Generation and detection by nuclear magnetic resonance spectroscopy of a simple tetrahedral intermediate, dimethyl hemiorthoformate

Capon, Brian; Gall, James H.; Grieve, Duncan McL. A.

doi:10.1039/c39760001034

Cited by 14 publications

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“…Experiments have recently been reported of the direct observation of the two types of intermediates of the hydrolysis of ortho esters (1)(2)(3)(4)(5)(6)(7). These experiments obviously verify the three-stage reaction mechanism commonly accepted for this hydrolysis (8).…”

supporting

confidence: 48%

The tetrahedral intermediate of a lactonization reaction

McClelland¹,

Alibhai²

1981

Can. J. Chem.

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ROBERTA. M C C L E L L A N D~~~MASUMA ALIBHAI. Can. J. Chem. 59, 1169Chem. 59, (1981. 'The hydrolysis of the ortho ester 1,l-diethoxy-l,3-dihydroisobenzofuran (1) is described. This hydrolysis proceeds with initial expulsion of an exocyclic ethoxy group, producing upon hydration of the oxocarbonium ion I-hydroxy-1-ethoxy-1,3-dihydroisobenzofuran (7), the tetrahedral intermediate of the lactonization of ethyl (2-hydroxymethyl)benzoate (6) to phthalide (8). Based on the kinetic behavior of the ortho ester hydrolysis, the pH variation in the ratio of 6:8 initially formed from the ortho ester, and the kinetic behavior of the lactonization reaction, rate constants for the breakdown of the tetrahedral intermediate 7 have been determined, along with the equilibrium constant for its formation from the hydroxy ester 6. The breakdown occurs in an extremely rapid hydroxide-ion-catalyzed reaction, with the rate being at the diffusion limit. Hydronium ion catalysis is also observed; this breakdown is also rapid although considerably less so than the hydroxide ion reaction. The changeover from H+ to OH-catalysis occurs at pH 3.5. The rate of breakdown is a minimum at this point, and corresponds to a half-life for the tetrahedral intermediate of about 0.1 s. It is concluded that this allows sufficient time for conformational changes in the tetrahedral intermediate prior to breakdown; this factor must be taken into account in stereoelectronic considerations.ROBERT A. MCCLELLAND et MASUMA ALIBHAI. Can. J. Chem. 59,1169Chem. 59, (1981. On dkcrit I'hydrolyse de I'ortho ester diethoxy-1,l dihydro-1,3 isobenzofuranne (1). Cette hydrolyse se fait avec une expulsion initiale d'un groupe ethoxy exocyclique conduisant aprks hydratation a I'ion oxocarbonium hydroxy-1 Cthoxy-1 dihydro-1,3 isobenzofuranne (7), I'intermediaire tttraedrique de la lactonisation du (hydroxymethy1)-2 benzoate d'ethyle (6) en phtalide (8). On a determine la constante de vitesse de rupture de I'intermediaire tttraedrique 7 ainsi que la constante d'equilibre conduisant a sa formation a partir de I'hydroxy ester 6 en se basant sur le comportement cinktique de I'hydrolyse de I'ortho ester, sur la variation du pH dans le rapport du produits 6:8 qui se forment initialement a partir de I'ortho ester et sur le comportement cinetique de la reaction de lactonisation. La rupture se produit au cours d'une reaction extrcmement rapide catalysee par I'ion hydroxyde dont la vitesse est limitee par la diffusion. On observe egalement la catalyse par I'ion hydronium; cette rupture est egalement rapide quoique considerablement plus faible que celle de la reaction catalysee par I'ion hydroxyde. Le changement de catalyseur de H+ a OH-se produit a un pH de 3,s. La vitesse de rupture est minimale i c e point et correspond a une demie-vie de I'intermediaire tetraedrique d'environ 0,l s. On en conclut que ceci accorde suffisamment de temps a des changements conformationnels de I'intermediaire tktrakdrique avant sa rupture. On doit tenir compte de ce facteur dans les considerations ste...

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supporting

confidence: 48%

The tetrahedral intermediate of a lactonization reaction

McClelland¹,

Alibhai²

1981

Can. J. Chem.

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“…+ OAr (15) O Relatively accurate estimates have been made of the lifetimes of tetrahedral intermediates which might be expected in various acyl-group-transfer reactions.2111'290'35 A direct measurement of the decomposition of dimethyl hemiorthoformate in acetone-water at -35 °C has indicated that these estimates are at least of the correct order of magnitude. 36 The magnitude of these rate constants for anionic and zwitterionic tetrahedral intermediates (VII and VIII) is of the order 7-1010 s'1; provision of more powerful leaving groups such as chloride or activated phenolate anion could yield a tetrahedral adduct in a favorable case which cannot exist as a discrete compound (i1/2 less than that of a bond vibration 10'13 s), thus favoring a concerted displacement; in this context there has recently been a challenge to the conventional postulate of a stepwise mechanism of acylation in chymotrypsin catalysis.37…”

Section: IImentioning

confidence: 99%

Structure-reactivity studies on the equilibrium reaction between phenolate ions and 2-aryloxazolin-5-ones: data consistent with a concerted acyl-group-transfer mechanism

CURRAN¹,

Farrar²,

Niazy³

et al. 1980

J. Am. Chem. Soc.

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Hz, H(3)). Recrystallization from ethanol-hexane at -20 °C gave colorless prisms, mp 95.5-97 °C. Attempted Acid Hydrolysis of 7. To 2 mg of epoxy acetate 7 was added 0.5 mL of tetrahydrofuran (distilled under N2 from Na) and 0.2 mL of 7% perchloric acid. The mixture was heated in a Microflex vial for 4 days at 55 °C, at which time TLC indicated the absence of starting 7 and appearance of a more polar product. Product isolation with ether (aqueous NaCl wash, MgS04) and chromatography on Florisil with 10% ethyl acetate in hexane afforded 1.5 mg of a solid which showed no ester absorption in the IR: mass spectrum (70 eV) m/z (relative intensity) 304 (M\ 12), 271 (22), 260 (24), 205 (32), 189 (70), 81 (100); NMR 3.56 (dd, J = 10.2, 7.0 Hz, H(3)). These data suggest the retention of the epoxide and the acid-catalyzed hydrolysis of the acetate to the epoxy alcohol 8.3-Keto-15-rippertene (9). To a stirred, 5-10 °C solution of 9.5 mg of alcohol 5 in 0.4 mL of spectrograde acetone was added dropwise Jones' reagent until TLC indicated absence of starting material. Excess Jones' reagent was quenched with 1 drop of 2-propanol, the solvent was removed, and the crude oil was chromatographed on Florisil with 5% ethyl acetate-hexane to give 9 mg of ketone 9 which was homogeneous by TLC and GLC.NMR showed the absence of the H(3) carbinyl proton and methyl resonances at 0.94 (d, J = 7 Hz), 0.99 (d, J = 7 Hz), and 1.27 (s, s, CH3 ( 17), ( 18)). Mass spectrum (70 eV): m/z (relative intensity) 286 (M+, 61), 271 (M+ -CH3, 100). Measurement of the CD spectrum of a 1:10 dilution of the 9 mg of ketone in 5 mL of purified hexane gave Ac310 = +2.87, <3( = +3.51, and «293 = +3.37. Multiple Cotton effects for d,7-unsaturated ketones have also been observed for testosterone derivatives.10 X-ray Structure Determination of 7. The data crystal of 3a-acetoxy-15-epoxyrippertane, a colorless prism obtained from hexane-ethanol at -20 °C, was mounted on an Enraf-Nonius CAD 4A diffractometer under the control of a PDP 11 /45 computer system and subjected to Cu X radiation (X = 1.5418 Á). The space group was P2{2{2X with a = 11.202 (1) k,b = 28.575 (7) Á, c = 6.299 (2) Á, and Z = 4 and paM = 1.14 g/cm3. The data were reduced (p = 0.04), and the structure was solved by using the multan direct-method series, using the programs of the Enraf-Nonius structure determination package developed chiefly by Okaya and Frenz. Of the 1899 reflections measured (0°< 2$ < 72°), 1167 with Ff > 1a(Ff) were used in the subsequent refinement, which converged to values of 0.047 and 0.051 for R and Rw respectively.Fractional atomic coordinates are presented in Table II. The thermal parameters, bond angles and distances, and observed and calculated structure factors can be obtained as supplementary material.Acknowledgment is made to the National Science Foundation (Grant DEB-7823257) and to the University Awards Committe/Joint Awards Council of the State University of New York for financial support of this work. We also thank Drs. T. Eisner and R. Silberglied for N. ep...

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“…After trying a large number of conditions unsuccessfully, we found that in a mixture of [2H6]acetone (95-85 volumes) and deuterium oxide (5-15 volumes) it was possible to detect hemiorthoformate in the hydrolysis of acetoxydimethoxymethane by proton NMR spectroscopy, as indicated in Scheme I. 33 The decomposition of acetoxydimethoxymethane generates acetic acid; hence the rate constant of the decomposition of the dimethyl hemiorthoformate measured after the disappearance of the acetoxydimethoxymethane is for a solution which contains a concentration of acetic acid equivalent to that of the starting material (i.e., 0.15 M). It is therefore probably a composite constant and contains terms for spontaneous and acid catalyzed hydrolyses which we have not separated.…”

mentioning

confidence: 99%

“…Although it is impossible to make an exact extrapolation, the two figures do not appear to be inconsistent with one another. 33 We then set up a program of work to make compounds 31-36 where R = CH3 or C1CH2. The purpose tectable over a wider range of conditions.…”

mentioning

confidence: 99%

Direct observation of simple tetrahedral intermediates

Capon¹,

Ghosh²,

Grieve³

1981

Acc. Chem. Res.

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the stability of the OHat the active site is increased even more by long-range hydrogen-bonding interactions between the active (nucleophilic) H20 and components of what has been termed the "water chain" in the active site, indicating again the importance of residues around but not in the active site.Quantum and molecular mechanical calculations have thus provided insights into rate-enhancing factors in enzyme catalysis. Long-range electrostatic and hydrogen-bonding effects are crucial. It will be of interest to investigate these in a systematic manner to discover where the major portion of electrostatic stabilization energy in charge separation processes is centered. It will be further desirable to develop methods to calculate

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Generation and detection by nuclear magnetic resonance spectroscopy of a simple tetrahedral intermediate, dimethyl hemiorthoformate

Cited by 14 publications

References 0 publications

The tetrahedral intermediate of a lactonization reaction

The tetrahedral intermediate of a lactonization reaction

Structure-reactivity studies on the equilibrium reaction between phenolate ions and 2-aryloxazolin-5-ones: data consistent with a concerted acyl-group-transfer mechanism

Direct observation of simple tetrahedral intermediates

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