Synthesis and Prior Misidentification of 4- tert-Butyl-2,6-dinitrobenzaldehyde

Article abstract of DOI:10.1021/acs.joc.9b01737

Substituted 2,6-dinitrobenzaldehydes are valuable synthetic precursors and have been prepared by several methods. We report here that one reported synthetic method actually forms the 3,5-dinitro isomer, 4-tert-butyl-3,5-dinitrobenzaldehyde, instead of the

Full text of DOI:10.1021/acs.joc.9b01737

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Synthesis and Prior Misidentification of 4-tert-butyl-2,6-dinitrobenzaldehyde
Daniel J. Martin, Brandon Q. Mercado, and James M. Mayer
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01737 • Publication Date (Web): 21 Aug 2019
Downloaded from pubs.acs.org on August 23, 2019
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Synthesis and Prior Misidentification of 4-tert-butyl-2,6-dinitrobenzaldehyde
Daniel J. Martin,* Brandon Q. Mercado, and James M. Mayer*
Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA
*Correspondence to: daniel.j.martin@yale.edu, james.mayer@yale.edu
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Abstract. Substituted 2,6-dinitrobenzaldehydes are valuable synthetic precursors and have been prepared by
several methods. We report here that one reported synthetic method actually forms the 3,5-dinitro isomer, 4-
tert-butyl-3,5-dinitrobenzaldehyde, instead of the claimed 2,6-isomer, 4-tert-butyl-2,6-dinitrobenzaldehyde.
Improved syntheses for the large-scale preparation of both compounds and their single-crystal x-ray structures
are described.
Substituted 2,6-dinitrobenzaldehydes are useful reagents for the preparation of dyes, pigments and
macrocycles such as porphyrins and corroles.1–6 In particular, 2,6-dinitrobenzaldehydes are used in the synthesis
of tetrakis-5,10,15,20-(2′,6′-dinitrophenyl)porphyrins, precursor molecules for bis-picket fence porphyrin
derivatives.4 The acid-catalyzed condensation of 2,6-dinitrobenzaldehyde or related derivatives with pyrrole
produces substituted 2ʹ,6ʹ-dinitrophenylporphyrins, but typically only in low yields, ranging from 0.5% to 9%.
The highest yields are for the tetrakis-5,10,15,20-(4′-tert-butyl-2′,6′-dinitrophenyl)porphyrin, a common
derivative.3 In order to make reasonable amounts of this porphyrin target (>100 mg), its synthesis requires
sizable amounts of 4-tert-butyl-2,6-dinitrobenzaldehyde, the starting benzaldehyde precursor.
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Scheme 1. Preparations of 4-tert-butyl-2,6-dinitrobenzaldehyde and 4-tert-butyl-3,5-dinitrobenzaldehyde,
showing incorrect prior report (red), corrected reaction product (blue), previously available route
(black), and new—chromium and column-free—procedures (gold).
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Method A: reported synthesis in reference 6; actually yields 2 (this work). Method B: high yield synthesis of 2,
this work. Method C: previously reported synthesis of (1) requiring chromium reagents and chromatography
purification, reference 3. Method D: high yield, high throughput synthesis of (1), this work.
The synthesis of 4-tert-butyl-2,6-dinitrobenzaldehyde (1) has been reported using two different routes,
Methods A and C in Scheme 1.3,6 Method A reported what seemed to be the most direct synthesis, a one-pot
nitration and oxidation of 4-tert-butylbenzylalcohol.6 This synthesis was stated to be “noteworthy since it
occurs with concomitant chemoselective oxidation of the benzylic alcohol to the corresponding aldehyde and
represents the by far most practical route” to this common precursor.6 Following this preparation, we obtained a
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product in similar yields, which had H NMR and C NMR spectra identical to the reported spectra (Figures
S1-S2). Slow evaporation of this product from ethyl acetate yielded crystals suitable for single-crystal x-ray
diffraction. The single-crystal data revealed that the product of this reaction was not 1 but was instead the
isomeric 3,5-dinitro compound, 4-tert-butyl-3,5-dinitrobenzaldehyde (2) (Figure 1, Right; Scheme 1, Method
A). Presumably the hot HNO3/H2SO4 oxidation of the benzyl alcohol proceeds by initial formation of 4-tert-
butylbenzaldehyde, which directs nitration to positions meta to the aldehyde. Consistent with this possible
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intermediate formation, we report the synthesis of the 3,5-dinitro isomer, product 2, in much higher yields
(>95%) from the nitration of 4-tert-butylbenzaldehyde (Scheme 1, Method B; procedure in the Experimental
Section). After a literature search of articles citing reference 6, we believe that this incorrect assignment may
have led to a synthesis and misidentification of what is actually tetrakis-5,10,15,20-(4′-tert-butyl-3′,5′-
dinitrophenyl)porphyrin.7
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An earlier paper by Rose et al. reported a three-step preparation of the target 2,6-dinitro isomer (1) from
4-tert-butyltoluene (Scheme 1, Method C).3 Following this procedure, including chromatography and
recrystallization, we obtained a product with 1H NMR and 13C NMR spectra (Figures S3-S4) that were identical
to those reported in reference 3. Crystals were obtained from ethyl acetate/ethanol mixtures and single-crystal x-
ray diffraction showed that the product of this reaction was correctly assigned as 4-tert-butyl-2,6-
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dinitrobenzaldehyde (1) (Figure 1, Left). The H NMR and C NMR spectra for 1 and 2 are quite distinct, as
are the solid-state structures.
Figure 1. Thermal ellipsoid plots (50% probability level) of X-ray structures for 4-tert-butyl-2,6-
dinitrobenzaldehyde and 4-tert-butyl-3,5-dinitrobenzaldehyde. The unit cell of 1 contained two chemically
identical, crystallographically distinct molecules of 1 (Zʹ = 2); only one molecule is shown for clarity.
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It is unfortunate that the apparently scalable Method A does not produce the desired compound 1. While
Method C is suitable for the synthesis of 1 in small quantities, it does not scale well to larger amounts. After
three steps, the overall yield of 1 is only 41% from 4-tert-butytoluene, and the synthesis requires stoichiometric
amounts of chromium reagents and multiple chromatography columns. We are pleased to report an improved
route to 1, starting from inexpensive 4-tert-butyltoluene, that can be done on much larger scales and without the
need for chromatography or chromium reagents.
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Our synthesis of 1 (Method D, Scheme 1) was adapted from the reported syntheses of other ortho-
substituted aldehydes, including 2,6-dinitrobenzaldehyde.8,9 First, 4-tert-butyl-2,6-dinitrotoluene was prepared
by nitration of 4-tert-butyltoluene. The synthesis of this compound has been reported in several articles3,6,10,11
and we have found no reports of hazards such as being explosive or forming explosive species. Bromination
using N-bromosuccinimide yielded 4-tert-butyl-2,6-dinitrobenzylbromide. Heating 4-tert-butyl-2,6-
dinitrobenzylbromide with pyridine in ethanol resulted in the precipitation of 4-tert-butyl-2,6-dinitro-
benzylpyridinium bromide as a white, crystalline solid. Base-catalyzed condensation of the pyridinium salt with
N,Nʹ-dimethyl-4-nitrosoaniline
generated
the
N-(4-dimethylaminophenyl)-α-(4-tert-butyl-2,6-
dinitrophenyl)nitrone, which precipitated as an orange solid from cold ethanol/water. Acid-catalyzed hydrolysis
1
of the nitrone precipitated 1 as a yellow solid from acidic water. The H NMR and 13C NMR for all the
intermediates are reported in the supporting information (Figures S5-S12). While this synthesis has more steps,
it gives 1 in 65% overall yield (starting from one mole of the parent toluene) and requires only recrystallization
and solubility differences for purification (Method D, Scheme 1). An alternative synthesis via direct oxidation
of the benzyl bromide intermediate using DMSO/Et3N was briefly explored. While this gave the target product
in fewer steps than the method detailed here, it was not pursued because it required chromatography to separate
the unreacted benzyl bromide and was therefore less attractive at large scale.
In sum, we report here that a published method6 yields 4-tert-butyl-3,5-dinitrobenzaldehyde (2) rather
than the claimed 2,6-dinitro isomer, 4-tert-butyl-2,6-dinitrobenzaldehyde (1). Since the 2,6−isomer is a valuable
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synthetic intermediate, we have developed an improved synthesis without the need for chromatography or
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chromium reagents. This synthesis has been scaled to yield more than 150 grams of 1 with an overall yield of
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65%. We also report a convenient synthesis of 2. The H NMR and C NMR spectra and the x-ray crystal
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structures of both isomers are reported.
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Experimental Section
1
Instrumentation. H NMR spectra were recorded on an Agilent 500 MHz spectrometer and were
referenced to proteo solvent impurities. High resolution mass spectrometry was performed using a Waters Xevo
G2-XS QTof mass spectrometer. Gas-chromatography mass spectroscopy was performed using an Agilent
6890N/5973 mass spectrometer. Elemental analyses were performed by Robertson Microlit Laboratories,
Ledgewood, NJ.
Materials. Potassium nitrate (Sigma,-Aldrich, ReagentPlus®, >99%), sulfuric acid (J.T. Baker, 98%), 4-
tert-butylbenzylalcohol (Sigma-Aldrich, 95%), 4-tert-butylbenzaldehyde (Sigma-Aldrich, 97%), 4-tert-
butyltoluene (Sigma-Aldrich, 95%), N-bromosuccinimide (Sigma-Aldrich, ReagentPlus®, 99%), 2,2’-azobis(2-
methylpropionitrile (Sigma-Aldrich, 98%), pyridine (Sigma-Aldrich, 99.8%), N,N-dimethyl-4-nitrosoaniline
(Sigma-Aldrich, 97%), aqueous hydrochloric acid (Macron, 36-38% wt), sodium chloride (Sigma-Aldrich,
>99%), sodium bicarbonate (Sigma-Aldrich, >99%), sodium hydroxide (Macon, 95%), chloroform (Sigma-
Aldrich, 99.8%), ethyl acetate (Sigma-Aldrich, 99.8%), absolute ethanol (Decon Labs, 200 proof), diethyl-ether
(Sigma-Aldrich, 99%), and acetone (Sigma Aldrich, 99.8%) were all used as received. Dichloromethane was
degassed with argon and dried using a Pure Process Technology solvent system prior to use.
Single Crystal X-ray diffraction methods. Low-temperature diffraction data (ω-scans) were collected on
a Rigaku SCX Mini diffractometer coupled to a Rigaku Mercury275R CCD with Mo Kα radiation (λ = 0.71073
Å). The diffraction images were processed and scaled using Rigaku Oxford Diffraction software (CrysAlisPro;
Rigaku OD: The Woodlands, TX, 2015). The structures were solved with SHELXT and were refined against F2
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on all data by full-matrix least squares with SHELXL.1 All non-hydrogen atoms were refined anisotropically.
Hydrogen atoms were included in both models at geometrically calculated positions and refined using a riding
model. The isotropic displacement parameters of all hydrogen atoms were fixed to 1.2 times the U value of the
atoms to which they are linked (1.5 times for methyl groups). For 2, the dataset was refined as a 2-component
twin. The fractional volume contribution of the minor twin component was freely refined to a converged value
of 0.3850(19). For 1, the dataset yielded a unit cell containing two chemically identical, crystallographically
distinct molecules.
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The full numbering scheme of compounds 1 and 2 can be found in the full details of the X-ray structure
determinations (CIFs), which are included as Supporting Information. CCDC number 1923128 (1) and 1923129
(2) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/data_request/cif.
Mixed acid preparation for nitration reactions. Caution: Fuming nitric acid (FNA) is a corrosive
strong acid and a strong oxidant; concentrated sulfuric acid is a corrosive strong acid; and the mixture of the
two is considered a stronger acid and oxidant. All of these materials are highly hazardous and should be handled
with substantial caution with emphasis on appropriate specialized personal protective equipment (PPE). Our
laboratory’s standard operating procedure (SOP) for FNA and the mixed acid are included as Supporting
Information. Fuming nitric acid (FNA, +98%) was freshly prepared immediately before use via distillation of
HNO3 at 80 °C from a mixture of potassium nitrate and concentrated sulfuric acid, prepared as described in the
SOP. FNA (1 part by volume, for instance 50 mL) was cooled to 5 °C in an ice bath before slowly adding
concentrated sulfuric acid (1.4 parts by volume, for instance 70 mL). Upon addition, the mixed acid warms to
15 °C. The mixed acid solution was then cooled back to 5 °C before being used immediately for nitration
reactions.
Improved synthesis of 4-tert-butyl-3,5-dinitrobenzaldehyde (2). Approximately 120 mL of the mixed
H2SO4/HNO3 acid (see preparation above) was prepared in a 500 mL round bottom flask with a large stirbar and
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was cooled to 5 °C with an ice bath [Caution: hazardous! See above and SOP in Supporting Information].
Above the round bottom was suspended a dropping funnel filled with 4-tert-butylbenzaldehyde (25 mL, 0.149
mmol). The benzaldehyde was added dropwise to the stirring solution and the flow rate was adjusted such that
the reaction temperature did not rise above 15 °C. After complete addition, the solution was yellow/orange and
the reaction flask was allowed to warm to room temperature before being gently heated to 40 °C for 1-2h.
During this time, some off-white precipitate formed. The reaction was then quenched by carefully pouring the
entire reaction into a large amount of crushed ice (ca. 500 mL). The precipitated product was filtered off and
washed with excess water. The dilute, acidic filtrate was neutralized and added to the aqueous waste. After air
drying, the crude yellow solid (crude yield by weight: 36g, 97%) was dissolved in chloroform and filtered
through Celite to remove any over-oxidized 4-tert-butyl-2,6-dinitrobenzoic acid (the white solid formed during
synthesis). The filtrate was collected and removed with a rotary evaporator to dryness. The collected solid was
then recrystallized from boiling ethyl acetate to yield pale yellow crystals (Figure S18). After filtration and air
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drying, the isolated yield was 29 g (80% yield). H NMR (CDCl3, 500 MHz): δ (ppm) = 9.99 (s, 1H, CHO),
7.99 (s, 2H, Ar-H), 1.49 (s, 9H, C(CH3)3). 13C NMR (CDCl3, 500 MHz): δ (ppm) = 187.0, 153.7, 141.1, 135.3,
126.6, 38.2, 30.0. Anal. Calcd for C11H12N2O5: C, 52.38; H, 4.80; N, 11.11. Found: C, 52.13; H, 4.65; N, 10.95.
MS (EI) m/z = 252.1 ([M]+), 237.1 ([M]+ ‒ CH3).
4-tert-butyl-2,6-dinitrotoluene. This synthesis was adapted from the literature.4 Approximately 240 mL
of the mixed H2SO4/HNO3 acid (see preparation above) was prepared in a 1L round bottom flask with a large
stirbar and was cooled to 5 °C with an ice bath [Caution: hazardous! See above and SOP in Supporting
Information]. Above the round bottom was suspended a dropping funnel filled with 4-tert-butyltoluene (173
mL, 1.0 mol). The 4-tert-butyltoluene was added dropwise to the stirring solution over the course of three hours
such that the temperature of the reaction stayed between 5-10 °C. The yellow product formed and floated to the
reaction surface during the addition. After complete addition, the reaction flask was allowed to warm to room
temperature and was stirred for another 12h. The reaction was quenched by carefully pouring the reaction
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mixture into 500 mL of crushed ice. After filtration, the collected yellow solid was washed with excess water.
The dilute, acidic filtrate was neutralized and added to the aqueous waste. The damp solid was then
recrystallized from boiling EtOH (approx. 750 mL). Upon cooling, large yellow crystals formed (Figure S13).
The solution was cooled at 0 °C overnight before the crystals were filtered and washed with cold EtOH. After
drying, the isolated yield was 190 g flaky crystalline solid (80% yield). 1H NMR (CDCl3, 500 MHz): δ (ppm) =
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7.97 (s, 2H, Ar-H), 2.52 (s, 3H, CH3), 1.37 (s, 9H, C(CH3)3). C NMR (CDCl3, 500 MHz): δ (ppm) = 152.2,
151.6, 124.7, 124.1, 35.3, 30.8, 14.5. Anal. Calcd for C11H14N2O4: C, 55.46; H, 5.92; N, 11.76. Found: C, 55.42;
H, 5.78; N, 11.68. MS (EI): m/z = 238.1 ([M]+), 223.1 ([M]+ ‒ CH3).
4-tert-butyl-2,6-dinitrobenzylbromide. To a 3L three-necked round bottom flask was added a large
stirbar, 4-tert-butyl-2,6-dinitrotoluene (190 g, 0.798 mol, 1 eq.), N-bromosuccinimide (170 g, 0.998 mol, 1.25
eq.), and AIBN (1.5 g, 0.009 mol, 0.01 eq). Two of the three ports were stoppered and 1.5 L of dry
dichloromethane was added to the solids. The solution was sparged with N2 for 20 minutes before a condenser
was attached to the third port and the reaction was heated to a gentle reflux (45-50 °C). A white LED light (14
V dc, 0.7 A from Digi-Key) was clamped a few inches away from the flask and the reaction was loosely
shrouded in aluminum foil. At the 12h, 48h, 74h, and 82h marks, additional NBS (20 g, 0.117 ml, 0.15 eq.) and
AIBN (0.5 g, 0.0045 mol, 0.005 eq.) were added. The solid additions were made by funneling the NBS/AIBN
through an opened port under gently flowing N2 only after cooling the reaction to room temperature. After four
days, the reaction was nearly complete (>98% conversion based on the ratio of product to starting material by
1H NMR). The solvent was removed using a rotary evaporator to yield a damp solid. The solid was resuspended
in chloroform and filtered to remove the bulk of the succinimide. The filtrate was separated with sat. Na2CO3
solution to remove residual succinimide before being dried with MgSO4 and filtered. The solvent was removed
and the product was recrystallized from hot diethyl ether to yield extremely large pale-yellow crystals (5-7
grams apiece, Figure S14). Isolated yield was 235.5 g large yellow crystals and 13.2 g non-crystalline powder
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with matching H NMR spectra (97.7%). H NMR (CDCl3, 500 MHz): δ (ppm) = 8.04 (s, 2H, Ar-H), 4.84 (s,
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2H, CH2Br), 1.37 (s, 9H, C(CH3)3). C NMR (CDCl3, 500 MHz): δ (ppm) = 155.3, 150.1, 125.9, 123.6, 35.7,
30.7, 20.4. Anal. Calcd for C11H13BrN2O4: C, 41.7; H, 4.1; N, 8.8. Found: C, 41.69; H, 4.01; N, 8.71. MS (EI):
m/z = 301.0 ([M]+ ‒ CH3), 237.1 ([M]+ ‒ Br), parent ion not observed.
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4-tert-butyl-2,6-dinitrobenzylpyridinium bromide. The crude 4-tert-butyl-2,6-dinitrobenzylbromide
(246 g, 0.778 mol, 1eq.) was added to a 2 L beaker. The solid was dissolved in 1 L EtOH (200 proof) and was
heated to 78oC with stirring. Pyridine (130 mL, 1.55 mol, 2 eq.) was added dropwise to the stirring solution,
which darkened and eventually precipitated flocculent, white crystals (Figure S15). After complete addition, the
solution was stirred for an additional hour at reflux before an additional hour of stirring at room temperature.
The crystals were filtered and washed with EtOH and acetone. After drying, the first crop of crystals weighed
258 g. The filtrate was pumped to a solid using a rotary evaporator and was repeatedly recrystallized from
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EtOH to yield an additional 25 g of off-white solid with H NMR that matched the crystalline material (total
solid collected: 283.0 g, 91.3% yield. 1H NMR (d6-DMSO, 500 MHz): δ (ppm) = 9.06 (d, J = 6.0 Hz, 2H, 2,6-
py-H), 8.72 (t, J = 7.8 Hz, 1H, 4-py-H), 8.53 (s, 2H, Ar-H), 8.21 (t, J = 7.1 Hz, 2H, 3,5-py-H), 6.14 (s, 2H, Ar-
CH2-py), 1.41 (s, 9H, C(CH3)3). 13C NMR (d6-DMSO, 500 MHz): δ (ppm) = 157.9, 152.0, 146.7, 144.5, 128.5,
127.6, 116.5, 56.0, 36.2, 30.5. Anal. Calcd for C16H18N3O4Br: C, 48.50; H, 4.58; N, 10.60. Found: C, 48.31; H,
+
4.32; N, 10.38. HRMS (ESI/Q-TOF) m/z: [M ‒ Br]+ calcd for C16H18N3O4 316.1297; found 316.1296.
N-(4-dimethylaminophenyl)-α-(4-tert-butyl-2,6-dinitrophenyl)nitrone. To a large Erlenmeyer flask was
added approximately 1/3 of the dry 4-tert-butyl-2,6-dinitrobenzylpyridinium bromide (85.4 g, 0.215 mol, 1 eq.)
and N,N-dimethyl-4-nitrosoaniline (40.0 g, 0.266 mol, 1.24 eq). The solids were suspended in 1.0 L of ethanol
(200 proof) and the solution was cooled to 5 °C with an ice bath. An addition funnel was suspended above the
reaction and was filled with 600 mL of 1 N-sodium hydroxide solution. With vigorous stirring, the NaOH
solution was added dropwise such that the temperature was kept between 5-10 °C. After complete addition, the
solution was stirred for another 2h before being diluted with 1 L ice water. The nitrone precipitated as an orange
solid (Figure S16), which was filtered and washed with excess water. This procedure was repeated until nearly
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all of the benzylpyridinium bromide was used (279.3 g, 0.714 mol). All of the orange solids were collected and
dried in a vacuum oven at 50oC until reaching a constant mass (2-3 days). After drying, the yield was 257.7 g of
orange powder (92.4% yield). 1H NMR (CDCl3, 500 MHz): δ (ppm) = 8.44 (s, 1H, Ar-CH=N), 8.30 (s, 2H, Ar-
H), 7.67 (d, J = 9.1 Hz, 2H), 6.67 (d, J = 9.1 Hz, 2H), 3.04 (s, 6H, N(CH3)2), 1.42 (s, 9H, C(CH3)3). 13C NMR
(CDCl3, 500 MHz): δ (ppm) = 155.3, 152.1, 149.6, 136.8, 126.1, 122.8, 122.5, 117.8, 111.4, 40.5, 35.9, 30.9.
Anal. Calcd for C19H22N4O5: C, 59.06; H, 5.74; N, 14.50. Found: C, 58.92; H, 5.56; N, 14.34. HRMS (ESI/Q-
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TOF) m/z: [M + H+] calcd for C19H23N4O5 387.1668; found 387.1682.
4-tert-butyl-2,6-dinitrobenzaldehyde (1). In
a
large beaker, nearly all of the N-(4-
dimethylaminophenyl)-α-(4-tert-butyl-2,6-dinitrophenyl)nitrone (257.2 g) was suspended in 2L of water.
Concentrated sulfuric acid was added slowly and the solution warmed to approximately 50 °C. The suspension
was stirred for 30 minutes, during which the solution color lightened to a pale yellow-brown. The suspension
was filtered and the collected solid was washed with excess water. After drying, 164 g of pale-yellow powder
was collected (98% yield). The solid can be recrystallized from hot ethanol or from mixtures of ethanol/ethyl
1
acetate to yield golden flake-like crystals (Figure S18). H NMR (CDCl3, 500 MHz): δ (ppm) = 10.57 (s, 1H,
CHO), 8.45 (s, 2H, Ar-H), 1.45 (s, 9H, C(CH3)3). 13C NMR (CDCl3, 500 MHz): δ (ppm) = 186.2, 157.1 147.7,
129.0, 126.8, 36.1, 30.9. Anal. Calcd for C11H12N2O5: C, 52.38; H, 4.80; N, 11.11. Found: C, 52.13; H, 4.61; N,
10.94. MS (EI) m/z = 252.1 ([M]+), 237.1 ([M]+ ‒ CH3).
Supporting Information Available
1
i) Copies of H NMR and 13C NMR spectra. (ii) Crystallographic information files (CIF) and data for
compounds 1 and 2. This material is available free of charge via the Internet at http://pubs.acs.org." (iii)
Standard Operating Procedures for working with concentrated nitric and sulfuric acids, with emphasis on safety
precautions.”
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Acknowledgements
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This research was supported as part of the Center for Molecular Electrocatalysis, and Energy Frontier
Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences.
D.J.M. gratefully acknowledges support by a Graduate Research Fellowship from the National Science
Foundation. We thank Dr. Fabian Menges (Yale Chemical and Biophysical Instrumentation Center) for
assistance with mass spectroscopy and recognize support from the National Science Foundation grant 1828190
for support of mass spectrometry facilities.
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