Addition of water to 1-alkynylamines. Kinetics and mechanism

Verhelst, W. F.; Drenth, W.

doi:10.1021/ja00828a025

Cited by 18 publications

(11 citation statements)

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“…4). There are numerous studies on the acid-catalyzed addition of alcohols and phenols to olefink bonds (16,17). The suggested mechanism for such reactions is of an electrophilic type, involving the attack of H + species on the olefinic center followed by the nucleophilic addition of the alcohol to form the ether linkage.…”

Section: Resultsmentioning

confidence: 99%

Kinetics of acid‐catalyzed degradation of cyclosporin A and its analogs in aqueous solution

Oliyai

Safadi

Meier

et al. 1994

International Journal of Peptide and Protein Research

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The kinetics and mechanism of the degradation of cyclosporin A have been studied under aqueous acidic conditions. The rate of degradation was found to be specific acid‐catalyzed over the pH range studied (1–4), with isocyclosporin A as the predominant degradation product. Selective reduction of the olefinic bond of the amino acid 2‐N‐methyl‐(R)‐((E)‐2‐butenyl)‐4‐methyl‐l‐threonine (MeBmt) did not affect the overall degradation kinetics and product distribution of cyclosporin A. These observations indicate that the alternative degradation pathway involving intramolecular alkoxy addition to the olefinic bond of amino acid MeBmt apparently does not significantly contribute to the overall degradation kinetics of cyclosporin A in the pH range 1–4. The chemical reactivity of O‐acetyl‐cyclosporin A was examined to probe the governing mechanism for the isomerization of cyclosporin A. Under identical conditions, O‐acetyl‐cyclosporin A showed a much greater chemical stability than cyclosporin A, consistent with a mechanism involving the hydroxyoxazolidine intermediate. The chemical stability of cyclosporin C, which contains two β‐hydroxyl groups, was also examined. The rate and product distribution for the degradation of cyclosporin C suggest that under aqueous acidic conditions it undergoes N,O‐acyl migration solely at the amino acid residue MeBmt. Additionally, the impact of side‐chain bulkiness of amino acid MeBmt was examined by studying the degradation kinetics of a series of cyclosporin A analogs. The apparent rate constants for the isomerization of these analogs were not significantly different from that of cyclosporin A, indicating that the terminal bulkiness of amino acid MeBmt may not play a critical role in controlling the rate and extent of N,O‐acyl migration in cyclosporin A.

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Section: Resultsmentioning

confidence: 99%

Kinetics of acid‐catalyzed degradation of cyclosporin A and its analogs in aqueous solution

Oliyai

Safadi

Meier

et al. 1994

International Journal of Peptide and Protein Research

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“…For this solvent the ionic strength was maintained a t unity with anhydrous sodium perchlorate. This was obtained by heating the monohydrate (AnalaR) grade) at 200 "C under vacuum (1 mmHg) for 6 h. 23 Solutions of sodium deuterioxide in D,O were obtained by dissolving the required amount of dry sodium metal in the solvent. Solutions of deuteronium ion in D,O were obtained by addition of a small amount of HC10, in D,O to lM-NaC10, in D,O.…”

mentioning

confidence: 99%

Rapid acid-catalysed and uncatalysed hydration of ketenimines

McCarthy¹,

Hegarty²

1980

J. Chem. Soc., Perkin Trans. 2

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“…Tertiary ynamines cannot tautomerize to ketenimines, but evidence that they are formed by photodecarbonylation of our tertiary aminocyclopropenones comes from yet another previous investigation . It was found in this previous work that authentic tertiary ynamines prepared by established methods protonate rapidly on carbon, eq 7, giving keteniminium cations, 9 , which upon hydration produce amide enols, 10 ; the enols then ketonize to give amides, 8 , as the ultimate reaction products.…”

Section: Resultsmentioning

confidence: 86%

“…Product Studies. The hydration of tertiary ynamines is known to produce carboxylic acid amides, as is also the hydration of ketenimines 10 formed by tautomerism of secondary ynamines. Carboxylic acid amides are thus expected to be the ultimate products of the reactions we have studied.…”

Section: Resultsmentioning

confidence: 99%

“…Primary and secondary ynamines, for example, undergo facile tautomerization to nitriles and ketenimines, and they therefore have been observed previously only in the gas phase or in low-temperature matrices . Tertiary ynamines cannot isomerize in this way, and they have consequently been prepared and characterized, but they are nevertheless quite reactive, and only one previous investigation of their chemistry in aqueous solution has been carried out …”

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confidence: 99%

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Flash Photolytic Generation of Primary, Secondary, and Tertiary Ynamines in Aqueous Solution and Study of Their Carbon-Protonation Reactions in That Medium

et al. 1996

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A group of nine phenylynamines (PhCtCNH 2 , PhCtCNHCH(CH 3 ) 2 , PhCtCNHC 6 H 11 , PhCtCNHC 6 H 5 , PhCtCNHC 6 F 5 , PhCtCN(CH 2 ) 5 , PhCtCN(CH 2 CH 2 ) 2 O, PhCtCN(CH 2 CH 2 CN) 2 , and PhCtCN(CH 3 )C 6 F 5 ) were generated in aqueous solution by flash photolyic decarbonylation of the corresponding phenylaminocyclopropenones, and the kinetics of their facile decay in that medium were studied. This decay is catalyzed by acids for all ynaminessprimary, secondary, and tertiarysand also by bases for primary and secondary ynamines. Solvent isotope effects and the form of acid-base catalysis show that the acid-catalyzed path involves formation of keteniminium ions by rate-determining proton transfer to the β-carbon atoms of the ynamines. The ions generated from primary and secondary ynamines then lose nitrogen-bound protons to give ketenimines, and the ketenimines obtained from secondary ynamines are hydrated to phenylacetamides, whereas that from the primary ynamine tautomerizes to phenylacetonitrile. Keteniminium ions formed from tertiary ynamines have no nitrogen-bound protons that can be lost, and they are therefore captured by water instead, and the amide enols thus produced then ketonize to phenylacetamides. The base-catalyzed decay of primary and secondary ynamines also generates ketenimines, but protonation on the β-carbon is now preceeded by proton removal from nitrogen. Rate constants for β-carbon protonation of PhCtCNHCH(CH 3 ) 2 and PhCtCN(CH 2 ) 5 by a series of carboxylic acids give linear Bronsted relations with exponents R ) 0.29 and 0.28, respectively, whereas inclusion of literature data for protonation of PhCtCN-(CH 2 ) 5 by a group of weaker acids gives a curved Bronsted relation whose exponent varies from 0.25 to 0.97. Application of Marcus rate theory to this curved Bronsted relation produces the intrinsic barrier ∆G q o ) 3.26 ( 0.19 kcal mol -1 and the work term w r ) 8.11 ( 0.15 kcal mol -1 .1-Aminoacetylenes, commonly called ynamines, are very reactive substances. Primary and secondary ynamines, for example, undergo facile tautomerization to nitriles and ketenimines, and they therefore have been observed previously only in the gas phase or in low-temperature matrices. 1 Tertiary ynamines cannot isomerize in this way, and they have consequently been prepared and characterized, 2 but they are nevertheless quite reactive, and only one previous investigation of their chemistry in aqueous solution has been carried out. 3 We have found that all three classes of ynamines can be generated by photodecarbonylation of phenylaminocyclopropenones, eq 1 (R 1 , R 2 ) H, alkyl, aryl), and that their reactions in aqueous solutions may be studied using flash photolytic techniques. We present here the results of a detailed examination of the representative series of phenylynamines listed in Chart 1. 4 Experimental SectionMaterials. Phenylaminocyclopropenones were prepared by treating the corresponding amines with phenylchlorocyclopropenone, as shown in eq 2, which was itself obtained either by partial hydroly...

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Addition of water to 1-alkynylamines. Kinetics and mechanism

Cited by 18 publications

References 0 publications

Kinetics of acid‐catalyzed degradation of cyclosporin A and its analogs in aqueous solution

Kinetics of acid‐catalyzed degradation of cyclosporin A and its analogs in aqueous solution

Rapid acid-catalysed and uncatalysed hydration of ketenimines

Flash Photolytic Generation of Primary, Secondary, and Tertiary Ynamines in Aqueous Solution and Study of Their Carbon-Protonation Reactions in That Medium

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