Residual Solvent Signal of CDCl3as a qNMR Internal Standard for Application in Organic Chemistry Laboratory

Article abstract of DOI:10.1021/acs.joc.0c02744

A nuclear magnetic resonance (NMR) spectrometer is a key instrument in the organic synthesis laboratory for structure determination, reaction control, and compound purity analysis. In addition to qualitative analysis, the application of NMR for quantitati

Full text of DOI:10.1021/acs.joc.0c02744

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Article
Residual Solvent Signal of CDCl3 as a qNMR Internal Standard for
Application in Organic Chemistry Laboratory
Ruslan Muhamadejev, Renate Melngaile, Paula Paegle, Ieva Zibarte, Marina Petrova, Kristaps Jaudzems,
and Janis Veliks*
Cite This: J. Org. Chem. 2021, 86, 3890−3896
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ABSTRACT: A nuclear magnetic resonance (NMR) spectrometer is a key
instrument in the organic synthesis laboratory for structure determination,
reaction control, and compound purity analysis. In addition to qualitative
analysis, the application of NMR for quantitative analysis (qNMR) is gaining
popularity. qNMR allows for simple quantification of crude product
mixtures, determination of reaction yields, and purity of organic compounds.
The determination of NMR yield requires the addition of an internal
standard to each sample. Herein, we report a method where CDCl3 residual
solvent signal is used as an internal standard for qNMR after quantification in
the solvent batch. This method significantly simplifies sample preparation
and allows straightforward recovery of the analyte by the simple evaporation
of the NMR solvent. The accuracy of the method is comparable to qNMR
with 1,3,5-trimethoxybenzene as an internal standard if the herein described
guidelines are followed.
solvent batch. Determination of the concentration of the
CHCl3 residue for each batch of CDCl3 used in the lab does
not require much effort in comparison with the expected value
of quantitative information on compound concentrations in all
measured samples. We show that the residual solvent signal of
CDCl3 can be used as an internal standard for qNMR and that
its concentration remains constant for the batch if it is stored
properly. Figure 1 shows our approach in comparison with the
conventional qNMR method.
INTRODUCTION
■
A nuclear magnetic resonance (NMR) spectrometer is the
most commonly used instrument for structure elucidation in
organic chemistry.1 An access to an NMR spectrometer is a
requirement for a modern organic synthesis lab. For example, a
research group working in the area of synthetic organic
chemistry usually runs hundreds of samples per month.2
Besides “making sure one made the right compound”, chemists
use it for determination of purity of a sample, mechanistic
experiments, and determination of reaction (NMR) yields by
qNMR3 which requires the addition of an internal standard to
the sample. This approach is also used for the quality control
of pharmaceutical ingredients4 and in other areas where
quantification of organic compounds is important.5
CDCl3 is one of the most commonly used NMR solvents in
the organic synthesis lab. It is the preferred solvent due to its
affordable price, good solubilizing properties of many organic
compounds, and straightforward recovery of the sample after
analysis by simple evaporation. The recovery of a sample after
qNMR analysis is, however, often problematic even from
volatile solvents if the internal standard applied is nonvolatile.2
A signal due to incompletely deuterated NMR solvent
residue is always present in the NMR spectrum. An
experienced chemist would quickly recognize a singlet at
7.26 ppm and might use it to adjust the ppm scale.6 Here, we
propose to take full advantage of this mostly ignored signal in
the NMR spectrum as it carries extra valuable information, i.e.,
a defined concentration of protons in a deuterated NMR
There are numerous reports on qNMR3 including two
where residual protons in D2O and dimethyl sulfoxide
(DMSO)-d6 are considered as potential internal standards
for the quantification of natural products.7,8 However, it is not
a common practice in organic synthesis labs to use residual
solvent as a qNMR standard. To gain maximum accuracy of
this approach, the best practices of the qNMR sample
preparation and sample acquisition3,9 should be taken into
consideration. The purpose of this study is to demonstrate the
practicality of this approach in an organic synthesis laboratory
setting for daily use with simple sample preparation efforts and
easy recovery of the analyte.
Received: November 16, 2020
Published: February 12, 2021
https://dx.doi.org/10.1021/acs.joc.0c02744
© 2021 American Chemical Society
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Figure 1. (A) NMR internal standard should be added to each sample. (B) No need for the addition of extra internal standard after the
determination of residual CHCl3 concentration in CDCl3.
Table 1. T1 Relaxation Time for CHCl3 and TMB (400 MHz)
T1, s
CHCl3
TMB 2,4,6-CH
TMB 1,3,5-OCH3
average (n = 3 measurements)
6.314 0.004
3.688 0.004
1.760 0.002
Based on the measured T1 values, we chose the qNMR
acquisition parameters as follows: 14° pulse, recycle delay 30 s,
and 32−128 scans yielding experiment times of 21−75 min
(on a 400 and 300 MHz instrument, respectively). The
theoretical recovery of the CHCl3 magnetization during the
recycle delay is 99.97% and practically 100% for TMB protons
as well as other compounds of similar or larger size. Reduction
of the recycle delay to 7 s would yield an experiment time of
8−26 min and still ensure >99% recovery of the CHCl3
magnetization. As expected, on both instruments, we observed
a good linear correlation (linearity) between the concentration
RESULTS AND DISCUSSION
■
We started our study with the determination of the
concentration of nondeuterated CHCl3 residual solvent in a
CDCl3 batch using the internal standard 1,3,5-trimethox-
ybenzene (TMB).2 Since CHCl3 is a smaller molecule than the
usual internal standards, its relaxation is expected to be slower
and care must be taken to use appropriate experimental
parameters (pulse length and recycle delay) for the qNMR
experiments. Therefore, we determined the T1 relaxation time
for CHCl3 and TMB as a primary internal standard (Table 1).
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of the internal standard c(TMB) and its corresponding integral
value I(TMB), when the integral value I(CHCl3) of the CHCl3
signal was set to 100 (for 400 MHz data see Figure 2, for 300
MHz data see the Supporting Information).
using TMB, the corresponding maximum errors are 5.2 and
8.6%. These results indicate that the accuracy of our proposed
method is comparable to the conventional approach using
TMB as an internal standard.
The precision expressed as a standard deviation for repeated
measurements using CHCl3 as an internal standard was in the
range of 0.06−1.66% with one exception. The results for the
aldehyde 4 displayed lower repeatability (standard deviation of
4.36%) at 300 MHz, which could be explained by the
instability of the sample during a longer measurement time, as
was required for this instrument. The standard deviation of the
measurements using TMB was between 0.02 and 0.86%. This
indicates that the precision is notably higher than the accuracy
using both approaches.
As with qNMR in general, the present method requires good
solubility of the tested compounds in the NMR solvent. The
compound 8 displayed only partial solubility in CDCl3;
therefore, cosolvent was added to improve solubility. The
obtained results for this compound show some of the largest
errors with respect to balance weight; however, also, in this
case, the results using CHCl3 or TMB as an internal standard
are comparable. Another limitation of the method is the
potential overlap of the analyte signals with CHCl3 signal,
which limits its applicability to compounds that do not show
signals around 7.26 ppm. With regard to the detection limit
and useful CHCl3 concentration, the number of scans may
need to be adjusted to reach the desirable S/N ratio for the
signals under analysis taking into consideration the best
practices of qNMR.2 Additionally, the analyte concentration
may need to be adjusted by dilution using an appropriate
volume of CDCl3 to obtain both CHCl3 and analyte signal
intensities at the desired signal-to-noise ratio as well as in the
working range of the spectrometer’s analog-to-digital con-
verter. For this purpose, the sample can be prepared in
appropriate size vials (equipped with a screwing cap to avoid
evaporation losses), which would allow us to use a higher
volume of CDCl3. For the best result, a precise determination
of CDCl3 weight is crucial. Therefore, we recommend using a
balance for measuring the CDCl3 weight, as this is very easy to
do and guarantees the best accuracy. We do not recommend
using simple hypodermic syringes for this purpose, as this will
add extra uncertainty to the measurement (see the Supporting
Information). The concentration of CHCl3 should be
determined for each bottle regardless if it has the same or
different LOT number. This will remove any uncertainties that
might arise due to varying manufacturing, packing, storage, and
shipment conditions. For example, two different CDCl3
batches with D 99.8% content used for the experiments in
Table 2 (batch A and B) have approximately a 3% difference in
the CHCl3 concentration.
Figure 2. Integral value of internal standard 1,3,5-trimethoxybenzene
(TMB) as a function of its concentration, when residual CHCl3
integral value is set to 100 (400 MHz).
To determine the CHCl3 concentration in our CDCl3 batch,
we prepared three independent samples and performed three
measurements for each sample. The obtained c(CHCl3) was
16.231 0.138 mM (standard deviation of 0.85%). To test the
stability of the CHCl3 content in CDCl3, we repeated the
determination of CHCl3 concentration after 1 month and
obtained 16.144 0.037 mM (standard deviation of 0.23%).
The difference of −0.087 mM or −0.54% is within the
standard deviation of the first measurement, which indicates
that the CHCl3 concentration remains constant for at least 1
month.
Once the precise CHCl3 concentration in a CDCl3 batch has
been determined, the residual solvent signal can be used as an
internal standard for qNMR. To assess the accuracy of this
approach, we used it to determine the weight m(qNMR CHCl3) of
nine compounds and compared the obtained values with the
balance weight m(balance) as well as cross-checked the results
with those from qNMR using the accepted internal standard
TMB (Table 2). All measurements were repeated three times
and the standard deviation was calculated to determine the
precision of the measurement. The accuracy of the method was
evaluated by calculating the percentage errors of the
determined qNMR weight m(qNMR) with respect to the balance
weight m(balance) using both CHCl3 and TMB as internal
standards. The sample purity provided by the suppliers was
taken into account. All samples were measured on both 400
MHz and 300 MHz instruments and the results were
compared.
The selected test compounds include common solvents
(Table 2, 1−3), reagents in different states of matter (solid 4,
5; oil 7), a pharmaceutical drug (6), and a compound with
limited solubility in CDCl3 (8, with MeCN additive as a
solubilizing cosolvent). On average, the obtained m(qNMR CHCl3)
values differ by 3.0% from the balance weight m(balance) and by
2.5% from the weight determined using TMB as internal
standard m(qNMR TMB). At the same time, the m(qNMR TMB)
To exemplify the utility of the current technique in the
organic synthesis laboratory, we present its application in the
synthesis of vinyl sulfone 9. The compound 9 can be prepared
in three steps (Scheme 1 and Table 3) starting from 1-phenyl-
1H-tetrazole-5-thiol (10), which is alkylated with 1,2-dichloro-
methane to yield 5-((2-chloroethyl)thio)-1-phenyl-1H-tetra-
zole (11). Further, oxidation of sulfide 11 to a corresponding
sulfone 12 can be accomplished using NaIO4 in the presence
of catalyst RuCl3·H2O.10 Purity of the crude intermediate 12
was determined using the herein described qNMR method,
which helped to adjust the quantity of the required base in the
next step (Table 3). The desired product, vinyl sulfone 9,
turned out to be unstable in dichloromethane when using
values differ by about 2.5% from the balance weight m(balance)
.
The difference between the results obtained from two different
CDCl3 solvent batches is similarly in a range of 2−3% (Table
2, 1). The maximum qNMR error between the measurements
with CHCl3 as internal standard is 6.2 and 8.8% using 400 and
300 MHz instruments, respectively. Among the measurements
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Table 2. Compound Weight Determined by qNMR m(qNMR) Using CHCl3 or 1,3,5-Trimethoxybenzene and Balance m(balance)
a
All calculations were performed using CDCl3 batch A (Eurisotop, chloroform D, 99.80% D, Lot: S1541) c(CHCl3) = 16.231 mmol/L unless
b
otherwise stated. CDCl3 batch B (Aldrich, chloroform-d, 99.80% D, Lot # STBJ5818) c(CHCl3) = 16.700 mmol/L. Signals of protons highlighted in
bold were used for integration. As indicated in the certificate of analysis provided by the supplier. Sample weight measured on analytical balance d
c
d
e
= 0.01 mg. Error calculated as the difference between the balance weight and qNMR weight taking into consideration the compound purity.
f
g
Three independent measurements for each sample. Due to compound 4 instability in solution, lowered accuracy was observed on 300 MHz
instrument (acquisition time 1 h 15 min).
1
excess Et3N as a base (Table 3, entry 1). Therefore, a careful
adjustment of the reaction conditions (entries 2−4) was
performed to find an optimal reaction solvent and
stoichiometry of base. Using the CDCl3 qNMR method,
both, H NMR yields and the purity of product 9 was easily
evaluated for the crude and the isolated product 9, thereby
allowing rapid identification of optimal reaction conditions
(entry 4). The elimination reaction from 12 to product 9
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Scheme 1. Synthesis of Sulfone 12
Table 3. Reaction Optimization Using CDCl3 qNMR Technique
b
NMR yield of 9, %
a
c
d
be
,
entry
conditions
crude
isolated
balance yield of 9, %
NMR purity of 9, %
1
2
3
4
DCM, RT, 4 h, 2.5 equiv TEA
4.8
87.0
100
100
Et2O, 0 °C, 15 min, 2.27 equiv TEA
Et2O, 0 °C, 15 min, 1.12 equiv TEA
MTBE, 0 °C, 15 min, 1.12 equiv TEA
86.4
97.1
99.5
97
103
103
89
95
97
a
b
All reactions were performed on 0.301 mmol scale of 12. qNMR performed on a 400 MHz instrument using residual CHCl3 as an internal
standard. The crude 9 used for analysis. Product isolated using silica gel column chromatography (PE/EtOAc 5:1 to 1:1). Balance yield, NMR
yield, and purity determined for the same sample. NMR purity calculated following eq 5, see Experimental Section.
c
d
e
under the optimized conditions turned out to be a quantitative
process. The balance yield of isolated 9 includes the weight of
impurities, whereas the qNMR yield is calculated for a pure
substance in a sample, thereby allowing us to estimate the
sample purities (entries 2−4). Application of the residual
CHCl3 as an internal standard made possible the complete
recovery of the analyzed samples by simple solvent
evaporation.
We advise chemists who routinely use NMR in their work to
quantify the CHCl3 concentration of the particular solvent
batch and label the bottle with the determined concentration,
which is a simple task to do. This needs to be done once for
each batch of CDCl3 and, if properly stored, the value should
be constant for at least 1 month. Our results show that the
present method is sufficiently accurate and precise for qNMR
applications in routine organic chemistry. This method offers a
simple alternative to an external standard or the ERETIC
qNMR methods.12 According to the literature, ERETIC gives
approximately 3% of error,12a which is comparable to the
average error of using CHCl3 (3.00%) and TMB (2.46%) as
internal standards (Table 2). To adopt it as an analytical
chemistry tool or evaluate its suitability for other purposes, we
suggest to validate this method for the compound of interest
using an established internal standard on your own instrument
and determine the uncertainties of the measurement.
standard. The valuable quantitative information carried by the
residual solvent adds an extra dimension besides the usual
qualitative interpretation of the H NMR data. Our results
1
indicate that the residual CHCl3 gives comparable accuracy
with 1,3,5-trimethoxybenzene as an internal standard. In
addition, the use of NMR solvent residue as an internal
standard simplifies qNMR sample preparation and provides an
opportunity for very straightforward sample recovery by simple
NMR solvent evaporation. This approach has a huge potential
in reaction optimization and fast purity assessment of the
reaction intermediates and common lab chemicals without the
necessity to add any foreign materials to the sample.
EXPERIMENTAL SECTION
■
General Experimental Details. The weights of the internal
standard 1,3,5-trimethoxybenzene (TMB), CDCl3, and compounds
1−9 were measured using analytical balance BOECO d = 0.01 mg
placed on a stone table. All of the prepared samples were measured
within 24 h to avoid errors from solvent evaporation losses. Spectra
were recorded on (1) a 400 MHz Bruker Avance Neo spectrometer
equipped with 5 mm double-resonance broadband CryoProbe
Prodigy using the parameters: 14° pulse (90° pulse = 12 μs), d1 =
30 s, ns = 32, acquisition time = 4.19 s (32k points), spectral width
19.5333 ppm centered at 6.175 ppm and (2) a 300 MHz Bruker
Fourier spectrometer equipped with 5 mm dual-channel EasyProbe
using the parameters: 14° pulse (90° pulse = 14.5 μs), d1 = 30 s, ns =
128, acquisition time = 5.37 s (32k points), spectral width 20.3339
ppm centered at 6.175 ppm. The chosen interscan (pulse) delay d1
was based on the measured T1 relaxation times of the standard and
analyte to ensure a near-complete (>99.97%) relaxation of CHCl3.3
However, in most cases, the interscan delay can be reduced to
approximately 10 s (which ensures 99.4% relaxation using 14° pulse
tip angle) without deteriorating the accuracy of the method (as
CONCLUSIONS
■
We have proposed a very simple approach for the fast
determination of NMR yield in the organic synthesis lab by the
determination of residual solvent concentration in each CDCl3
batch and using the residual solvent signal as an internal
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demonstrated in the Supporting Information). Each qNMR spectrum
was taken three times (two for only CDCl3). 1,3,5-Trimethox-
ybenzene TraceCERT, purity = 99.96% (Lot# BCBW3670) and
99.82 (Lot# BCC9688) was purchased from Sigma-Aldrich. CDCl3
batch A: Eurisotop, chloroform D, 99.80% D, (Lot: S1541). CDCl3
Application of qNMR CDCl3 Technique in the Reaction
Optimization Experiments.10 5-((2-Chloroethyl)sulfonyl)-1-phe-
nyl-1H-tetrazole (12).10 To a mixture of 1-phenyl-1H-tetrazole-5-
thiol (10) (3.178 g, 17.83 mmol, 1.00 equiv) and Cs2CO3 (17.4 g,
53.5 mmol, 3.0 equiv) was added 1,2-dichloroethane (116 mL, 1480
mmol, 93 equiv) and MeCN (4 mL) at RT. The reaction mixture was
stirred at 60 °C for 3 days. TLC (PE/EtOAc 5:1) showed full
conversion. The reaction mixture was diluted with water (150 mL)
and extracted with DCM (3 × 200 mL). The combined organic
phases were dried over anh. NaSO4, filtered, and evaporated to give
the intermediate product 5-((2-chloroethyl)thio)-1-phenyl-1H-tetra-
zole (11) (4.30 g, 100%) as an off-white solid, which was subjected to
1
batch B: Aldrich, chloroform-d, 99.80% D, (Lot # STBJ5818). H
NMR spectra were transformed and analyzed with Mestrenova
software (Mestrelab Research). All spectra before integration were
transformed with the baseline correction (Whittaker Smoother).
General Procedure A for the CHCl3 Concentration Deter-
mination in CDCl3. In a 4 mL vial equipped with a screwing cap
internal standard 1,3,5-trimethyoxybenzole (TMB) (>∼11 mg) was
precisely weighed. The capped vial with TMB was placed on an
analytical balance and tare was measured. To the vial, CDCl3 (∼1
mL) was added, the vial immediately sealed with a screwing cap, and
the precise weight of CDCl3 was measured by analytical balance. The
sample was shaken till all TMB dissolved. The clear TMB solution
was transferred to an NMR tube and 1H NMR spectrum was recorded
using the above-described parameters. The signals of CHCl3 at 7.26
ppm and those of 1,3,5-trimethyoxybenzole at 6.09 and 3.77 ppm
were integrated. Average c(CHCl3) was calculated from three
independent measurements (three repeats for each) using eq 1
1
the next step without additional purification. H NMR (400 MHz,
CDCl3) δ 7.56−7.44 (m, 3H), 3.91−3.86 (m, 2H), 3.72−3.62 (m,
2H).10,11 To a mixture of crude sulfide from previous step (4.212 g,
17.50 mmol, 1.0 equiv) in CHCl3 (12 mL) and MeCN (12 mL) was
added NaIO4 (37.4 g, 175 mmol, 10 equiv). To the mixture, a
solution of RuCl3 hydrate (83 mg, 0.37 mmol, 0.02 equiv) in water
(42 mL) was added dropwise over 10 min at room temperature. The
reaction mixture was stirred for 5 h at room temperature. The
reaction progress was monitored by TLC (PE/EtOAc 5:1). After the
completion, 100 mL of water was added to the mixture. The reaction
mixture was extracted with MTBE (3 × 50 mL). The combined
organic phases were washed with sat. NaHCO3 and filtered through a
plug of silica gel covered with anh. Na2SO4. The plug was washed
with MTBE till no more product was detected by TLC in the filtrate.
The filtrate was evaporated under reduced pressure to give the desired
product (3.549 g, 74%, NMR(qNMR CDCl3) purity = 82%) as an off-
white solid.
I
× c(TMB) × N
I(TMB)
(CHCl3)
(TMB)
c(CHCl )
=
3
(1)
where c(CHCl3) is the concentration of the CHCl3 residue in CDCl3,
(TMB) is the concentration of internal standard, and N(TMB) is the ratio
c
of the number of protons of the signal used for integration in internal
standard (TMB) and the number of protons in solvent residue
(CHCl3). I(CHCl3) is the integral of solvent residue (at 7.26 ppm) and
I(TMB) is the integral of the internal standard signal (for TMB, the
aromatic CH signal at 6.09 ppm was used).
1H NMR (400 MHz, CDCl3) δ 7.75−7.48 (m, 5H), 4.23−4.07 (m,
2H), 4.10−3.96 (m, 2H).10,11
Reaction Optimization for the Synthesis of 1-Phenyl-5-(vinyl-
sulfonyl)-1H-tetrazole (9). To a chloride 12 (100 mg, 82% purity,
0.301 mmol, 1.0 equiv) in a solvent (4 mL) (see Table 3) at 0 °C was
added triethylamine (46.9 μL, 0.337, 1.12 equiv). A white precipitate
formed. The reaction mixture was stirred for 15 min at 0 °C. The
white precipitate was filtered off, filter-cake washed with solvent (1
mL), and the filtrate was evaporated under reduced pressure. To the
crude product, ∼3 g of precisely weighted CDCl3 with previously
determined CHCl3 concentration was added (following general
procedure B). After the measurement of 1H NMR under qNMR
conditions, the product weight in the sample was determined
according to eq 2. The NMR yield for the crude was calculated by
eq 4
General Procedure B for the Analyte Weight Determination
by 1H NMR Using CDCl3 Solvent Residue or TMB as an
Internal Standard. The analyte (>∼11 mg) was weighed in a 4 mL
vial equipped with a screwing cap. To crosscheck the results, TMB
(∼11 mg) was also added to the reference samples listed in Table 2.
The capped vial with a sample was placed on an analytical balance and
tare was measured. To the vial, CDCl3 (∼1 mL) was added, the vial
was immediately sealed with a screwing cap, and the precise weight of
CDCl3 was measured by an analytical balance. The sample was shaken
till all of the analyte dissolved. The sample solution was transferred to
1
the NMR tube and H NMR spectrum was recorded. The signal of
CHCl3 at 7.26 ppm and a signal of choice from the analyte were
integrated. The analyte weight was calculated using the previously
determined C(CHCl3) concentration following eq 2
m
(qNMR CDCl3)
yield(qNMR)
=
× 100%
m(theoretical)
(4)
c
× I(X) × M(X) × m
(CHCl3)
(CDCl3)
m
=
(qNMR CHCl3)
The NMR sample was completely recovered by solvent evaporation
under reduced pressure and the obtained residue was purified by silica
gel column chromatography (PE/EtOAc 5:1 to 1:1) to give product
2. The qNMR yield for the isolated product was obtained as
previously mentioned using eq 4. The product qNMR purity was
calculated by eq 5
I(CHCl ) × N(X) × ρ
(CDCl3)
(2)
3
For comparison, the compound weight m(qNMR IS) using 1,3,5-
trimethoxybenzene (TMB) as the internal standard was calculated
following eq 3
I(X) × N(TMB) × M(X) × m(TMB)
m
m(qNMR TMB)
=
× TMB purity
(3)
(qNMR CDCl3)
I(TMB) × N(X) × M(TMB)
purity
=
× 100%
(qNMR)
m(balance)
(5)
1H NMR (400 MHz, chloroform-d) δ 7.71−7.56 (m, 5H), 7.13 (dd, J
= 16.5, 9.8 Hz, 1H), 6.71−6.62 (m, 1H), 6.49 (dd, J = 9.9, 1.1 Hz,
1H).
where c(CHCl3) is the calculated protonated chloroform concentration
[mM/L], I(X) is the integral intensity of the studied compound,
I(CHCl3) is the integral intensity of protonated chloroform [100], M(X)
is the molecular weight test item [g/mol], m(CDCl3) is the sample
weight of chloroform [g], N(X) is the number of protons for the
integrated signal in the molecule of an analyte, ρ(CDCl3) is the density
of chloroform [1500 mg/mL], N(TMB) is the number of protons for
the integrated signal in the molecule of standard, m(TMB) is the sample
weight of standard [mg], and M(TMB) is the molecular weight standard
[g/mol].
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02744.
The errors were calculated using the equation error% = (m(balance)
purity − m(qNMR))/(m(balance) × purity) × 100%.
×
The tables with data and NMR spectra (PDF)
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1
Using H NMR Spectroscopy. J. Agric. Food Chem. 2012, 60, 2778−
AUTHOR INFORMATION
Corresponding Author
Janis Veliks − Latvian Institute of Organic Synthesis, LV-1006
Riga, Latvia; orcid.org/0000-0003-0955-8257;
Email: janis.veliks@osi.lv
■
̈
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Quantitative 1H NMR. Development and Potential of an Analytical
Method: An Update. J. Nat. Prod. 2012, 75, 834−851.
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H.; Gottlieb, H. E.; Nudelman, A.; Stoltz, B. M.; Bercaw, J. E.;
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Authors
Ruslan Muhamadejev − Latvian Institute of Organic
Synthesis, LV-1006 Riga, Latvia
Renate Melngaile − Latvian Institute of Organic Synthesis,
LV-1006 Riga, Latvia
Paula Paegle − Latvian Institute of Organic Synthesis, LV-
1006 Riga, Latvia
Ieva Zibarte − Latvian Institute of Organic Synthesis, LV-
1006 Riga, Latvia
Marina Petrova − Latvian Institute of Organic Synthesis, LV-
1006 Riga, Latvia
Kristaps Jaudzems − Latvian Institute of Organic Synthesis,
LV-1006 Riga, Latvia; orcid.org/0000-0003-3922-2447
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Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02744
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
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Financial support by the Latvian Council of Science project
LZP-2019/1-0258. The authors wish to thank Prof. Dr. Aigars
Jirgensons for scientific discussion. Dr. Juris Popelis for NMR
service. P.P. and I.Z. wish to thank Riga State Gymnasium Nr.
2.
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