Material guide: isoambrettolide, the second most-supplied macrolactone, and the notes field says it covers alcohol

In short: one of the few -olide names that is not lying. The first synonym says lactone and the formula agrees. What is worth noting is the strength field: medium, which is uncommon among musks.

Fields

Field	Value
CAS	28645-51-4
EINECS	249-120-7
First synonym	hexadec-9-en-1,16 lactone
Formula	C16H28O2, MW 252.398
Database category	flavor and fragrance agents
Appearance	colorless to pale yellow clear liquid (est)
Assay	95.00 to 100.00
Boiling point	307-308 C @ 760 mmHg; 185-190 C @ 16 mmHg
Flash point	> 100 C
logP	5.50 (est)
Specific gravity	0.949-0.957 @ 20 C
Water solubility	0.5925 mg/L @ 25 C (est)
Odour type	musk
Odour	sweet; musk; ambrette; fruity; waxy; fatty
Strength	medium, evaluate at 10% or less (rank 2)
Substantivity	248 hours (neat)
Shelf life	24 months
Occurrence	not found in nature
Suppliers	43
Regulatory	JECFA 1991, FEMA 4145, FLAVIS 10.063
Structure class	I
Cosmetic uses	perfuming agents
Oral toxicity	rat LD50 > 5000 mg/kg
Dermal toxicity	rabbit LD50 > 5000 mg/kg
GHS	H315 skin irritation; H319 serious eye irritation; H320 eye irritation
Note	Maybe used as a prefixer for alcohol, to tone down the alcohol smell. Used as a food additive

The name is not lying

The -olide suffix mostly does not indicate a structure. I measured that in What are the -olides: hit rates of 44% and 8% in the two directions.

This material is on the side where the name holds up.

The first synonym reads hexadec-9-en-1,16 lactone: sixteen carbons, one double bond at position 9, a lactone ring closed between positions 1 and 16. The formula C16H28O2 has two oxygens and a degree of unsaturation of 3 (one ring, one C=O, one C=C). It fits exactly.

For comparison: Galaxolide has one oxygen (cannot be an ester at all), and Helvetolide has three (an ester, but not a cyclic one). This one you can trust without looking further.

The strength field reads medium

Most musks I have written up read "high" at rank 3. This one reads medium, rank 2, with evaluation recommended at 10% or less.

Among musk-type materials in the database that puts it in a minority.

(That does not mean weak. A substantivity of 248 hours is on the long side; it just does not press as hard in the air. The difference between those two is unpacked in the phenethyl salicylate article.)

Its odour description field quotes supplier copy saying it has exceptional diffusion and a very fine character. Good diffusion and medium strength can hold at once.

Two that are easy to confuse

The asker who listed materials wrote ambrettolide. The database has two records:

	CAS	Formula	Odour type	Suppliers
ambrettolide	7779-50-2	C16H28O2	soapy	13
isoambrettolide	28645-51-4	C16H28O2	musk	43

Same formula, two CAS numbers, two odour types, and the one with three times the suppliers is this one.

When ambrettolide comes up on a forum, which one is meant usually is not stated. Check the CAS before buying.

"Not found in nature"

The occurrence field reads not found in nature.

Worth pausing on, because its name points at the seed of ambrette (Abelmoschus moschatus), and the odour field even carries the word ambrette.

The name comes from what it imitates, not from where it comes from. The "iso" prefix is saying it is the isomeric version.

(That is the mirror image of the natural-material problem: a synthetic has no origin variation. The numbers on the natural side are in How much does a natural actually vary.)

That line in the notes field

"Maybe used as a prefixer for alcohol. To tone down the alcohol smell."

Across nearly a hundred materials I have written up, I have seen that sentence only on this record.

It addresses a specific practical problem: a freshly mixed alcoholic perfume smells of alcohol for the first few seconds, and this material is being suggested to cover that stretch.

I have no way to verify the use. What I can say is that it does not conflict with the physical properties: logP 5.50 and water solubility 0.5925 mg/L make it strongly lipophilic and soluble in high-proof ethanol, and it does not evaporate itself (248 hours of substantivity), so it will not leave with the alcohol.

Which receptor it goes through

Emter and colleagues worked on three human musk receptors in Chemical Senses in 2024. Their division of labour: OR5A2 is the key receptor for polycyclic musks, linear musks and most macrocyclic lactones, while OR5AN1 dominates macrocyclic ketones such as muscone and some nitro musks.

This is a macrocyclic lactone, so it falls on the OR5A2 side.

That receptor carries a P172L substitution which reduces sensitivity around 50-fold; panellists homozygous for it show sensory detection thresholds 40 to 60 times higher for selective OR5A2 ligands.

So some people will find this material very faint while the same person smells muscone entirely normally.

(Shirasu and colleagues saw the same boundary earlier, in Neuron in 2014: the glomeruli muscone activates are highly specific to macrocyclic ketones, while synthetic musks with nitro or polycyclic moieties or ester bonds activate distinct but nearby glomeruli.)

What this doesn't establish

• I have not smelled it. This is database fields plus two papers.
• "The name holds up" is verified only to the point that formula and degree of unsaturation are consistent. Confirming the ring needs a structure, which I did not check.
• I have not verified the alcohol-covering use at all. It is one line in the notes field, and all I checked is that it does not conflict with the physical properties.
• "Medium" strength is the database's judgement. How that field is assigned is not documented.
• The 248-hour substantivity was measured neat and is not comparable with records measured at 10% dilution, for the reasons in the rose oxide article.
• I cannot tell whether the odour-type difference between the two ambrettolides (soapy against musk) is a real difference or a cataloguing one. The evaluators and eras may differ.
• Emter 2024's receptor assignments hold within the 440-compound commercial set they selected.
• The 40- to 60-fold figure from P172L applies to "selective OR5A2 ligands", and I could not tell whether this material was in that test set.
• Shirasu 2014's glomerular work was in mice.
• Water solubility and logP are both estimates.