Photolysis of Tertiary Amines in the Presence of CO2: The Paths to Formic Acid, α-Amino Acids, and 1,2-Diamines

Article abstract of DOI:10.1021/acs.joc.7b02407

The photolysis of triethylamine (1a) in the presence of carbon dioxide leads to the hydrogenation of CO₂, the α-C-C coupling of 1a, and the CO₂ insertion into the α-C-H σ-bond of amine 1a. This reaction is proposed to proceed through the radical ion pair [R₃N^?+·CO₂^?-] generated by the photoionization of amine 1a and the electron capture by CO₂. The presence of lithium tetrafluoroborate in the reaction medium promotes the efficient and stereoselective α-C-C coupling of 1a by enhancing the production of α-dialkylamino radicals and the isomerization of N,N,N′,N′-tetraethylbutane-2,3-diamine (4a).

Full text of DOI:10.1021/acs.joc.7b02407

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Article
Photolysis of tertiary amines in the presence of CO2:
the paths to formic acid, #-aminoacids and 1,2-diamines
Mateo Berton, Rossella Mello, Rafael Acerete, and María Elena González-Núñez
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02407 • Publication Date (Web): 14 Dec 2017
Downloaded from http://pubs.acs.org on December 15, 2017
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Photolysis of tertiary amines in the presence of CO2:
the paths to formic acid, αꢀaminoacids and 1,2ꢀ
diamines
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Mateo Berton, Rossella Mello, Rafael Acerete, María Elena González Núñez*
Departamento de Química Orgánica. Facultad de Farmacia. Universidad de Valencia.
Avda. Vicente Andrés Estellés s.n. 46100-Burjassot. Valencia. Spain.
Eꢀmail: elena.gonzalez@uv.es
Abstract. The photolysis of triethylamine (1a) in the presence of carbon dioxide leads to the
hydrogenation of CO2, the αꢀCꢀC coupling of triethylamine (1a), and the CO2–insertion into the
αꢀCꢀH σꢀbond of amine 1a. This reaction is proposed to proceed through the radical ion pair
—+
—ꢀ
[R3N —CO2 ] generated by the photoionization of amine 1a and the electron capture by CO2.
The presence of lithium tetrafluoroborate in the reaction medium promotes the efficient and
stereoselective αꢀCꢀC coupling of 1a by enhancing the production of αꢀdialkylamino radicals
and the isomerization of N,N,N’,N’ꢀtetraethylbutaneꢀ2,3ꢀdiamine (4a).
Introduction
The CꢀC and CꢀH bondꢀforming reactions of CO2 have become a major research topic
in chemistry as a response to the global challenge of reducing anthropogenic CO2
emissions to the atmosphere.1 The research endeavor aimed to use CO2 as a
renewable feedstock for synthetic fuels, and commodity chemicals have produced a
variety of transition metal complexes, enzymes and advanced materials as catalysts for
the thermal, photochemical, electrochemical and photoelectrochemical reduction of
CO2.2 These systems confront the significant kinetic and thermodynamic barriers posed
by a change in molecular geometry from linear to bent, associated with the single
—ꢀ
electron transfer to the antibonding π* orbital of CO2 [Eo(CO2/CO2 ) = ꢀ2.1 V vs. SCE].3
This reaction, however, can lead to CO2ꢀfixation products, provided that the radical
—ꢀ
anion intermediate [CO2 ], a strong reductant itself, finds efficient downꢀhill reaction
pathways, alternative to the back electron transfer to reducible species in the reaction
medium. For instance, the efficient hydrogen atom transfer reaction from thiols to the
—ꢀ
radical anion [CO2 ],4 coupled to the ability of CO2 to capture solvated electrons,5 has
allowed us to devise efficient CO2 reduction to formic acid by using iodide as a
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—ꢀ
photocatalyst.6 These results showed that the reactivity of the radical anion [CO2 ] is a
crucial factor for developing reductive CO2ꢀfixation processes, and prompted us to
further explore electron transfer reactions that involve CO2.
Triethylamine (1a) has been used as a sacrificial electron donor7 in the oligo(pꢀ
phenylenes) photocatalyzed reduction of CO2 to formic acid and carbon monoxide,8
and this reaction has been explored theoretically9 in order to design a taskꢀspecific
recyclable amine for selective CO2 reduction to formic acid.10 Recently, this reaction
has been applied to the αꢀcarboxylation of tertiary amines.11 These reports have shown
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—+
that tertiary amine 1 and its radical cation [1 ] are the actual species which perform the
activation of CO2 in these reactions. However, the reaction paths followed by different
reaction intermediates, the competitive processes involved, and the final products
derived from 1 under different reaction conditions, which should provide critical
—ꢀ
information about the reactivity of the radical anion [CO2 ], have not been accurately
described to date. In order to bridge this gap, and to thus acquire additional information
on the reductive pathways of CO2, we decided to explore the photoionization of tertiary
amines 1 under UV irradiation12 in the presence of CO2 to avoid interferences in the
electron and hydrogen transfer steps associated with the use of photocatalysts.
We herein report that the UVꢀphotolysis of tertiary amines 1 in the presence of CO2
leads to formic acid (2) and αꢀamino acids 3 as CO2ꢀcapture products, and also to 1,2ꢀ
diamines 4. The product distributions found under the different reaction conditions
—+
—ꢀ
reveal the involvement of the radical ion pair [1 —CO2 ], iminium ions and αꢀaminoalkyl
radicals as reaction intermediates. The information disclosed herein about the
chemistry of the radical anion [CO2 ] and the reaction paths under these reaction
—ꢀ
conditions will be useful for designing CO2ꢀcapture processes.
Results
Triethylamine (1a) was selected as the model substrate for the first series of
experiments.13 Amine 1a, used either neat or in anhydrous acetonitrile solution (0.3 M),
was placed inside a quartz test tube, which was capped with a rubber septum, and was
o
treated with CO2 (20 psi) at 0 C for 20 min with stirring. The concentration of CO2 in
acetonitrile was estimated to be 0.241 M from the solubility reported for CO2 in
propionitrile14 at 1 bar and 25 C (initial molar ratio 1a: CO2 of 1.24:1). The reaction
o
mixture was irradiated for 3 h at room temperature with a compact twinꢀtube germicidal
lamp (254 nm, 36 W) to give transparent solutions with a thin solid layer on the tube
wall for the reactions in acetonitrile, and white solid suspensions for the neat reactions
and in the presence of LiBF4. The acidic reaction products were quantified by removing
the volatiles under vacuum, dissolving the residue in either a basic or neutral solution
of phenol as an external standard in D2O, and analyzing the sample by NMR. The
analysis and quantification of the basic products were performed in a second identical
experiment, in which the reaction mixture was treated with 37% hydrochloric acid prior
to removing the volatiles under a vacuum. The residue was then dissolved in a phenol
solution, used as the external standard, in D2O, and was analyzed by NMR. The workꢀ
up procedures prevented acetaldehyde being detected in the reaction mixtures. The
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Table 1. Photolysis of triethylamine (1a) and CO2 under
different conditions.a
O
N
CO2
N
N
OH
N
+
+
Et2NH
(1)
HCOOH +
h
254 nm
1a
2
3a
4a
Product distribution (%)d
5a
Run
Reaction
conditionsb
Conv.c
(%)
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3a/
2a
2
3a
4a
5a
D,L:meso
1e
2e
3e
neat, CO2
ACN, CO2
15
36
44
8
15
15
12
7
40
14
16
1.9
1:1.1
22
14
40
1:1.3
0.7
0.9
ACN, CO2
(6 h)
46
1.2:1
4
5
6
ACN, CO2,
LiBF4 (1.5 h)
28
72
77
11
8
20
14
15
69
2.6:1
ꢀꢀ
ꢀꢀ
ꢀꢀ
2.0
1.9
1.6
ACN, CO2,
LiBF4
79
4:1
ACN, CO2,
LiBF4 (6 h)
10
75
5.8:1
2
7e
8e
CH, CO2
ACN, Ar
6
3
4
30
20
1.3
ꢀꢀ
14
ꢀꢀ
ꢀꢀ
22
1:1.4
9e
ACN, Ar,
LiBF4
25
ꢀꢀ
ꢀꢀ
6
77
ꢀꢀ
1.3:1
a
The reactions performed at room temperature with a 35 W lowꢀpressure
mercury lamp. CH: cyclohexane, ACN: acetonitrile. The figures are the
average of at least three independent experiments and fall within a
b
standard deviation of 15 %. The reactions performed for 3 h, except
c
where noticed. Amine 1, captured as the ammonium salt of acids 2 and
d
3, was considered unconverted. Molar distribution. Mass balances >80
%. e Additional products16 were found in yields within the 0.2ꢀ18 % range,
depending on the reaction conditions.
reaction products were identified by comparing with the authentic samples prepared by
alternative procedures, and were quantified from their integrals in the 1H NMR
spectrum. The results obtained under the different conditions are shown in Equation 1
and Table 1.
The control experiments performed with 13CO2 showed no evidence for oxalic acid,
formaldehyde or methanol as products. The solutions of formic acid (2) in acetonitrile
proved stable under irradiation in the presence of excess triethylamine (1a) (1a:2 2:1),
while the reaction run in the presence of LiBF4 led to an 8% loss of formic acid (2). The
reactions performed with water as a cosolvent led to the quantitative recovery of the
unreacted starting materials, which was attributed to the formation of unreactive
triethylammonium hydrogencarbonate.15 The UV spectra of the amine 1a solutions in
anhydrous acetonitrile (3—10ꢀ3 M), recorded before and after CO2ꢀintake at 20 psi for 20
min at room temperature, showed no significant differences (Figure 1).
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Figure 1. UV spectra of a 4.3 x 10ꢀ3 M solution of triethylamine (1a) in acetonitrile
before and after saturation with CO2 at 20 psi and room temperature. The
concentration of CO2 was estimated to be 0.241 M from the solubility reported14 for
CO2 in propionitrile at 1 bar and 25 oC.
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The irradiation of triethylamine (1a), both neat and in acetonitrile solution, and
saturated with CO2, led to substrate conversions of 15% and 36%, respectively, to give
diethylamine (5a) (40%), N,Nꢀdiethylalanine (3a) (15%) and formic acid (2) (8%) for the
neat reaction (Run 1, Table 1), and with diethylamine (5a) (14%), amino acid 3a (15%),
formic acid (2) (22%) and N,N,N’,N’ꢀtetraethylbutaneꢀ2,3ꢀdiamine (4a) (40 %) as a ca.
1:1 D,L:meso mixture for the reaction in acetonitrile (Run 2, Table 1). Prolonging the
irradiation time to 6 h did not significantly improve the conversion of 1a, but diminished
formic acid formation (2) (Run 3, Table 1). Note that the formation of unreactive
ammonium salts from amino acid 3a, formic acid (2) and N,Nꢀdiethylcarbamic acid from
CO2 and diethylamine (5a)15 precluded the quantitative conversion of substrate 1a.
The irradiation of an acetonitrile solution of triethylamine (1a) and CO2 in the presence
of LiBF4 (0.1 M) under our standard conditions (Run 5, Table 1) led to a 72% substrate
conversion, which gave N,N,N’,N’ꢀtetraethylbutaneꢀ2,3ꢀdiamine (4a) as the major
product (79 %), with small amounts of amino acid 3a (14 %) and formic acid (2) (8 %).
The ionic additive suppressed diethylamine (5a) formation and promoted more
selective reactions (Runs 4ꢀ6, Table 1). It was noteworthy that diamine 4a formed as a
4:1 D,L:meso mixture under these conditions, unlike the unselective reactions
observed in the absence of LiBF4 (Run 2, Table 1), and that the D,L:meso isomer ratio
increased from 2.6 to 5.8 as the irradiation time was prolonged from 1.5 h to 6 h (Runs
4ꢀ6, Table 1). The irradiation of a 1:1.3 D,L:meso mixture of diamine 4a, CO2 and LiBF4
in acetonitrile under our standard conditions, performed as a control experiment, led to
a 1.2:1 D,L:meso isomer ratio. However in this case, no significant CO2ꢀcapture
products were formed. The small amounts of formic acid (2) observed in the presence
of LiBF4 (Runs 4ꢀ6, Table 1) can be attributed to its depletion through competing
photolytic pathways, as suggested by the control experiments.
The reactions in cyclohexane as the solvent (Run 7, Table 1) proceeded, however, with
a very low substrate conversion (6 %) to give diethylamine (5a) as the main product (30
%), with small amounts of formic acid 2 (3 %), amino acid 3a (4 %), and diamine 4a (2
%), and a complex mixture of basic products.
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The photolysis of triethylamine (1a) in an inert atmosphere was performed as the
control experiments (Runs 8 and 9, Table 1) and was analyzed as described above.
The reaction in acetonitrile gave diethylamine (5a) (20%), diamine 4a as a ca. 1:1
D,L:meso mixture (22%), and smaller amounts of additional basic products,16 which
agrees with the reported results.13 Substrate conversion was 14% in this case. The
presence of LiBF4 in the reaction medium slightly increased the substrate conversion
(25%) and changed the product distribution to preferentially give diethylamine (5a)
(Run 8, Table 1). These reactions were expected to compete under our reaction
conditions.
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The reactions of a series of asymmetric tertiary amines 1 with CO2 were performed in
the acetonitrile solution under our standard conditions. The reaction mixtures were
analyzed by NMR, and the acidic reaction products were identified by comparing with
authentic samples prepared by alternative procedures. Substrate conversions were
established from the NMR spectra after the acidic workꢀup. The complexity of the
reaction mixtures in these cases prevented the basic products that derived from
amines 1cꢀf being identified and quantified. The results are shown in Table 2.
Table 2. Photochemical carboxylation of tertiary amines 1 with CO2 in acetonitrile.a
Product (yield %)c
Eo
(V)b
Conv.
ox
Run
1
3/2
(%)
36
41
60
63
65
79
ꢀꢀ
3
2
20
12
5
0.7317
0.7317
0.8318
0.6817
0.8017
0.6519
0.5620
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
3a (15)
3b (22)
3c (9)
0.7
1.8
1.8
14.0
2.2
2.0
ꢀꢀ
3d’ (3)
3e’ (10)
5
3d (68)
3e (8)
8
3e’ (13)
ꢀꢀ
6
1g
ꢀꢀ
CH3
N
CH3
N
N
N
CH3
N
N
CH3
CH3
CH3
1a
1b
1c
1d
1e
1f
TMS
N
COOH
N
N
COOH
N
COOH
CH3
N
CH3
1g
3a
3b
3c
COOH
N
N
N
N
COOH
CH3
CH3
COOH
COOH
3d
3d'
3e
3e'
a
Reactions performed at room temperature for 3 h with a 36 W
lowꢀpressure mercury lamp. Products were identified by
comparison with authentic samples. See Supplementary
a
b
c
Information for details.
Product yields referred to converted amine 1.
Oxidation potentials vs. SCE.17ꢀ20
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The irradiation of amines 1 and CO2 produced amino acids 3 and formic acid (2) as
CO2ꢀactivation products (Table 2). The carboxylation reaction showed a strong
preference for the methyl positions in all cases, except for Nꢀmethylpyrrolidine (1d),
which preferentially reacted at the ring position (Run 4, Table 2). The carboxylation of
Nꢀ(trimethylsilyl)methylpiperidine (1f) took place at the sililated carbon atom exclusively
(Run 6, Table 2). Selectivity amino acid (3):formic acid (2) was found to be ca 2:1,
except for triethylamine (1a) (3a:2 1:1.5) and Nꢀmethylpyrrolidine (1d) (3d:2 14:1). 1,4ꢀ
Diazabicyclo[2,2,2]octane (DABCO) (1g) was unreactive under our reaction conditions.
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Discussion
The results reported in Table 1 show that the photolysis of triethylamine (1a) in a CO2
environment in the absence of photocatalysts leads to formic acid (2) and amino acid
3a as CO2ꢀcapture products, and to diamine 4a as the CꢀC coupling product. The
different product distribution observed in relation to the reactions run in an inert
atmosphere, and the improvement of reaction productivity observed by increasing the
polarity of the solvent and the ionic strength of the solution (Table 1), strongly suggest
the involvement of electron transfer processes21,22 and the radical ion pair [1 —CO2 ] as
—+
—ꢀ
—+
—ꢀ
the primary reaction intermediate. The generation of the radical ion pair [1a —CO2 ]
may proceed through the photoionization of triethylamine (1a),12 [Eo(1a /1a) = 0.73 V
—+
vs. SCE],17 and the capture of the ejected electron by CO2,6 [Eo(CO2/CO2 ) = ꢀ2.1 V vs.
—ꢀ
SCE].3 The absence of a significant charge transfer band in the UV spectrum of
triethylamine (1a) and CO2, both neat and in acetonitrile solution (Figure 1), and the
equilibrium constant of 0.046 reported23 for the formation of the electron donorꢀ
acceptor complex [1a—CO2] in pentane at 25oC and 100 psi (6.89 bar), suggest that the
electron donorꢀacceptor complex [1a—CO2] plays a minor role in this process.
—+
Reaction products can be rationalized in terms of the reactivity of the radical ions [1a ]
—ꢀ
8.9
and [CO2 ], which has been described in the photocatalytic reduction of CO2 and
other substrates7 with triethylamine (1a) used as sacrificial electron donors (Scheme 1).
—+
Thus the hydrogen atom transfer from the amine radical cation [Et3N ] to the radical
—ꢀ
anion [CO2 ] gives an iminium and formate ion pair (III) in equilibrium with 1ꢀ
(diethylamino)ethyl formate V, which leads to formic acid, diethylamine (5a) and
acetaldehyde in the aqueous workꢀup (Scheme 1).
Conversely, the formal CO2ꢀinsertion into the CꢀH σꢀbond adjacent to the nitrogen atom
to give amino acid 3a can be rationalized through the proton transfer from the amine
radical cation [1a ] to the radical anion [CO2 ], followed by the coupling of the resulting
αꢀdiethylaminoethyl and formyl radicals (II) in the solvent cage (Scheme 1).24 This
reaction path of the radical ion pair [1a —CO2 ] is not described in the theoretical study
available in the literature,9 which shows that the reaction coordinate initiated by the
proton transfer from the amine radical cation to the oxygen atom of the CO2 radical
anion bifurcates to downhill paths leading to the hydrogen transfer to the carbon atom
and to a back electron transfer to amine 1a and CO2.
—+
—ꢀ
—+
—ꢀ
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Scheme 1. Primary reaction paths in the photolysis of triethylamine (1a) and CO2.8,9
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The increase in the solvent’s polarity from cyclohexane, to triethylamine (1a) and to
acetonitrile improves both formic acid (2) and diamine 4a production (Runs 1, 2 and 7,
Table 1). Indeed polar solvents are expected to enhance formic acid formation (2)
since the dipole moment of the reacting system increases in the hydrogen atom
transfer step, which leads to a ion pair, while it decreases in the proton transfer step,
which leads to a radical pair (Scheme 1).25 The fact that amino acid 3a formation does
not significantly diminish under conditions that favor the separation of the radical ion
pair, e.g., polar solvents and ionic additives (Runs 2 and 5, Table 1),25 implies that
proton and hydrogen atom transfer reactions are faster than the dissociation of the
—+
—ꢀ 21,22
contact radical ion pair [1a —CO2 ]
and, therefore, the free solvated radical anion
—ꢀ
[CO2 ] is not a significant intermediate under our conditions unless it arises from formic
acid (2) or formate VI through alternative processes.26
The enhanced diamine 4a formation observed when going from cyclohexane, to
triethylamine (1a) and to acetonitrile as solvents (Runs 1, 2 and 7, Table 1), and in the
presence of LiBF4 (Runs 2 and 5, Table 1), suggests that the solvent’s polarity and the
ionic strength of the solution improve the production of αꢀdiethylaminoethyl radicals
(VII). These intermediates probably arise from iminium cations V27 formed through the
ionization of 1ꢀ(diethylamino)ethyl formate (IV) (Scheme 1), which compete with CO2
for the electrons photoꢀejected from amine 1a (Scheme 2). The proton transfer reaction
—+ 7
from amine radical cation [1a ] to the αꢀdiethylaminoethyl radical (VII) from the
reductive process in the solvent cage (Scheme 2), or to free amine 1a in solution,
further improves the formation of radicals VII for the CꢀC coupling reaction. Polar
solvents and ionic additives promote i) electron and hydrogen transfer processes,22,25 ii)
the ionization of the (diethylamino)ethyl formate (IV), and iii) the separation of the
iminiumꢀformate ion pair III (Scheme 1),25 thus enhancing the release of iminium
cations V and formate anions (VI) to the solution, and therefore diamine 4a formation at
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Scheme 2. Reaction paths leading to 2,3ꢀbis(diethylamino)butane (4a).
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the expense of diethylamine (5a) (Run 5, Table 1). The results show that formic acid
formation (2) diminishes under these conditions (Run 5, Table 1),26 which is probably
due to side reactions of formic acid (2) and formate VI with the radical and radical ion
intermediates.
The coupling of the pair of αꢀdiethylaminoethyl radicals (VII) is expected to give
diamine 4a as a ca. 1:1 D,L:meso mixture, and this is indeed the case for the reactions
performed in acetonitrile (Runs 2 and 3, Table 1). The reactions run in the presence of
LiBF4 (Runs 4ꢀ6, Table 1), however, showed the progressive isomerization of diamine
4a to give its D,L-isomer as the reaction time increased. The isomerization of 1,2ꢀ
diamines under electron transfer conditions is known to proceed28 through the
exergonic βꢀCꢀC σꢀbond cleavage (Scheme 3) to give an iminium ion and an αꢀ
aminoalkyl radical, followed by a back electron transfer to the iminium cation, and also
—+
by the coupling of the resulting radical pair.28 With diamine 4a [Eo(1a /1a) = 0.57 V vs.
SCE],17 the isomerization equilibrium displaces toward the D,L stereoisomer as the
relative spatial orientation of methyl groups C1 and C4 determines29 that, first, the
antiperiplanar conformation required for the βꢀcleavage28 is more stable for the meso
—+
—+
intermediate [mesoꢀ4a ] than for its D,L stereoisomer [D,Lꢀ4a ]; and, second, the
sinperiplanar conformation, established by the N,Nꢀtwoꢀcentreꢀthreeꢀelectrons30
—+
—+
interaction, is more stable for [D,Lꢀ4a ] than for [mesoꢀ4a ] (Scheme 3). The presence
of LiBF4 in the reaction medium improves the electron transfer processes22 and thus
—+
facilitates the isomerization process. The radical cation [1a ], the iminium cation V and
CO2 may be suitable oxidants to generate the radical cation [4a ] under our reaction
—+
conditions. This unproductive side process, along with the capture of the starting amine
1 as unreactive ammonium salts by carboxylic acids 2 and 3, and the carbamic acid
formed from secondary amines 5 and CO2,15 and the competition of iminium ion
intermediates V with CO2 as electron sinks, contribute to reduce the efficiency of the
CO2ꢀreduction processes under these conditions.
The regioselectivity observed in the carboxylation of unsymmetrical amines 1bꢀf with
CO2 in acetonitrile solution to give αꢀamino acids 3 (Table 2) well agrees with the
—+
relative ability of the radical cation [1 ] to meet the stereoelectronic requirement for Cꢀ
H σꢀbond activation; i.e., the alignment of the αꢀCꢀH σꢀbond antiperiplanar to the singly
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Scheme 3. Isomerization of 2,3ꢀbis(diethylamino)butane (4a) under electron transfer
conditions.
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occupied non bonding orbital of the nitrogen atom.7 Thus the activation of the αꢀCꢀH
—+
—+
bonds in the nꢀbutylꢀ and isoꢀpropyl groups of the species [1b ] and [1c ] respectively
requires one methyl/propyl and two methyl/methyl gauche interactions, but only
hydrogen/alkyl gauche interactions in the case of the methyl groups. Accordingly,
carboxylation occurs exclusively in the methyl groups of amines 1b and 1c (Entries 2ꢀ3,
Table 2) which are, moreover, statistically favored. The regioselectivity observed in the
carboxylation of Nꢀmethylpyrrolidine (1d) can be attributed to a favorable geometry to
activate the ring positions, and also to the relief of the eclipsing interactions in the ring
system associated with the formation of the radical intermediate,31 which are
responsible for the low bond dissociation energy reported31c for the αꢀCꢀH bond of fiveꢀ
membered heterocycles compared to their linear and sixꢀmembered ring
counterparts.31c Nꢀmethylpyperidine (1e), which lack this efficient activation, undergoes
carboxylation evenly at the ring positions and in the methyl group. DABCO (1g) is
generally unreactive under electron transfer conditions because its rigid bicyclic
geometry prevents the activation of αꢀCꢀH bonds.7 Finally, the reluctance of diamine 4a
to give CO2ꢀcapture products under our standard reaction conditions may result from
—+
the N,Nꢀinteraction29,30 established in the amine radical cation [4a ], which prevents it
from adopting the conformation required to activate the αꢀCꢀH σꢀbond.7 The
carboxylation of Nꢀtrimethylsilylmethylpiperidine (1f) (Run 6, Table 2) appears to prefer
the trimethylsilyl group to the proton in order to migrate to the oxygen atom of the
—ꢀ
radical anion [CO2 ].32
The results shown in Table 2 reveal a different impact of the substrate structure on the
—+
—ꢀ
proton and hydrogen atom transfer paths of the radical ion pair [1 —CO2 ]. Thus the
proton transfer is more efficient for amines 1b,c,e, with 3:2 ratios ca. 2:1, which might
be attributed to a statistical preference of the proton transfer to one of the two oxygen
—ꢀ
atoms of the radical anion [CO2 ] over the hydrogen transfer to the carbon atom.
However, Nꢀmethylpyrrolidine (1d) (3:2 14:1) and triethylamine (1a) (3:2 1:1.4) deviate
from this trend in opposite directions (Table 2). These results suggest that the
—+
stereoelectronic requirements for the activation of the αꢀCꢀH bond of [1 ] are stronger
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for the proton transfer step than for the hydrogen atom transfer step since the reactive
—+
conformation of the radical cation [1a ] has entropic and conformational barriers which
—+
are absent in the cyclic radical cation [1e ]. Further rationalization of these
observations would require a more accurate description of the coordinates and
transition states of the reactions than that presently available.9
9
The results show that the substrate structure and the reaction conditions determine the
reaction paths in the photolysis of amines 1 in the presence of CO2. Some features are
relevant for designing photochemical CO2ꢀcapture reactions with tertiary amines 1 as
reductants: i) the photoinduced electron transfer from amine 1 to CO2 competes with
the reaction paths available for the photoexcited amine 1, and becomes less efficient
as the structural complexity of amine 1 increases; ii) the structural factors which favor
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—+
the reactive conformation of radical cation [1 ] improves the proton transfer process
and the αꢀcarboxylation reaction over the hydrogen atom transfer and the formation of
formic acid (2); iii) Nꢀmethylpyrrolidine (1d) proved to be particularly well suited for
carboxylation at the ring αꢀpositions, while triethylamine (1a) preferentially undergoes
hydrogen transfer to give formic acid (2); iv) the involvement of free amine 1 as a base
in these reactions contributes to diminish the substrate conversion; v) polar solvents
and ionic additives favor the electron transfer processes, yet trigger polar pathways
which release αꢀdialkylaminoalkyl radicals into the solution and lead to 1,2ꢀdiamines 4
as the major products.
Conclusions
In summary, the reactions of tertiary amines 1 with CO2 under UV irradiation lead to the
CO2ꢀinsertion into the αꢀCꢀH σꢀbond of amine 1, the hydrogenation of CO2, and the αꢀ
CꢀC coupling of amine 1. These reactions are proposed to initiate with the
photoionization of amine 1 and the capture of the photodetached electrons by CO2 to
—+
—ꢀ
give the radical ion pair [R3N —CO2 ]. The reaction products reveal the dual character
—ꢀ
of the radical anion [CO2 ], which abstracts either a hydrogen atom or a proton from the
—+
radical cation [R3N ] to give the secondary reactive intermediates that lead to formic
acid (2), amino acids 3 and diamines 4. The reaction is extremely sensitive to the
reaction conditions and the substrate structure. The reaction paths that lead to CO2ꢀ
fixation products under these conditions are hampered by the side processes
associated with the reaction products, such as the formation of ammonium
carboxylates and carbamates, and the competition of iminium ions with CO2 as electron
acceptors.
Experimental Section
General. Solvents were purified by standard procedures,33 degassed by freezeꢀpumpꢀ
thaw, and stored under argon. Commercial amines 1 were distilled from sodium
hydroxide and stored under argon. High resolution mass spectrometry (HRMS) was
performed with a TRIPLETOFF 5600 (ABSciex) by using Electrospray in positive mode
(ESI+).
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Synthesis of Nꢀ((trimethylsilyl)methyl)piperidine (1f).34 Piperidine (6.2 mL, 62.8
mmol) and (chloromethyl)trimethylsilane (4 mL, 28.6 mmol) g) were placed into a 25
mL stainless steel reactor equipped with a magnetic stirring bar. The reactor was firmly
closed and was allowed to stand for 15 days at 60 oC with stirring. The reaction mixture
was transferred to a separatory funnel with pentane and water. The organic layer was
dried with anhydrous MgSO4 and the solvent was evaporated under a vacuum to give
4.6 g (94 % yield) of a colorless liquid. The liquid residue was treated with benzoyl
chloride (1.1 equiv) at room temperature with stirring for 10 min. The mixture was
treated with water (0.5 mL) and NaHCO3 (0.2 g) for 30 min with stirring. The residue
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o
was distilled from solid NaOH under a vacuum (30 C, 10ꢀ2 mbar) to give a colorless
liquid (4.0 g, 82 % yield).
Nꢀ(Trimethylsilyl)methylpiperidine (1f) [17877ꢀ17ꢀ7].35 82%, 4.0 g, colorless liquid;
1H NMR (300 MHz, D2O): δ (ppm) 0.05 (s, 9 H), 1.36 (dt, J = 11.3, 5.8 Hz, 2 H), 1.55
(dt, J = 11.0, 5.6 Hz, 4 H), 1.88 (s, 2 H), 2.31 (br t, 4 H); 13C NMR (75 MHz, CDCl3): δ
(ppm) ꢀ0.90, 24.0, 26.4, 51.9, 58.6. MS (EI+, 70ev) m/z: 41 (5), 55 (4), 73 (7), 98 (100),
142 (2), 156 (10), 171 (8). HRMS (ESI+) m/z: (M+H+) Calcd for C9H22NSi: 172.1522,
found: 172.1509.
Preparation of N,Nꢀdialkylꢀαꢀaminoacids (3aꢀe). General procedure.36 A 0.8 M
solution of αꢀbromoacetic acid in diethylether (5.8 mmol) was added dropꢀwise to 3 mL
o
of NꢀmethylꢀNꢀ(1ꢀmethylethyl)amine (28.8 mmol) at 0 C with magnetic stirring. The
mixture was allowed to stand for 10 h at room temperature with stirring. Volatiles were
removed under a vacuum and the residue was treated with 8 mL of a 1.5 M aqueous
solution of NaOH (11.6 mmol) at room temperature with stirring. The mixture was
o
evaporated under a vacuum at 40 C until constant weight was reached. The solid
residue was dissolved in D2O and the solution was analyzed by 1H and 13C NMR. The
solid was dissolved in 10 mL of ultrapure water and the solution was treated with a
standardized 0.5 M hydrochloric acid at room temperature and with stirring until a sharp
change in pH was observed (pH 4.3, 13 mL). The resulting solution was evaporated
under a vacuum and the solid was washed with 3x10 mL of absolute ethanol with
stirring and was centrifuged. The ethanolic solution was evaporated under a vacuum
and the solid residue was redissolved in water and evaporated under a vacuum until
the NMR spectra in D2O showed that ethanol was absent. The hygroscopic solid (0.7 g,
93 % yield) was stored in a desiccator. The products were also characterized in basic
medium.
Preparation of N,Nꢀdialkylꢀαꢀaminoacids (3d’ꢀe’). General procedure.37 To a
solution of proline (0.5 g, 4.3 mmol) in 60 mL of methanol placed in a 25ꢀmL stainless
steel tubular reactor, 0.52 mL of a 37 % aqueous formaldehyde (1.6 equiv) and 0.125 g
palladium on carbon 10 % w.w. (0.03 equiv) were added at room temperature with
stirring. The reactor was tightly closed, pressurized with hydrogen (10 bar) and allowed
to stand at room temperature for 12 h with stirring. The reaction mixture was filtered
and the solid was washed with methanol. The solution was evaporated under a
vacuum and the solid residue was dried under a vacuum at 50 oC for 8 h. The product
(0.5 g, 89 % yield) was stored in a desiccator. The products were also characterized in
basic medium.
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2ꢀ(Diethylamino)propanoic acid (3a) [98204ꢀ12ꢀ7].38 85%, 1.1 g, white solid; 1H NMR
(300 MHz, D2O): δ (ppm) 1.32 (q, J=7.2 Hz, 6H), 1.48 (d, J= 7.2 Hz, 3H,), 3.09ꢀ3.40 (m,
4H), 3.87 (q, J= 7.2 Hz, 1H). 13C RMN (75 MHz, D2O): δ (ppm) 8.9, 9.8, 12.0, 45.5,
45.6, 62.0, 174.8. MS (EI+, 70ev) m/z: 42 (11), 44 (23), 56 (17), 70 (8), 72 (33), 100
—+
(100), 130 (5), 145(M , 4). HRMS (ESI+) m/z : (M+H+) Calcd for C7H16NO2: 146.1176,
found: 146.1168.
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2ꢀ(NꢀisopropylꢀNꢀmethylamino)acetic acid (3b) [1105044ꢀ89ꢀ0].39 93%, 0.7 g, white
solid; 1H NMR (300 MHz, D2O): δ (ppm) 1.33 (dd, J= 6.0 Hz, 6H), 2.83 (s, 3H), 3.53 (d,
J= 15.0Hz, 1H), 3.62 (m, J = 6 Hz, 1H), 3.81 (d, J = 15 Hz, 1H) ; 13C RMN (75 MHz,
D2O): δ (ppm) 16.0, 16.5, 37.9, 55.2, 58.4, 171.1; EM (EI+, 70ev) m/z: 42(12), 44(100),
—+
56(10), 70 (15), 116 (24), 131 (M , 5). HRMS (ESI+) m/z (M+H+): Calcd for C6H14NO2 :
132.1025, found: 132.1004.
2ꢀ(NꢀButylꢀNꢀmethylamino)acetic acid (3c) [23590ꢀ11ꢀ6].40 82%, 1.0 g, white solid;
1H NMR (300 MHz, D2O): δ (ppm) 0.98 (t, J = 7.5 Hz, 3H), 1.43 (m, J = 7.5 Hz, 2H),
1.77 (m, J = 9.0 Hz, 2 H), 2.95 (s, 3H), 3.09ꢀ3.36 (m, 2H), 3.78 (dd, J = 18.0 Hz, 7.5
Hz, 2H). 13C RMN (75 MHz, D2O): δ (ppm) 13.2, 19.5, 26.1, 41.7, 57.2, 58.6, 170.8. MS
(EI+, 70ev) m/z: 29 (14), 41 (33), 42 (54), 44 (92), 58 (85), 74 (85), 100 (84), 102 (100),
—+
145 (M , 18). HRMS (ESI+) m/z (M+H+): Calcd for C7H16NO2: 146.1181, found:
146.1173.
Nꢀmethylꢀ2ꢀpyrrolidincarboxylic acid (3d) [68078ꢀ09ꢀ1].36 85%, 0.5 g, white solid; 1H
NMR (300 MHz, D2O): δ (ppm) 1.91ꢀ2.25 (m, 3H), 2.42ꢀ2.60 (m, 1H), 2.94 (s, 3H),
3.08ꢀ3.23 (m, 1H), 3.68ꢀ3.81 (m, 1H), 3.85ꢀ3.95 (m, 1H). 13C RMN (75 MHz, D2O): δ
(ppm) 23.2, 29.2, 41.1, 56.7, 71.0, 174.1. MS (EI+, 70ev) m/z: 42 (30), 57 (5.5), 70 (6),
—+
82 (13), 84 (100) 129 (M , 1). HRMS (ESI+) m/z (M+H+): Calcd for C6H12NO2:
130.0868, found: 130.0859.
2ꢀ(Pyrrolidineꢀ1ꢀyl)acetic acid (3d’) [37386ꢀ15ꢀ5].36 73%, 1.0 g, white solid; 1H RMN
(300 MHz, D2O): δ (ppm) 2.10 (m, 4H), 3.25ꢀ3.65 (br m, 4H), 3.82 (s, 2H). 13C RMN (75
MHz, D2O): δ (ppm) 23.2, 55.2, 57.9, 171.5). MS (EI+, 70ev) m/z: 42 (20), 55 (10), 70
—+
(1.5), 84 (100), 129 (M , 4). HRMS (ESI+) m/z (M+H+): Calcd for C6H12NO2: 130.0868,
found: 130.0858.
1
Nꢀmethylꢀ2ꢀpiperidinecarboxylic acid (3e) [7730ꢀ87ꢀ2].37 86%, 0.5 g, white solid; H
NMR (300 MHz, D2O): δ (ppm) 1.52ꢀ1.90 (m, 5H), 2.15ꢀ2.27 (br d, 1H), 2.86 (s, 3H),
3.03 (dt, J = 13.5, 3.0 Hz, 1H), 3.42ꢀ3.55 (m, 2H). 13C RMN (75 MHz, D2O): δ (ppm)
21.3, 22.9, 28.4, 42.7, 54.7, 69.4, 174.6. MS (EI+, 70ev) m/z: 42(13), 55(3.5), 70 (26),
—+
82 (2.5), 84 (2.0), 98 (100), 143(M , 1). HRMS (ESI+) m/z (M+H+): Calcd for C7H14NO2:
144.1024, found: 144.1019.
1
2ꢀ(Piperidinꢀ1ꢀyl)acetic acid (3e’) [3235ꢀ67ꢀ4].41 93%, 0.27 g, white solid; H RMN
(300 MHz, D2O): δ (ppm) 1.50 (m, 1H), 1.50 (m, 5H), 2.99 (dt, J = 12 Hz, 3 Hz, 2H),
3.56 (br d, 2H), 3.67 (s, 2H). 13C RMN (75 MHz, D2O): δ (ppm) 21.4, 23.1, 54.3, 59.0,
—+
170.5. MS (EI+, 70ev) m/z: 42 (11), 55 (7), 70 (6), 98 (100), 143 (M , 2). HRMS (ESI+)
m/z (M+H+): Calcd for C7H14NO2: 144.1024, found: 144.1004.
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2ꢀ(Diethylamino)propanoic acid hydrochloride [3a(H+)].38 1H NMR (500 MHz, D2O,
HCl): δ (ppm) 1.06 (t, J=9.0 Hz, 6H), 1.29 (d, J= 6.0 Hz, 3H), 2.84ꢀ3.20 (m, 4H), 4.06
(q, J= 9.0 Hz, 1H). 13C RMN (126 MHz, D2O, HCl): δ (ppm) 9.1, 9.7, 10.6, 46.7, 47.7,
59.2, 171.6.
Sodium 2ꢀ(diethylamino)propanoate (3aCOONa) [98204ꢀ12ꢀ7].38 1H NMR (500 MHz,
D2O): δ (ppm) 1.12 (t, J = 12 Hz, 6 H), 1.30 (d, J = 15 Hz, 3 H), 2.71ꢀ2.95 (m,4 H), 3.50
(q, J = 12 Hz, 1 H); 13C NMR (126 MHz, D2O): δ (ppm) 10.9, 14.6, 44.7, 61.6, 179.9.
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Sodium 2ꢀ(NꢀisopropylꢀNꢀmethylamino)acetate (3bCOONa) [1105044ꢀ89ꢀ0].39 1H
NMR (500 MHz, D2O): δ (ppm) 1.02 (d, J = 5 Hz, 6 H), 2.23 (s, 3 H), 2.88 (m, J = 5 Hz,
1 H),3.08 (s, 2 H); 13C NMR (126 MHz, D2O): δ (ppm) = 17.6, 37.4, 52.8, 57.2, 179.5.
Sodium 2ꢀ(NꢀbutylꢀNꢀmethylamino)acetate (3cCOONa) [23590ꢀ11ꢀ6].40 1H NMR
(500 MHz, D2O): δ (ppm) 0.90 (t, J = 7.4 Hz, 3 H), 1.30 (m, 2 H), 1.46 (m, 2 H), 2.27 (s,
3 H), 2.47ꢀ2.44 (m, 2 H),3.05 (s, 2 H); 13C NMR (126 MHz, D2O): δ (ppm) 13.3, 20.2,
28.4, 41.4, 56.2, 60.6, 178.8.
Sodium Nꢀmethylꢀ2ꢀpyrrolidincarboxylate (3dCOONa) [849145ꢀ28ꢀ4].36 1H NMR
(300 MHz, D2O): δ (ppm) 1.69ꢀ1.84 (m, 3H), 2.03ꢀ2.18 (m, 1H), 2.27 (s+m, 4H), 2.79
(m, 1H), 2.95 (m, 1H). 13C RMN (75 MHz, D2O): δ (ppm) 22.5, 29.7, 40.1, 55.7, 70.8,
182.0.
Sodium 2ꢀ(pyrrolidinꢀ1ꢀyl)acetate (3d’COONa) [201931ꢀ57ꢀ9].42 1H NMR (500 MHz,
D2O): δ (ppm) 1.79 (m, 4 H), 2.63 (m, 4 H), 3.17 (s, 2 H); 13C NMR (126 MHz, D2O): δ
(ppm) 23.4, 53.6, 59.6, 178.9.
Sodium Nꢀmethylꢀ2ꢀpiperidinecarboxylate (3eCOONa) [7730ꢀ87ꢀ2].36 1H NMR (500
MHz, D2O): δ (ppm) 1.18ꢀ1.8 (m, 7H), 2.04 (td, J = 3 Hz, 12 Hz, 1H), 2.13 (s. 3H), 2.49
(dd, J = 3 Hz, 9 Hz, 1H), 2.82 (dt, J = 12 Hz, 3 Hz, 1H); 13C NMR (126 MHz, D2O): δ
(ppm) 23.6, 25.3, 53.9, 63.0, 178.7.
Sodium 2ꢀ(piperidinꢀ1ꢀyl)acetate (3e’COONa) [91724ꢀ68ꢀ4].42 1H NMR (500 MHz,
D2O): δ (ppm) 1.43 (m, 2H), 1.56 (m, 4 H),2.47 (br m, 4 H), 2.97 (s, 2 H). 13C NMR (126
MHz, D2O): δ (ppm) 23.2, 24.9, 53.6, 62.6, 178.3.
Photochemical reactions of amines 1 and CO2. General procedures. Triethylamine
(1a), either used neat or in anhydrous acetonitrile solution (0.3 M), was placed (3.7 mL)
inside a quartz test tube that was capped with a rubber septum, and was treated with
CO2 (20 psi) for 20 min at 0 oC with stirring. After removing the stirring bar, the test tube
was sealed with a rubber septum, and was then fixed to the motor unit of a rotary
evaporator (150 rpm). Reaction mixtures were irradiated for 3 h at room temperature
with a compact twinꢀtube germicidal lamp (254 nm, 36 W) placed in parallel 2 cm
above the test tube. Reaction mixtures were transparent solutions with a thin solid layer
on the tube wall for the reactions in acetonitrile solution, and white solid suspensions
for the reactions used neat. After removing volatiles under a vacuum, the residue was
dissolved with 3 mL of a 0.078 M solution of phenol, used as the external standard, in
D2O to which one drop of 37 % hydrochloric acid was added to improve solubility. The
solution was analyzed by NMR to quantify the acidic reaction products. The analysis
and quantification of the basic products were performed in a second identical
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experiment, which was treated with 37 % hydrochloric acid prior to removing volatiles
under a vacuum. The residue was dissolved with 3 mL of a 0.078 M solution of phenol,
used as the external standard in D2O, and the solution was analyzed by NMR. The
sodium salts of the acidic products were characterized in a third experiment by
evaporating the reaction mixture under a vacuum by dissolving the residue in 3 mL of a
0.75 M solution of sodium hydroxide, and using 0.05 M of phenol as an external
standard in D2O, and the basic solution was extracted with 3 mL of benzene. The
aqueous layer and the organic layer were respectively analyzed by NMR and gas
chromatographyꢀmass spectrometry.
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Preparation of N,N,N’,N’ꢀtetraethylbutaneꢀ2,3ꢀdiamine (4a). A 0.3 M acetonitrile
solution of triethylamine (1a) (3 mL) was placed inside a quartz test tube that was
capped with a rubber septum, and was treated with CO2 (20 psi) for 20 min at 0 oC with
stirring. After removing the stirring bar, the test tube was sealed with a rubber septum,
and was then fixed to the motor unit of a rotary evaporator, set at 150 rpm. The solution
was irradiated for 3 h at room temperature with a compact twinꢀtube germicidal lamp
(254 nm, 36 W) placed in parallel 2 cm above the test tube. The same reaction was
performed 6 times. The combined reaction mixtures were treated with 37 %
hydrochloric acid prior to removing volatiles under a vacuum. The residue was treated
with 10 mL of a 2.5 M solution of sodium hydroxide and the basic solution was
extracted with 3x10 mL of nꢀpentane. The organic layer was dried with anhydrous
MgSO4 and evaporated under a vacuum to yield a colorless liquid (0.79 g, 73%), which
was analyzed by NMR in acidic D2O and by gas chromatographyꢀmass spectrometry.
N,N,N’,N’ꢀtetraethylbutaneꢀ2,3ꢀdiamine (4a) [4a: 3653ꢀ11ꢀ0; 4a—HCl: 1071696ꢀ23ꢀ
5].43 73%, 0.79 g, colorless liquid; 1H NMR (300 MHz, D2O, HCl): δ (ppm) D,L 0.86 (t,
12 H), 0.94 (d, 6H), 2.82 (br m, 4 H), 2.93 (br m, 2 H), 3.50 (br q, 2H); meso 0.87 (t, 12
H), 1.00 (d, 6 H), 2.75 (br m, 4 H), 3.10 (br m, 2 H), 3.40 (br q, 2 H). 13C RMN (75 MHz,
D2O, HCl): δ (ppm) D,L 9.9, 46.1, 47.4, 58.3; meso 9.6, 46.4, 48.6, 57.8. MS (EI+,
70ev) m/z: 29 (7.6), 42 (9.8), 44 (18.6), 56 (12), 70 (9.1), 72 (15), 84 (2.7), 86 (1.8), 99
—+
(4.5), 100 (100), 112 (1.2), 128 (4.5), 141 (0.1), 155 (2.3), 169 (2.9), 200 (M , 1).
Acknowledgements
Financial support from the Ministerio de Economía y Competitividad (CTQ2016ꢀ80503ꢀ
P), and Fondos FEDER is gratefully acknowledged. MB thanks the Spanish Ministerio
de Economía y Competitividad for a fellowship (BESꢀ2011ꢀ043933). We thank the
SCSIE (Universidad de Valencia) for access to their instrumental facilities.
Supporting Information. The Supporting Information is available free of charge on the
ACS Publications website at DOI: XXXXXX. 1H and 13C NMR spectra (PDF).
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NꢀethylꢀN,3ꢀdimethylpentanꢀ2ꢀamine,
N,Nꢀ
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