Abstract

A series of N-benzoyloxyamines were pyrolyzed and their decomposition temperatures correlated well with the amine architecture's ability to stabilize a N-centered radical. A variety of amine substrates were treated with a biphasic mixture of benzoyl peroxide (BPO), CH₂Cl₂ and an aqueous carbonate buffer (at pH 10.5). Primary and secondary amines were successfully N-benzoyloxylated in good yield. Tertiary amines and BPO gave low yields of the corresponding N-oxide and complex product mixtures, presumably via radical decomposition. Electron deficient amines (such as fluorinated aliphatic amines, -aminoacids, -aminoesters, and -aminoamides) were not N-benzoyloxylated under these conditions. Instead, N-benzoylation was observed with the fluorinated amines and the reaction was sensitive to temperature and the pH of the aqueous medium. A one-pot-two-step synthesis of N-FMOC- -Leu-N^β-(benzoyloxy)-β-alanine ethyl ester, a peptide containing both an - and a novel β-amino acid framework, was also developed.

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Author Keywords: thermal stability; amine oxidation; N-benzoyloxyamines; hydroxamic acids; β-peptides

Article Outline

1. Introduction

2. Results and discussion

2.1. Thermal studies

2.2. Synthetic scope and limitations

3. Conclusions

4. Experimental

4.1. Materials and methods

4.2. TGA–DTA studies

4.3. General procedure for amine oxidation

4.4. General pyrolysis procedure

4.4.1. N-Hexylbenzamide 6a[20]

4.4.2. N-Hexyldibenzamide 6b

4.4.3. N-Cyclohexylbenzamide 7a[20]

4.4.4. N-(Benzoyloxy)-N-cyclohexylbenzamide 7b

4.4.5. N-Benzylbenzamide 9a[20]

4.4.6. N-Benzyldibenzamide 9b

4.4.7. N-Methylbenzamide 10a[20]

4.4.8. N-(Benzoyloxy)benzylmethylamine 10

4.4.9. N-(Benzoyloxy)methylphenethylamine 12

4.4.10. Reaction of phenethylamine with 11 to give 13

4.4.11. Tributylamine N-oxide 18[20]

4.4.12. N-(Benzoyloxy)-dibutylamine 20

4.4.13. Reaction of 22 and BPO using different aqueous buffer solutions

4.4.14. N-(1H,1H-Heptafluorobutyl)benzamide 23

4.4.15. N-(2,2,2-Trifluoroethyl)benzamide 24[20]

4.4.16. N-(Benzoyloxy)-β-alanine ethyl ester 26

4.4.17. S-3-{Benzoyloxy-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methyl-pentanoyl]-amino}-propionic acid ethyl ester, 29

Acknowledgements

References