Structure and reactivity in neutral organic electron donors derived from 4-dimethylaminopyridine

Article abstract of DOI:10.3762/bjoc.6.73

The effects on the redox properties of modifying the molecular skeleton of neutral bis-2-(4-dimethylamino)pyridinylidene electron donors, derived from 4-dimethylaminopyridine (4-DMAP), have been explored, by varying two parameters: (i) the length of a polymethylene chain linking the two pyridine-derived rings and (ii) the nature of the nitrogen substituents on the 4 and 4″ positions of the precursor pyridines. Restricting the bridge length to two methylene units significantly altered the redox profile, while changes in the nitrogen-substituents at the 4 and 4' positions led to only slight changes in the redox potentials.

Full text of DOI:10.3762/bjoc.6.73

Structure and reactivity in neutral organic electron
donors derived from 4-dimethylaminopyridine
Jean Garnier1, Alan R. Kennedy1, Leonard E. A. Berlouis1,
Andrew T. Turner2 and John A. Murphy*1
Full Research Paper
Open Access
Address:
WestCHEM, Department of Pure and Applied Chemistry, University
of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, U.K. and
PR&D Laboratory Building, AstraZeneca, Silk Road Business Park,
Beilstein J. Org. Chem. 2010, 6, No. 73. doi:10.3762/bjoc.6.73
1
Received: 27 April 2010
Accepted: 09 June 2010
Published: 05 July 2010
2
Charterway, Macclesfield SK10 2NA, United Kingdom
Email:
Guest Editor: J. Murphy
Jean Garnier - jeangarn@hotmail.com; Alan R. Kennedy -
a.r.kennedy@strath.ac.uk; Leonard E. A. Berlouis -
l.berlouis@strath.ac.uk; Andrew T. Turner -
andrew.t.turner@astrazeneca.com; John A. Murphy* -
john.murphy@strath.ac.uk
© 2010 Garnier et al; licensee Beilstein-Institut.
License and terms: see end of document.
*
Corresponding author
Keywords:
dication; 4-DMAP; electron donor; electron transfer; radical cation;
redox; reduction
Abstract
The effects on the redox properties of modifying the molecular skeleton of neutral bis-2-(4-dimethylamino)pyridinylidene electron
donors, derived from 4-dimethylaminopyridine (4-DMAP), have been explored, by varying two parameters: (i) the length of a poly-
methylene chain linking the two pyridine-derived rings and (ii) the nature of the nitrogen substituents on the 4 and 4′ positions of
the precursor pyridines. Restricting the bridge length to two methylene units significantly altered the redox profile, while changes in
the nitrogen-substituents at the 4 and 4′ positions led to only slight changes in the redox potentials.
Introduction
Neutral organic compounds 1 and 4–10 (Figure 1) have valene (TTF, 1, E11/2 = 0.37 V; E21/2 = 0.67 V in DCM vs SCE)
attracted considerable attention as ground-state electron donors [1], one of the weakest of these donors, reduces arene-
[
1-38], and many are now being employed as reagents in diazonium salts to aryl radicals [2-12], but is not strong enough
organic transformations. Such a range of reagents with different to react with alkyl and aryl halides. The driving force for its
redox potentials leads to the expectation of considerable oxidation is the attainment of some degree of aromaticity in the
selectivity in their reductions of organic substrates, and evi- formation of its radical cation salt 2 on the loss of one electron,
dence is steadily accumulating to support this. Tetrathiaful- and full aromaticity in its dication salt 3 on loss of two elec-
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Beilstein J. Org. Chem. 2010, 6, No. 73.
Figure 1: Neutral organic electron donors 1 and 4–10.
trons, as well as the stabilization of both the positive charge and to an aryl anion [39]. Whatever about the standard potentials, in
radicals by the lone pairs on the sulfur atoms. The effect of practice, the formation of aryl anions is only observed when the
aromatic stabilization is enhanced in the extended analogue 4; electron donor has E1/2 = −1 V or is more negative [40]. In line
however, unlike TTF, this compound affords only an irrevers- with this, both the imidazole-derived donor 7 (E1/2 = −1.20 V vs
ible oxidation Ep = −0.14 V in MeCN (assuming that the SCE in DMF) [22-25] and the 4-dimethylaminopyridine
reported value is measured relative to SHE, that would corres- (4-DMAP)-derived donor 8 [E1/2 (DMF) = −1.69 V vs Fc/Fc+]
pond to −0.38 V vs SCE) [13]. Tetrakis-dimethylaminoethene [26-29], which would equate to −1.24 V vs SCE [E
(
TDAE, 5: E11/2 = −0.78 V; E21/2 = −0.61 V vs SCE in MeCN) (DMF)Fc/Fc+ = 0.45 V vs SCE] [41] react with aryl iodides to
is a stronger reducing agent and converts electron-deficient afford aryl anions. As an indication of their enhanced donor
alkyl bromides to the corresponding anions [14-17] and notably properties, these two donors can also cleave appropriate arenes-
the iodide CF3–I to trifluoromethyl anion, −CF3, [15] but is not ulfonamides [25], aryl alkyl sulfones [25,26], Weinreb amides
powerful enough to react with aryl halides. Despite not experi- [28] and acyloin derivatives [29]. They are also prone to
encing any aromatic stabilization on oxidation, the molecule is transfer two electrons rather than one, with the cyclic voltam-
such a good donor as a result of the ability of the nitrogen atoms mogram (c.v.) of 8 showing a single 2-electron reversible redox
in 5 to stabilize both the positive charge and an unpaired elec- wave [26] while in donor 7 the potentials of the successive elec-
tron upon oxidation; this stabilization is greater than is afforded tron transfers are close enough that the c.v. gives the appear-
by sulfur in TTF.
ance of a single reversible peak, but has a slight shoulder [24].
Molecules 9 (E1/2 = −1.00 V vs SCE in DMF) [30-32] and 10
Benzimidazole-derived donor 6 (E11/2 = −0.82 V; E21/2 = [33,35,37] extend the range of designs of neutral organic elec-
0.76 V vs SCE in DMF) [18-20], combines the stabilization of tron donors, although we are not aware of them being investi-
−
positive charge and of an unpaired electron provided by four gated as yet for the reduction of organic substrates.
nitrogens, with aromatic stabilization in its oxidised forms. This
exceptional donor has the power to reduce aryl iodides (E0 = In order to design both more potent electron donors, and donors
−
2.2 V) to aryl radicals, but not to aryl anions [21]. This is para- with calibrated and targeted properties, the factors that drive the
doxical in view of the standard potential of the second step; E0 electron transfer(s) need to be clearly understood, and this paper
0.05 V vs SCE in MeCN for the conversion of an aryl radical now probes two factors that could impact on that.
=
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Beilstein J. Org. Chem. 2010, 6, No. 73.
Results and Discussion
chain – a longer chain should afford greater flexibility and
Donor 8 has a number of attractive features. It is simply might afford a stronger donor, mirroring the findings of Ames
prepared from the reaction of 4-DMAP with 1,3-diiodopropane, et al. with a different series of compounds [18-20,22]. In
followed by treatment of the product with base [26-28]. A wide contrast, shortening the polymethylene chain as in 14 should
range of analogues of 4-DMAP, which have been well studied constrain rotation of the pyridine rings in the dication 16, and
in acylation chemistry [42,43], is already available. This hence make formation of 16 more difficult. To determine the
suggests that preparation of analogues of 8 should also be effect of bridge-length on redox potential, the analogous donors
straightforward. Hence, donor 8 was selected as the target for 14 and 15 were prepared in situ and converted to their
modification. The effect of modifying the length of a poly- respective oxidized salts 16 and 18, as shown in Figure 2, by
methylene chain linking the two pyridine-derived rings and the reaction with iodine. Anion exchange to afford the corres-
nature of the substituents on the 4- and 4′-positions of those ponding hexafluorophosphate salts 16′ and 18′ was then carried
pyridine rings were the points of particular interest. TDAE, 5, out prior to cyclic voltammetry. (The iodide anions were
has been used extensively as a two-electron transfer reagent, exchanged since iodide ions would be electrochemically active,
and many salts that feature its dication have been analysed by albeit at more positive potentials than feature in our studies.)
X-ray crystallography [44]. In these dications, the two ends of
the molecule are twisted extensively to minimize interaction Cyclic voltammetry studies were carried out by adding deoxy-
between the two positive charges. It is tempting to think that the genated solutions of the oxidized disalts 16′–18′ (rather than the
degree of twist is linked to the power of the reducing agent. If electron donors) to the electrochemical cell and then carrying
twisting was not possible, then the driving force for removal of out the electrochemistry under an inert gas. The donors them-
the second electron, for the conversion of the radical cation to selves are highly sensitive to traces of oxygen, and so are less
the dication, should be diminished. To see if the same twist convenient to weigh out than the disalts. All of the cyclic
occurs with our donor 8, the crystal structure of the disalt 17 voltammograms showed reversible redox chemistry, featuring
was determined [twist (N–C–C–N = 52.5(3) degrees] the transfer of two electrons, as indicated by calibration with
(
Figure 2). The degree of twist is limited by the three-carbon ferrocene/ferrocenium (Fc/Fc+).
Figure 2: Formation of donors and oxidation to form diiodide salts, together with the ORTEP diagram of diiodide salt 17 (only the cation is shown).
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Beilstein J. Org. Chem. 2010, 6, No. 73.
1
5 relative to 8. Taking the idea of flexible rotation between the
two halves of the molecule to its limit, we prepared compound
0′ [27] (Figure 5) and determined its cyclic voltammetric
2
behaviour. As shown in Figure 4b, this [E1/2 (DMF) = −1.27 V
vs SCE (calibrated using Fc/Fc+)] shows little difference from
that of 17′. [E1/2 (DMF) = −1.24 V vs SCE (calibrated using Fc/
Fc+)]. Accordingly, permitting a freer rotation than seen in 17′
by extending the tether between the two pyridine-derived rings
does not lead to enhanced donor properties.
The other site of relatively easy variation in 8 was the dialkyl-
amino group. 4-Pyrrolidinopyridine and 4-guanidinopyridine
are significantly better catalysts [42,43] in acylation reactions
than 4-DMAP. Their effectiveness depends on the delocaliza-
tion of the electron pair on the 4-substituent into the pyridine
Figure 3: Cyclic voltammograms vs Fc/Fc+ of 17′ ↔ 8 (red) and 16′ ↔
4 (blue).
1
Restricting the bridge length to two carbons made donor 14 a ring. Accordingly, the disalts 21 and 22 were prepared from
less effective reducing agent (Figure 3) compared to 8, under- these 4-substituted pyridines [43,45] and converted into their
lining the importance of flexibility of the inter-ring bond. Here, hexafluorophosphates 21′ and 22′, and then examined by cyclic
donor 8 shows a single two-electron wave [E11/2 (DMF) = voltammetry. Each showed a reversible two-electron redox
−
1.24 V vs SCE (calibrated using Fc/Fc+)], while donor 14 wave (Figure 6). Redox equilibria related to 21 showed that the
shows two one-electron waves [E11/2 (DMF) = −1.21 V, and corresponding donor 23 was a stronger donor than donor 8 by
E21/2 (DMF) = −0.98 V vs SCE (calibrated using Fc/Fc+)]. The about 90 mV for the transfer of its first electron, while the
potential for loss of the first electron is similar in both com- second electron occurs at the same potential as seen for donor 8,
pounds; however, the loss of the second electron from 8 is about while 24 transferred both of its electrons at the same potential
3
00 mV more negative than from 14. This indicates a greater and was within 10mV of 17′.
driving force for loss of the second electron in 8 than in 14,
consistent with the predicted difficulty in forming 14 as an The reactivity of these two donors was also investigated with
essentially planar dication, where repulsion between the two substrate 27. Here, 23 and 24 were prepared in situ from 25′ and
charges would be more severe.
26. This afforded the reductive de-iodination product 28 in good
yield (84% when using 25′, and 68% when using 26).
In contrast, comparison of the cyclic voltammograms of 18′ and
1
7′ (Figure 4a) showed only minor differences, with both These results are in accord with the previous reactions of donor
showing a single wave corresponding to a two-electron revers- 8, and show that significantly more powerful donors than 8
ible process at essentially the same potential (within 10 mV), so cannot be attained simply by altering the tether length between
the increased flexibility does not benefit the two-electron donor the two pyridine units. Similarly, simple modifications to the
Figure 4: (a) Cyclic voltammograms vs. Fc/Fc+ of 17′ ↔ 8 (red) and 18′ ↔ 15 (blue) and (b) of 17′ ↔ 8 (red) and 20′ ↔ 19 (blue).
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Beilstein J. Org. Chem. 2010, 6, No. 73.
Figure 5: Electron donors, their oxidized dications and their reactions with 27.
Figure 6: Cyclic voltammograms vs Fc/Fc+ (a) of 17′ ↔ 8 (red) and 21′ ↔ 23 (blue) and (b) of 17′ ↔ 8 (red) and 22′ ↔ 24 (blue) (at half the concn
used for 17′).
4
′-substituent do not lead to very large changes in the redox lated below in Table 1.] These outcomes are already helping our
properties of 8. [The oxidation potentials of these new donors design of new, versatile and more powerful organic electron
and the preceding examples mentioned in this paper are tabu- donors.
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Beilstein J. Org. Chem. 2010, 6, No. 73.
Table 1: Oxidation potentials of organic electron donorsa
Electron Donor
E11/2
E21/2
Structure
1b
0.37 V
0.67 V
4
c
c
−0.38 V(irr)
−0.78 V
5
−0.61 V
−0.76 V
6
−0.82 V
7
−1.20 Ve
8
9
−1.24 Ve
−1.00 Vd
−0.32 Ve
10
14
−1.21 V
−0.98 V
1
5
9
−1.23 Ve
1
−1.27 Ve
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Beilstein J. Org. Chem. 2010, 6, No. 73.
Table 1: Oxidation potentials of organic electron donorsa (continued)
23
−1.33 V
−1.24 V
24
−1.24 Ve
aAll numbers have been converted for comparison with SCE; all experiments recorded in DMF, except where otherwise stated.
bRecorded in DCM.
cRecorded in MeCN.
dRecorded in THF.
eTwo-electron wave.
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