Mechanochemical borylation of aryldiazonium salts; merging light and ball milling

Article abstract of DOI:10.3762/bjoc.13.144

Merging of photo- and mechanochemical activation permitted studying the role of eosin Y in the borylation of aryldiazonium salts in a ball mill. Simultaneous neat grinding/irradiation of the reactants and the photocatalyst led to the formation of boronates in a molten state. On the other hand, the catalyst-free liquid-assisted grinding/irradiation reaction also led to product formation, featuring a direct photolysis pathway facilitated by substrate–solvent charge-transfer complex formation.

Full text of DOI:10.3762/bjoc.13.144

Mechanochemical borylation of aryldiazonium salts; merging
light and ball milling
José G. Hernández
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2017, 13, 1463–1469.
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg
doi:10.3762/bjoc.13.144
1, D-52074 Aachen, Germany
Received: 22 May 2017
Accepted: 14 July 2017
Published: 26 July 2017
Email:
José G. Hernández - jose.hernandez@oc.rwth-aachen.de
This article is part of the Thematic Series "Mechanochemistry".
Associate Editor: I. R. Baxendale
Keywords:
aryldiazonium salts; borylation; eosin Y; mechanochemistry;
photocatalysis
©
2017 Hernández; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
Merging of photo- and mechanochemical activation permitted studying the role of eosin Y in the borylation of aryldiazonium salts
in a ball mill. Simultaneous neat grinding/irradiation of the reactants and the photocatalyst led to the formation of boronates in a
molten state. On the other hand, the catalyst-free liquid-assisted grinding/irradiation reaction also led to product formation,
featuring a direct photolysis pathway facilitated by substrate–solvent charge-transfer complex formation.
Introduction
The use of mechanical force to process materials or to induce to develop more sustainable syntheses. Typically, mechano-
chemical transformations is perhaps as old as the history of chemical reactions by milling are conducted in non-translucent
mankind itself [1]. Similarly, from time immemorial light has containers (e.g., agate, ceramics, steels, and tungsten carbide).
also been present on earth, being perhaps photosynthesis and While this diversity of milling media materials enables control-
visions the most fundamental connections between light and ling, for example, the energy input during the mechanical
living organisms [2]. However, combining synergistically process, it becomes an obstacle for in situ characterization of
photo- and mechanical activations in organic synthesis is still mechanochemical reactions, or to facilitate synergistic activa-
challenging despite the enormous potential of having both acti- tion types involving, for example, light and mechanical energy.
vation modes acting simultaneously.
Recently, however, the in situ study of mechanochemical trans-
formations has been accomplished by combining translucent
In recent years, mechanochemistry, which encompasses the use milling vessels made of poly(methyl methacrylate) (PMMA)
of mechanical means by milling, grinding, shearing, cavitation with powder X-ray diffraction (PXRD) [6,7], Raman spectros-
or pulling to induce chemical transformations [3] has become copy [8], or a combination of both techniques [9]. On the other
fundamental for discovering new chemical reactivity [4,5] and hand, attempts to combine photo- and mechanical activation to
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favor chemical processes have been mainly explored in the Subsequently, with the aim to determine the role of the light,
photodimerizations of olefins by manual grinding of the reac- PC and the mechanical milling in the borylation of the aryldia-
tants followed by long UV-light exposure [10], or by vortex zonium salts, and especially to exclude a potential background
grinding [11]. However, until now, studies of photocatalyzed borylation reaction triggered by either thermal, mechanical or
mechanochemical reactions involving, for example, metal com- light-induced heterolytic cleavage of aryldiazonium salts,
plexes [12] or organic photocatalysts (PC) [13] has been under- various control reactions were conducted. First, an equimolar
explored [14], despite photocatalysis could clearly benefit from mixture of the diazonium salt 1a and B2pin2 (2) was milled for
the excellent mixing under neat or liquid-assisted grinding 2 h at 25 Hz in a mixer mill, using a Teflon milling jar and ZrO2
(
LAG) [15] conditions. Additionally, in contrast to solution- ball bearings. The safe use of diazonium salt under ball milling
based methods, reactions by milling do not suffer from solu- conditions has been previously reported in the literature [19].
bility restrictions due to the possibility to bring reactants and The analysis of the reaction mixture by 1H NMR spectroscopy
catalysts of very different solubility, into close proximity for revealed just the presence of both reactants, both in the
achieving chemical reactivity. This last aspect is foreseen as presence or absence of the organic photocatalyst eosin Y
highly valuable in transformations using low-soluble PCs (e.g., (5.0 mol %). Ruling out a sole mechanochemical activation
porphyrins) [16] or during the photochemical synthesis or modi- pathway (Table 1, entries 1 and 2).
fication of polymers [17].
Repeating the reaction in the presence of the PC in the trans-
The aforementioned context makes one wonder about the poten- parent PPMA milling jar yielded the same negative result
tial for conducting chemical reactions under simultaneous proving that ambient light did not mediate the photoredox cata-
photo- and mechanical activation. To test this idea, the photo- lytic borylation reaction under mechanochemical conditions
catalyzed borylation of aryldiazonium salts, first reported in (Table 1, entry 3). Furthermore, neat grinding of a catalyst-free
solution by Yan and co-workers was selected as a model reac- mixture of 1a and 2 under blue LEDs (light-emitting diodes)
tion [18]. In the original study, irradiation for 18 h of a MeCN light did not afford the borylated product 3a. In addition to the
solution of aryldiazonium salts, bis(pinacolato)diboron (B2pin2, 1H NMR analysis in solution, this result was confirmed by
2
) and eosin Y with a 25 W visible light lamp led to the corre- immediate ex situ analysis using IR spectroscopy of the solid
sponding arylboronates in moderate to good yields [18].
reaction mixture, which revealed only the presence of both
starting materials. Thereby, excluding a direct thermal [20,21]
or photolysis pathway operating under solventless conditions
Results and Discussion
To commence, a PMMA milling jar was designed to enable (Table 1, entry 4). Then, a premilled mixture of 1a, B2pin2, and
external light irradiation of the reaction mixture while having eosin Y was subjected to irradiation with blue LEDs for 2 h in
simultaneously the high-speed ball milling acting on the mix- the absence of milling (Table 1, entry 5). After the irradiation
ture of reactants and PC (Figure 1; for details, see Supporting was halted, the reaction mixture was immediately analyzed by
Information File 1).
1H NMR spectroscopy. This time trace quantities of product 3a
Figure 1: (a) Cartoon representing the merging of light and mechanical energy. (b) 25 mL transparent PMMA milling jar. (c) Experimental setup for si-
multaneous photo- and mechanical-activation with an external light source.
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Table 1: Screening of the reaction conditions.a
Entry
Eosin Y (mol %)
Time (h)
Light
1a:3a (%)b
1
2
3
4
5
6
7
8
9
1
1
1
1
c
–
2
–
100:0
100:0
100:0
100:0
94:6
c
(5)
(5)
–
2
–
2
ambient
2
blue LEDs
blue LEDs
blue LEDs
blue LEDs
blue LEDs
blue LEDs
blue LEDs
blue LEDs
green LEDs
green LEDs
d
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(0.5)
2
0.5
1
83:17
54:46
27:73
15:85
59:41
51:49
6:94
1.5
2
0e
1f
2
2
2
1
3
1.5
63:37
aReaction conditions: a mixture of 1a (0.369 mmol), 2 (0.369 mmol) and eosin Y was mixed in a 25 mL PMMA milling jar with 15 ZrO2 balls of 5 mm in
diameter at 25 Hz. bDetermined by 1H NMR spectroscopy. cA 25 mL Teflon milling jar was used. d1a, 2 and the PC were mixed for 30 s in the PMMA
jar, then the mixing was stopped and the milling jar was exposed to the light irradiation for 2 h. eThe irradiation was stopped after 1 h of reaction. fThe
milling was stopped after 1 h of reaction.
were detected (Table 1, entry 5). This interesting result under Indeed, milling the product 3a under the standard milling condi-
solvent-free conditions encouraged performing the light irradia- tions using the LEDs led to its melt. Similarly, milling a mix-
tion accompanied by milling to improve mixing and to increase ture of 1a, 2 and 3a for 1 h under light irradiation reached a
the surface exposure of the reaction mixture. In a following set eutectic melt phase. The need for simultaneous light and me-
of experiments, milling of the reactants and PC was carried out chanical milling was also confirmed after conducting experi-
for a time in the range of 15 min to 2 h. The analysis of the ments for 2 h where either the milling or the irradiation was
composition of the reaction mixture showed significant forma- stopped after the first hour. In both cases the outcome of the
tion of the product after 30 min of milling/irradiation (Table 1, reaction gave similar results compared to having both energy
entry 6). Monitoring the progress of a mixture of the reactants sources acting together for 1 h (Table 1, entries 7, 10, and 11).
and PC in CD3CN at room temperature by 1H NMR spectrosco-
py over a period of time of 20 h showed a composition (98:2; Next, further tuning of the reaction conditions revealed green
1
a:3a), ruling out the formation of the 3a during the standard LEDs to be a more efficient light source for the reaction with
analysis time. Furthermore, the presence of 3a in the mixture eosin Y (for details, see Table S1 in Supporting Information
coincided with the observation of an initial molten state of the File 1). This change permitted the transformation to take place
mixture inside the milling jar [22]. This more homogeneous after 1 h of milling/irradiation. Under these conditions, the ratio
mixture could have increased the mobility of the reactants 1a:3a in the reaction mixture reached 6:94 (entry 12 in Table 1).
favoring the SET process. Reaching the molten state clearly re- Alternatively, longer reaction times allowed reducing the
quired having both activation modes acting simultaneously, amount of the organic photocatalyst to 1.0 mol % and
since only milling of 1a (mp 138–141 °C), 2 (mp 139–140 °C) 0.5 mol % (entry 13 in Table 1; for more details, see Table S1
and eosin Y (mp 305–307 °C), or just irradiation of the mixture in Supporting Information File 1). Then, using the green LEDs
did not lead to an observable melting of the solids (Table 1, an experiment in the presence of 1,1-diphenylethene (4) as a
entries 2–4 and 5). Besides, propagation of this molten state radical inhibitor was conducted. After the standard 1 h of
could have been favored by the gradual rise in concentration of milling, the formation of 3a was slowed down and the analysis
the lower-melting product 3a (mp 69–70 °C) in the mixture. of the reaction mixture by gas chromatography–mass spectrom-
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etry showed the presence of the phenyl radical trapping adduct Analogously to the case of 1a, the fluoro and chloro substituted
5
(Scheme 1).
aryldiazonium salts 1b and 1c did react affording the boronates
b and 3c (Table 2, entries 1 and 2). It was noticed, however,
3
With the optimized reaction conditions in hand, we explored the that the milling/irradiation time required for these substrates to
photomechanochemical borylation of the halogenated aryldia- react varied in comparison with the reaction of 1a. Furthermore,
zonium salts 1a–d (Table 2).
attempts to react the 4-iodobenzenediazonium tetrafluoroborate
Scheme 1: Borylation of 1a in the presence of 1,1-diphenylethene (4).
Table 2: Borylation of aryl diazonium salts 1 with 2.a
Entry
1
Aryldiazonium salt
Product
Time (min)
90
Yield (%)b
60
1b
1c
1a
1d
1e
3b
3c
3a
3d
3e
2
3
4
5
45
60
55
68
41
49
120
120
aReaction conditions: a mixture of 1 (0.369 mmol), 2 (140.6 mg; 0.554 mmol) and photocatalyst (5 mol %) was mixed in a 25 mL PMMA milling jar
with 15 ZrO2 balls of 5 mm in diameter at 25 Hz. bAfter column chromatography.
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(
1d) with 2 were made with low success even after 2 h of reac- was anticipated to have the potential for switching the activa-
tion time (Table 2, entry 4). As indicated above, the develop- tion mode from a SET process to a direct heterolytic photolysis.
ment of a molten state upon irradiation and milling appears to Jacobi von Wangelin et al. noticed that the borylation product
be a key prerequisite for the photomechanochemical borylation 3a could also occurred in the absence of eosin Y, upon irradia-
to occur [14,22]. Reaching that molten state in the reaction with tion of a MeCN solution of the reactants with white LEDs
the iodo derivative 1d proved challenging, only a part of the [23,25]. Pleasingly, LAG (MeCN or DMSO η = 0.25) of 1a and
reaction mixture seemed homogeneous. Differential scanning 2 under blue LEDs, and in the absence of eosin Y did also
calorimetry (DSC) analysis of the aryldiazonium salts 1a–d generate the product 3a. In contrast, LAG experiments using
revealed that 1a–c melt followed by decomposition of the sam- n-heptane failed at producing 3a (Scheme 2; for details, see
ples. However, the DSC profile of the iodobenzenediazonium Table S2 in Supporting Information File 1).
salt 1d showed a direct thermal decomposition upon heating.
NMR analysis of the molten 1d revealed the presence of Similarly, control LAG/irradiation experiments conducted in a
1
-fluoro-4-iodobenzene (for details, see Supporting Informa- Teflon milling jar, only formed trace quantities of the product
tion File 1). Therefore, the difference in melting point tempera- 3a, ruling out a sole thermal activation of the system by the
tures of the substrates and their thermal stability could have a light source. These results not only illustrates the versatility of
direct correlation with the observed reactivity in the ball mill mechanochemistry to control the chemical reaction pathway
(
Table 2). Control experiments by stirring/heating 1a–d and 2 in operating in the process, but also sheds light on the role of the
an oil bath until the melting of the mixture was reached, showed photocatalyst in the borylation of the aryldiazonium salts.
predominantly thermal decomposition of the aryldiazonium
salts 1a–d into the 1-halo-4-fluorobenzene derivatives [23] and Under non-catalyzed LAG/irradiation conditions, charge-
only in some cases trace quantities of 3a–d were detected. transfer complexes between 1a and appropriate organic sol-
Meaning that the external light contributes to both, heating the vents could be responsible for the fast generation of the aryl
reaction mixture to its eutectic and it also initiated the cations in the ball mill, leading to the direct formation of 3a
photoredox process. Similarly, a photocatalyzed reaction be- [26,27]. This observation is in agreement with the findings by
tween 2 and 4-nitrobenzenediazonium tetrafluoroborate (1e), a Jacobi von Wangelin et al., who described that upon irradiation
salt found also to undergo decomposition at 423 K, turned out of a solution of 1a in MeCN direct heterolytic cleavage of the
difficult (for the DSC traces of 1a–e see Supporting Informa- aryldiazonium salt occurred [23,25]. However, the formation of
tion File 1).
3a under solvent-free milling conditions (vide supra) could have
been indeed the result of a photoredox transformation where the
After 2 h of milling/irradiation the corresponding product 3e organic photocatalyst eosin Y played a key role in triggering the
was obtained in moderate yield. In general, after the milling/ir- SET process.
radiation experiments no aryldiazonium salt was observed in the
reaction mixture, however, the moderate yields for the products Conclusion
3
a–e, even in the presence of 1.5 equiv of 2, could have been In summary, simultaneous activation of an organic system by
the result of background reactions undergone by 1a–e under the light and ball milling techniques has been successfully accom-
reaction conditions, especially due to the rise in temperature ob- plished for the first time. The utilization of translucent milling
served upon light irradiation.
vessels permitted the study of the photoborylation of aryldiazo-
nium salts in the presence and in the absence of the organic
As mentioned above, LAG, an alternative to the standard neat photocatalyst eosin Y. The results of this proof-of-concept
grinding, has become an useful parameter in mechanochem- demonstration revealed that under neat grinding conditions the
istry to control chemical selectivity and product composition by PC does play a role in initiating a SET borylation. Furthermore,
having catalytic volumes of organic solvent during the milling the implementation of a LAG/irradiation approach allowed the
[
24]. Here, a change in the milling approach from neat to LAG borylation reaction to occur under catalyst-free conditions. This
Scheme 2: Light-mediated LAG borylation of 1a. aDetermined by 1H NMR spectroscopy using internal standard. bAfter column chromatography.
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6
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Experimental procedures, experimental set-ups and
characterization data, NMR spectra, and DSC traces.
2
1
1
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[http://www.beilstein-journals.org/bjoc/content/
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Acknowledgements
This research was possible thanks to the financial support from
the RWTH Aachen University through the 1) RWTH Start-up
grant StUpPD_221-16 funded by the Excellence Initiative of the
German federal and state governments and 2) the Distinguished
Professorship Program. Dr. J. Langanke, Dr. C. Rosorius, M.Sc.
A. Ernst (CAT Catalytic Center Aachen) are acknowledge for
the access to DSC and the technical assistance. Prof. Dr.
Carsten Bolm is gratefully acknowledged for generous support
and valuable advice.
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