Introduction
(International Nomenclature for Cosmetic Ingredients (INCI) name) (1-(1,2,3,4,5,6,7,8-ottaidro-2,3,8,8,-tetrametil-2-naftil)etan-1-one) is a synthetic ketone fragrance also known as OTNE (octahydrotetramethyl acetophenone) and by other commercial trade names such as: Iso E Super, Iso Gamma Super, Anthamber, Amber Fleur, Boisvelone, Iso Ambois, Amberlan, Iso Velvetone, Orbitone, Amberonne. It is a synthetic woody odorant and is used as a fragrance ingredient in perfumes, laundry products and cosmetics.[1]
Iso & Super a woody ambery scent. Key features include a medium strength, woody floral ambergris profile with a velvety sensation. Ideal for enhancing fragrances, it’s a top choice in modern fine perfumery and soaps, boasting a high gamma isomer content.
1. THE AROMATIC HISTORY OF PROGRESS (EVOLUTION): THE BIRTH OF ISO E SUPER ®
The road that eventually opened the world to the fruition of Iso E Super ® dates back to the 1960s, period during which many scientists began experimenting with and researching compounds derived from, or with a ionone-like structure. The first step towards the creation of this compound was taken by John B. Hall and James M. Sanders from International Flavors & Fragrances (IFF) who, in 1973, filed the patent for that would then be considered a direct predecessor of the Iso E Super ®, a compound called “Isocyclemone E”. After an unspecified period of time of experimentation, the formula was refined, the synthesis method improved, and from this, what we now call Iso e Super ® was born.
Although nowadays the Iso E Super ® is widely used in many fragrances with many different purposes, at the time, as often happens, the reception of this new mixture was varied. The skepticism, or overall lack of interest surrounding this new component in the field of perfumery, led it to be mainly used in household products or, thanks to its characteristic olfactory properties that will be later discussed in this article, as a functional addition to woody fragrances.
In 1975, after two years from its original creation, Iso E Super ® was used for the first time in a proper perfume, albeit in much smaller quantities compared to its use in modern fragrances: Halston Woman 1975 (25%).
While Halston Woman confirmed that Iso E Super ® could be seriously approached in the highly competitive field of perfumery, not only as an enhancer for specific fragrances, but also as a standalone component, its first major breakthrough in the industry did not come until 1988. Perfumer Jean-Louis Sieuzac, under the guidance of Maurice Roger, sought to create a new fragrance that would break the shackling clichés of the past perfumes. The result was Christian Dior Fahrenheit, the first fragrance primarily based on Iso E Super ® and the first example of Iso E Super ® “Overdose”. This groundbreaking fragrance represented a significant milestone for the mixture, proving that its adaptability extended beyond its use as a mere enhancer.
In 2006, Geza Schön created a fragrance line called Escentric Molecules, which included a perfume called Molecule 01. This fragrance contains the highest amount of Iso E Super ever used in a single perfume, with a concentration of 100%.
2. Iso E Super, its merits, its faults, Geza Schoen and Jean Claude Ellena
The chemistry of fragrances seems like an arcane side-path in the vast avenue of pretty smells. Those who venture there are either chemists, eternal students or people reading perfume boards. On those last ones, Iso E Super is nom du jour due to recent rumours of restricting its use to specific ratios in products (and they’re many!) and due to its increasing popularity, some of it attached to the work of master perfumer Jean Claude Ellena who has experimented with its magic properties many a time in the past to glorious effect: Terre d’Hermès, Poivre Samarkande and Déclaration are utilizing lots of it, exploring minimalism: the play of scents note-for-note with no sentimentality attached
Even and Entier composition, Molecule 01 by perfumer Geza Schöen of niche brand Escentric Molecules (his Escentric 01 also features it in high ratios along with pink pepper, lime peel, orris and incense) is composed of nothing else but it, diluted in solvent, because the perfumer loved it so! I am hereby reminding you that he is the perfumer who created HSIDEWS for artist Sissel Tolaas and he has collaborated with the London-based niche brand Ormonde Jayne.
The theory behind Molecule 01 and IsoE Super was that it would create an appealing effect to those smelling it on the wearer without it being perceived as a “perfume”; the ultimate skin-scent, much like natural ambergris to which it mimics certain aspects would act. Another scent which officially contains it is Maitresse by Agent Provocateur, while the masculine fragrance Fahrenheit by Dior (1988) iincludes a 25% Iso E Super in the compound.
In the legendary woody oriental Féminité du Bois by Shiseido, under the maestro Serge Lutens’s direction, the material serves as an harmoniser between the plummy effect of the fruits with the violet ionones and the cedarwood bottom notes. Iso E Super is used in so many fragrances today that it would be hard to compile an actual list that would not bore everyone silly! But what the hell is Iso E Super?, you might ask. Let’s take matters at the top.
Iso E Super® is the trademark name of aromachemical 7-acetyl, 1,2,3,4,5,6,7,8-octahydro-1,1,6,7-tetramethyl naphthalene and I guess it’s pretty obvious why it’s called that instead of its long organic chemistry name. According to International Fragrances and Flavors Iso E Super is
“Smooth, woody, amber with unique aspects giving a ”velvet” like sensation. Used to impart fullness and subtle strength to fragrances. Superb floralizer found in the majority of newer fine fragrances and also useful in soaps. Richer in the desirable gamma isomer than isocyclemone e”.
Arborone is the odor active enantiomer of Iso E Super, with its clean woody and pleasing aroma.[1] The uses of Iso-E Super are legion: from bleach and deo sticks to soaps, shampoos, laundry detergents and fine fragrance. Given that its colour is almost transparent to very light yellow it poses no problems in being incorporated in formulae and is also used in the pharmaceutical industry.
Despite the IFF being the company to trademark it, Chinese companies such as Zhejiang Winsun Imp. & Exp. Co., Ltd. do provide it at a concentration of 90% for various uses. Home-made mixes would suggest one part Iso-E Super to 9 parts base, such as dipropylene glycol/perfumer’s alcohol (therefore a 10% concentration). Although neat use on skin isn’t recommended, minor “accidents” of spillage have not produced anything sinister.
Taking in mind that it is quite inexpensive, it is perhaps of interest for apprentices and amateurs alike to experiment themselves at high dilution.
Smelling it in itself one is surprised by how almost non-existent a smell Iso-E Super has; not something one would describe as a smell in so many words, it’s unapologetically synthetic and perhaps vaguely cedar-like, slightly sweet. It seems to vanish very quickly and resurface on skin in intervals from time to time very discreetly:
The heat of the skin is intergral to its volatilising properly and it seems that any test on paper would not give an accurate perception of its true nature. It is however quite recognisable once you get to sample it and you will have fun detecting it in many major fragrances on the market todat. This subtle “skin-scent” effect is what in perfume-lingo is used to evoke that a fragrance stays close to the skin, not projecting in a wide radius; but also that it has some skin compatibility effect that makes it smell not like a usual perfume.
Therefore IsoE Super soon gained the reputation of it acting like a pheromone, that invisible aroma that is supposed to attract same species potential sexual partners and ensures recognition of compatibility between mates. Plainly explained, pheromones act to the vomero nasal organ ensuring that pigs mate with pigs and not rhinoceruses for instance!
Much as the matter is exciting and intriguing hower, the scientific community has not been able to conclusively establish validity in the theory of pheromones working in humans so far, although popular mythology is rampant with examples of products aimed to achieve this magical attraction (such as Androstenol, Androstadienone, and Androsterone). In an
interview given by perfumer Geza Schöen on the creation of Molecule 01, he intimated:
“When I was introduced to ISO E Super in 1990 I gave it to a friend of mine to wear. We went out to this bar in our hometown and it took only a few minutes until this woman steered straight into our direction to inquire about who smelled so lovely! Since then I knew that this stuff is special indeed. I suggested it to the guy who was in charge of Diesel back then and he said that he felt that this is a bit too much – even for them!” [2]
He’s quick to elaborate however that it does not act as a pheromone (that’s a misconception if scientifically examined) but that simply it’s “not possible not to like it”, as no one has ever commented he/she doesn’t like its particular smell per se.
Perhaps the most vexing matter to perfume enthusiasts however has been how Iso E Super is one of the 14 chemicals that have been recommended for study by the National Toxicology Program (NTP) with impending restrictions on its use.
Ever since as early as 2000 the matter has been in discussion. In a letter by Betty Bridges, RN Fragranced Products Information Network (http://www.fpinva.org/) addressed to Dr. Scott A. Masten, Ph.D. from the Office of Chemical Nomination and Selection, Environmental Toxicology Program of the National Institute of Environmental Health Sciences in 2002 we read the following:
“International Flavors and Fragrance’s suggested use levels of Iso E Super is up to 10% of the fragrance formula and is recommended for use in a variety of products (IFF, 2002). Isocyclemone E’s (a material with a different ratio of isomers, same CAS# 54464-57-2) suggested use level is up to 30% and is recommended in a variety of applications.(IFF, 2002) […] Considering Iso E Super’s similar structure to AETT and AHTN, two polycyclic musk compounds with known concerns, it is likely that Iso E Super and other chemically similar materials would also bioaccumulate in human tissue, persist in the environment, and have health concerns.
There are concerns related to AHTN causing liver toxicity and discoloration. Galaxolide, another polycyclic musk has similarconcerns, but to a lessor degree (SCCNFP, 2000) Chromogenic properties have been associated with neurotoxicity (Sabri, 2002)”
3. Synthetic terpenoids in the world of fragrances: Iso E Super® is the showcase
Guest Editor: J. S. Dickschat
Beilstein J. Org. Chem. 2019, 15, 2590–2602. https://doi.org/10.3762/bjoc.15.252
Received 22 Jul 2019, Accepted 26 Sep 2019, Published 31 Oct 2019
1. Abstract
The history of fragrances is closely associated with the chemistry of terpenes and terpenoids. For thousands of years mankind mainly used plant extracts to collect ingredients for the creation of perfumes. Many of these extracts contain complex mixtures of terpenes, that show distinct olfactoric properties as pure compounds. When organic synthesis appeared on the scene, the portfolio of new scents increased either in order to substitute natural fragrances without change of olfactoric properties or to broaden the scope of scents.
This short review describes the story of the most successful synthetic fragrance ever which is called Iso E Super® as it is an ingredient in a large number of perfumes with varying percentages and is the first example being used as a pure fragrance. Structurally, it is related to natural terpenes like many other synthetic fragrances. And indeed, the story began with a classic in the field of fragrances, the natural product ionone.
2. Introduction – classical terpenes in perfumes
Perfumes (Latin “per fumus”, which means “through smoke”) have accompanied mankind for thousands of years dating back well before biblical times [2,3]. Plants and resins served as source for perfumes after alcoholic extraction. These extracts were not only used as fragrances but also as medicine (aqua mirabilis), aphrodisiac and elixir of life (aquavitae).
In 1882 ‘Fougere Royale’ was created, a composition of coumarin, oak moss, geranium and bergamot, commercially launched by Houbigant [4]. The major constituents of geranium oil include myrcene (1), menthone (2), α-pinene (3), geraniol (4a), geranyl acetate (4b), geranyl butyrate (4c), citronellol (5), limonene (6) and linalool (9a). As for the bergamot oil monoterpenes limonene (6, 37%), γ-terpinene (7, 7%), β-pinene (8, 6%), linalool (9a, 9%) and linalyl acetate (9b, 30%) are key ingredients (Figure 1). The ratio of (R)-linalool and (R)-linalyl acetate (commonly >99.3% ee) is one of the quality indices as it affects the aroma of the essence of bergamot [5].
3. The discovery and modern applications of Iso E Super®
It has to be stressed that musky odours were not the only scents of interest but also the spectrum of fragrances from violet flower oils. In fact, these were the most expensive of all available essential oils. Exorbitant quantities of flower petals were extracted to collect the oil, used directly in cosmetic formulations or spread on laundry to generate a characteristic smell. As for musk fragrances, there was a quest in the perfume industries to find a synthetic solution to create scents that mimic violet flower oils. First, a similarly smelling but more affordable orris root oil (Iris pallida Lam., fam. Iridaceae) was chosen for structural analysis. Thiemann and Krüger isolated irone (27, Figure 3), whose molecular formula was first falsely assigned as C13H20O [10].
4. Synthetic aspects of individual Iso E Super® components
The first target-specific synthesis of (−)-Georgywood® (35) utilised the (S)-Corey–Bakshi–Shibata catalyst (36) for the enantioselective Diels–Alder cycloaddition . The corresponding enantiomer (+)-Georgywood® (35) was also prepared using the corresponding (R)-CBS catalyst (36)
In contrast, the enantiomer (+)-Georgywood® (35) was found to possess a relatively weak odour which was described as distinctly unpleasant and acrid-musty by several members of the Corey group [33]. The same approach led to the discovery of (+)-Iso E Super Plus®
(34) as a highly active component Fráter et al. confirmed these experiences after isolation of active olfactory compounds of Iso E Super Plus® (34) and Georgywood® (35). Racemic resolution provided a crystalline material that served to obtain an X-ray structure of the oxime derivative of (−)-(1R,2S)-Georgywood® ((−)-35) [33,34].
5. Conclusion and Outlook
Here, we presented a short story on Iso E Super® and derivatives formed during synthesis, a group of molecules that has changed the perfume industry, but has its roots in the terpenoid ingredients of classical essential oils geranium and bergamot (Figure 5). Starting from ionone (30) an “evolutionary process” towards synthetic products with similar olfactory properties led to Iso E Super® (34), Iso E Super Plus® (35) and Georgywood® (35), a development that took almost hundred years and saw koavone and timberole as intermediates.
An analysis of today´s fine fragrances reveals that almost all of them combine synthetic scent molecules with traditional essential oils, despite the fact, that the ongoing consumer trend is towards natural ingredients. Avoiding synthetics like Iso E Super® (33) would rule out many favourite scents. In fact, about 100 natural fragrance ingredients are known, but perfumers have more than 3,000 synthetic molecules at hand of which several examples 60–66 with terpene-like structures are listed in Figure 6. Noteworthy, the fragrance properties of synthetically-derived unnatural compounds commonly mimic those of natural products.
Biotechnology is another way to harness fragrance components be it enzymatic or microbial. Nowadays engineered microbes are at hand that, e.g., produce scents, such as patchouli, by fermenting sugar. Patchouli is a complex mixture of sesquiterpenes ((−)-patchoulol, (+)-norpatchoulenol, (+)-α-bulnesene, (−)-α-guajene, (−)-β-patchoulene and (−)-seychellene) with a slightly camphoraceous, woody balsamic odour [6].
Enzymatic derivatisation of terpenes by means of biocatalysis is another opportunity to create new fragrance molecules or to achieve chiral resolution of racemates. The former process is commonly associated with oxidation reactions, while the latter process is often based on the action of lipases. Very recently, a new concept was disclosed that probed sesquiterpene cyclases to accept unnatural farnesyl pyrophosphates and generate unnatural cyclisation products with unusual backbones. Thus, in the presence of presilphiperfolan-8-β-ol synthase (Bot2) a novel tricyclic product 70 was obtained from unnatural farnesyldiphosphate ether 69. The olfactory analysis revealed an ethereal, peppery and camphoric scent (Scheme 10) [39].
4. Tetramethylacetyloctahydronaphthalenes
1. Uses
Iso E Super is a very common perfume ingredient, providing a sandalwood-like and cedarwood-like fragrance, in soap, shampoo, perfumes, detergents, fabric fresheners, antiperspirants or deodorants, and air fresheners. It is also used as a tobacco flavoring (at 200–2000 ppm), as a plasticizer and as a precursor for the delivery of organoleptic and antimicrobial compounds.[5]
2. Production
so E Super is produced commercially by Diels–Alder reaction of myrcene with 3-methyl-3-penten-2-one in the presence of aluminium chloride to give a monocyclic intermediate that is cyclized in the presence of 85% phosphoric acid.[6]
3. Physical-chemical properties
OTNE is a clear yellow liquid at 20 °C. Its melting point is below −20 °C at atmospheric pressure, and its boiling point is determined to be at around 290 °C (modified OECD 103 method). All physicochemical data have been obtained from the OTNE REACH registration dossier.[7]
4. Environmental data
OTNE is classified as H410 Very toxic to aquatic life with long-lasting effects (EU-CLP) or R51/53 Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment (EU DSD).[7] The biodegradation of OTNE in fresh water (T1/2) is at most 40 days, and at most 120 days in sediment (OECD 314 test), though the biodegradation within the 28day window was around 11% (OECD 301-C). Given the outcome of the OECD 314 test OTNE does not meet the criteria for “Persistent” (P) or “very Persistent” (vP).
The measured Bio Concentration Factor (BCF) is 391 L/kg, which is well below the EU limit of 2000 and US limit of 1000 for Bioaccumulation (B) classification. The LogKow for OTNE has been measured to be 5.65.[7]
Question
1. Iso E Super uses
Iso e super is used to create woody and cedar-like scents. Fragrance creators make this ingredient in a lab using various methods. It can be derived from myrcene, which occurs naturally in apricots, blueberries, citrus fruits, coffee, cotton, and more.
2. Is Iso E Super safe on skin?
Iso e super is a thoroughly evaluated and commonly used fragrance ingredient. It has been identified by European Union scientific bodies as a potential skin sensitizer. This means that Iso e super has the potential to cause a skin reaction (such as red, bumpy, or itchy skin).
3. What are ISO benefits?
Reduce Time & Costs: ISO would help you to give a standard framework to your employees and guide them to work more precisely. Obviously, everything takes time. But, later it will reduce all the extra time and costs too. Meanwhile, it will improve in streamlining processes and liability.
4. What does musk smell like?
Depending on what it is blended with, musk can range from dark and earthy to light and floral. Musk can be described as powdery, soft, somewhat sweet, and is sometimes likened to a seductive version of “natural skin scent.” Because of its warm and rich scent, musk belongs to the amber fragrance family.
5. What is the cost of Iso E Super?
100% ISO E Super by IFF (Aids Diffuesion & Blender/Modifier), For Perfumery, Packaging Size: 100gm at Rs 1500/kg in Chennai.