γ,δ- and δ,ε-unsaturated aldehydes from γ- and δ-lactones in one step: Preliminary communication

Article abstract of DOI:10.1002/hlca.200490153

A one-step transformation of δ- and δ-(spiro)lactones into δ,δ- and δ,ε-unsaturated aldehydes with an excess of formic acid in the vapor phase over a supported manganese catalyst is described for the first time. The scope and limitations of this new reaction are shown with different lactones as substrate, and a mechanistic rationale is proposed.

Full text of DOI:10.1002/hlca.200490153

Helvetica Chimica Acta Vol. 87 (2004)
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g,d- and d,e-Unsaturated Aldehydes from g- and d-Lactones in One Step
Preliminary Communication
by Wolfgang Giersch and Ferdinand Naef*
Firmenich SA, Corporate R&D Division, CH-1211 Geneva 8
(phone: ‡41227803034; fax: ‡41227803334; e-mail:ferdinand.naef@firmenich.com)
Dedicated to G¸nther Ohloff on the occasion of his 80th birthday
A one-step transformation of g- and d-(spiro)lactones into g,d- and d,e-unsaturated aldehydes with an
excess of formic acid in the vapor phase over a supported manganese catalyst is described for the first time. The
scope and limitations of this new reaction are shown with different lactones as substrate, and a mechanistic
rationale is proposed.
1.Introduction. One of the most efficient syntheses of aldehydes consists of the
one-step reduction of carboxylic acids by means of the so called PiriaÀLimpricht
reaction first published in 1856 and more or less forgotten in the meantime [1][2]. In
the original procedure, a mixture of the calcium salts of the acid to be reduced and
formic acid as reducing agent were pyrolyzed in a retort by heating with a Bunsen
burner. The resulting reaction products were the aldehyde, H2O, and CO2. After
further refinement of the method and the use of barium instead of calcium salts [3][4],
the reaction could be rendered catalytic by Sabatier and Mailhe [5][6] in 1912 14 by
using titanium or manganese oxides as catalysts at temperatures between 3008 and 3608,
with yields of 50 70%. More surprisingly, and already in 1907, a patent of the Badische
Anilin und Sodafabrik (BASF) [7] disclosed the catalytic reduction in the gas phase of
carboxylic acids to aldehydes with H2 at ca. 3008. In the 1980s, this reaction was
rediscovered and refined as can be seen from the patent literature (for some leading but
not exhaustive references see [8 12]).
As we were seeking an efficient process for the synthesis of the fragrance aldehyde
(Æ)-3-[4-(tert-butyl)cyclohex-1-en-1-yl]propanal (1) [13], we asked ourselves whether
it might be possible to transform the known lactone 2 (64 :36 mixture of cis- and trans-
8-(tert-butyl)-1-oxaspiro[4.5]decan-2-one (2a and 2b, resp.)) [14] in one step into the
unsaturated aldehyde 1 (Scheme 1) by making use of a PiriaÀLimpricht-type reduction
with simultaneous lactone opening.
2.Results.
When a solution of lactone 2 (64 :36 mixture 2a/2b throughout this
report, not further specified) in 5 volumes of formic acid was allowed to pass through a
quartz tube filled with a catalyst of manganese oxide on pumice1) (for apparatus, see
1
)
Pumice is a light kind of lava, usually consisting of obsidian made spongy or porous by the escape of steam
or gas during the process of cooling.

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 1
Exper.Part ) at ca. 4008, we obtained the unsaturated aldehyde 1 in 47% yield. To
optimize the reaction conditions, we varied the metal salts (Fe, Cu, Ag, Pd, Ni, Co, Zn,
Mn, Zn/Mn, Ru/Sn salts), the support (coarse and fine pumice, Al2O3), catalyst
quantity, column dimensions, and temperature. Interestingly, some catalysts furnished
structures other than the desired aldehyde 1 (see Scheme 2 and Table 1).
Scheme 2
Table 1. Reduction of Spirolactone 2 with Formic Acid and Different Catalysts
Entry
Catalysta)
Temp.
Product mixture
1
2
3
4
1
2
3
4
5
6
MnSO4/pumice
CuSO4/pumice
AgNO3/pumice
CdSO4/pumice
Zn(OAc)2/pumice
Zn(OAc)/Mn(OAc)2/pumice
4008
4408
4408
44084%
4408
51%
1%
49%
20%
17%
30%
30%
32%
42%
14%
3%
42%
40%
20%
13%
60%
33%
4408
7%
a) For catalyst preparation, see Exper.Part. However, the nature of the actual catalytic species remains
unknown.
In our preliminary experiments MnII salts showed the best selectivity and yield of all
the salts tested. With a ZnII catalyst and formic acid, we obtained mostly acid 3 and only
traces of the desired aldehyde 1. A result that suggests that the first step in our new

Helvetica Chimica Acta Vol. 87 (2004)
1699
reaction is a Lewis acid catalyzed opening of the lactone to the unsaturated acid 3,
which then undergoes a PiriaÀLimpricht reduction. Under stronger reaction con-
ditions, however, and with the same catalyst, in addition to 3, major amounts of ketone
4 were formed. This product can be accounted for as an intra-molecular FriedelÀ
Crafts-type acylation of unsaturated acid 3.
Therefore, we decided to test a mixed catalyst containing ZnII in addition to MnII on
pumice, which turned out to be a much better system in our hands. With formic acid as
reducing agent and solvent (twelve-fold excess) at 4008 in an N2 stream, 1 (60%)
besides 2 (7%) and 3 (3%) were obtained (Table 1, Entry 6).
Preliminary experiments with H2 as reducing agent instead of formic acid (see [7
12]) gave low yields of aldehyde 1 and were, therefore, not further pursued.
To explore the structural scope and limitations of the reaction, we tested a variety of
five- and six-membered lactones. Thus, lactones 5 14 were transformed to aldehydes
6 13 in the presence of different catalysts (see Table 2).
Table 2. Reduction of Various Lactones with Formic Acid and Different Catalysts at 4508
Entry Starting materials
Catalyst
Products
Yield
1
MnSO4/pumice
27.9%
2
3
MnSO4/pumice
MnSO4/pumice
6%
35.7%
4
MnSO4/pumice
31.4%
8%
5
6
RuCl3/SnCl2/pumice
Mn(OAc)2/Zn(OAc)2/pumice
Mn(OAc)2/Zn(OAc)2/pumice
0%
15.3%

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Helvetica Chimica Acta Vol. 87 (2004)
3.Discussion.
As exemplified in Table 2, this new reaction converts in one step
five- and six-membered lactones to the corresponding g,d- and d,e-unsaturated
aldehydes, however, not always in satisfactory yields for preparative purposes. The best
yields resulted from the five- and six-membered spirolactones 5 and 9 and the octahydro-
2H-1-benzopyranone 11 (28 36%; Table 2, Entries 1, 3, and 4). In the case of the
monosubstituted five- and six-membered lactones 12 and 14, low yields of the same
linear, unsaturated aldehyde 13 with (E)-configuration were obtained (Entries 5 and 6).
For a mechanistic rationale of this surprising reaction, we would like to discuss the
following possibility (see Scheme 3). We postulate as a first intermediate the mixed
anhydride 15, which is assumed to be formed with formic acid under concomitant ring
opening of the lactone directly or via the unsaturated acid 3. The reaction is probably
assisted by our MnII catalyst (see also [15]). The anhydride must then form a complex
with the amphoteric (acidÀbase) MnX2 catalyst of the polar structure type 16 which, in
close similarity to the MeerweinÀPonndorfÀVerley reduction [16][17], favors a 1,3-H
2
shift to 17, helped by the MnX2 catalyst and energetically driven by the formation of CO2 ).
Scheme 3
To establish that mixed formic carboxylic anhydrides may be intermediates in the
PiriaÀLimpricht reaction, we pyrolyzed the readily accessible formic octanoic anhydride
(19; prepared from 18 as shown in Scheme 4). The mixed anhydride 19 proved extremely
unstable and was transformed at room temperature into the symmetrical octanoic
anhydride (20) and formic acid. Excess of formic acid should then drive the equilibrium
towards the mixed anhydride (see also the preparation of acetic formic anhydride from
acetic anhydride and formic acid [18]). At 3008 over a MnII/ZnII catalyst, 19
decomposed to octanal (21; 3%), octanoic acid (22; 34%), and pentadecan-8-one
(23; 62%) (originating from the symmetrical anhydride 20 being formed under the
reaction conditions). However, 19 in the presence of a two-fold excess of formic acid
gave octanal (21; 19%), octanoic acid (22; 63%), and ketone 23 (only 11%) (Scheme 4).
2
)
The involvement of a possible metal hydride as a reducing agent was discounted mainly due to the absence
of any alcohol by-products as well as the absence of CˆC bond reduction in the unsaturated aldehydes
obtained.

Helvetica Chimica Acta Vol. 87 (2004)
1701
Scheme 4
However, the proposed mechanism does not explain the reduction of carboxylic
acids (or of our lactone 2) with H2 at 300 4008 in the presence of the same type of
heterogeneous catalysts [7 12], an interesting question beyond the scope of the
present study, but which should be addressed in future investigations.
4.Conclusions.
In spite of many open mechanistic questions, this new one-step
transformation of (spiro)lactones into unsaturated aldehydes is attractive from a
preparative point of view. Further examples and yet better catalysts will be needed to
show the real value of this surprising reaction.
The authors are indebted to Mrs. V.Revillet and C.Bise for careful experimental work, to Prof. P.Vogel ,
EPF-Lausanne, for helpful mechanistic discussions, to Mr. W.Thommen for having recorded the spectral data,
to Dr. O.Haefliger for LC/MS measurements, and to Dr. E.Walther for reference samples.
Experimental Part
1. General. Flash chromatography (FC):Silica gel 60, 30 70 mm. GC: Varian STAR 3400; He as carrier gas;
fushed-silica capillary columns SPB-1 and Supelcowax¾, each 30 m  0.25 mm i.d. with 0.25 mm film. IR
1
Spectra: Perkin-Elmer-1600-FT-IR spectrometer; nÄ in cmÀ1. H- and 13C-NMR Spectra: Bruker-DPX-400 or -
AV-500 spectrometers; d in ppm downfield from SiMe4, J in Hz. GC/MS: Hewlett-Packard-5890 or -6890 system
equipped with a capillary column, 30 m  0.25 mm i.d. coupled with a Hewlett-Packard-MSD-5972 or -5973
quadrupole mass spectrometer; electron energy ca. 70 eV; in m/z (rel. int. in % of the base peak).
2. Catalyst Preparation. 2.1. MnII/Pumice. Mn(OAc)2 (Merck; 5 g), pumice stones (Riedel de Hae»n; 50 g;
diameter ca. 1 3 mm), and H2O (200 ml) were stirred at 508 for 1 h. Then the mixture was filtered and the solid
washed with distilled H2O (100 ml) and finally dried at 4508.
2.2. CuII/Pumice. As described in 2.1, with CuSO4 (Reactolab S.A.; 5 g), pumice stones (50 g), and H2O
(200 ml).
2.3. AgI/Pumice. As described in 2.1, with AgNO3 (Acros; 6 g), pumice stones (50 g), and H2O (150 ml) (3 h).
2.4. CdII/Pumice. CdSO4 ¥ 8 H2O (Merck; 3 g), pumice stones (100 g), and H2O (300 ml) were stirred at 508
for 1 h. Then the mixture was evaporated and the residue dried at 4008.
2.5. ZnII/Pumice. Zn(OAc) ¥ 2 H2O (Fluka; 5 g), pumice stones (50 g), and H2O (100 ml) were stirred at 508
for 1 h and stored overnight at r.t. Then the mixture was evaporated and the residue dried at 4308.
2.6. ZnII/MnII/Pumice. As described in 2.5, with Zn(OAc)2 ¥ 2 H2O (Fluka; 2.5 g), Mn(OAc)2 (Merck;
2.5 g), pumice stones (50 g), and H2O (100 ml).
2.7. RuIII/SnII/Pumice [12]. RuCl3 hydrate (Fluka; 2 g), SnCl2 (Fluka; 10 g), and 3n HCl (15 ml) were stirred
»
at 908 (water bath) for 1 h. Then pumice stones (Riedel de Haen; 50 g; diameter 1.4 mm) were added at r.t. The
mixture was stored overnight, then dried at 4508 in a steam of N2 in a column, and finally reduced with H2 during
4 h at 4508.

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Helvetica Chimica Acta Vol. 87 (2004)
3. Thermal Reaction. 3.1. Thermolysis: General Procedure. The apparatus consisted of an oven (Carbolite)
and a quartz column (1 m  30 mm i.d.) filled with catalyst (length 10 cm) in its upper part (see Fig.). A 10%
soln. of lactone in formic acid (Acros; 99%) was introduced at the top of the column (10 ml/h) with an automatic
syringe pump (Bioblock Scientific-Razel Scientific Instruments, Inc.) in an N2 stream (300 ml/min) at 370 4508.
t
The pyrolysate was trapped in a flask (cooled with ice) connected to a gas washer (filled with BuOMe). The
combined org. soln. was washed with brine and then distilled.
Figure. Apparatus used
3.2. ( Æ )-3-[4-(tert-Butyl)cyclohex-1-en-1-yl]propanal (1). The pyrolysate was distilled at 1208/0.6 mbar: 1.
1H-NMR:0.85 ( s, 9 H); 5.41 (br. s, 1 H); 9.75 (t, J ˆ 2, 1 H). 13C-NMR:24.1 ( t); 26.8 (t); 27.2 (q); 29.7 (t); 29.9
‡
(t); 32.2 (s); 41.9 (t); 44.0 (d); 122.1 (d); 135.5 (s); 202.8 (d). MS:194 (7, M ), 150 (10), 137 (9), 120 (23), 94
(43), 79 (30), 57 (100), 41 (49).
3.3. 3-(Cyclohex-1-en-1-yl)propanal/3-Cyclohexylidenepropanal (6). The pyrolysate was distilled at 1158/
0.13 mbar and then purified by FC (pentane/Et2O 8 :2):mixture 6 of CˆC bond isomers, not separated by GC.
1H-NMR:5.41 (br. s); 5.52 5.71 (m); 9.77 (ca. 70%) and 9.79 (ca. 30%) (2t, J ˆ 2, 1 H). 13C-NMR:major
isomer:22.4 ( t); 22.8 (t); 25.2 (t); 28.4 (t); 30.2 (t); 41.9 (t); 121.9 (d); 135.7 (s); 202.8 (d); minor isomer:21.3 ( t);
‡
25.3 (t); 28.2 (t); 28.7 (t); 34.6 (t); 41.4 (t); 128.0 (d); 130.8 (d). MS:138 (9, M ), 120 (12), 109 (13), 94 (88), 79
(100), 67 (41), 41 (27).
3.4. (Cyclohex-1-en-1-yl)acetaldehyde/Cyclohexylideneacetaldehyde (8). The pyrolysate was distilled at
‡
1008/0.15 mbar:complex mixture containing 8. MS (less polar peak):124 (16, M ), 109 (6), 95 (31), 80 (100), 67
(37), 53 (19), 39 (28).
3.5. 4-(Cyclohex-1-en-1-yl)butanal/4-Cyclohexylidenebutanal (10). The pyrolysate was distilled at 1508/
0.4 mbar and then purified by FC (toluene/Et2O 9 :1):7:3 mixture 10 of two CˆC bond isomers. 1H-NMR:5.03
(t, J ˆ 7, 1 H) and 5.42 (br. s, 1 H); 9.73 (br. s, 1 H). 13C-NMR:major isomer:20.1 ( t); 22.5 (t); 22.9 (t); 25.2 (t);
28.1 (t); 37.3 (t); 43.4 (t); 122.1 (d); 136.5 (s); minor isomer:26.8 ( t); 27.7 (t); 28.6 (t); 28.7 (t); 37.1 (t); 44.3 (t);
‡
118.7 (d); 140.5 (s); 202.7 (d). MS:major isomer:152 (1, M ), 134 (57), 108 (62), 93 (68), 93 (68), 79 (100), 67
‡
(50), 41 (38); minor isomer:152 (2, M ), 134 (69), 108 (65), 93 (56), 81 (93), 67 (100), 41 (56).
3.6. Non-3-enal/Non-4-enal (13). The pyrolysate was distilled at 1508/30 mbar and then purified by FC
(cyclohexane/Et2O 9 :1):mixture 13 contaminated with some nonanal. 1H-NMR:0.88 ( t, J ˆ 7, 3 H); 5.31 5.52
(m, 2 H); 9.77 (m, 1 H). 13C-NMR:major isomer:13.7 ( q); 22.0 (t); 29.1 (t); 31.8 (t); 31.9 (t); 43.6 (t); 127.6 (d);
132.1 (d); 202.5 (d); minor isomer:14.0 ( q); 22.1 (t); 29.2 (t); 31.6 (t); 32.1 (t); 44.0 (t); 127.0 (d); 131.7 (d); 203.0

Helvetica Chimica Acta Vol. 87 (2004)
1703
‡
(d). MS:major isomer:140 (1, M ), 122 (14), 96 (42), 84 (100), 67 (49), 55 (77), 41 (81); minor isomer:140 (1,
‡
M ), 122 (17), 96 (72), 81 (90), 67 (78), 55 (96), 41 (100).
3.7. 3-[4-(tert-Butyl)cyclohex-1-en-1-yl]propanoic Acid (3). The pyrolysate from 2 was purified by FC
(toluene/Et2O 9 :1). 1H-NMR:0.86 ( s, 9 H); 1.12 1.31 (m, 2 H); 1.72 1.85 (m, 2 H); 1.93 2.05 (m, 3 H);
2.21 2.31 (m, 2 H); 2.42 2.53 (m, 2 H); 5.41 (br. s, 1 H). 13C-NMR:24.2 ( t); 26.8 (t); 27.2 (q); 29.8 (t); 32.1 (t);
‡
32.2 (s); 32.7 (t); 44.0 (d); 121.9 (d); 135.6 (s); 180.3 (s). MS:210 (12, M ), 195 (4), 154 (40), 136 (54), 93 (59),
57 (100).
1
3.8. 6-(tert-Butyl)-2,3,4,5,6,7-hexahydro-1H-inden-1-one (4). H-NMR:0.91 ( s, 9 H); 1.25 1.32 (m, 2 H);
1.73 1.81 (m, 1 H); 1.92 1.99 (m, 1 H); 2.31 2.55 (m, 7 H). 13C-NMR:21.7 ( t); 23.7 (t); 27.3 (q); 29.6 (t); 32.4
‡
(s); 35.1 (t); 44.1 (d); 139.3 (s); 173.7 (s); 209.3 (s). MS:192 (28, M ), 177 (8), 136 (100), 121 (21), 91 (14), 79
(15), 57 (42), 41 (27).
3.9. Formic Octanoic Anhydride (19). To a soln. of formic acid (6.5 g, 140 mmol) in N,N-dimethylaniline
(Fluka; 17.8 ml, 140 mmol) was added dropwise octanoyl chloride (18) (Fluka; 20 g, 123 mmol) at À58 (ice/salt
bath) with stirring. After 1 h, the mixture was poured onto ice and extracted with pentane. This soln. was washed
with ice-cold 10% HCl soln., ice-cold NaHCO3 soln., and ice-cold brine, then dried (Na2SO4), and evaporated at
108:14.3 g of crude 19. IR:1762.3, 1787.7. 1H-NMR:0.88 ( t, J ˆ 7, 3 H); 1.28 1.35 (m, 8 H); 1.69 (quint., J ˆ 7,
2 H); 2.5 (t, J ˆ 7, 2 H); 9.1 (s, 1 H). 13C-NMR:14.1 ( q); 22.6 (t); 23.9 (t); 28.80 (t); 28.81 (t); 31.6 (t); 34.3 (t);
156.4 (d); 170.8 (s).
3.10. Octanoic Anhydride (20). As described in 3.9, but washing at r.t. resulted in rearrangement to 20. IR:
1
1749.4, 1817.3. H-NMR:0.88 ( t, J ˆ 7, 6 H); 1.21 1.38 (m, 16 H); 1.67 (quint., J ˆ 7, 4 H); 2.45 (t, J ˆ 7, 4 H ) .
13C-NMR:14.05 ( q); 14.13 (q); 22.6 (t); 22.7 (t); 24.3 (t); 28.9 (t); 29.7 (t); 31.6 (t); 35.3 (t); 169.7 (s).
3.11. Octanal (21). Crude 19 (14 g) was subjected to thermolysis at 4008 in an N2 stream (catalyst:
Zn(OAc)2/Mn(OAc)2 on pumice, 15-cm catalyst bed), and the product was cooled in two traps (ice cooling).
Distillation of the pyrolysate at 95 1758/0.28 mbar gave 9.7 g of 21 (2.7%), octanoic acid (22; 33.2%), and
pentadecan-8-one (23; 62.2%) (by GC/MS).
The same thermolysis (14 g of 19) but in the presence of formic acid (7.7 g, 2 mol-equiv.) furnished a crude
mixture (8.8 g) of 21 (18.6%), 22 (62.7%), and 23 (11.3%).
‡
Data of 21:MS:128 (2, M ), 110 (18), 100 (27), 95 (19), 84 (100), 69 (58), 57 (96), 43 (94).
‡
Data of 22:MS:144 (2, M ), 115 (15), 101 (34), 85 (28), 73 (80), 60 (100), 43 (31).
‡
Data of 23:MS:226 (3, M ), 155 (18), 142 (25), 127 (100), 109 (10), 99 (13), 82 (23), 71 (37), 57 (87), 43 (25).
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Received February 19, 2004