Synthesis 2018; 50(22): 4490-4500
DOI: 10.1055/s-0037-1610199
paper
© Georg Thieme Verlag Stuttgart · New York

Unconventional Rose Odorants: Serendipitous Discovery and Unique Olfactory Properties of 2,2-Bis(prenyl)-3-oxobutyronitrile and Its Derivatives

Nicole Hauser*
a  ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland   Email: nicole.hauser@org.chem.ethz.ch   Email: carreira@org.chem.ethz.ch
,
b  Givaudan Fragrances S&T, Ingredients Research, Überlandstrasse 138, 8600 Dübendorf, Switzerland   Email: philip.kraft@givaudan.com
,
a  ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland   Email: nicole.hauser@org.chem.ethz.ch   Email: carreira@org.chem.ethz.ch
› Author Affiliations
Further Information

Publication History

Received: 14 June 2018

Accepted: 14 June 2018

Publication Date:
26 June 2018 (eFirst)

Published as part of the Special Section dedicated to Scott E. Denmark on the occasion of his 65th birthday

Abstract

2,2-Bis(3-methylbut-2-enyl)-3-oxobutanenitrile [2,2-bis(prenyl)-3-oxobutyronitrile], an unusual bifunctional nitrile odorant with a fruity rosy, green odor was found to exhibit surprising differences in its detection thresholds (0.25 ng/L air for hyperosmics; 19 ng/L air for hyposmics) and perceived odor characters. To investigate this remarkable phenomenon, 13 derivatives of 2,2-bis(3-methylbut-2-enyl)-3-oxobutanenitrile were synthesized by either monoalkylation of 3-oxo-2-phenylbutanenitrile, or by dialkylation of sodium 1-cyano-2-oxopropan-1-ide or methyl or ethyl cyanoacetate, or by direct derivatization of 2,2-bis(3-methylbut-2-enyl)-3-oxobutanenitrile via its vinyl triflate and Negishi cross coupling. These systematic permutations of the substitution pattern allowed some insight to be gained into the underlying structure–odor relationships and the construction of a simple olfactophore model, albeit no final conclusion could be drawn as to whether the nitrile or carbonyl function acts as the prime osmophore of the bifunctional compounds. Depending on slight genetic variations and the corresponding differences in the receptor morphology both can engage in H-bond interactions with the olfactory receptors, which might explain the observed largely diverging sensitivities. Methyl 2-cyano-2,2-bis(3-methylbut-2-enyl)acetate with a uniform odor threshold of 0.38 ng/L air turned out to be the most interesting floral, rosy odorant of this study, followed by 3-methyl-2,2-bis(3-methylbut-2-enyl)but-3-enenitrile with only a nitrile function and varying odor thresholds (0.40 ng/L air vs. 125 ng/L air).

 
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