Selective formation of α,ω-ester amides from the aminocarbonylation of castor oil derived methyl 10-undecenoate and other unsaturated substrates

Article abstract of DOI:10.1039/c4cy00158c

The reaction of long chain alkenes with CO and aniline in the presence of palladium complexes of 1,2-bis-(ditertbutylphosphinomethyl)benzene produces amides with high linear selectivity, with much higher rates and catalyst stability when 2-naphthol and sodium or potassium iodide are added. Unsaturated esters including methyl 10-undecenoate from castor oil give α,ω- ester amides, whilst reactions in THF give N-phenylpyrrolidine.

Full text of DOI:10.1039/c4cy00158c

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Selective formation of α,ω-ester amides from
the aminocarbonylation of castor oil derived
methyl 10-undecenoate and other
unsaturated substrates†
Cite this: Catal. Sci. Technol., 2014,
4, 2332
Cristina Jiménez-Rodriguez,a Angel A. Núñez-Magro,a Thomas Seidensticker,a
b
a
a
*
Graham R. Eastham, Marc R. L. Furst and David J. Cole-Hamilton
Received 7th February 2014,
Accepted 12th April 2014
The reaction of long chain alkenes with CO and aniline in the presence of palladium complexes of
1,2-bis-(ditertbutylphosphinomethyl)benzene produces amides with high linear selectivity, with much higher
rates and catalyst stability when 2-naphthol and sodium or potassium iodide are added. Unsaturated
esters including methyl 10-undecenoate from castor oil give α,ω-ester amides, whilst reactions in THF
give N-phenylpyrrolidine.
DOI: 10.1039/c4cy00158c
www.rsc.org/catalysis
Milstein and co-workers17 developed a ruthenium-based
catalyst for producing an amide directly from an alcohol and
Introduction
As part of a programme aimed at producing monomers for
polyesters1–3 and polyamides, we report the selective synthe-
sis of terminal amides by aminocarbonylation reactions of
alkenes, including methyl 10-undecenoate, which is available
from castor oil.4
an amine. An interesting synthesis of amides involving the
aminocarbonylation of alkenes has been developed but has
found use mainly in cyclisation reactions.18–20
We now report that the system involving palladium com-
plexes of 1,2-bis(ditertbutylphosphinomethyl)benzene (DTBPMB),
which has been developed for the methoxycarbonylation of
aromatic halides,21 unsaturated compounds,3,22–25 and fatty
acids1–3,26–29 usually with very high selectivity towards the
linear products, is also highly active for aminocarbonylation
using aniline and other amines. The Pd/DTBPMB system has
been shown to give very high terminal selectivity for the iso-
merisation–methoxycarbonylation of alkenes, wherever the
double bond is in the chain.1–3,22,26–29 Exceptionally, the same
catalytic system also gives high branched selectivity to lactic
acid precursors when used for the methoxycarbonylation of
vinyl acetate.23–25 In this paper we start by examining the
selectivity of aminocarbonylation of simple alkenes, then move
on to unsaturated esters before demonstrating the reaction on
the naturally sourced methyl 10-undecenoate.
Amides are important industrial chemicals used in deter-
gents5 and as thickeners.6,7 Diamides and ester amides have
the potential for reduction, preferably by hydrogenation,8–11 to
give useful monomer feedstocks for polyamides and polyester
amides. Amides are usually prepared in the laboratory by the
Schotten–Baumann reaction12,13 involving the condensation
reaction of an amine with an acyl chloride, which is highly
wasteful as chloride has to be introduced and then removed
for disposal. It is also hazardous, because acyl chlorides are
unstable upon exposure to the atmosphere or moisture and
produce fumes of HCl. Several amide syntheses have been
developed over the past century, among them the Schmidt
reaction14 involving a ketone and an azide, the Ugi reaction15
producing bis-amides by using a ketone (or an aldehyde), an
isocyanide, a carboxylic acid and an amine, and the Chapman
thermal rearrangement16 of aryl imino ethers. More recently,
Results and discussion
Aminocarbonylation of alkenes
a EaStCHEM, School of Chemistry, University of St Andrews, St Andrews,
KY16 9ST, Scotland, UK. E-mail: djc@st-andrews.ac.uk; Fax: +44 (0)1334 463 808;
Tel: +44 (0)1334 463 805
b Lucite International, Technology Centre, PO Box 90, Wilton, Middlesborough,
TS6 8JE, England, UK. E-mail: graham.eastham@lucite.com; Fax: +44 (0)1642 447 119;
Tel: +44 (0)1642 447 109
Aniline was used as the nucleophile since it is a liquid and is
moderately nucleophilic. Carbonylation of 1-octene (1) in the
presence of aniline (2) and a catalyst, prepared in situ from
PdCl2 and DTBPMB, at 100 °C under CO (30 bar) for 3 h
produced a linear amide, N-phenylnonanamide (3, Fig. 1) as
the only amide product in ~40% yield regardless of excess ani-
line used (Table 1, entries 1 and 2). There was also an extensive
isomerisation of the alkene and the catalyst solution was
† Electronic supplementary information (ESI) available: Including details of
reactions of methyl acrylate, representative GC analyses of selected products
and full characterisation of methyl 12-oxo-12-(phenylamino)dodecanoate (22)
are available. See DOI: 10.1039/c4cy00158c
2332 | Catal. Sci. Technol., 2014, 4, 2332–2339
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N-phenyl 4-methylhexanamide (14, 97.9% linearity). These
reactions are outlined in Fig. 2 and Table 1.
Fig. 1 Catalytic aminocarbonylation of 1-octene to linear amide.
2-Naphthol and NaI as promoters
Although the reactions described above produced amides
with good conversion and good linear selectivity, the catalyst
loadings were high (2 mol%), the reaction times were long
(3–6 h) and the catalyst was found to have decomposed when
the autoclave was opened. Drent and co-workers have reported
that the addition of phenol or naphthols and NaI allows the
successful aminocarbonylation of 1 with 3-dimethylamino-
1-propylamine (15), when using Pd(OAc)2 in the presence
of 1,2-P,P'-bis(9-phosphabicyclo[3,3,1 or 4,2,1]nonyl)ethane
as the catalyst precursor. Turnovers in 1 h can be as high as
1500 with linearities up to 98.5%.30 Using our catalytic
system under similar conditions to those employed by Drent
in toluene, one of Drent's favoured solvents, no conversion
was obtained when using a catalyst loading of 0.2 mol% either
with aniline or the more nucleophilic 15 in the absence of
2-naphthol (Table 2, entries 1 and 2), but significant activities
(31% conversion for aniline (Table 2, entry 3), 61% for 15
(Table 2, entry 4) with excellent linear selectivities (>99% for
both amine substrates), were obtained for both substrates
when both NaI and 2-naphthol were present. Omission of
either 2-naphthol (Table 2, entries 1 and 2) or NaI (Table 2,
black at the end suggesting substantial catalyst decomposition.
Extending the reaction time to 6 h allowed quantitative
conversion to amides (98% linear, Table 1, entry 3) perhaps
suggesting that catalyst decomposition occurs on cooling
and/or decompression. Aminocarbonylation of 1-hexene
(4) proceeded smoothly to yield the desired linear amide
(5, >99.9%, Table 1, entry 9) with almost none of the branched
isomer 6. Lowering the temperature to ambient inhibited the
reaction (and isomerisation) with 1-octene as the substrate
(Table 1, entry 4). Lowering the pressure to 10 bar increased
the conversion in 3 h to 100%, with rather poorer linearity
(65%, Table 1, entry 5). Lowering the pressure (2 bar) still
further inhibited the reaction despite an extended reaction
time (Table 1, entry 6). The fact that the linearity of the
product is so high, despite extensive alkene isomerisation
observed when the reaction is incomplete, suggests that, as
with methoxycarbonylation,1–3,22,26–29 internal alkenes iso-
merise to terminal alkenes which are trapped by carbonyla-
tion. We have therefore investigated 2- (7) and 4-octene (8) as
substrates. In both cases (Table 1, entries 7 and 8), 100%
conversion to amides is observed with 97% linearity.
The effect of the position of the double bond in the
chain was further investigated using methylpentenes.
2-Methyl-1-pentene (2-M-1-P, 9, Table 1, entry 10) and
2-methyl-2-pentene (2-M-2-P, 10, Table 1, entry 11) both gave
predominantly N-phenyl 5-methylhexanamide (11), although
the alternative product N-phenyl 3-methylhexanamide (12)
was also formed, especially from 9. 11 is formed by carbonyl-
ation at the less sterically crowded end of the molecule, but
12 can be formed from 9 without the unfavoured double
bond isomerisation past the quaternary centre occurring.
3-Methyl-1-pentene (3-M-1-P, 13, Table 1, entry 12) produced
Fig. 2 Products from aminocarbonylation of methylpentenes.
Table 1 Products from the aminocarbonylation of simple alkenesa
Entry
Substrate
T/°C
pCO/bar
Time/h
Conversion of 1/%
Isomersb/%
3/%
Branched/%
1c
2
3
4
5
6
7
8
9
1-Octene (1)
1
1
1
1
1
2-Octene (7)
4-Octene (8)
1-Hexene (4)
2-M-1-P (9)
2-M-2-P (10)
3-M-1-P (13)
100
100
100
20
100
100
100
100
100
100
100
100
30
30
30
30
10
2
30
30
30
30
30
30
3
3
6
3
3
22
6
6
3
6
85
89
100
0
100
0
100
100
100
100
100
100
45
51
0
0
32
0
0
0
0
0
40
38
98
0
65
0
97
97
0
0
2
0
3
0
3
3
99.9 5
59d
85d
0.1 6
41e
15e
10
11
12
6
6
0
0
98f
f
2g
g
a
Conditions: alkene (6 mmol), aniline (1 mL, 11 mmol), PdCl2 (32 mg, 0.2 mmol), DTBPMB (98 mg, 0.25 mmol), diethyl ether (10 mL), 3–6 h.
b
Conversions and selectivities are from GC-FID integrations using measured response factors. Double bond isomers of starting alkene.
c
d
e
f
Aniline (2 mL, 22 mmol). N-phenyl 5-methylhexanamide (11). N-phenyl 3-methylhexanamide (12). N-phenyl 4-methylhexanamide (14).
N-phenyl 2,3-dimethylpentanamide
g
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Table 2 Aminocarbonylation reactions of 1-octene (1) in the presence of phenolic additives and NaIa
Entry
Amine
Additive
[Additive]b
pCO/bar
TON
Conversion/%
Selectivity to 3/%
1
2
3
4
5
6
7
8
PhNH2 (2)
Me2N(CH2)3NH2 (15)
2
15
—
2
—
—
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.75
0.75
0.75
0.75
20
20
20
20
20
20
20
20
20
20
20
10
20
40
50
—
—
158
310
5c
—
40
—
—
95
—
433
402
350
236
—
—
31
61
1c
—
—
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthold
2-Naphthole
2-Naphthole
1-Naphthol
1-Naphthol
PhOH
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
>99
>99
>99
—
>99
—
—
>99
—
>99
>99
>99
>99
—
8
2
15
15
2
2
2
2
2
2
—
—
19
—
85
82
67
46
9
10
11
12
13
14
15
a
Conditions: 1-octene (2 ml, 12.7 mmol), amine (12.74 mmol), Pd(OAc)2 (0.025 mmol), DTBPMB (25.1 mg, 0.064 mmol), MSA (10 μl, 0.15 mmol),
additive (6.37 or 9.6 mmol), NaI (9.5 mg, 0.06 mmol), toluene (10 ml), 170 °C. Conversions and selectivities were determined by GC-FID using
measured response factors, 1 h. b Equivalents relative to 1-octene. c Naphthyl nonanoate. d No NaI was added. e No MSA was added.
entry 6) gave no conversion. Interestingly, the less acidic phenol
was not effective in this type of reaction (Table 2, entry 11)
despite the fact that sodium phenoxide has been shown to be
effective as proposed in Fig. 3 during the aminocarbonylation of
aryl chlorides.31 1-Naphthol was less effective than 2-naphthol
(Table 2, entries 9 and 10). These reactions were carried out in
the presence of methane sulfonic acid, but the relatively acidic
character of anilinium salts apparently allowed generation of
some hydridopalladium complexes and hence some conver-
sions in the absence of added MSA (Table 2, entry 7). For the
more basic 3-(dimethylamino)-1-propylamine (15), no conver-
sion was obtained (Table 2, entry 8) when MSA was omitted.
The best results were obtained with aniline, TON > 400 in 1 h,
employed 0.75 equivalents of 2-naphthol (relative to 1-octene),
a temperature of 170 °C and moderate pressure (10–20 bar,
Table 2, entries 12 and 13). Higher pressures inhibited the
reaction (Table 2, entries 14 and 15).
It has been shown that, at least for methoxycarbonylation,
the rate determining step for this kind of reaction is the
attack of the nucleophile onto the acylpalladium species.22,32–34
Using imidazole as a nucleophilic promoter in the amino-
carbonylation of haloaromatic compounds, Hallberg has
proposed an initial attack of the promoter onto the
acylpalladium species generating the corresponding amide,
which undergoes transamidation to give the final product.35
Thus, a plausible explanation for the role of 2-naphthol in
our system (Fig. 3) involves the attack of the aryl alcohol
onto the acylpalladium species to generate the aryl ester and
the hydridopalladium complex which restarts the catalytic
reaction. In order to prove this hypothesis we tried to run
the reaction in the absence of amine; only a very low conver-
sion to naphthyl nonanoate was obtained (Table 2, entry 5).
We note that I− is the best σ-donor of the halides,35,36 but its
exact role in these reactions is unclear.
Aminocarbonylation of unsaturated esters
The goal is to achieve the aminocarbonylation of natural fatty
acid esters for preparing a range of esteramides that could
be reduced to esteramines or amino alcohols, precursors to
bio-derived polyamides and polyesteramides. We therefore
studied shorter chain unsaturated esters to optimise the
yields and the conversions to the desired linear products.
Initial reactions using methyl acrylate as the substrate, for
which we changed the solvent to dioxane and the iodide
source to KI so as to maximise its solubility, are reported in
the ESI.† These reactions were generally unsuccessful, with
Michael addition of aniline being favoured over amino-
carbonylation under all conditions studied. This may be due
to the conjugation of the CC bond with the CO bond
of the ester function preventing the reaction from occurring,
although better results were obtained when using butyl acrylate
or methyl methacrylate as substrates (see ESI† Table S1 and
Scheme S1).
Ethyl 3-hexenoate (16) does not have a conjugated
double bond so using it as the substrate in amino-
carbonylation reactions was attempted next (Fig. 4). The reac-
tion conditions previously used with methyl acrylate failed to
produce the desired amidoester. Only low conversion, mainly to
N-phenylhexenamide (17) by transamidation of the ester group,
was observed (Table 3, entry 1). It seemed the conjugation
of the double bond was not the source of inefficiency of the
reaction when using acrylate esters as substrates. Changing the
Fig. 3 Possible role of 2-naphthol in the aminocarbonylation of
1-octene. (R = 1-octyl; R′ = Ph (2) or Me2N(CH2)3-(15), Ar = 2-naphthyl).
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Fig. 4 Products from the aminocarbonylation of ethyl 3-hexenoate.
solvent back from dioxane to toluene led to a marginally
improved selectivity for some amidoester isomers (Table 3,
entry 2).
Fig. 5 Products from the aminocarbonylation of methyl 10-undeconate.
Unfortunately, warming to 115 °C did not increase the
conversion to esteramides 18 and 19 but led to a higher con-
version to the undesired 17 (Table 3, entry 3). However, leav-
ing the reaction running for 64 h increased the conversion to
the esteramide, with increased selectivity to the desired linear
product 18 (27 : 1) (Table 3, entry 4), although still producing
a high yield of 17. On raising the temperature to 140 °C, the
conversion stayed the same, but the selectivity to 18 dropped
dramatically (Table 3, entry 5). A test reaction without using
a 2-naphthol promoter under the same conditions dramati-
cally decreased the conversion to 18 and 19 (Table 3, entry 6).
Finally, a reaction with the promoter at high temperature
gave a lower selectivity to 18 than at lower temperature
(Table 3, entry 7). Some Michael addition to the conjugated
unsaturated ester formed by double bond isomerisation was
observed in all of these reactions as product 20.
Following the conclusions obtained when using 16 as the
substrate (the higher the temperature the lower the conver-
sion to the desired product, Table 3) we screened a range of
temperatures between 60 and 140 °C (Table 5), finding that
high temperatures produced the amidation product 24 but
some aminocarbonylation also occurred (Table 4, entry 1).
Although the conversion of the substrate decreased at 100 °C
and 120 °C, the selectivity of aminocarbonylation was signifi-
cantly increased, becoming comparable to amidation (Table 4,
entries 2 and 3). Increasing the amount of MSA from 10 to
100 μL (Table 5, entries 4–7) did not significantly affect the
conversion, but the selectivity to esteramides 22 and 23 was
greatly increased especially at lower temperatures (Table 4,
entries 6 and 7) where amide formation became almost insig-
nificant and the selectivity to the desired linear amide, 22,
was 92% at 80 °C (Table 4, entry 6). Extending this reaction
at 80 °C over a longer time (64 h instead of 16 h, Table 4,
entry 10), a significant increase in the conversion to the
esteramide with good selectivity to 22 was observed although
24 was again a product.
The most dramatic improvement came when the reaction
was carried out in diethyl ether rather than toluene for 64 h.
The conversion to the esteramides was more than 99%, with
96% selectivity to 22 (Table 4, entry 11).
It seemed that diethyl ether was the key solvent for the
reaction, but the reaction time was very long (64 h). The
temperature and the amount of potassium iodide (KI) were
varied in order to try to speed up the reaction (Table 5).
Screening a range of temperatures between 90 and 110 °C
while increasing the amount of KI from 0.06 (Table 4)
to 0.2 equivalents was carried out. Using 0.1 equivalent,
Aminocarbonylation of methyl 10-undecenoate from castor oil
One possible problem with these reactions of ethyl
3-hexenoate (16) is that double bond isomerisation must
precede aminocarbonylation if the terminal amide is to be
formed. It has been shown for 1-octene that isomerisation
is slow compared with methoxycarbonylation,22 so direct
amidation of the ester function will compete effectively with
the desired isomerising aminocarbonylation. It has also been
shown that methoxycarbonylation of terminal double bonds
competes with isomerisation. We therefore investigated
methyl 10-undecenoate (21), an unsaturated ester with a
terminal double bond obtained from the thermal cracking
of castor oil.4 The potential products of aminocarbonylation
are shown in Fig. 5.
Table 3 Products from the aminocarbonylation of ethyl 3-hexenoate (16) with aniline (2)
Entrya
T/°C
t/h
Conversion of 16/%
18/%
19/%
17/%
20/%
Others/%
1b
2
3
85
85
16
16
16
64
16
16
64
46
52
68
90
89
87
94
0
2
1
27
21
5
0
1
0
1
18
0
28
20
38
29
22
46
40
1
1
1
6
6
6
5
17
28
28
27
22
30
20
115
115
140
140
140
4
5
6c
7
15
14
a
Conditions: ethyl 3-hexenoate (2.02 mL, 12.7 mmol), aniline (1.16 mL, 12.7 mmol), Pd2(dba)3 (114 mg, 0.0125 mmol), DTBPMB (251 mg,
0.0637 mmol), toluene (10 mL), MSA (10 μL), 2-naphthol (1.4 g, 9.5 mmol), KI (10 mg, 0.064 mmol), pCO = 50 bar. Conversions and selectivities
were determined by GC-FID using response factors calculated using a literature method36 and an internal standard. “Others” are double bond
isomers of the starting material and the Michael addition product of 17. b Dioxane was used instead of toluene. c Without 2-naphthol.
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Table 4 Aminocarbonylation of methyl 10-undecenoate (21) with aniline (2)
Entrya
T/°C
t/h
MSA/μL
Conversion of 21/%
22/%
23/%
24/%
25/%
1
2
3
4
5
6
7
8
140
120
100
120
100
80
16
16
16
16
16
16
16
16
16
64
64
10
10
10
51
32
34
38
48
38
29
38
15
74
>99
7
12
15
10
20
35
26
7
1
1
2
1
1
1
1
3
0
2
3
41
17
18
26
26
2
2
26
6
2
2
0
1
1
0
0
2
0
1
0
100
4000
100
100
100
100
100
100
60
100
100
80
9b
10
11c
9
62
96
10
0
80
a
Conditions: methyl 10-undecenoate (1.42 mL, 6.35 mmol), aniline (1.16 mL, 12.7 mmol), Pd(dba)2 (115 mg, 0.2 mmol), DTBPMB (99 mg, 0.25 mmol),
toluene (10 mL), 2-naphthol (1368 mg, 9.5 mmol), KI (10 mg, 0.06 mmol), pCO = 50 bar. Conversions and selectivities were determined by GC FID
using response factors calculated using a literature method36 and an internal standard. b Solvent: dimethyl sulfoxide. c Solvent: diethyl ether.
the optimal temperature (95 °C) gave a 70% selectivity to
22 (Table 5, entry 2).
However, at higher KI loading (0.2 equiv.), 99% selectivity
to 22 at full conversion could be obtained after 16 h at
110 °C (Table 5, entry 5) with little drop off in performance
at 95 °C (Table 5, entry 4). These excellent results allow for
Fig. 6 Products obtained from THF (26), γ-butyrolactone (27), succinic
an efficient route to esteramides from the naturally derived
methyl 10-undecenoate. Nevertheless, the isolation of the
product was difficult. Indeed, two chromatography columns
followed by recrystallization were necessary to obtain a
product with sufficient purity. Therefore, a GC yield of 99%
led to a 60% isolated yield only (Table 5, entry 5).
anhydride (28) and furan (29, trace only) under aminocarbonylation
conditions with aniline (2) as the nucleophile.
N-phenylformamide (3% after 6 h) and an unknown product
of higher retention time (7% after 6 h) were also produced;
N-phenylformamide was obtained in small quantities as the
only product when carrying out similar reactions in toluene.
No reaction occurred in the absence of either DTBPMB
(Table 6, entry 3) or CO (Table 6, entry 4), suggesting that the
active species in the catalytic cycle contains both of them.
The conversion of THF to pyrrolidines requires the breaking
of 2 C–O bonds and the forming of 2 C–N bonds.
Walkup and Searles reported the synthesis of such com-
pounds from a variety of cyclic ethers with primary aromatic
amines in 20% yield using an activated alumina catalyst
at 270–350 °C.37 Higher activity was found using titania at
250–300 °C.38 As far as we are aware the palladium catalysed
reaction we are describing is the first example of the synthe-
sis of N-phenylpyrrolidine by the reaction of THF with
aniline under mild liquid phase conditions. The reaction
proved to be quite general for five membered rings, the
best conversions being obtained with γ-butyrolactone (giving
N-phenylpyrrolidone, Fig. 6, 27, Table 6, entry 6) and succinic
anhydride (giving N-phenylsuccinimide, Fig. 6, 28, Table 6,
entry 8), although methanol was added to solubilise the
anhydride and this gave the ring opened products, dimethyl
1,4-butanedioate and PhNC(O)(CH2)2CO2Me together with a
trace of monomethyl 1,4-butanedioate. Furan gave very low
conversion to 29 (Fig. 6, Table 6, entry 5). Tetrahydropyran
(THP, six membered ring, Table 6, entry 7) was unreactive, as
was 1,4-dioxane (traces of N-phenylformamide observed) as
were amines other than aniline (Table 6, entries 9–12).
Synthesis of N-heterocyles
During the course of solvent screening when investigating
the aminocarbonylation of 1-octene, we noticed that reac-
tions in tetrahydrofuran, THF, produced 1-phenylpyrrolidine
(Fig. 6, 26). 1-Octene was not required for these reactions
so further studies were carried out in its absence. A low yield
of 26 was obtained after 6 h but higher conversion (53%,
albeit with lower selectivity, see ESI† Fig. S6) was achieved
after 22 h (Table 6, entries 1 and 2). Small amounts of
Table 5 Aminocarbonylation of methyl 10-undecenoate (21) with
aniline in Et2O
Entrya
T/°C
KI/equiv.
22/%
1
2
3
4
5
90
95
110
95
0.1
0.1
0.1
0.2
0.2
10
70
21
91
99b
110
a
Conditions: methyl 10-undecenoate (1.42 mL, 6.35 mmol), aniline
(1.16 mL, 12.7 mmol), DTBPMB (395 mg, 1 mmol), Et2O (10 mL), MSA
(100 μL), Pd2(dba)3 (92 mg, 0.1 mmol), 2-naphthol (1368 mg, 9.5 mmol),
KI (17 mg, 0.1 mmol or 33 mg, 0.2 mmol), pCO = 30 bar, 16 h.
Conversions and selectivities were determined by GC-FID using
response factors calculated using a literature method36 and an internal
standard. b Isolated yield: 60%.
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Table 6 Reaction of amines with cyclic ethers
Entrya
Substrate
Solvent
Time/h
Selectivity/%
1
Aniline
Aniline
Aniline
Aniline
THF
THF
THF
THF
6
22
6
6
6
21 (26)
60 (26)
0 (26)
0 (26)
2
3b
4c
5
Aniline
Furan
3 (29)
6
Aniline
γ-butyrolactone
6
100 (27)
7
8
Aniline
Aniline
o-Aminomethylbenzoate
Octylamine
Cyclohexylamine
Propylamine
THP
3
3
3
6
6
6
<1
Succinic anhydride/MeOH
27,d 53,e 20 f
9g
10
11
12
THF
THF
THF
THF
0
0
0
0
a
Conditions: aniline (11 mmol), PdCl2 (32 mg, 0.2 mmol), DTBPMB (98 mg, 0.25 mmol), solvent (10 ml), pCO = 30 bar, 100 °C. Conversions,
determined by GC-FID using calculated response factors,36 are based on aniline consumed. No DTBPMB was added. No CO. 28.
b
c
d
e
f
g
PhNC(O)(CH2)2CO2Me. (CH2CO2Me)2 (uncalibrated GC areas). Aniline 7 mmol.
polymerise with diacids, but a more attractive possibility would
be to use 22 to form amino alcohol 31 or diamine 32. It is
evident that under our optimised conditions for the formation
of 22, transamidation of the ester function does not occur, so
it is possible that ammonia might only transamidate with the
aniline derived part of the molecule. Attempts to hydrogenate
22 in the presence or absence of ammonia are among our
next targets.
Conclusion
We conclude that linear amides can be produced with high
selectivity from the aminocarbonylation of long chain alkenes
or unsaturated esters. In the case of esters, the double bond
is preferentially at the end of the chain, such as in the castor oil
derived methyl 10-undecenoate. Aniline is the preferred
amine, and diethyl ether is the preferred solvent. Significant
advantages in terms of catalyst activity and stability are
obtained if the reactions are carried out in the presence of
2-naphthol and sodium or potassium iodide. If the double
bond is buried in the chain, as in ethyl 3-hexenoate, iso-
merisation is too slow to compete with reaction of the ester
group with the amine, whilst if it is conjugated with the
ester, as in methyl acrylate, Michael addition of the amine
across the double bond dominates. If a five membered oxygen
containing heterocycle is used as the solvent, an unusual
O for NPh exchange occurs to give, in the case of THF,
N-phenylpyrrolidine.
Experimental
All reactions were performed using standard Schlenk
techniques. All solvents were degassed with nitrogen. Unless
otherwise stated, solvents were used as supplied and were not
1
previously dried. H and 13C nuclear magnetic resonance
(NMR) spectra were recorded at 298 K using a Bruker 400 MHz
for 1H NMR and 100 MHz for 13C NMR spectrometer, using the
residual solvent peak to reference the spectra to tetramethyl-
silane at δ = 0 ppm. Elemental analyses were performed by
the Elemental Analysis Service of the London Metropolitan
University. Gas chromatograms were recorded using a Hewlett
Packard 6890 series GC system equipped with an Agilent
J&W HP-1 general purpose column (fused silica capillary)
with an HP 5973 Mass selective detector for qualitative (MS)
The production of useful monomers from methyl
10-undecenoate (21) would require reduction to an amino
alcohol or a diamine, as shown in Fig. 7. Simple reduction of
22, possibly using one of our amide hydrogenation catalysts,8,9
would give 12-hydroxydodecylphenylamine, 30, which might
Fig. 7 Possible conversion of 22 to useful monomers for polyamides or polyester amides.
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and FID detector for quantitative analysis. A Hewlett-Packard
Chemstation was used for the computerized integration of
peak areas. Method: flow rate 1 ml min−1 (He carrier gas),
split ratio 100 : 1, starting temperature 50 °C (4 min) ramp
rate 20 °C min−1 to 130 °C (2 min), ramp rate 20 °C min−1
to 220 °C (15.5 min). PdCl2 (Lancaster), 1-naphthol (May &
Baker LTC), 2-naphthol, phenol, Pd2(dba)3, Pd(dba)2 (dba
is dibenzylideneacetone), sodium iodide, potassium
iodide, aniline, 1-hexene, 1-octene, 2-octene, 4-octene,
2-methyl-1-pentene, 2-methyl-2-pentene, 3-methyl-1-pentene,
methyl acrylate, ethyl 3-hexenoate (Sigma Aldrich), 1,2-bis
(ditertbutylphosphinomethyl)benzene (Lucite International),
methyl 10-undecenoate (Tokyo Chemical Industry) and
methane sulfonic acid (Alfa Aesar) were used as supplied.
Solvents were obtained from a solvent purification system.
was set between 30 and 50 bar. The autoclave was heated to
between 70 and 140 °C for 16 h. After cooling, venting
and opening, a sample was taken for GC-FID analysis using
calculated response factors36 and an internal standard and
for GC-MS analysis.
Aminocarbonylation of methyl 10-undecenoate; isolation
of methyl 12-oxo-12-(phenylamino)dodecanoate (22)
Under air, Pd2 (dba)3 (92 mg, 0. 1 mmol), 1, 2-bis
(ditertbutylphosphinomethyl)benzene (395 mg, 1 mmol),
2-naphthol (1.4 g, 9.5 mmol) and KI (32 mg, 0.2 mmol) were
introduced into a Hastelloy autoclave, which was sealed
and purged with nitrogen. Diethyl ether (10 mL), methyl
10-undecenoate (1.42 mL, 6.35 mmol) and aniline (1.16 mL,
12.7 mmol) were degassed for 10 minutes with nitrogen in an
ice-cold Schlenk flask and introduced into the autoclave by
cannula. Methane sulfonic acid (0.1 mL, 1.5 mmol) was
added separately to the autoclave by cannula. The autoclave
was purged three times with CO and the pressure was set to
30 bar. The autoclave was heated to 110 °C for 16 h. After
cooling, venting and opening, the remaining black mixture
was solubilised in dichloromethane and the mixture filtered
through paper. A sample was taken for GC analysis (conver-
sion 99%). The solvent was removed using a rotary evapora-
tor. The remaining solid was passed through a first silica
chromatography column (ethyl acetate : hexane, 1 : 3) and the
solid obtained on evaporation of the appropriate fractions
was passed through a second silica chromatography column
(ethyl acetate : hexane, 1 : 9). After evaporation of the appro-
priate fractions, the solid was recrystallised from ethyl ace-
tate/hexane. Isolated yields: from 49% to 60%. Elemental
analysis: found C 71.45, H 9.09, N 4.29%; C19H29O3N requires
C 71.44, H 9.15, N 4.38%. Melting point 79–80 °C (average
General procedure for the aminocarbonylation of alkenes
Under air, PdCl2 (32 mg, 0.2 mmol) was introduced into a
Hastelloy autoclave, which was sealed and purged with nitro-
gen. 1,2-Bis(ditertbutylphosphinomethyl)benzene was dissolved
in diethyl ether (10 mL) in a degassed Schlenk tube. Alkene
(6 mmol) and aniline (1 mL, 11 mmol) were added to the
solution, which was transferred into the autoclave via cannula.
The autoclave was pressurised with CO (20 bar) and heated
to 100 °C for 3 to 6 h, cooled, vented and the content
was analysed by GC-FID using measured response factors
(quantitative) and by GC-MS (identification of products).
Aminocarbonylation of 1-octene in the presence
of a promoter
Under air, 2-naphthol (1.4, 9.5 mmol) and NaI (9.5 mg,
0.064 mmol) were introduced into a Hastelloy autoclave,
which was sealed and purged with nitrogen. 1,2-Bis
(ditertbutylphosphinomethyl)benzene (25 mg, 0.0637 mmol) and
Pd(OAc)2 (5.6 mg, 0.025 mmol) were dissolved in tolu-
ene (10 mL) in a degassed Schlenk flask. 1-Octene (2 mL,
12.7 mmol), methane sulfonic acid (10 μL, 0.15 mmol) and
aniline (1.2 mL, 12.74 mmoles) were added to the solution,
which was transferred into the autoclave via cannula. The
autoclave was pressurised with CO (20 bar) and heated to
170 °C for 1 h, cooled, vented and the content was analysed
by GC-FID using calculated response factors and an internal
standard and by GC-MS.
1
of three measurements). H NMR (400 MHz; CDCl3): δ = 7.51
(d, J = 8.1 Hz, 2H, PhH), 7.31 (t, J = 7.8 Hz, 2H, PhH), 7.16
(s, 1H, NH), 7.09 (t, J = 7.3 Hz, 1H, PhH), 3.66 (s, 3H, –OCH3),
2.35 (t, J = 7.6 Hz, 2H, –CH2CONHPh), 2.30 (t, J = 7.5 Hz, 2H,
–CH2CO2Me), 1.72 (quintet, J = 7.4 Hz, 2H, –CH2CH2CONHPh),
1.61 (quintet, J = 7.5 Hz, 2H, –CH2CH2CO2Me), 1.28 (s, 12 H, alkyl
chain). 13C NMR (100 MHz; CDCl3): δ = 174.72 (s, –CH2CONH Ph),
171.68 (s, –CH2CO2Me), 129.33 (s, –CPh), 124.48 (s, –CPh),
120.04 (s, –CPh), 51.81 (s, –COOCH3), 38.19 (s, –CH2CONHPh), 34.45
(s, –CH2CO2Me), 29.6629.43 (alkyl chain), 25.92 (s, –CH2CH2CONHPh),
25.27 (s, –CH2CH2CO2Me).
General procedure for the aminocarbonylation of
unsaturated esters
Under air, Pd2(dba)3 (114 mg, 0.125 mmol), 1,2-bis
(ditertbutylphosphinomethyl)benzene (251 mg, 0.064 mmol),
2-naphthol (1.4 g, 9.5 mmol) and KI (10 mg, 0.064 mmol) were
introduced into a Hastelloy autoclave, which was sealed and
purged with nitrogen. The solvent (10 mL), unsaturated ester
(12.7 mmol) and aniline (1.16 mL, 12.7 mmol) were degassed
for 10 minutes with nitrogen in a Schlenk flask and introduced
into the autoclave by cannula. Methane sulfonic acid (10 μL,
0.15 mmol) was added separately to the autoclave by cannula.
The autoclave was purged three times with CO and the pressure
Synthesis of N-heterocycles
1,2-Bis(ditertbutylphosphinomethyl)benzene (25 mg, 0.98 mmol)
and PdCl2 (32 mg, 0.2 mmol) were dissolved in the solvent
(10 mL) in a degassed Schlenk flask and aniline (11 mmol)
was added to the solution, which was transferred to the
autoclave via cannula. The autoclave was pressurised with
CO (30 bar), heated to 100 °C for 1 h, cooled, vented and the
content was analysed by GC-FID using calculated response
factors36 and by GC-MS.
2338 | Catal. Sci. Technol., 2014, 4, 2332–2339
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19 C. Coperet, T. Sugihara and E. Negishi, Tetrahedron Lett.,
1995, 36, 1771.
Acknowledgements
We thank Lucite International (C. J-R., A. A. N-M.), the
University of St Andrews (M. R. L. F.) and the Erasmus
Project (T. S.) for studentships.
20 S. P. Zhao, S. I. Sassa, H. Inoue, M. Yamazaki, H. Watanabe,
T. Mori and Y. Morikawa, J. Mol. Catal. A: Chem., 2000, 159, 103.
21 C. Jiménez-Rodriguez, G. R. Eastham and D. J. Cole-Hamilton,
Dalton Trans., 2005, 1826.
22 C. J. Rodriguez, D. F. Foster, G. R. Eastham and
D. J. Cole-Hamilton, Chem. Commun., 2004, 1720.
23 A. J. Rucklidge, G. E. Morris and D. J. Cole-Hamilton,
Chem. Commun., 2005, 1176.
24 A. J. Rucklidge, G. E. Morris, A. M. Z. Slawin and
D. J. Cole-Hamilton, Helv. Chim. Acta, 2006, 89, 1783.
25 H. Ooka, T. Inoue, S. Itsuno and M. Tanaka, Chem. Commun.,
2005, 1173.
26 D. Quinzler and S. Mecking, Angew. Chem., Int. Ed., 2010,
49, 4306.
27 F. Stempfle, D. Quinzler, I. Heckler and S. Mecking,
Macromolecules, 2011, 44, 4159.
Notes and references
1 M. R. L. Furst, R. Le Goff, D. Quinzler, S. Mecking,
C. H. Botting and D. J. Cole-Hamilton, Green Chem., 2012,
14, 472.
2 M. R. L. Furst, T. Seidensticker and D. J. Cole-Hamilton,
Green Chem., 2013, 15, 1218.
3 C. Jiménez-Rodriguez, G. R. Eastham and D. J. Cole-Hamilton,
Inorg. Chem. Commun., 2005, 8, 878.
4 D. S. Ogunniyi, Bioresour. Technol., 2006, 97, 1086.
5 K. Isobe, T. Azuma, H. Nishikawa and T. Imamura,
US5693605, 1997.
6 H. Kelkenberger, W. Riback and N. Engel, US5009814, 1991.
7 G. Oetter, K. Oppenlander, K. Trefensee and M. Zimstein,
US6165971, 2000.
8 J. Coetzee, D. L. Dodds, J. Klankermayer, S. Brosinski,
W. Leitner, A. M. Z. Slawin and D. J. Cole-Hamilton,
Chem. – Eur. J., 2013, 19, 11039.
9 J. Coetzee, H. G. Manyar, C. Hardacre and D. J. Cole-Hamilton,
ChemCatChem, 2013, 2843.
10 R. Burch, C. Paun, X. M. Cao, P. Crawford, P. Goodrich,
C. Hardacre, P. Hu, L. McLaughlin, J. Sa and J. M. Thompson,
J. Catal., 2011, 283, 89.
11 M. Stein and B. Breit, Angew. Chem., Int. Ed., 2013, 52, 2231.
12 E. Baumann, Ber. Dtsch. Chem. Ges., 1886, 19, 3218.
13 E. Fischer, Ber. Dtsch. Chem. Ges., 1903, 26, 2982.
14 M. B. Smith and J. March, in March's Advanced Organic
Chemistry, John Wiley and Sons, Hoboken, 6th edn., 2007.
15 I. Ugi and C. Steinbruckner, Angew. Chem., Int. Ed. Engl.,
1960, 72, 267.
16 A. W. Chapman, J. Chem. Soc., Trans., 1925, 127, 1992.
17 C. Gunanathan, Y. Ben-David and D. Milstein, Science, 2007,
317, 790.
28 F. Stempfle, P. Roesle and S. Mecking, ACS Symp. Ser., 2012,
1105, 151.
29 G. Walther, J. Deutsch, A. Martin, F.-E. Baumann, D. Fridag
and A. Köckritz, ChemSusChem, 2011, 4, 1052.
30 M. M. De Castro Loureiro Barreto Rosa, H. M. Gillespie,
A. K. Van Helden, P. D. Savage, E. Drent and E. G. McKenna,
US6103927, 2000.
31 J. R. Martinelli, T. P. Clark, D. A. Watson, R. H. Munday and
S. L. Buchwald, Angew. Chem., Int. Ed., 2007, 46, 8460.
32 G. R. Eastham, R. P. Tooze, M. Kilner, D. F. Foster and
D. J. Cole-Hamilton, J. Chem. Soc., Dalton Trans., 2002, 1613.
33 P. Roesle, C. J. Duerr, H. M. Moeller, L. Cavallo, L. Caporaso
and S. Mecking, J. Am. Chem. Soc., 2012, 134, 17696.
34 S. M. A. Donald, S. A. Macgregor, V. Settels, D. J. Cole-Hamilton
and G. R. Eastham, Chem. Commun., 2007, 562.
35 Y. Q. Wan, M. Alterman, M. Larhed and A. Hallberg, J. Org.
Chem., 2002, 67, 6232.
36 J. C. Sternberg, D. T. Gallaway and L. Jones, in Gas
Chromatography, ed. N. Brenner, N. S. Gallaway, J. E. Callen
and D. Weiss, Academic Press, New York, 1962, p. 231.
37 R. E. Walkup and S. Searles, Tetrahedron, 1985, 41, 101.
38 D. C. Hargis and R. L. Shubkin, Tetrahedron Lett., 1990,
31, 2991.
18 K. Okuro, H. Kai and H. Alper, Tetrahedron: Asymmetry,
1997, 8, 2307.
This journal is © The Royal Society of Chemistry 2014
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