Synthesis of 1,3,5-trioxanes: Catalytic cyclotrimerization of aldehydes

Article abstract of DOI:10.1055/s-1998-2053

A series of 1,3,5-trioxanes derived from a single aldehyde, or from two aldehydes, were synthesized with methylrhenium trioxide as a catalyst. Cyclotrimerization of the aldehydes gave excellent yields under proper conditions, as did diethyl ketomalonate. A possible intermediate in the case of propionaldehyde was observed using ¹H NMR spectroscopy. Water inhibits both forward and reverse reactions.

Full text of DOI:10.1055/s-1998-2053

April 1998
SYNTHESIS
417
Synthesis of 1,3,5–Trioxanes: Catalytic Cyclotrimerization of Aldehydes
Zuolin Zhu, James H. Espenson*
Ames Laboratory and Department of Chemistry, Iowa State University, Ames, Iowa 50011, USA
Fax +1(515)2945233; E-mail: espenson@ameslab.gov
Received 20 March 1997; revised 22 July 1997
Abstract: A series of 1,3,5-trioxanes derived from a single alde-
hyde, or from two aldehydes, were synthesized with methylrhe-
nium trioxide as a catalyst. Cyclotrimerization of the aldehydes
gave excellent yields under proper conditions, as did diethyl keto-
malonate. A possible intermediate in the case of propionaldehyde
was observed using 1H NMR spectroscopy. Water inhibits both
forward and reverse reactions.
dient optimization method. Each optimized structure
found the R groups of the trioxanes were preferred in
equatorial positions. The NMR spectra of the isolated
products support the all-equatorial configuration. A sin-
gle-crystal X-ray determination was carried out to con-
firm this point, and also to show definitively that a trimer
was formed. The ORTEP diagram is displayed in the Fig-
ure. The structure is characterized by bond distances and
angles that are all within the normal ranges; for example:
d(O–C1) = 142.1 pm, d(C1–C2) = 150.6 pm, d(C2–C3) =
149.6 pm, Є(C2–C1–O1) = 109.4°, Ð(C3–C2–C1) =
113.1°, and Ð(O1–C1–O1b) = 109.5°.
Key words: methylrhenium trioxide (MTO), 1,3,5-trioxane, cata-
lytic cyclotrimerization
Practical applications abound for 1,3,5-trioxanes1 in dif-
ferent fields: as constituents of a stabilizing solution in col-
or photography, as burning regulators in fumigants for
potato tuber sprouting inhibition and as the basis for many
polymers and co-polymers reported in the patent litera-
ture.2,3 Relatively few reports have dealt with the trimeriza-
tion of aldehydes to form 1,3,5-trioxanes, limited to the
following: acetaldehyde, propionaldehyde, isobutyralde-
hyde, isovaleraldehyde, and 4-tert-butylbenzaldehyde.1,4–6
The reported methods require pretreatment of the catalyst,1
the use of a catalyst insoluble in the nonpolar solvent,6 or
result in a reaction that gives rise to several byproducts.4–6
Here we report a new method, based on the catalyst meth-
ylrhenium trioxide (MeReO3, abbreviated as MTO), that
does not suffer from these limitations.We have undertaken
research to describe the synthesis of 1,3,5-trioxanes from a
series of aldehydes and from one keto ester (Scheme 1).
Scheme 1
Figure: ORTEP Diagram for the 1,3,5-Trioxane Prepared from Phe-
nylacetaldehyde (12), Showing the All-Equatorial Stereochemistry
The 1,3,5-trioxanes were prepared by the catalytic cyclo-
trimerization of aldehydes (Scheme 1). Acetaldehyde,
propionaldehyde, and diethyl ketomalonate were used
neat or as solutions in chloroform or benzene; the other al-
dehydes were used as neat liquids. Nearly all of the alde-
hydes gave high yields of the trimeric product, although
the yields were lower for large R groups. No other prod-
ucts were observed: dimers, tetramers, and aldol conden-
sation products were absent. The data for the 1,3,5-
trioxanes are summarized in Table 1. No difference in the
reaction time or the product yield was observed for puri-
fied butyraldehyde as compared to the commercial mate-
rial. Diethyl ketomalonate is the only non-aldehyde
carbonyl compound found that undergoes this reaction, al-
though many others were tried; it provides a 1,3,5-triox-
ane with six substituents at the 2, 4 and 6-positions.
Mixed 1,3,5-trioxanes can be obtained from one aldehyde
taken in limiting amount, the other as the solvent, with a
catalytic concentration of MTO (Scheme 2). As shown in
Table 2, the mixed trioxanes contain one R group from the
limiting compound, two from the other.
Scheme 2
Although a good yield of the 1,3,5-trioxane was obtained
from PhCH2CHO, no reaction was found for Ph2CHCHO
or PhCH(Me)CHO. The introduction of a bulky or elec-
tron-withdrawing substituent at the a-position of the alde-
Scheme 1 shows the R groups of the trioxanes in equato- hyde inhibited the reaction. No trioxane or other product
rial positions,7 the more thermodynamically stable iso- was obtained from PhCHO, BrCH2CHO, CH2ClCHO,
mer.8 An MM2 calculation on 1,3,5-trioxanes was CBr3CHO, CCl3CHO, or RCH=CHCHO (R = H, alkyl, ar-
performed using the CAChe system with a conjugate gra- yl), 2-ethylhexanal. It was suggested16 that the failure of

418
Papers
SYNTHESIS
oxygen in 1,3,5-trioxane is derived from the 18O-label of
MTO and further supports the catalytic role assigned to
MTO.
Table 1. 1,3,5-Trioxanes 20–38 obtained from the Trimerization of
Aldehydes 1–19b
Aldehyde
(RCHO)
Reaction Conditions Product Yieldb
This experiment is not without its difficulties, however, in
that a number of peaks were detected. If the parent peak is
set at 100%, then no other peak rises above 5%. This al-
lows us to report that no molecule with two 18O’s rises
much above background level.
Time (d) Temp (°C)
(%)
MeCHO (1)
EtCHO (2)
PrCHO (3)
BuCHO (4)
C5H11CHO (5)
C6H13CHO (6)
C7H15CHO (7)
C8H17CHO (8)
1
1
1
2
2
2
3
4
1
1
4
r.t.
r.t.
r.t.
< –10
< –10
< –10
< –30
< –30
r.t.
20
21
22
23
24
25
26
27
28
29
30
> 99
> 99
> 98
> 99
> 92
> 95
> 95
90
For several of the aldehydes it proved feasible to observe
but not to isolate an intermediate. In the 1H NMR spectra,
these species had spectra similar to that of related, inde-
pendently characterized bis(alkoxy)rhenium compounds,9
prepared from an epoxide and MTO. The methyl group la-
beled as being attached to rhenium has a chemical shift
c-C6H11CHO (9)
i-PrCHO (10)
87
> 88
> 92
r.t.
< –10
(E)-Me(CH2)4CH
=CH(CH2)2CHO (11)
PhCH2CHO (12)
PhCH2CH2CHO (13)
MeCH(Me)CH2CHO (14)
MeCH2CH(Me)CHO (15)
MeCH2CH2CH(Me)CHO (16) 6
t-BuCHO (17)
CH2=CH(CH2)8CHO (18)
EtO2CCOCO2Et (19)
4
5
3
4
< –30
< –30
< –30
< –30
< –50
r.t.
31
32
33
34
35
36
37
38
82
80
85
90
90
82
90
84
Table 3. Comparison of the 1H NMR spectra [CDCl3/TMS, d, J (Hz)]
of the Rhenium Intermediates from Propylene Oxide and Propional-
dehyde
3
3
2
From MTO+Propylene Oxidea
From MTO+Propionaldehydeb
< 0
r.t.
2.48 (s, 3H, Re-CH3), 1.43 (d, 3H, 2.37 (s, 3H, Re-CH3), 0.93
J=6), 4.55 (dd, 1H, J=6.6, 9.3), 5.08 (t, 3H, J=7.2), 1.91 (m, 2H),
a
Analytical and spectroscopical data are given in the experimental
section.
(dd, 1H, J=5.4, 9.3), 5.29 (m, 1H)
5.08 (t, 1H, J=5.1)
h A specified yield of < 100% implies that some starting material re-
mained and was separated. A yield designated with the symbol > im-
plies some trioxane was detected in the filtrate.
a
b
certain compounds to react, CCl3CHO for example, might
derive from an inhibiting amount of water present in a hy-
droscopic compound. It seems to us that two other effects
are more likely in operation: (1) the electron-attracting a-
substituents significantly reduce the electron density on
the carbonyl oxygen, reducing the extent of its coordina-
tion to rhenium; and, (2) three large substituents such as
the chlorine atoms pose a barrier to coordination to MTO.
Table 4. Effect of Water on the Formation of the 1,3,5-Trioxane 23
from Butyraldehydea
Mol % of
H2O to Aldehyde
Yieldb
(%)
The catalytic role of MTO was analysed by 18O tracer
studies. In one experiment, propionaldehyde was treated
with well above the usual catalytic level of 18O-labeled
MTO. The isolated 1,3,5-trioxane was studied by high
resolution MS. In addition to the parent peak with a mass
of 174.2399, the product showed a peak at 176.2404. That
compares well with 176.2399 calculated for the product
containing one 18O. This result also suggests that only one
0
l
5
10
20
> 99
79
46
~ 1
0
a In the neat aldehyde, after 2 d with 1 mol% MTO at r.t.
Measurement of the yield is simply carried out by taking the H
NMR spectrum of the reaction mixture in CDCl3.
h
1
Table 2. Mixed 1,3,5-Trioxanes 39–44 Prepared by the Trimerization of 2 Different Aldehydes
Aldehydes
Reaction Conditions
Product
Yielda
(%)
R¢CHO (limiting)
RCHO (excess)
Time (d) Temp (°C)
c-C6H11CHO (9)
c-C6H11CHO (9)
c-C6H11CHO (9)
c-C6H11CHO (9)
MeCHO (1)
MeCHO (1)
2
1
1
2
2
6
r.t.
39
40
41
42
43
44
> 99
85
87
MeCH2CH(Me)CHO (15)
MeCH(Me)CH2CHO (14)
PhCH2CHO (12)
c-C6H11CHO (9)
PrCHO (3)
< 0
< 0
< 0
r.t.
69
87
b
PhCHO (45)
< –50
–
a Isolated yield after 100% conversion of limiting aldehyde.
b The product 44 was detected by 1H NMR spectroscopy at < –25°C, which reverts to the starting aldehydes within 30 min in CHCl3 in the
presence of 1 mol% MTO at ≥ –25°C.

April 1998
SYNTHESIS
419
Fully Symmetric 1,3,5-Trioxanes; General Procedure:
downfield to the one attached to carbon, as expected. A
comparison to the intermediate formed from propionalde-
hyde is shown in Table 3.
The appropriate neat aldehyde 1–19 (5 mL) was allowed to stand with
1% MTO for 1–5 d at r.t., the reaction progress being monitored inter-
mittently by GC/MS. Products were isolated by vacuum distillation or
often by simple filtration in those cases where the reaction mixture so-
lidifies on standing. In the latter cases, the solid was filtered under
vacuum to remove the last few drops of aldehyde, and then rinsed with
ice-cold water to remove the MTO (Table 1). The products were iden-
Water inhibits the rate of formation of the 1,3,5-trioxane
and reduces its yield. The variation of the product yields
with water concentration is given in Table 4. At ≥ 20
mol% H2O relative to aldehyde, no trioxane was formed.
On the other hand, addition of MTO to the trioxane cata-
lyzed the reverse reaction quite slowly: in chloroform,
tribenzyl-1,3,5-trioxane with 5 mol% MTO yielded 50%
phenyl acetaldehyde in 10 days. When 5 mol% water was
added, however, no decomposition of the trioxane was
noted within 10 days. Since the entropy change for form-
ing the trioxane is clearly unfavorable, these observations
taken together suggest that the reaction depicted in
Scheme 1 represents a negative standard Gibbs energy
arising from the enthalpic contributions.
tified by their mass spectra and by comparison of their H and 13C
1
NMR spectra with the values reported in the literature.1,4–6,13–15
2,4,6-Trimethyl-1,3,5-trioxane (20):5 This compound was prepared
by two methods: by reacting the aldehyde 1 (5 mL) with MTO in chlo-
roform (20 mL) or as neat at r.t. for 1 d. The product was isolated by
vacuum distillation.
1H NMR: d = 1.38 (d, J = 5.1 Hz, 9 H), 5.04 (q, J = 5.1 Hz, 3 H).
13C NMR: d = 20.61, 98.47.
IR (neat): n = 1166 (s), 1104 (s), 1055 cm–1 (s) (C–O–C).
2,4,6-Triethyl-1,3,5-trioxane (21):5 Prepared in the same manner as
above from 2 (5 mL) and MTO in CHCl3 (20 mL) or as neat at r.t. for
1 d. The product was isolated by vacuum distillation.
1H NMR: d = 0.95 (t, J = 7.5 Hz, 9 H), 1.70 (m, 6 H), 4.79 (t, J =
5.1 Hz, 3 H).
In conclusion, it can be stated that some of the trimeriza-
tion reactions of aldehydes are inefficient: bulky substitu-
ents and electron-withdrawing substituents inhibit the
reaction. In the course of these reactions an intermediate
was observed; a four-membered ring species may reason-
ably be an intermediate. Although there is certainly a
stage in the reaction at which two aldehydes have been
coupled, it is not likely that an independent 1,3-dioxetane
exists, at least at an easily detected concentration, in that
it appears to be unstable with respect to the parent alde-
hyde and the trioxane.10 More plausibly, each aldehyde in
succession interacts with MTO, building the product
within the coordination sphere of the rhenium. The con-
centration of the intermediate is comparable to that of
MTO, but much lower than that of the aldehyde; we thus
infer that the intermediate is a rhenium-containing spe-
13C NMR: d = 7.82, 27.53, 102.40.
IR (neat): n = 1171 (s), 1099 cm–1 (s) (C–O–C).
2,4,6-Tripropyl-1,3,5-trioxane (22): Obtained by reacting the neat 3
with MTO at r.t. for 1 d. The product was isolated by vacuum distilla-
tion.
1H NMR: d = 0.93 (t, J = 5.4 Hz, 9 H), 1.42 (m, 6 H), 2.25 (m, 6 H),
4.86 (t, J = 5.1 Hz, 3 H).
13C NMR: d = 13.91, 16.96, 36.51, 101.49
IR (neat): n = 1156 (s), 1104 (s), 1064 cm–1 (s) (C–O–C).
Anal. Found: C, 66.71; H, 11.13. C12H24O3 requires: C, 66.63; H,
11. 18.
2,4,6-Tributyl-1,3,5-trioxane (23): This compound was prepared by
reacting the neat 4 and MTO at < –10°C for 2 d. The product was iso-
lated by filtration at < –10°C; mp 5–6°C.
1
cies, an assignment supported by the H spectrum. This
1H NMR: d = 0.90 (t, J = 7.8 Hz, 9 H), 1.36 (m, 12 H), 1.67 (m, 6 H),
4.84 (t, J = 5. 1 Hz, 3 H).
may also explain why benzaldehyde itself yields a cross-
linked trimer when benzaldehyde was used as limiting
with respect to propionaldehyde.
13C NMR: d = 13.89, 22.42, 25.65, 34.11, 101.64.
IR (neat): n = 1162 (s), 1107 (s), 1074 cm–1 (s) (C–O–C).
Anal. Found: C, 69.64; H, 11.82. C15H30O3 requires: C, 69.72; H,
11.70.
The aldehydes, diethyl ketomalonate, and solvents are commercially
available. They were purified by shaking with NaHCO3 for ca. 1 h to
remove the carboxylic acid, and then dried with anhyd CaSO4. The
pure aldehyde was obtained by distillation, or, if necessary, by distil-
lation at reduced pressure under argon.11 MTO was either prepared
from Rh2O7 and SnMe412 or purchased.
2,4,6-Tripentyl-1,3,5-trioxane (24): From the neat aldehyde 5 and
MTO at < –10°C for 2 d. The product was isolated by filtration at
< –10°C; mp 9–10°C.
1H NMR: d = 0.89 (t, J = 8.4 Hz, 9 H)), 1.38 (m, 18 H), 1.66 (m, 6 H),
4.84 (t, J = 5.1 Hz, 3 H).
13C NMR: d = 13.92, 22.47, 25.19, 31.53, 34.33, 101.63.
IR (neat): n = 1152 (s), 1109 (s), 1050 cm–1 (s) (C–O–C).
Anal. Found: C, 72.04; H, 11.94. C18H36O3 requires: C, 71.95; H,
12.08.
18O-Labeled MTO was prepared under argon as follows: MTO was
dissolved in anhyd MeCN, then > 4 ´ mole ratio of H2 18O was added.
The solvents were removed under vacuum after 30 min. Then 18O-la-
beled MTO was sublimed under vacuum at about 40 °C.
1
2,4,6-Trihexyl-1,3,5-trioxane (25): From the neat aldehyde 6 and
MTO at <–10°C for 2 d. The product was isolated by filtration at
<0°C; mp 6–7°C.
HRMS were performed on a Kratos MS 50 spectrometer. H NMR
and 13C NMR spectra were obtained at 300 MHz in CDCl3 solution
unless otherwise noted; chemical shifts are relative either to internal
TMS (1H NMR) or to the solvent resonance (13C NMR). GC/MS was
performed on Magnum GC/MS from Finnegan with temperature pro-
gramming: 60°C, 2 min; 10°C/min to 260°C; 260°C for 20 min.
CAChe calculations were performed on a Power Macintosh 8500/
120. IR spectra were recorded neat using 3M disposable IR cards,
Type 61. The melting points of all products which were recrystallized
from CHCl3 were recorded on a Fisher Digital Melting Point Analyz-
er Model 355. Separations by HPLC were performed with a Waters
501 HPLC system equipped with an Econosil C18 column. The yields
reported are isolated yields unless otherwise noted.
1H NMR: d = 0.88 (t, J = 5.4 Hz,9 H), 1.33 (m, 24 H), 1.66 (m, 6 H),
4.84 (t, J = 5.1 Hz, 3 H).
13C NMR: d = 14.02, 22.53, 23.49, 29.01, 31.68, 34.40, 101.65.
IR (neat): n = 1150 (s), 1112 (s), 1052 cm–1 (s) (C–O–C).
Anal. Found: C, 73.64; H, 12.39. C21H42O3 requires: C, 73.63; H,
12.35.
2,4,6-Triheptyl-1,3,5-trioxane (26): From the neat aldehyde 7 and
MTO at <–30°C for 3 d.The product was isolated by filtration at r.t.;
mp 36–37°C.

420
Papers
SYNTHESIS
1H NMR: d = 0.88 (t, J = 5.1 Hz, 9 H), 1.39 (m, 30 H), 1.65 (m, 6 H),
4.83 (t, J = 5. 1 Hz, 3 H).
13C NMR: d = 14.04, 22.62, 23.55, 29.15, 29.32, 31.75, 34.40, 101.7.
IR (neat): n = 1148 (s), 1114 (s), 1061 cm–1 (s) (C–O–C).
Anal. Found: C, 75.02; H, 12.51. C24H48O3 requires: C, 74.94; H,
12.58.
q
l
2,4,6-Trioctyl-1,3,5-trioxane (27): From the neat aldehyde 8 and
MTO at <–30°C for 4 d. The product was isolated by filtration at r.t.;
mp 63–64°C.
1H NMR: d = 0.88 (t, J = 6.9 Hz, 9 H), 1.39 (m, 36 H), 1.68 (m, 6 H),
4.84 (t, J = 5.1 Hz, 3 H).
s
13C NMR: d = 14.06, 22.64, 23.54, 29.20, 29.36, 29.44, 31.85, 34.40,
101.67.
IR (neat): n = 1147 (s), 1115 (s), 1071 cm–1 (m) (C–O–C).
Anal. Found: C, 76.10; H, 12.86. C27H54O3 requires: C, 76.00; H,
12.75.
2,4,6-Tricyclohexyl-1,3,5-trioxane (28): From the neat aldehyde 9
and MTO at r.t. for 1 d. The product was isolated by filtration at r.t.;
mp 204–205°C.
1H NMR: d = 0.99 (m, 6 H), 1.73 (m, 27 H), 4.47 (d, J = 6 Hz, 3 H).
13C NMR: d = 25.65, 26.46, 27.03, 41.95, 104.28.
IR (neat): n = 1164 (s) 1127 (s), 1071 cm–1 (m) (C–O–C).
Anal. Found: C, 74.92; H, 10.70. C21H36O3 requires: C, 74.95; H,
10.78.
s
D
2,4,6-Tri(isopropyl)-1,3,5-trioxane (29):1,4 From the neat aldehyde
10 and MTO at r.t. for 1 d. The product was isolated by filtration at
r.t.; mp 59–60°C (Lit.4 mp 60°C).
1H NMR: d = 0.93 (d, J = 6.9 Hz, 18 H), 1.85 (m, 3 H), 4.49 (d, J =
5.7 Hz, 3 H).
13C NMR: d = 16.68, 32.40, 104.75.
IR (neat): n = 1161 (s), 1102 (s), 1048 cm–1 (m) (C–O–C).
2,4,6-Tri-[(E)-non-3-enyl]-1,3,5-trioxane (30): From the neat alde-
hyde 11 and MTO at < –10°C for 4 d. The product was isolated by fil-
tration at r.t.; mp 19–20°C.
s
l
a
1H NMR: d = 0.88 (t, J = 6.6 Hz, 9 H), 1.23 (m, 18 H), 1.74 (m, 6 H),
1.96 (m, 6 H), 2.10 (m, 6 H), 5.40 (m, 6 H), 4.83 (t, J = 5.4 Hz, 3 H).
13C NMR: d = 14.05, 22.51, 26.53, 29.20, 31.34, 32.49, 34.12,
101.00, 131.2, 128.8
w
IR (neat): n = 1161 (s), 1140 (s), 1065 cm.–1 (m) (C–O–C).
Anal. Found: C, 77.96; H, 11.76. C30H54O3 requires: C, 77.87; H,
11.76.
2,4,6-Tribenzyl-1,3,5-trioxane (31): From the neat aldehyde 12 and
MTO at < –30°C for 4 d. The product was isolated by filtration at
<0°C and washed with cold acetone; mp 151–152°C.
1H NMR: d = 2.99 (d, J = 5.4 Hz, 6 H), 4.93 (t, J = 5.4 Hz, 3 H), 7.22
(m, 15 H).
q
13C NMR: d = 40.99, 101.68, 126.6, 128.12, 129.9, 135.49.
IR (neat): n = 1126 (s), 1079 (s), 1055 cm–1 (s) (C–O–C).
Anal. Found: C, 79.92; H, 6.74. C24H24O3 requires: C, 79.97; H, 6.71.
X-Ray Data: Summary of data collection, structure solution, and re-
finement details are listed in Table 5.
2,4,6-Tris(2-phenylethyl)-1,3,5-trioxane (32): From the neat alde-
hyde 13 and MTO at < –30°C for 5 d. H2O was then added to the re-
action mixture to deactivate MTO. After a further period of stirring,
the product was filtered at r.t.
1H NMR: d = 2.03 (m, 6 H), 2.76 (m, 6 H), 4.81 (t, J = 5.4 Hz, 3 H),
7.21 (m, 15 H).
13C NMR: d = 29.56, 35.60, 100.59, 125.9, 128.38, 128.43, 141.29.
IR (neat): n = 1195 (s), 1130 (s), 1062 (s), 1050 cm–1 (s) (C–O–C).
Anal. Found: C, 80.54; H, 7.61. C27H30O3 requires: C, 80.56; H, 7.51.
2,4,6-Tris(2-methylpropyl)-1,3,5-trioxane (33): From the neat alde-
hyde 14 and MTO at <–30°C for 3 d. The product was isolated by fil-
tration at < –30°C; mp 11–12°C.
a
b
g

April 1998
SYNTHESIS
421
1H NMR: d = 0.91 (d, J = 6.6 Hz, 18 H), 1.56 (dd, J = 5.7, 7.2 Hz, 6 13C NMR: d = 20.55, 25.60, 26.32, 26.96, 41.70, 98.46, 104.39.
H), 1.83 (m, 3 H), 4.92 (t, J = 5.7 Hz, 3 H).
13C NMR: d = 22.71, 22.46, 43.05, 100.68
IR (neat): n = 1162 (s), 1115 (s), 1045 cm–1 (s) (C–O–C).
Anal. Found: C, 69.69; H, 11.71. C15H30O3 requires: C, 69.72; H,
11.70.
IR(neat): n = 1176 (s), 1156 (s), 1105 (s), 1051 cm–1 (s) (C–O–C).
Anal. Found: C, 66.04; H, 10.06. C11H20O3 requires: C, 65.97; H,
10.06.
2-Cyclohexyl-4,6-di(isobutyl)-1,3,5-trioxane (40): From the limiting
aldehyde 9 and the excess aldehyde 15. The reaction required 1 d at
<0°C for the complete conversion of 9. The product was isolated by
filtration at <0°C; mp 79–80°C.
2,4,6-Tri(isobutyl)-1,3,5-trioxane (34):1 From the neat aldehyde 15
and MTO at <–30°C for 4 d. The product was isolated by filtration at
<–30°C; mp 6–7°C.
1H NMR: d = 0.78 (m, 12 H), 1.06 (m, 6 H), 1.47 (m, 11 H), 4.37 (d,
J = 4.8 Hz, 2 H), 4.48 (d, J = 4.2 Hz, 1 H).
1H NMR: d = 0.90 (m, 9 H), 1.21 (m, 15 H), 1.63 (m, 3 H), 4.60 (d, J
= 4.8 Hz, 3 H).
3C NMR: d = 11.53, 13.55, 24.00, 25.88, 26.68, 27.21, 39.08, 42.06,
99.12, 104.29.
13C NMR: d = 11.33, 13.33, 23.79, 38.88, 104.01.
IR (neat): n = 1162 (s), 1115 (s), 1045 cm–1 (s) (C–O–C).
IR(neat): n = 1168 (s), 1126 (s), 1096 (s), 1080 cm–1 (s) (C–O–C).
Anal. Found: C, 71.69; H, 11.54. C17H32O3 requires: C, 71.78; H,
11.34.
2,4,6-Tri(isopentyl)-1,3,5-trioxane (35): From the neat aldehyde 16
and MTO at < –50°C for 6 d. The product was isolated by filtration at
< –50°C; mp –7 to –9°C.
2-Cyclohexyl-4,6-bis(3-methylbutyl)-1,3,5-trioxane (41): The reac-
tion of the limiting aldehyde 9 and the excess aldehyde 14 required
1 d at <0°C for the complete conversion of 9. The product was isolated
by filtration at <0°C; mp 49–50°C.
1H NMR: d = 0.89 (m, 9 H), 1.38 (m, 21 H), 1.72 (m, 3 H), 4.58 (d, J
= 4.8 Hz, 3 H).
13C NMR: d = 14.20, 19.90, 33.20, 36.97, 104.03.
IR (neat): n = 1180 (s), 1104 (s), 1062 cm–1 (s) (C–O–C).
Anal. Found: C, 71.86; H, 12.27. C18H36O3 requires: C, 71.95 ; H,
12.07.
1H NMR: d = 0.90 (d, 12 H), 1.15–1.83 (m, 21 H), 4.47 (t, J = 4.8 Hz,
2 H), 4.89 (d, J = 4.2 Hz, 1 H).
13C NMR: d = 12.63, 15.76, 22.85, 23.63, 25.73, 26.54, 27.11, 41.86,
100.81, 104.56.
IR (neat): n = 1183 (s), 1162 (s), 1001 (s), 1069 cm–1 (s) (C–O–C).
Anal. Found: C, 72.02; H, 11.66. C19H36O3 requires: C, 73.02; H,
11.61.
2,4,6-Tri(tert-butyl)-1,3,5-trioxane (36): From the neat aldehyde 17
and MTO at r.t. for 3 d. The product was isolated by filtration at r.t.;
mp 66–67°C.
1H NMR: d = 0.91 (s, 27 H), 4.36 (s, 3 H).
13C NMR: d = 24.21, 35.32, 105.41.
2-Cyclohexyl-4,6-bis(2-phenylethyl)-1,3,5-trioxane (42): The reac-
tion of the limiting aldehyde 9 and the excess aldehyde 12 required 2
d at <0°C for the complete conversion of 9. The reaction mixture was
poured into H2O containing a little base to decompose MTO. After
continued stirring for 30 min, the solution was extracted with Et2O.
The Et2O layer was dried (Na2SO4) and the solvent evaporated. The
product was isolated by preparative HPLC with MeCN as eluent at a
rate of 4mL/min; mp 112–113°C.
IR (neat): n = 1210 (s), 1116 (s), 1060 cm–1 (s) (C–O–C).
Anal. Found: C, 69.68; H, 11.74. C15H30O3 requires: C, 69.72; H,
11.70.
2,4,6-Tri(8-decenyl)-1,3,5-trioxane (37): From the neat aldehyde 18
and MTO at <0°C for 3 d. The product was isolated by filtration at
< 0°C; mp 47–48°C.
1H NMR: d = 1.01–2.89 (m, 19 H), 4.49 (d, J = 4.2 Hz, 1 H), 4.81 (t,
J = 3.9 Hz, 2 H).
1H NMR: d = 1.33 (m, 36 H), 1.65 (m, 6 H), 2.02 (m, 6 H), 4.83 (t, J
= 5.1 Hz, 3 H), 4.94 (m, 6 H), 5.81(m, 3 H).
13C NMR: d = 25.08, 26.52, 27.11, 29.67, 35.69, 45.34, 100.64,
104.56, 125.98, 128.37, 128.69, 141.39.
13C NMR: d = 23.49, 28.87, 29.05, 29.30, 29.33, 29.38, 33.76, 34.36,
101.62, 114.07, 139.11.
IR (neat): n = 1179 (s), 1148 (s), 1106 (s), 1038 cm–1 (s) (C–O–C).
Anal. Found: C, 78.82; H, 8.54. C25H32O3 requires: C, 78.91; H, 8.47.
IR (neat): n = 1124 (s), 1062 (s), 993 cm–1 (s) (C–O–C).
Anal. Found: C, 78.48; H, 12.09. C33H60O3 requires: C, 78.51; H,
11.98.
2,4-Dicyclohexyl-6-methyl-1,3,5-trioxane(43): The reaction of the
limiting aldehyde 1 and the excess aldehyde 9 required 1 d at r.t. for
the complete conversion of 1. The product was isolated by preparative
HPLC with MeCN as eluent at a rate of 4mL/min; mp 106–107°C.
1H NMR: d = 1.03 (m, 4 H), 1.38 (d, J = 3.9 Hz, 3 H), 1.66 (m, 18 H),
4.54 (d, J = 4.2 Hz, 2 H), 5.00 (q, J = 3.9 Hz, 1 H).
2,2,4,4,6,6-Hexa(ethoxycarbonyl)-1,3,5-trioxane (38): From the neat
diethyl ketomalonate (19) and MTO or in solution in CHCl3 or ben-
zene at r.t. for 2 d. The product was isolated by preparative HPLC
with MeCN as eluent at 4 mL/min. The product decomposes slowly
even at –70°C, however, it gave acceptable elemental analyses; bp
166°C/60 Torr (dec).
13C NMR: d = 20.45, 25.37, 26.12, 26.76, 41.70, 98.76, 104.48.
IR (neat): n = 1181 (s), 1161 (s), 1106 (s), 1049 cm–1 (s) (C–O–C).
Anal. Found: C, 71.51; H, 10.66. C11H20O3 requires: C, 71.60; H,
10.51.
1H NMR: d = 1.32 (t, J = 7.2 Hz, 18 H), 4.34 (q, J = 7.2Hz, 12 H).
13C NMR: d = 14.08, 63.72, 90.20, 168.58.
Anal. Found: C, 48.25; H, 5.84. C21H30O15 requires: C, 48.28; H, 5.78.
2,4-Dipropyl-6-phenyl-1,3,5-trioxane (44): The reaction of the limit-
ing aldehyde 45 and the excess aldehyde 3 required 6 d at <–50°C for
the complete conversion of 45. The product could not be isolated and
was only observed by NMR spectroscopy. All of the trioxane reverted
to the aldehyde within 30 min at ≥25°C.
Mixed 1,3,5-Trioxanes 39–44; General Procedure:
The appropriate limiting aldehyde (16 mmol) and the aldehyde in ex-
cess were mixed in a 1:5 ratio; MTO (1%) was then added and the so-
lution allowed to stand for 1–6 d at the specified temperature, the
reaction progress being monitored intermittently by GC/MS (Table
2). Along with the mixed trioxane, the excess aldehyde used was con-
verted to its fully-symmetric trioxane. The products were isolated by
filtration when the mixed trioxane is a solid and the fully-symmetric
one a liquid at the temperature used; if not, they were separated by
preparative HPLC.
1H NMR: d = 0.95 (t, J = 3 H), 1.57 (m, 4 H), 5.12 (t, J = 5.4 Hz, 1 H),
5.85 (s, 1 H).
13C NMR: d = 213.94, 17.83, 37.34, 100.51, 104.5, 126.02, 128.2,
129.06, 135.82.
This research was supported by the U. S. Department of Energy,
Office of Basic Energy Sciences, Division of Chemical Sciences under
contract W-7405-Eng-82. Acknowledgment is made to the donors of
The Petroleum Research Fund, administered by the ACS, for partial
support of this research. Crystallographic data were provided by the
Iowa State University Molecular Structures Laboratory.
2-Cyclohexyl-4,6-dimethyl-1,3,5-trioxane (39): From the limiting al-
dehyde 9 and the excess aldehyde 1.The reaction was carried out for
2 d at r.t. and the product was isolated by filtration; mp 46–47°C.
1H NMR: d = 1.06 (m, 2 H), 1.37 (d, J = 3.9 Hz, 6 H), 1.64 (m, 9 H),
4.57 (d, J = 4.2 Hz, 1 H), 5.00 (q, J = 3.9 Hz, 2 H).

422
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