3.27 (c 0.61 in CH2Cl2); m/z (DCI) 343 (100%), 299 (10%), 287 (25%).
(Found: C, 55.04; H, 7.51; N, 8.57; S, 9.56. C15H24N2O4S requires C, 54.86; H, 7.37; N, 8.53; S, 9.76); δH(300 MHz; CDCl3): 0.90–0.94 (6H, m), 1.38–1.47 (1H, m), 1.47 (9H, s), 1.91–1.97 (2H, m), 3.74 (3H, m), 4.74 (1H, dd, J 8.7, 7.2), 7.29 (1H, d, J 1.3), 7.62 (1H, d, J 1.3); δC(75 MHz; CDCl3) 21.6, 22.6, 24.6, 28.2, 41.7, 53.1, 60.5, 85.4, 124.6, 127.6, 137.8, 167.3, 170.1; m/z (DCI) 329 (100%), 273 (90%), 229 (20%).
δ H(300 MHz; DMSO) 0.85 (3H, d, J 6.6), 0.88 (3H, d, J 6.6), 1.17–1.20 (1H, m), 1.81–2.02 (2H, m), 2.40 (3H, s), 4.62 (1H, dd, J 9.8, 6.0), 7.20 (1H, s); δC(75 MHz; DMSO) 11.6, 21.3, 22.6, 24.3, 58.0, 126.2, 148.3, 170.0.
δ H(300 MHz; D2O) 0.76 (3H, d, J 6.6), 0.78 (3H, d, J 6.6), 1.38–1.47 (1H, m), 1.88–2.05 (2H, m), 5.15 (1H, dd, J 10.4, 5.5), 7.51 (1H, d, J 1.3), 8.79 (1H, s); δC(75 MHz; D2O) 20.5, 22.2, 24.7, 39.0, 62.1, 125.5, 127.7, 138.8, 141.4, 147.5, 172.9. [α]D20 +72.6 (c 1.22 in EtOH).
(Found: C, 60.57; H, 6.17; N, 15.86. C14H17N3O3 requires C, 61.08; H, 6.22; N, 15.26); δH(300 MHz; DMSO + TFA) 3.11 (2H, d, J 6.6), 3.63 (3H, s), 3.92 (2H, d, J 5.6), 4.17 (2H, s), 7.24–7.31 (5H, m), 7.40 (1H, dd, J 6.4, 3.0), 7.87 (1H, dd, J 6.2, 3.0), 9.11 (1H, t, J 5.6); δC(75 MHz; DMSO + TFA) 36.2, 41.0, 52.1, 60.7, 125.6, 128.8, 129.8, 134.3, 167.4, 169.9; [α]D20−28.9 (c 0.94 in EtOH).
(Found: C, 59.62; H 5.14; N 13.68. C15H17N3O4 requires C, 59.40; H, 5.65; N, 13.85); δH(300 MHz; DMSO + TFA) 3.01 (1H, dd, J 14.3, 10.1), 3.21 (1H, dd, J 14.3, 5.5), 3.61 (3H, s), 3.89 (1H, d, J 5.9), 4.19 (1H, d, J 17.5), 4.34 (1H, d, J 17.5), 4.64–4.69 (1H, m), 7.18–7.27 (5H, m), 7.92 (1H, s), 8.79 (1H, t, J 5.7); 13C NMR (CDCl3, 75 MHz) 29.8, 36.2, 41.4, 52.7, 62.6, 115.3, 127.7, 129.1, 129.3, 135.5, 168.6, 168.9, 170.0; [α]D20−62.6 (c 1 in CH2Cl2).
(Found: C, 53.42; H 5.82; N 12.32, S 9.43. C15H19N3O4S requires C, 53.40; H, 5.68; N, 12.45; S, 9.50); δH(300 MHz; DMSO + TFA) two rotamers, ratio 3:1, major: 3.05–3.26 (2H, m), 3.60 (3H, s), 3.84 (2H, d, J 5.7), 4.00 (1H, d, J 17.5), 4.09 (1H, d, J 17.5), 4.54 (1H, t, J 7.7), 7.19–7.30 (5H, m), 8.07 (1H, s), 8.77 (1H, t, J 5.6), 8.87 (1H, br s), 9.70 (1H, br s); δC(75 MHz; CDCl3) 37.3, 41.9, 52.7, 54.7; 63.6, 127.9, 129.6, 130.1, 137.7, 164.8, 170.8, 171.3, 204.2; [α]D20−95.1 (c 1 in CH2Cl2); m/z (DCI) 338 (100%), 304, 265, 90, 76
(Found: C, 57.69; H, 5.76; N, 9.89; S, 7.75. C20H25N3O5S requires C, 57.26; H, 6.01; N, 10.02; S, 7.64); δH(300 MHz; CDCl3), two rotamers, ratio 9:1, major: 1.48 (9H,s), 3.17 (1H, dd, J 14.0, 9.4), 3.50 (1H, dd, J 14.0, 5.7), 3.71 (3H, s), 3.99 (2H, t, J 5.5), 4.81 (1H, dd, J 9.2, 5.8), 6.99–7.02 (2H, m), 7.16–7.22 (3H, m), 7.29 (1H, s), 7.32 (1H, d, J 1.1); δC(75 MHz; CDCl3) 28.3, 39.3, 41.5, 52.5, 62.9, 85.8, 124.7, 127.4, 127.7, 128.9, 129.0, 135.8, 138.5, 154.8, 168.4, 169.7; [α]D20−55.3 (c 0.85 in CH2Cl2); m/z (DCI) 420, 376, 320, 222, 79
δ H(300 MHz; CDCl3): 2.35 (3H, s), 3.17 (1H, dd, J 14.1, 9.6), 3.51 (1H, dd, J 14.1, 5.7), 3.70 (3H, s), 4.00 (2H, d, J 5.4), 4.90 (1H, dd, J 9.4, 5.5), 6.97–7.00 (2H, m), 7.06 (1H, s), 7.19–7.21 (3H, m), 7.26 (1H, s), 7.88 (1H, t, J 5.4); δC(75 MHz; CDCl3) 18.1, 39.1, 41.3, 52.4, 62.5, 118.3, 127.3, 128.7, 128.8, 135.9, 136.1, 137.6, 168.9, 169.9; m/z (ESI) 334; [α]D20−54.5 (c 0.22 in CH2Cl2)
δ H(300 MHz; D2O) 3.32 (1H, dd, J 13.9, 10.0), 3.54 (1H, dd, J 13.9, 5.9), 3.93 (1H, d, J 17.9), 4.02 (1H, d, J 17.9), 5.38 (1H, dd, J 9.0, 6.0), 7.14–7.17 (2H, m), 7.29–7.31 (3H, m), 7.44 (1H, s), 8.65 (1H, s); δC(75 MHz; CDCl3) 38.4, 41.5, 63.7, 127.9, 128.0, 129.0, 129.2, 129.3, 134.9, 138.5, 169.6, 173.0; [α]D20−96.9 (c 0.8 in CH2Cl2); m/z (ESI) 304
δ H(300 MHz; CDCl3): 1.43 (9H, s), 2.16–2.38 (2H, m), 2.39 (3H, s), 2.71 (2H, t, J 7.4), 3.51 (3H, s), 3.72 (3H, s), 4.35 (1H, m), 5.77 (1H, br d, J 7.0), 6.77 (1H, s); δC(75 MHz; CDCl3) 19.0, 23.3, 28.7, 29.9, 32.9, 52.7, 53.9, 80.1, 121.9, 133.2, 148.3, 156.0, 173.1
δ H(300 MHz; CDCl3): 1.43 (9H, s), 2.11–2.37 (2H, m), 2.72 (2H, t, J 7.7), 3.54 (3H, s), 3.70 (3H, s), 4.35 (1H, m), 5.60 (1H, br d, J 7.7), 6.77 (1H, s), 6.89 (1H, s); δC(75 MHz; CDCl3) 22.8, 28.4, 30.1, 32.6, 52.5, 53.3, 80.2, 120.8, 127.1, 147.0, 155.7, 172.9
Footnote |
† Electronic supplementary information (ESI) available: 1H and 13C NMR spectra. See DOI: 10.1039/b810678a |
This journal is © The Royal Society of Chemistry 2009 |