Chemistry of Fragrance Ingredients Dr. William L. Schreiber Chemlumina LLC Monmouth University Presented at Fairleigh Dickenson University November 7, 2006

To be discussed What is a perfume? History Natural Ingredients Synthetic Ingredients Chemical Process Examples Research on New Synthetics The Science of Olfaction

What Are Perfumes? Mixtures that are created for use in a wide variety of applications: expensive couturier perfumes, cosmetics, personal grooming products, laundry products, household cleaning products, air fresheners, candles, etc., etc., etc.. From a palette of several thousand materials, most of which are manufactured by chemical processing methods.

History of Perfumes 5000 BC – Egyptian First Dynasty – earliest evidence 3000 BC – Mesopotamia: extraction pots, early apparatus 1400 BC – Book of Exodus “anointing with oils” 370 BCE – Theophrastus writings on use of oils to make fragrances longer lasting. 800 AD – Alembic distillation apparatus – Jabir ibn Hayyan 1200 AD – Essential oils produced in pharmacies 1600 AD – Quality of many natural extracts established 1860 AD – First synthetics (naturally occuring materials) 1900 AD – First non-natural synthetics (ionones, nitro-musks)

Alembic Distillation Appratus

What are Fragrance Ingredients? Odorants, Diluents and Fixatives Naturals and Synthetics Chemicals having 6 – 18 carbon atoms (mostly), and usually one oxygenated functional group. There are also some multi-functional materials as well as a few sulfur- and nitrogen-containing chemical compound.

What are Fragrance Ingredients?

Performance in Use Volatility Stability Function of molecular weight (how many carbons) and chemical type. Stability Function of chemical type and use condition (acidity, alkalinity, oxidizing, open, closed). Odor Threshold and dose/response Function of chemical structure (molecular shape and chemical type).

Natural Ingredients Mostly of vegetative origin, a few from animal secretions – largely replaced. Any part of a plant may be used: flowers, fruits, leaves, twigs, roots, wood. Synthetics have long overtaken naturals in volume of use. Naturals still very valuable and provide odor reference points for all materials.

Types of Naturals Concretes – extracts with solvent removed Absolutes – concretes re-dissolved and filtered to remove waxes, etc. Essential oils – distillates, often with steam

Narcisse Concrete

Most important constituents: Rose Most important constituents:

Most important constituents Jasmine Most important constituents

Patchouli Most important constituents: tricyclic sesquiterpene alcohols

Sandalwood Alpha Santalol: Beta Santalol:

First Synthetics

Synthesis of Vanillin

Synthesis of Coumarin

Synthesis of Ionones

Terpene Alcohols from -Pinene

Terpene Alcohols from -Pinene

More Products from -Pinene via Myrcene

Sandalwood “Molecular Engineering” Alpha Santalol: Beta Santalol:

Synthetic Sandalwoods

Musks

Galaxolide Synthesis

Newer Musk Synthesis

Research and Development Analytical Application of new gc methods (head space with spme) Use of more sensitive and better computerized instrumentation: gc-ms, nmr, ft-ir. Live flowers – above methods used to analyze odors of flowers before picking. New extraction methods for naturals: supercritical CO2

(often a combination of all three) Synthetic Research Considerations: Structure – relationship to materials of known value – natural or synthetic Raw materials Process (often a combination of all three)

Synthetic Research Practical only for largest companies. Hundreds of materials synthesized each year for evaluation. In-depth evaluation must include testing in fragrances and in applications. Decision to develop cannot be taken lightly.

Development of New Synthetics Processes must be very well worked out in laboratory, pilot plant and factory. Best economics, safety and workplace hygiene. Testing is required to meet industry safety standards and international PMN requirements for all new chemicals. Cost to register new ingredients worldwide is well over $300,000.

How We Smell

Smell and Taste are Chemical Senses In order to perceive smells or tastes, chemical substances must contact receptors in the nose or on the tongue. Perception is the result of the processing of signals from these receptors by the brain.

Recent Developments 1991 – Richard Axel and Linda Buck discover a family of genes that appear to be responsible for olfactory receptors. (received Nobel Prize – 2005) 1998 – Stuart Firestein expresses a receptor from one of those genes and shows it responds to different odorants. 2000 – Linda Buck shows that odor perception is based on combinatorial interaction of odorants with receptors.

Combinatorial Odor Perception We have ~350 active odor receptors. One odorant activates multiple receptors. Each receptor binds multiple odorants. Perception of different odors results from distinct combinations of activated receptors. L. Buck, et. al., Cell, 1999.

A Code in the Nose

Combinatorial Detection Receptors 1 2 3 4 5 6 7 8 9 10 …. A           B           C           D           E           F           Odorants 350 Receptors: 2350 = 2.3X10105 Combinations  = Unactivated  = Activated

In Conclusion… Fragrance ingredients are a complex part of a the even more complex world of perfumes. Understanding what they are, where they come from and what they do is the key to making better smelling and better performing fragrances. Thank you for the opportunity to participate in your class this evening.