TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 9207–9210
Odorless substitutes for foul-smelling thiols: syntheses and
applications
Manabu Node,* Kamal Kumar, Kiyoharu Nishide, Shin-ichi Ohsugi and Tetsuo Miyamoto
Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan
Received 5 October 2001; revised 25 October 2001; accepted 29 October 2001
Abstract—Several alkanethiols and p-alkylphenylmethanethiols were synthesized, and their odors were compared with those of
ethanethiol and benzyl mercaptan by human and instrumental sensors. Among the various thiols analyzed, 1-dodecanethiol (1)
and p-heptylphenylmethanethiol (3) were revealed to be odorless. 1-Dodecanethiol (1) has been used instead of ethanethiol for
dealkylation of ethers, and p-heptylphenylmethanethiol (3) can replace benzyl mercaptan in the preparation of a 1,3-mercapto
alcohol from an a,b-unsaturated ketone. These odorless thiols will greatly improve the physical environment of the researcher
working with these foul-smelling compounds. © 2001 Elsevier Science Ltd. All rights reserved.
Thiols are a fundamental and important functional
group in organic chemistry, and the literature contains
ample reports of organic and bioorganic chemistry on
this group.1 Commonly used thiols like ethanethiol and
benzyl mercaptan have a foul smell making them
difficult and unpleasant to use in the laboratory with-
out fume hoods. The problem becomes even worse in
industry where these malodorous reagents are used on a
large scale. Odorless substitutes are therefore always
required. While experimental assessment of human
olfactory thresholds has been reported for four alkan-
ethiols including 1-dodecanethiol,2 there have been no
serious attempts to pursue this research. We report
here, for the first time, the synthesis of new odorless
thiols to replace the usual foul-smelling ones, as well as
various applications in organic reactions.
reeked in spite of being a crystalline compound, a result
which seemed contradictory to the relationship between
volatility and odor. To understand this apparent con-
tradiction and to find other useful odorless thiol substi-
tutes, we planned to test the odor of a number of
alkanethiols. All of the alkanethiols were commercially
available except for 1-tetradecanethiol which was pre-
pared by reacting the tetradecyl Grignard reagent with
sulfur4 followed by lithium aluminum hydride
reduction.
The relative odor index of these thiols with the foul-
smelling ethanethiol perceived by the human nose of
two test subjects is listed in Table 1. The index of the
most malodorous thiol is 5; the index of the odorless
thiol, 0. The odor of a thiol depends virtually entirely
on its purity, i.e. 1-hexadecanethiol (2) purified by
HPLC on a GPC column was found to be almost
odorless,5 while the commercial 1-hexadecanethiol had
essentially the same odor as indicated in a chemical
catalog. Therefore, purification of all these thiols was
done on HPLC using a GPC column before analyzing
their respective odors. Among the alkanethiols, 1-dode-
canethiol (oil) was found to be odorless, while lower
carbon-chain thiols were found to be malodorous.
These facts suggest that the foul smell of thiol toward
the human olfactory cell is related to the length of its
carbon-chain.
Recently, we published an asymmetric Michael addition
to a,b-unsaturated carbonyl compounds using 10-mer-
captoisoborneol as the hydrogen sulfide equivalent.3
During the course of the study, we looked for an
odorless thiol substitute for the foul-smelling
ethanedithiol for the thiol exchange reaction of the
vinyl sulfide. Two commercially available thiols, 1-
dodecanethiol (1) and 1-hexadecanethiol (2), were
selected for odor testing because it was thought that the
smell of thiols was related to their volatility. Unexpect-
edly, 1 turned out to be an odorless liquid whereas 2
Furthermore, these alkanethiols were subjected to a
Fragrance and Flavor analyzer FF-1,6 as shown in Fig.
1.7 FF-1 consists of an odor concentration tube and 6
odor sensors (made by metal oxide semiconductors).
Keywords: odorless thiols; synthesis; odor scale; dealkylation;
Michael addition.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02024-X