β-amino alcohol properfumes

Article abstract of DOI:10.1002/hlca.200390241

Amino-alcohol derivatives of fragrant, volatile aldehydes and ketones were synthesized in a one-pot procedure by sequential cyanohydrin formation with trimethylsilyl cyanide and reduction with lithium aluminium hydride, or by ammonolysis of epoxide precursors. The amino alcohols are nonvolatile, stable properfumes releasing fragrant carbonyls by oxidation with sodium periodate or sodium bismuthate. Examples include amino alcohol properfumes of citronellal, Lilial, lauryl aldehyde, menthone, benzaldehyde, and anisaldehyde.

Full text of DOI:10.1002/hlca.200390241

2
928
Helvetica Chimica Acta ± Vol. 86 (2003)
b-Amino Alcohol Properfumes
1
by Yongzheng Yang, Denis Wahler ), and Jean-Louis Reymond*
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern
(
fax: ‡41316318057; e-mail: jean-louis.reymond@ioc.unibe.ch)
Amino-alcohol derivatives of fragrant, volatile aldehydes and ketones were synthesized in a one-pot
procedure by sequential cyanohydrin formation with trimethylsilyl cyanide and reduction with lithium
aluminium hydride, or by ammonolysis of epoxide precursors. The amino alcohols are nonvolatile, stable
properfumes releasing fragrant carbonyls by oxidation with sodium periodate or sodium bismuthate. Examples
¾
include amino alcohol properfumes of citronellal, Lilial , lauryl aldehyde, menthone, benzaldehyde, and
anisaldehyde.
Introduction. ± Over 3000 fragrance ingredients are available today for use in
perfumery [1][2]. Factors such as chemical instability, reactivity, and evanescence,
which are intrinsic to many fragrant compounds, however, strongly limit the choices for
certain applications, in particular, when the active ingredients must be stored for some
time before being released. Time-delayed fragrance-delivery systems have been
developed, such as spray-dried and micro-encapsulated perfumes, and inclusion
complexes with cyclodextrins [3]. Another approach consists in employing fragrance
precursors or properfumes. This concept is the direct analog of the prodrug principle
used in the pharmaceutical industry. Existing systems include the release of fragrant
alcohols from esters by using either lipases or a photoisomerization-triggered
lactonization of coumarate esters [4], and the release of aldehydes and ketones by a
photochemical Norrish-II fragmentation of 2-oxo esters of the corresponding alcohols
[
5]. Herein, we report a novel properfume strategy, whereupon fragrant volatile
aldehydes and ketones are released from stable nonvolatile b-amino-alcohol precursors
by periodate oxidation in H O.
2
Results and Discussion. ± NaIO is a versatile oxidant best known for its ability to
4
cleave the CÀC bond of 1,2-diols to release two CˆO groups [6]. Recently, we have
shown that the reaction can also be used for fluorogenic and chromogenic enzyme
assays [7]. Interestingly, 1,2-amino alcohols are oxidized even faster than 1,2-diols. We
reasoned that the reaction might be used to release fragrant aldehydes and ketones,
which are difficult to store due to their volatility and chemical instability, from b-amino
alcohol precursors, themselves readily obtainable by cyanohydrin formation and
reduction (Scheme 1). The advantage would be that both the periodate oxidant and the
b-amino alcohol are nonvolatile and quite stable.
1)
Present address: Prot e¬ us S.A., 70, all e¬ e Graham Bell, Parc Georges Besse, F-30000 NÓmes.

Helvetica Chimica Acta ± Vol. 86 (2003)
2929
Scheme 1. Preparation and Oxidative Activation of b-Amino Alcohol Properfumes
i) TMSCN, cat. KCN/18-crown-6 ; ii) LiAlH4
OH
aq. NaIO4
O
NH2
R1
R1
R2
2
R
CH2O, NH4OH
stable properfume
fragrant volatile carbony
1
2
R , R = H, alkyl, aryl
We prepared a series of b-amino alcohols, 1 ± 12, from volatile carbonyl fragrances,
¾
including citronellal, used in soaps and detergents, Lilial (ˆ 3-[4-(tert-butyl)phenyl]-2-
methylpropanal), which serves as a base component in many perfumes, and lauryl
o
aldehyde, a fatty-orange note used in −Chanel N 5' [1]. b-Amino alcohol derivatives
were obtained in excellent purity and good yields by a one-pot procedure involving
reaction with Me SiCN (TMSCN) under anionic catalysis by KCN/18-crown-6,
3
followed by reduction with LiAlH [8] and an aqueous extractive workup, which
4
avoided the use of chromatographic purification. All b-amino alcohols were racemic,
¾
or, in the case of citronellal, menthone, and Lilial , mixtures of stereoisomers
(
Scheme 2).
Amino alcohols are also easily prepared from epoxides by ammonolysis. We looked
into that possibility to prepare a precursor for the volatile butanal, which is an
important odor component for butter. Interestingly, reaction of 2-butyloxirane with
aqueous NH gave a crystalline product, which was identified as the yet unreported
3
secondary amine 13 (Scheme 3), resulting from double substitution of ammonia with
the epoxide by reaction at the terminal epoxide C-atom. The structure was established
by mass spectrometry as well as by NMR analysis of the acetylated derivative 14.
Although there was only one set of NMR signals, the formation of a single
diastereoisomer seems improbable, and we assume that both possible diastereoisomers
1
13
have identical H- and C-NMR signatures.
All the amino alcohols prepared were nonvolatile, completely odorless products.
Properfume activation by periodate oxidation was carried out under three different
formulations. In the first case, anhydrous Na SO was ground with 1%-weight of the
2
4
amino alcohol and solid NaIO . The resulting colorless powder was completely
4
odorless, but slowly released its active component when left exposed to air, due to the
slow uptake of humidity, which solubilized the component sufficiently for the reaction
to take place. A distinct odor was perceptible even after several weeks in these
preparations. By comparison, anhydrous Na SO ground with 1%-weight of the volatile
2
4
carbonyl compounds themselves initially released a very strong fragrance, but any odor
had disappeared within 12 h of exposure to air. Similar results were obtained with MgO,
or mixtures of Na SO and MgO as the inorganic support for the properfumes.
2
4

2
930
Helvetica Chimica Acta ± Vol. 86 (2003)
Scheme 2. Structures of b-Amino Alcohol Properfumes. Yields obtained with the one-pot cyanohydrin
formation/reduction procedure are given in parentheses.
Scheme 3. Reaction of 2-Butyloxirane with Ammonia
1. aq. NH4OH (70%)
OR
OR
R
N
O
1
3 (R = H)
2. Ac2O, py (100%)
14 (R = Ac)

Helvetica Chimica Acta ± Vol. 86 (2003)
2931
In the second formulation, acidic salts of the amino alcohols were prepared by
reaction with 1 equiv. of either HCl, AcOH, or PhCOOH in MeOH, and evaporation.
Aqueous solutions of these salts were prepared at a concentration of 50 mm. While
these solutions were completely odorless, the immediate, strong fragrance was released
when adding an equal volume of an aqueous 50 mm solution of NaIO , or by adding
4
solid NaIO . The aqueous solutions of b-amino alcohol salts were stable and odorless
4
over weeks at room temperature, and released their fragrance upon treatment with
periodate independent of the length of the storage period. Organic solvent extracts
(AcOEt) of the properfume aqueous solution were free of any detectable product
under analysis by GC/MS, and showed the expected volatile carbonyl as the only
detectable product after treatment with NaIO , showing that the oxidation reaction
4
produced only the expected product (Fig.).
Figure. GC/MS Analysis of organic extracts of properfume solutions. A) FID Total-ion-current trace for acetate
salt of pro-citronellal (1) after treatment with NaIO
hydrochloride salt of pro-menthone (3) after treatment with NaIO
detectable signals in the GC traces of the organic phase under the same conditions before treatment with
NaIO
4
, B) signal at m/z 154; C) FID-total-ion-current trace for
4
, D) signals at m/z 154. There were no
4
.

2
932
Helvetica Chimica Acta ± Vol. 86 (2003)
In the third formulation, we made use of the higher reactivity of b-amino alcohols
towards periodate oxidation in comparison to 1,2-diols. A simple release system was
build with two superimposed sheets of filter paper, one of which had been impregnated
with a b-amino alcohol solution and dried. The sheets were held together by a piece of
scotch-tape, with a small amount of solid NaIO added on the glue-face in contact with
4
the nonimpregnated filter paper. Addition of a few drops of H O to the filter-paper
2
device immediately released the fragrances, indicating that both the amino alcohol and
the b-amino alcohol dissolved rapidly in H O, and that the oxidative properfume
2
release took place faster than the reaction of periodate with 1,2-diols present in the
cellulose of the paper (Table).
Table. Properfume Properties upon Release from Filter Papera)
Properfume
Amount [mg]
Fragrance
Citronellal
Lilial
Menthone
Benzaldehyde
Anisaldehyde
Lauryl aldehyde
Description
Persistanceb)
1
2
3
4
5
6
0.26
0.47
0.37
0.27
0.33
0.40
Citronella, strong
Fresh lila, weak
Mint, strong
Almond, strong
Cinnamon, middle
Fatty orange, middle
30 min
> 30 min
10 min
10 min
20 min
¾
> 30 min
a) 0.02 ml of a 0.1m ethanolic solution of b-amino alcohol was adsorbed on a filter paper and dried. NaIO
4
b
Treatment was carried out by addition of H
2
O as described in the text and judged qualitatively. )Time after
which the fragrance was not detectable any more. Compounds 7 ± 12 were similarly tested. The released
carbonyls had stingy (9 ± 11), sweet (7 and 12), or only weak (8) fragrances.
It should be mentioned that we did not detect the odor of either formaldehyde or
ammonia, which are by-products of the periodate oxidation reaction, in any of the
properfume formulations. These components, which do not have a very strong intrinsic
odor per unit of weight when compared to most fragrances, are also sufficiently H O-
2
soluble to not show significant vapor pressure at the concentrations used. We also did
not detect any significant fatty acid smells that could result from overoxidation during
or after the reaction, even when using an excess of periodate. The fragrances released,
which are relatively hydrophobic, are most likely immediately removed from the
aqueous phase used for the oxidation of the amino alcohol with periodate.
Secondary amines behaved similarly to the other amino alcohols with respect to
NaIO oxidation, thus representing further interesting low-volatility precursors for
4
volatile carbonyl compounds. For example, secondary amine 13 released butanal upon
treatment with NaIO . Similarly, ephedrine (15), also bearing a secondary amine,
4
reacted with NaIO to give PhCHO, also obtained from amino alcohol 4, confirming the
4
suitability of secondary amines for the oxidation chemistry (Scheme 4). The rate of
oxidation of 4 and ephedrine (15) was almost identical, as shown by the fact that both
amino alcohols were consumed to the same extent by treatment of an equimolar
solution of these with 1 equiv. of NaIO . Ephedrine (15) was, however, not completely
4
equivalent to 4 as a properfume. Indeed, it was possible to detect the acrid smell of
MeCHO as one of the by-products of 15. Amino alcohols of tertiary amines did not
react with periodate. This was shown by the fact that pretreatment of NaIO (10 mm in
4

Helvetica Chimica Acta ± Vol. 86 (2003)
2933
H O) with excess triethanolamine (ˆ2,2',2''-nitrilotris[ethanol]; 20 mm) for 30 min at
2
208 did not reduce its oxidizing power towards amino alcohols.
Scheme 4. Amino Alcohols with Secondary Amines as Properfumes
NaIO4
OH
OH
O
H
N
13
O
OH
NaIO4
H
N
15
Since NaIO is potentially problematic for applications due to its reported toxicity,
4
we looked for alternative oxidants to perform the oxidative cleavage of amino-alcohol
properfumes. There was no measurable reaction with H O or NaMnO . However, we
2
2
4
found that NaBiO , which is reportedly nontoxic (for example, bismuth salicylate is
3
prescribed in large amounts against stomach pain), slowly reacted with the amino
alcohols to release the perfumes over weeks. Thus, a slurry of NaBiO and pro-
3
citronellal (1) could be left open at air for several weeks and kept releasing a fresh
citrus smell.
Conclusions. ± The above experiments show that b-amino alcohols are stable, non-
volatile, and odorless precursors of fragrant aldehydes and ketones, which can be
released by reaction with NaIO or NaBiO . These properfumes are readily prepared
4
3
from the parent carbonyl compounds in an efficient one-pot procedure involving
cyanohydrin formation and reduction, and obtained pure by simple extractive workup.
Alternatively, amino alcohols are readily prepared from epoxides, with both primary
and secondary amines, to give oxidizable properfumes, a strategy that allows to
formulate completely nonvolatile precursors of volatile carbonyls. This simple process
represents an attractive properfume strategy for a variety of applications, including
experimental demonstrations for students. The oxidative chemistry of b-amino alcohols
should also be of general value to release any active but sensitive carbonyl component
from more-stable precursors, in particular, in the area of prodrug formulations.
This work was supported by the University of Bern, the Swiss National Science Foundation, and Prot e¬ us SA
(
NÓmes, France).
Experimental Part
General. All reagents were purchased from either Aldrich or Fluka. Et
apparatus; uncorrected. IR Spectra: Perkin-Elmer Spectrum One series. H- and C-NMR spectra: Bruker AC-
2
O was dried over Na. M.p. B¸chi 510
1
13
3
00 spectrometer. Mass spectra were provided by Dr. Thomas Schneeberger (University of Bern).

2
0
934
Helvetica Chimica Acta ± Vol. 86 (2003)
1
-Amino-4,8-dimethylnon-7-en-2-ol (1). A soln. of 18-crown-6 (132 mg, 0.5 mmol) and KCN (32.5 mg,
.5 mmol) in 10 ml of MeOH was stirred at 258 for 10 min. The solvent was evaporated, and the residue was
Cl , and treated with citronellal (620 mg, 4 mmol) and Me SiCN (397 mg, 4 mmol).
After completion of the reaction (TLC, 14 h), the solvent was evaporated, and the residue was redissolved in dry
Et O (10 ml) and treated with LiAlH (400 mg, 12 mmol). After completion of the reaction (7 h at 258), the
mixture was cooled to 08, and the reaction was quenched by dropwise addition of aq. 2n HCl (30 ml). The aq.
phase was washed with Et O (3 Â
O (3 Â 30 ml), basified with 15% aq. NaOH (70 ml), and extracted with Et
0 ml). The org. phase was washed with brine (2 Â 30 ml), dried (Na SO ), and evaporated to dryness to give 1
680 mg, 3.67 mmol, 91%). Colorless liquid. IR (CHCl ): 3437, 2967, 2925, 1635, 1489, 1094, 1057. H-NMR
300 MHz, CDCl
): 5.10 (br. t, J ˆ 6, 1 H); 3.61 (m, 1 H); 2.81 (ddd, J ˆ 12.5, 5.5, 3.3, 1 H); 2.50 (dt, J ˆ 12.5, 8.0,
H); 2.0 (br. s, 3 H); 1.65 (s, 3 H); 1.58 (s, 3 H); 1.48 ± 1.02 (m, 4 H); 0.94, 0.92 (2d, J ˆ 6.6, 3 H). C-NMR
75 MHz, CDCl ): 132.0; 125.5; 70.9 (70.5); 48.9 (48.4); 43.0 (42.9); 38.7 (37.6); 30.1 (29.7); 26.5; 20.7; 19.9; 18.5.
EI-MS (pos.): 186 ([M ‡ H] ), 135. HR-MS: 185.177900 (C11
-Amino-4-[(tert-butyl)phenyl]-3-methylbutan-2-ol (2). Application of the procedure for 1 starting with 3-
4-(tert-butyl)phenyl]-2-methylpropanal (160 mg, 0.78 mmol; reaction times: 10 h with Me SiCN and 10 h with
): 3398, 2965, 1641, 1570, 1514, 1463, 1364,
): 7.28 (d, J ˆ 8.1, 2 H); 7.09 (d, J ˆ 8.1, 2 H);
redissolved in 10 ml of CH
2
2
3
2
4
2
2
3
(
(
1
(
2
4
1
3
3
1
3
3
‡
‡
H
23NO ; calc. 185.177965).
1
[
3
LiAlH
4
) gave 2 (130 mg, 0.55 mmol, 71%). Colorless oil. IR (CHCl
3
1
1
3
270, 1110, 1075, 1020, 807, 758, 711. H-NMR (300 MHz, CDCl
3
.51 ± 3.30 (m, 1 H); 2.92 (m, 1 H); 2.75 (m, 1 H); 2.56 (m, 1 H); 2.31 (m, 1 H); 2.0 ± 1.5 (br. m, 3 H); 1.30
1
3
(
(
1
s, 9 H); 0.89, 0.81 (2d, J ˆ 7.0, 3 H). C-NMR (75 Hz, CDCl
3
): 129.9 (129.7); 126.1 (126.0); 76.3 (75.3); 46.2
‡
45.4); 40.2 (40.1); 39.5 (39.4); 32.3; 16.0 (14.9). EI-MS (pos.): 235, 236 ([M ‡ H] ), 204, 205, 189, 174, 147, 148,
‡
31, 132, 117, 91, 60, 57, 41. HR-MS: 235.193700 (C15
H
25NO ; calc. 235.193615).
1
-(Aminomethyl)-5-methyl-2-(1-methylethyl)cyclohexanol (3). Application of the procedure for 1 starting
with menthone (mixture of isomers; 620 mg, 4 mmol, reaction times: 14 h with Me SiCN and 7 h with LiAlH
): 3429, 2955, 2927, 2871, 1644, 1578, 1457,
): 2.88 ± 2.46 (m, 2 H); 2.17 ± 1.91 (m, 1 H);
3
4
)
gave 3 (630 mg, 3.40 mmol, 85.0%). Pale yellow liquid. IR (CHCl
3
1
1
388, 1295, 1168, 1105, 1030, 938, 706. H-NMR (300 MHz, CDCl
3
1
0
7
.84 (m, 1 H); 1.79 ± 1.63 (m, 2 H); 1.63 ± 1.26 (m, 5 H); 1.17 ± 1.05 (m, 1 H); 1.03, 0.94 (2d, J ˆ 7.0, 3 H); 0.92 ±
13
.84 (m, 5 H); 0.77(d, J ˆ 7, 3 H ) . C-NMR (75 MHz, CDCl
3
; mixture of three diastereoisomers) 74.9 (74.7,
4.4); 52.3 (48.4, 46.7); 46.5 (50.5, 50.1); 43.3 (46.3, 42.1); 35.8 (35.9, 31.5); 30.7 (29.5, 28.5); 26.9 (26.7, 26.0); 25.4
‡
(25.3, 24.4); 24.2 (23.5, 21.5); 23.1 (23.2, 22.9); 20.2 (21.6, 18.8). EI-MS (pos.): 185 ([M ‡ H] ), 155, 137, 112, 95,
8
1, 69, 55, 43, 41, 39.
-Amino-1-phenylethanol (4). Application of the procedure for 1 starting with PhCHO (423 mg, 4 mmol;
2
reaction times: 18 h with Me
CHCl
3
SiCN and 5 h with LiAlH
): 3366, 3030, 2925, 2872, 1579, 1478, 1453, 1331, 1204, 1064, 749, 699. H-NMR (300 MHz, CDCl
4
) gave 4 (203 mg, 1.48 mmol, 37%). Colorless oil. IR
1
(
3
3
): 7.31 ±
1
3
7
.17 (m, 5 H); 4.52 (dd, J ˆ 7.7, 4.0, 1 H); 2.80 (dd, J ˆ 12.9, 4.0, 1 H); 2.67 (dd, J ˆ 12.9, 7.7, 1 H). C-NMR
‡
(
75 MHz, CDCl
1, 39.
3
): 143.3; 129.0; 128.1; 126.5; 74.9; 49.9. EI-MS (pos.): 137 ([M ‡ H] ), 118, 107, 91, 79, 77, 65, 51,
4
2-Amino-1-(4-methoxyphenyl)ethanol (5). Application of the procedure for 1 starting with anisaldehyde
(
545 mg, 4 mmol; reaction times: 12 h with Me
3
SiCN and 4 h with LiAlH
4
) gave 5 (210 mg, 1.26 mmol, 32%).
1
Colorless oil. IR (CHCl
3
): 3417, 1645, 1514, 1467, 1250, 1178, 1029, 831, 815. H-NMR (300 MHz, CDCl
3
): 7.23
(
(
(
d, J ˆ 8.4, 2 H); 6.85 (d, J ˆ 8.4, 2 H); 4.53 (dd, J ˆ 7.7, 4.0, 1 H); 3.79 (s, 3 H); 2.87 (dd, J ˆ 12.5, 4.0, 1 H); 2.73
13
dd, J ˆ 12.5, 8.1, 1 H). C-NMR (75 MHz, CDCl
3
): 159.4; 135.1; 127.5; 114.1; 74.4; 55.6; 49.7. EI-MS (pos.): 167
‡
[M ‡ H] ), 149, 137, 121, 109, 94, 77, 66, 59, 51, 39.
1-Aminotridecan-2-ol (6). Application of the procedure for 1 starting with laurinaldehyde (737 mg,
4
mmol; reaction time: 4 h with Me
3
SiCN and 4 h with LiAIH
4
) gave 6 (326 mg, 1.51 mmol, 38%). Colorless
1
liquid. IR (KBr): 3368, 2957, 2918, 2851, 1596, 1491, 1471, 1380, 1133, 1085, 719. H-NMR (300 MHz, CDCl
3
):
3
.45 ± 3.52 (m, 1 H); 2.80 (dd, J ˆ 12.51, 3.33, 1 H); 2.45 (dd, J ˆ 12.51, 8.46, 1 H); 1.37 ± 1.42 (m, 4 H); 1.34
13
(
2
s, 20 H); 0.84 (t, J ˆ 6.99, 3 H). C-NMR (75 Hz, CDCl
3
): 72.8; 48.1; 35.5; 32.6; 30.5; 30.4; 30.4; 30.3; 30.1; 26.4;
‡
3.4; 14.8. EI-MS (pos.): 215 ([M ‡ H] ), 205, 198, 197, 180, 168, 97, 83, 70, 60, 56, 43, 41, 39.
1
-Amino-2-methyloctan-2-ol (7). Application of the procedure for 1 starting with octan-2-one (513 mg,
mmol; reaction times: 5 h with Me SiCN and 12 h with LiAlH ) gave 7 (580 mg, 3.64 mmol, 91.0%). Pale
): 3368, 2958, 2933, 2861, 1575, 1489, 1469, 1378, 1329, 1163, 1105, 947, 823, 725.
4
3
4
yellow liquid. IR (CHCl
3
1
H-NMR (300 MHz, CDCl
3
): 2.60 (d, J ˆ 12.8, 1 H); 2.53 (d, J ˆ 12.8, 1 H); 1.8 ± 1.6 (br. s, 2 H); 1.43 ± 1.26
13
(
m, 11 H); 1.08 (s, 3 H); 0.84 (m, 3 H). C-NMR (75 MHz, CDCl
3
): 72.2; 51.5; 40.4; 32.5; 30.6; 24.8; 24.5; 23.3;
‡
1
4.7. EI-MS (pos.): 160 ([M ‡ H] ), 144, 129, 111, 85, 74, 69, 55, 43, 41, 39.
1-(Aminomethyl)cyclohex-2-en-1-ol (8). Application of the procedure for 1 starting with cyclohexen-2-one
(
390 mg, 4 mmol; reaction times: 12 h with Me SiCN and 3 h with LiAlH ) gave 8 (60 mg, 0.47 mmol, 12%).
3
4

Helvetica Chimica Acta ± Vol. 86 (2003)
2935
1
Pale yellow liquid. IR (CHCl
3
): 3418, 2932, 2862, 1651, 1572, 1449, 1339, 1155, 1066, 916, 754. H-NMR
1
3
(
(
300 MHz, CDCl
75 MHz, CDCl
9, 70, 55, 41, 39.
-Amino-3-methylhex-3-en-2-ol (9). Application of the procedure for 1 starting with 2-methylpent-2-enal
3
): 5.88 ± 5.82 (m, 1 H); 5.55 (d, J ˆ 9.9, 1 H); 2.60 (m, 2 H); 2.09 ± 1.49 (m, 9 H). C-NMR
‡
3
): 131.8; 131.3; 69.8; 54.2 (51.9); 34.3; 26.1; 19.7. EI-MS (pos.): 128, 129 ([M ‡ H] ), 110, 97, 91,
7
1
(
393 mg, 4 mmol; reaction times: 2 h with Me
Orange, waxy solid. IR (CHCl
300 MHz, CDCl
3
SiCN and 7 h with LiAlH
): 3374, 2964, 2935, 2876, 1569, 1488, 1463, 1380, 1332, 1069, 865, 755. H-NMR
): 5.39 (br. t, J ˆ 7, 1 H); 3.86 (dd, J ˆ 7.4, 4.8, 1 H); 2.76 (dd, J ˆ 12.8, 4.4, 1 H); 2.64 (dd, J ˆ
4
) gave 9 (510 mg, 3.95 mmol, 99%).
1
3
(
1
3
13
2.8, 7.7, 1 H); 2.02 (quint, J ˆ 7, 2 H); 1.88 (br. s, 2 H); 1.56 (s, 3 H); 0.91 (t, J ˆ 7, 3 H ) . C-NMR (75 MHz,
‡
CDCl
MS: 129.115390 (C
3
): 135.1; 129.1; 78.0; 46.3; 21.4; 14.7; 12.7. EI-MS (pos.): 129 ([M ‡ H] ), 112, 100, 99, 81, 71, 55, 43. HR-
‡
7
H
15NO ; calc. 29.115364).
(
E)-1-Aminooct-3-en-2-ol (10). Application of the procedure for 1 starting with (E)-hept-2-enal (449 mg,
4
mmol; reaction times: 3 h with Me
M.p. 49 ± 518. IR (CHCl
CDCl
3
SiCN and 3 h with LiAlH
): 3333, 2958, 2927, 2859, 1572, 1467, 1378, 1330, 1063, 969, 822. H-NMR (300 MHz,
): 5.77 ± 5.67 (m, 1 H); 5.38 (dd, J ˆ 15.4, 6.6, 1 H); 4.03 ± 3.96 (m, 1 H); 2.78 (dd, J ˆ 12.9, 4.4, 1 H); 2.59
4
) gave 10 (250 mg, 1.75 mmol, 44%). Milky rime.
1
3
3
13
(
(
dd, J ˆ 12.9, 8.6, 1 H); 2.01 (m, 2 H); 1.90 ± 1.55 (br. s, 3 H); 1.43 ± 1.24 (m, 4 H); 0.86 (t, J ˆ 7, 3 H ) . C-NMR
‡
75 MHz, CDCl
3
): 133.9; 130.9; 73.8; 48.1; 32.6; 31.9; 22.9; 14.6. EI-MS (pos.): 143, 144 ([M ‡ H] ), 126, 113, 99,
‡
9
5, 82, 69, 57, 55, 43, 41, 39. HR-MS: 143.131010 (C
8
H
17NO ; calc. 143.131014).
(
Z)-1-Aminooct-5-en-2-ol (11). Application of the procedure for 1 starting with (Z)-hept-4-enal (449 mg,
4
mmol; reaction times: 3 h with Me
3
SiCN and 3 h with LiAlH
4
) gave 11 (490 mg, 3.42 mmol, 86%). Colorless
1
liquid. IR (CHCl
3
): 3438, 2965, 2935, 1635, 1572, 1489, 1337, 1069, 724. H-NMR (300 MHz, CDCl
3
): 5.42 ± 5.27
(
m, 2 H); 3.55 ± 3.47 (m, 1 H); 2.78 (dd, J ˆ 12.5, 3.3, 1 H); 2.48 (dd, J ˆ 12.5, 8.4, 1 H); 2.21 ± 1.99 (m, 7 H);
13
1
1
1
.49 ± 1.40 (m, 2 H); 0.92 (t, J ˆ 7.3, 3 H). C-NMR (75 MHz, CDCl
3
): 132.6; 128.9; 72.1; 47.8; 35.1; 23.8; 20.9;
‡
‡
4.7. EI-MS (pos.): 143, 144 ([M ‡ H] ), 128, 65, 84, 72, 69, 43, 41, 39. HR-MS: 143.131560 (C
8
H
17NO ; calc.
43.131014).
1-Amino-2,5-dimethylhept-5-en-2-ol (12). Application of the procedure for 1 starting with 5-methylhex-5-
en-2-one (449 mg, 4 mmol; reaction times: 3 h with Me
8%) as a pale yellow liquid. IR (CHCl
300 MHz, CDCl
3
SiCN and 3 h with LiAlH
): 3431, 2973, 2939, 1647, 1570, 1490, 1376, 1330, 1135, 887. H-NMR
): 4.69 (d, J ˆ 0.7, 2 H); 2.55 (dd, J ˆ 22.8, 12.9, 2 H); 2.03 (m, 2 H); 1.73 (s, 3 H); 1.60 ± 1.45
4
) gave 12 (390 mg, 2.72 mmol,
1
6
(
(
3
3
13
m, 2 H); 1.12 (s, 3 H). C-NMR (75 MHz, CDCl
3
): 146.9; 110.2; 72.1; 51.5; 38.3; 32.6; 24.8; 23.4. EI-MS (pos.):
‡
‡
1
44 ([M ‡ H] ), 128, 126, 113, 112, 95, 86, 74, 69, 55, 43, 41, 39. HR-MS: 144.1394 (C
8
H
18NO, [M ‡ H] ; calc.
1
44.1388).
-[(2-hydroxypentyl)amino]pentan-2-ol (13). A solution of 2-pentyloxirane (860 mg, 10 mmol) in 25% aq.
OH was stirred at r.t. for 24 h, then the soln. was filtered and dried to give 13 (700 mg, 68%). Colorless solid.
1
NH
4
M.p. 101 ± 1038. IR (CHCl
H-NMR (300 MHz, CDCl
3
): 3326, 3299, 2956, 2926, 2903, 2874, 2834, 1463, 1451, 1337, 1126, 1026, 905, 890, 846.
): 3.68 ± 3.60 (m, 1 H); 2.66 (dd, J ˆ 12.2, 3.3, 1 H); 2.47 (dd, J ˆ 12.2, 8.8, 1 H);
1
3
1
3
1
.52 ± 1.30 (m, 4 H); 0.90 (t, J ˆ 7.35, 3 H). C-NMR (75 MHz, CDCl
3
): 70.2; 55.7; 37.6; 19.2; 14.5. EI-MS (pos.):
‡
‡
(
M ), 189, 146, 116, 98, 69, 42. HR-MS: 189.172870 (C10
H23NO
2
; calc. 89.172879).
N,N-Bis(2-acetoxypentyl)acetamide (14). Acetylation of 13 (100 mg) in Ac
4 h at 208, followed by evaporation with toluene, gave 14 quantitatively. Pale yellow oil. H-NMR (300 MHz,
2
O (1 ml) and pyridine (1 ml) for
1
2
CDCl
H); 1.47 ± 1.41 (m, 4 H); 1.39 ± 1.31 (m, 4 H); 2.08 (s, 3 H); 2.08 (s, 3 H); 2.00 (s, 3 H); 1.47 ± 1.41 (m, 4 H);
.39 ± 1.31 (m, 4 H); 0.94 ± 0.86 (m, 6 H). 13C-NMR (75 MHz, CDCl
): 171.8; 171.5; 170.9; 72.2; 71.4; 52.2; 48.8;
3
): 5.05 (ddd, J ˆ 10.7, 8.8, 4.05, 2 H); 3.76 (dd, J ˆ 14.3, 8.8, 1 H); 3.49 ± 3.32 (m, 2 H); 3.19 (d, J ˆ 14.7,
1
1
3
3
4.9; 34.7; 22.2; 21.8; 21.6; 19.2; 19.1; 14.49; 14.48.
Preparation of Acidic Salts. Acidic salts of the amino alcohols were prepared by adding either 2 equiv. of 1m
aq. HCl or 1 equiv. of AcOH or PhCOOH to a soln. of amino alcohol (100 mg) in 10 ml of EtOH. The soln. were
briefly heated at 408 and evaporated to dryness. The salts showed NMR, MS, and IR data in accordance with the
expected products.
Preparation of Amino Alcohol-Impregnated Supports. Na
alcohol (10 mg) and NaIO (10 mg), and thoroughly ground. Alternatively, a filter-paper disk (10-cm diameter)
was impregnated with 60 ml of a 0.1m soln. of amino alcohol in EtOH and dried. The impregnated filter-paper
disk was put on top of a second, non-impregnated filter-paper disk. Solid NaIO (50 mg) in grains was attached
2 4
SO or MgO (1 g) were mixed with the amino
4
4
to the other side of this second filter paper with scotch tape. Both the powder formulation and the filter-paper-
device formulation could be stored under anh. conditions at r.t. Fragrance released could be triggered at will by
addition of a few drops of H
2
O, even after several months of storage. When left in moist air, the devices slowly
released the fragrant carbonyl.

2
936
Helvetica Chimica Acta ± Vol. 86 (2003)
GC/MS Experiments. An aq. soln. of the AcOH salt of amino alcohol 1 (pro-citronellal; 0.07 ml, 0.1m) was
stirred with 1 ml of AcOEt. GC/MS Analysis of the org. phase showed no detectable peak. NaIO
4 2
(0.1m in H O,
0
.07 ml) was then added. After 10 min, the org. phase was separated and analyzed by GC/MS, showing the
presence of citronellal. The experiment with the hydrochloride salt of promenthone 3 gave identical results.
REFERENCES
[
1] a) P. Kraft, J. A. Bajgrowicz, C. Denis, G. Fr a¬ ter, Angew. Chem. 2000, 112, 3106; Angew. Chem., Int. Ed.
2000, 39, 2980; b) K. Bauer, D. Garbe, H. Surgburg, −Common Fragrance and Flavor Materials×, Wiley-
VCH, Weinheim, 1997.
[
[
[
2] M. Gautschi, J. A. Bajgrowicz, P. Kraft, Chimia 2001, 55, 379.
3] C. Quellet, M. Schudel, R. Ringgenberg, Chimia 2001, 55, 421.
4] a) W. Paget, D. Reichlin, R. L. Snowden, E. C. Walborsky, C. Vial (Firmenich), WO 95/04809, 1995; b) D.
Anderson, G. Fr a¬ ter (Givaudan), EP 98 810 114 A1, 1998.
[5] a) J. Pika, A. Herrmann, C. Vial (Firmenich), WO 99/60990, 1999; b) S. Rochat, C. Minardi, J.-Y. de Saint
Laumer, A. Herrmann, Helv. Chim. Acta 2000, 83, 1645.
[
[
6] A. J. Fatiadi, Synthesis 1974, 229.
7] a) F. Badalassi, D. Wahler, G. Klein, P. Crotti, J.-L. Reymond, Angew. Chem. 2000, 112, 4233 ± 4236; Angew.
Chem., Int. Ed. 2000, 39, 4067; b) D. Wahler, F. Badalassi, P. Crotti, J.-L. Reymond, Angew. Chem. 2001,
113, 4589; Angew. Chem., Int. Ed. 2001, 40, 4457; c) D. Wahler, F. Badalassi, P. Crotti, J.-L. Reymond,
Chem. Eur. J. 2002, 8, 3211.
[8] D. A. Evans, L. K. Truesdale, Tetrahedron. Lett. 1973, 4929.
Received April 11, 2003