Research Article Cite This: ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
Hydrogenation of Naturally-Derived Nepetalactone as a Topical Insect Repellent Sourav K. Sengupta,*,†,§ Keith W. Hutchenson,†,§ David L. Hallahan,†,∥ Yamaira I. Gonzalez,†,⊥ Leo E. Manzer,†,# Scott C. Jackson,†,∇ Mark A. Scialdone,†,○ and Bo Kou‡,◆ †
E. I. du Pont de Nemours and Company Experimental Station, 200 Powder Mill Road, Wilmington, Delaware 19803, United States E. I. du Pont of Canada Kingston Technical Center, 461 Front Road, Kingston, Ontario K7L 5A5, Canada
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S Supporting Information *
ABSTRACT: Dihydronepetalactone (DHN) is a safe and effective topical insect repellent,5,6,8 comparable in efficacy to that of N,N-diethyl-m-toluamide (DEET). The latter is the most commonly used active ingredient, found in many commercial insect repellents for a broad range of biting insects. DHN can be produced by hydrogenating nepetalactone (NL), which is the primary ingredient of the essential oil obtained from the renewably sourced catmint plant, Nepeta cataria. Optimizing the hydrogenation reaction to produce DHN from catmint oil is a key economic driver for the process. Prior to the study described here, Six Sigma methodologies were used to select palladium on carbon (5% Pd/C) as the catalyst of choice. The hydrogenation step was studied as a function of critical process variables and the composition of the oil. As described in this article, a robust, two-step hydrogenation process was developed to maximize the yield of the desired DHNs from treated catmint oil. It was observed that the composition of the catmint oil, vis-à-vis, the relative amounts of trans−cis and cis−trans-nepetalactone isomers, had a major impact on the activity and selectivity of the catalyst. This study also focused on minimizing the formation of a less desirable byproduct, puleganic acid. On the basis of the process variables tested in this study, temperature was found to have a strong effect on the activity and selectivity of the catalyst. Higher pressure enhanced the activity of the catalyst but it did not significantly impact the formation of undesired byproducts, such as puleganic and nepetalic acids. Spiking experiments with suspected catalyst poisons, such as dimethyl sulfide, dimethyl sulfoxide, nepetalic acid, and puleganic acid were also performed to study catalyst deactivation. Sulfur was identified as the main factor for the catalyst deactivation. Possible reaction mechanisms for the formation of less desirable puleganic and nepetalic acids have been suggested. KEYWORDS: Catmint oil, Nepetalactone, Dihydronepetalactone
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INTRODUCTION Many plant species produce essential oils, which are used as natural sources of insect repellent and fragrant chemicals.1−4 These oils are rich in volatile compounds, such as monoterpenoids, which have been associated with repellency. Certain plants of the genus Nepeta (catmints) produce an essential oil rich in a class of monoterpenoid compounds known as iridoids, specifically nepetalactones (NLTable 1).5 Iridoid monoterpenoids have long been known for their effects on insect behavior. Dihydronepetalactone (DHN), the reduced form of nepetalactone, has been reported as an effective insect repellent compound.6 DHN is comparable to commercial insect repellents in efficacy and is believed to be safer to use as a topical insect repellent ingredient compared to N,N-diethyl-m-toluamide (DEET).7,8 Catmint oil (CMO) is a sustainable, plant-derived feedstock obtained from the steam-distillation of catmint plants (Nepeta cataria).9 The principal constituent of this oil is nepetalactone © XXXX American Chemical Society
(Tables 1 and 2). Different chemotypes of Nepeta cataria exist, characterized by differences in the nepetalactone stereoisomer composition of their oils. Such oils come from different geographical locations around the globe and may be enriched in cis,trans-nepetalactone or trans,cis-nepetalactone, or contain roughly equal proportions of both nepetalactone stereoisomers. While the proportions of various constituents of the catmint oil might be different, depending partially on the location where the plant was harvested, the primary constituents are typically very similar. Table 2 lists the compositions of various catmint oils collected from suppliers around the world. Usually, the isomers of nepetalactones in catmint oil add up to >70 wt %. The oils also contain (ca. 2 wt %) dihydronepetalactone (DHN) as a minor natural Received: December 1, 2017 Revised: May 24, 2018
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DOI: 10.1021/acssuschemeng.7b04521 ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
Research Article
ACS Sustainable Chemistry & Engineering Table 1. Primary Constituents of Catmint Oil
Table 2. Compositions of Catmint Oil from Different Sources (in wt %)
oil
c,t-NL
t,c-NL
DHN-1
DHN-2
DHN-3
pulegenic acid
nepetalic acid
β-caryophyllene
carvone
A B C D
18.99 21.16 76.31 86.76
56.27 59.24 0.98 1.00
ND
