One-pot synthesis of nitrones from nitro compounds by in situ trapping of arylhydroxylamines

Article abstract of DOI:10.1007/s00706-016-1896-2

Abstract: Highly efficient, convenient, simple procedure and a highly chemoselective method has been described for the conversion of nitroarenes to their corresponding nitrone derivatives by employing SnCl₂·2H₂O and Na₂CO₃ in the grinding apparatus in solvent-free conditions. Biaryl nitrones can be achieved via the condensation of an aldehyde with an unstable arylhydroxylamine which is prepared in situ through the reduction of the corresponding nitro aromatic compound. Interestingly, the slow and nonselective reduction of nitroarene to arylhydroxylamine step was directed with the condensation of in situ-prepared arylhydroxylamine with aromatic aldehyde (second step). Moreover, this protocol was successfully used for preparation of valuable dinitrones from dialdehyde and nitro aromatic compounds. For dinitrone preparation, dialdehyde compounds were first synthesized by the reaction of salicylaldehyde and glycol derivatives. Then, dialdehydes were reacted with reduced nitro compounds in optimal conditions that we used for synthesis of biaryl nitrones. Graphical Abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s00706-016-1896-2

Monatsh Chem
DOI 10.1007/s00706-016-1896-2
ORIGINAL PAPER
One-pot synthesis of nitrones from nitro compounds by in situ
trapping of arylhydroxylamines
Foad Kazemi1,2 Moosa Ramdar1 Bahram Tavana1 Jamal Davarpanah1,3
•
•
•
Received: 3 October 2016 / Accepted: 10 December 2016
Ó Springer-Verlag Wien 2017
Abstract Highly efficient, convenient, simple procedure
and a highly chemoselective method has been described for
the conversion of nitroarenes to their corresponding nitrone
derivatives by employing SnCl2Á2H2O and Na2CO3 in the
grinding apparatus in solvent-free conditions. Biaryl
nitrones can be achieved via the condensation of an alde-
hyde with an unstable arylhydroxylamine which is
prepared in situ through the reduction of the corresponding
nitro aromatic compound. Interestingly, the slow and
nonselective reduction of nitroarene to arylhydroxylamine
step was directed with the condensation of in situ-prepared
arylhydroxylamine with aromatic aldehyde (second step).
Moreover, this protocol was successfully used for prepa-
ration of valuable dinitrones from dialdehyde and nitro
aromatic compounds. For dinitrone preparation, dialdehyde
compounds were first synthesized by the reaction of sali-
cylaldehyde and glycol derivatives. Then, dialdehydes
were reacted with reduced nitro compounds in optimal
conditions that we used for synthesis of biaryl nitrones.
Graphical Abstract
Keywords Arylhydroxylamine Á Nitrone Á Reduction Á
Solid phase synthesis Á Nitroarenes Á One-pot synthesis
Introduction
An important tool for sustainable chemistry is the ability to
perform more than one synthetic step in the same reaction
vessel without isolation of any intermediate, because it
helps to save time and energy and reduces the waste
products [1]. In this regard, promotion of very slow reac-
tion forward with the fast second step is very attractive.
In recognition of their widespread importance, arylhy-
droxylamines are frequently used as key intermediates in
the construction of numerous fine chemicals [2–9]. How-
ever, it is known that during the reduction of nitro aromatic
compounds, these unstable intermediates are rapidly
reduced to the corresponding amines and often side prod-
ucts such as hydrazines, azoarenes, and azoxyarenes are
also formed [10–20]. However, depending on the reaction
conditions, the intermediate hydroxylamines (2) can be
trapped by electrophiles such as aldehydes (3, 4) to produce
& Foad Kazemi
kazemi_f@iasbs.ac.ir
1
Department of Chemistry, Institute for Advanced Studies in
Basic Sciences (IASBS), Zanjan 49195-1159, Iran
2
Center for Climate and Global Warming (CCGW), Institute
for Advanced Studies in Basic Sciences (IASBS), Gava Zang,
Zanjan 45137-66731, Iran
3
Chemistry Department, Production Technology Research
Institute, ACECR, Ahvaz, Iran
123

F. Kazemi et al.
Scheme 1
nitrones (5, 6) [21–23] (Scheme 1). Hence, the nitrone can
be considered as a protected hydroxylamine [24].
in concentrated hydrochloric acid is one of the traditional
reagents for reduction of nitroarenes to the corresponding
arylamine. In this connection, more recent modifications
used water or ethanol as solvent with no added acid [49].
In continuing our work in methodological development,
especially in nitro chemistry [50–53], the importance of
nitrone synthesis via arylhydroxylamines prompted us to
explore the possibility of preparation of these compounds
using SnCl2Á2H2O as reductant. In the present work, we
wish to report chemoselective reduction of aromatic nitro
compounds to the corresponding hydroxylamines, which
react in situ with aldehydes to produce nitrone compounds.
Nitrones are valuable materials in organic synthesis, for
instance, the reaction of nitrones with alkenes are typically
employed in stereoselective formation of synthetically
useful 1,3-dipolar cycloaddition adducts [25–28]. For more
than a half century, many scientists have drawn special
attention to nitrones due to their successful application as
building blocks in the synthesis of various natural and
biologically active compounds, stable nitroxyl radicals, and
other important products for special purposes such as spin
traps for the study of radical processes including those that
take place in biological systems [29]. Another interesting
feature of nitrones is higher stability and better elec-
trophilicity in comparison to their corresponding imines,
which prompted their use as precursors of hydroxylamines
and amines through nucleophilic additions on to the C=N
bond [30–33]. However, only a few nitrones are currently
available commercially.
Results and discussion
In this paper, SnCl2Á2H2O was selected as reductant and
sodium carbonate was chosen as a mild basic support for
nitroarene reduction. Starting from nitrobenzene as the
model nitro compound (1 mmol), SnCl2Á2H2O (4–6 mmol)
and 1.5 g Na2CO3, showed low nitro consuming and after
2 h, several products including low amounts of aniline
(according to TLC monitoring) were achieved. Therefore,
this weak reducing condition prompted us to trap one of
these intermediates such as hydroxylamine to produce
nitrone. This reaction was repeated in the presence of
benzaldehydes (1 mmol). Quite surprisingly, the TLC
monitoring showed the disappearance of the starting
materials (nitro compound and aldehyde) in only
40–65 min. These reactions were investigated on other
basic supports, including basic alumina, sodium sulfate,
etc., demonstrating that better result was obtained with
anhydrous Na2CO3 (Scheme 2).
One of the most common procedures for the preparation
of nitrones is the condensation of aldehydes and ketones
with N-monosubstituted hydroxylamines [34–38]. These
reactions are limited by the inaccessibility of the hydrox-
ylamine precursors, and long reaction times. Direct
oxidation of secondary amines to the corresponding
nitrones was also studied in the past two decades and was
found to be a method for the preparation of nitrones
[39–45]. Although N-alkylation of oximes is a somewhat
attractive process, it is often failed by a competitive
O-alkylation.
There are few reports of the nitrone preparation through
one-pot formation from nitro compounds [46, 47]. Zinc-
mediated reduction of a nitro compound to mono-substi-
tuted hydroxyl amines has been reported [48]. SnCl2Á2H2O
123

One-pot synthesis of nitrones from nitro compounds by in situ trapping of arylhydroxylamines
Scheme 2
Table 1 One-pot synthesis of nitrones from aldehydes and nitro aromatic compounds
Entry
Ar1
Ar2
Prod
Time/min
SnCl2Á2H2O/mmol
Isolated yield/%
1
p-Me-C6H4
p-Me-C6H4
p-Me-C6H4
p-Me-C6H4
p-ClCH2-C6H4
C6H5
p-Cl-C6H4
C6H5CH=CH
p-OH-C6H4
o-OH-C6H4
p-Cl-C6H4
p-Cl-C6H4
p-Cl-C6H4
p-Cl-C6H4
p-Cl-C6H4
p-OMe-C6H4
p-Cl-C6H4
p-Cl-C6H4
m-OMe-C6H4
p-OMe-C6H4
5a
5b
5c
5d
5e
5f
50
60
45
40
50
65
55
55
65
45
60
65
40
50
4
5
5
4
4
5
5
5
5
5
5
6
5
5
80 (78a)
85
2
3
80
4
88
5
90
6
73
7
p-F-C6H4
5g
5h
5i
70
8
o-Me-C6H4
m-Me-C6H4
o-Me-C6H4
3,4-(Me)2-C6H4
o-OH-C6H4
m-Me-C6H4
C6H5
76
9
73
10
11
12
13
14
a
5j
79
5k
5l
73
78
5m
5n
72
80
Reaction conditions: 4-nitrotoluene (30 mmol), 4-chlorobenzaldehyde (30 mmol), SnCl2Á2H2O (120 mmol), three protons, in laboratory
grinder for 60 min
It was found that the amount of anhydrous Na2CO3
plays an important role in the reaction. Then, different
ratios of nitrocompound/Na2CO3 (mmol/g) including 1:1,
1:1.5, and 1:2 were examined and 1:1.5 was chosen due to
its better result and feasibility in grinding (Scheme 3).
To explore the scope of this chemoselective reaction, a
variety of substrates including electron withdrawing and
electron donating substituents were examined under optimal
conditions, in most cases good results were obtained
(Table 1, 5a–5n). Only in the case of most active nitro
compounds such as o-dinitrobenzene, p-cyanonitrobenzene,
the fast reduction to the corresponding amines was expected.
As a matter of fact, also due to the low nucleophilicity of the
corresponding intermediate hydroxylamines, their reduction
resulted only in aniline formation.
Characterization of nitrones was done considering their
1
physical properties such as H NMR, 13C NMR, and IR
spectroscopy. There is a well-known considerable low field
shift of ortho protons in a-aryl nitrones, as compared to that
in nitroaryl substituents [29, 54, 55].
Compounds with two nitrone groups (dinitrones) are
rarely observed in the literature. They can be used as a
bifunctional crosslinker in polymer and rotaxane synthesis
[56–59]. Owing to the importance of dinitrones (6) in
organic synthesis, we aimed to demonstrate the applica-
bility of our procedure to the reaction of nitroarenes
(1.5 mmol) with aromatic dialdehydes (3) (0.5 mmol) [59]
and generally obtained good results (6a–6f).
While the above-mentioned techniques are very suc-
cessful for small-scale organic synthesis and because of the
importance of scalability for laboratory and industrial
purposes, we conducted this reaction on a 30 mmol scale
and found them suitable for a smooth preparation of nitrone
derivatives in good yields. This reaction can be easily
scaled up to 30 mmol of nitrones (Table 1, entry 1).
Due to importance of Vallee et al.’s work [46], the
model reaction was repeated with zinc powder instead of
SnCl2Á2H2O, and after the same time no reaction occurred.
Conclusion
In conclusion, a novel and efficient synthesis of nitrones
and dinitrones has been developed via in situ trapping of
arylhydroxylamine with aldehydes using SnCl2Á2H2O and
Na2CO3. This one-pot procedure is simple, mild and effi-
cient. The directing of first reaction (slow reduction step)
with the condensation reaction (second step), product
selectivity and solvent-free condition are other advantages
of this work.
123

F. Kazemi et al.
Scheme 3
as the eluent. After the completion of the reaction, the
mixture was extracted with ether (3 9 10 cm3). The
extracts were concentrated in a rotary evaporator under
vacuum and the crude mixture was purified by recrystal-
lization with hexane/EtOAc (or column chromatography
with hexane/EtOAc (5:1)) to afford the corresponding
nitrones (Table 1). Compounds 5c, 5f, 5g, 5i, 5l–5n have
been reported before [11–20, 50–53].
Experimental
Chemicals were purchased from Fluka, Merck, and Aldrich
chemical companies. IR spectra were recorded on a
BOMEM MB-Series 1998 FT-IR spectrometer. The purity
determination of the products and reaction monitoring were
accomplished by TLC on silica gel PolyGram SILG/UV
1
254 plates. H NMR and 13C NMR spectra were recorded
on a Bruker spectrometer at 400 and 250 MHz in CDCl3
with TMS as an internal standard, and J values are given in
Hz.
Preparation of dinitrones 6 (general procedure)
The dialdehyde 3 (0.5 mmol), 1.5 g anhydrous Na2CO3,
SnCl2Á2H2O (4 mmol in four steps) and nitroarenes
(1.5 mmol), were ground in a mortar at room temperature
for an appropriate time (Table 2). The completion of
reaction was monitored by TLC, with hexane/EtOAc (3:2)
as the eluent. After the completion of the reaction, the
mixture was extracted with dichloromethane. The extracts
were concentrated in a rotary evaporator and the crude
mixture was purified by column chromatography with
Preparation of nitrones (general procedure)
The aldehyde (1 mmol), 1.5 g anhydrous Na2CO3, SnCl2-
2H2O (4–6 mmol in two steps) and nitroarene, were ground
in a mortar at room temperature for an appropriate time
(Table 1). Addition of a few drops of ethanol during
grinding accelerated the reaction rate. The completion of
reaction was monitored by TLC, using hexane/EtOAc (4:1)
123

One-pot synthesis of nitrones from nitro compounds by in situ trapping of arylhydroxylamines
J = 8.7 Hz) ppm; 13C NMR (62.9 MHz, CDCl3):-
Table 2 One-pot synthesis of dinitrones from dialdehydes and nitro
aromatic compounds
d = 17.03, 123.30, 126.72, 128.88, 129.50, 129.92,
131.25, 131.70, 136.24, 136.38, 148.57 ppm.
Entry Aldehyde
Nitroarene
Prod Time/ Isolated
min
yield/%
C-(4-Methoxyphenyl)-N-(2-methylphenyl)nitrone
(5j, C15H15NO2)
1
2
3
4
5
6
3a (n = 0) p-Me-C6H4-NO2
3b (n = 1) p-Me-C6H4-NO2
3c (n = 2) p-Me-C6H4-NO2
3d (n = 3) p-Me-C6H4-NO2
6a
6b
6c
6d
50
45
50
55
60
65
53
62
72
71
73
63
Yield 79%; oil; 1H NMR (250 MHz, CDCl3):d = 2.45
(3H, s), 3.89 (3H, s) 7.00-7.36 (6H, m), 7.51 (1H, s), 8.38
(2H, d, J = 8.8 Hz) ppm; 13C NMR (62.9 MHz, CDCl3):-
d = 17.09, 55.43, 14.02, 133.46, 123.53, 126.68, 129.24,
130.90, 131.44, 131.87, 137.27, 148.55, 161.48 ppm; IR
3c (n = 2) p-NH2-C6H4-NO2 6e
3d (n = 3) 1-NO2-naphthyl 6f
ꢀ
(neat(: IR (neat(: m = 443.9, 500.9, 521.6, 822.0, 842.1,
1075.9, 1399.1, 1419.4, 1542.1, 1589.8 cm-1
.
hexane/EtOAc (3:2) to afford the corresponding nitrones
(Table 2).
C-(4-Chlorophenyl)-N-(3,4-dimethylphenyl)nitrone
(5k, C15H14ClNO)
C-(4-Chlorophenyl)-N-(4-methylphenyl)nitrone
Yield 73%; 1H NMR (250 MHz, CDCl3):d = 2.30 (3H, s),
2.32 (3H, s), 7.20 (1H, d, J = 8.0 Hz), 7.25–7.45 (3H, m),
7.45 (1H, s), 7.86 (1H, s), 8.34 (2H, d, J = 8.5 Hz) ppm;
13C NMR (62.9 MHz, CDCl3):d = 19.54, 19.90, 118.68,
122.62, 128.84, 129.33, 130.05, 130.08, 132.80, 136.05,
137.81, 139.01 ppm.
(5a, C14H12ClNO)
1
Yield 80%; yellow crystal; m.p.: 178–181 °C; H NMR
(250 MHz, CDCl3): d = 2.41 (3H, s), 7.26 (2H, d,
J = 8.5 Hz), 7.43 (2H, d, J = 8.7 Hz), 7.64 (2H, d,
J = 8.5 Hz), 7.88 (1H, s), 8.34 (2H, d, J = 8.5 Hz) ppm;
13C NMR (62.9 MHz, CDCl3): d = 21.18, 121.41, 128.90,
129.25, 129.70, 130.11, 132.91, 136.17, 140.42, 146.64 ppm.
N,N0-[Ethane-1,2-diylbis[oxy(2,1-phenylene)(methylyli-
dene)]]bis[4-methylaniline oxide] (6a, C30H28N2O4))
Yield 53%; brown solid; m.p.: 145–146 °C; 1H NMR
(400 MHz, CDCl3): d = 2.39 (s, 6H, H1), 4.47 (s, 4H, H7),
7.01 (d, J = 8.4 Hz, 2H, H8), 7.12–7.18 (m, 6H), 7.38–
7.49 (m, 2H), 7.51 (d, J = 1.6 Hz, 4H), 8.32 (s, 2H), 9.50
(d, J = 8 Hz, 2H) ppm; 13C NMR (100.6 MHz, CDCl3):
d = 21.1, 67.4, 111.4, 120.6, 121.34, 121.67, 128.21,
128.9, 129.6, 131.9, 140.0, 147.2, 156.4 ppm; IR (neat):
C-(2-Phenylvinyl)-N-(4-methylphenyl)nitrone
(5b, C16H15NO)
Yield 85%; m.p.: 121–124 °C; 1H NMR (250 MHz,
CDCl3): d = 2.39 (3H, s), 7.10–7.84 (12H, m) ppm; 13C
NMR (62.9 MHz, CDCl3): = 21.16, 119.21, 121.17,
127.46, 128.89, 129.38, 129.60, 135.74, 136.19, 139.53,
140.26, 145.17, 151.46 ppm.
C-(4-Chlorophenyl)-N-(2-hydroxyphenyl)nitrone
(5d, C14H13NO2)
ꢀ
m = 753.4, 816.2, 1071.1, 1111.0, 1173.6, 1223.4, 1288.
Yield 88%; m.p.: 100–102 °C; 1H NMR (250 MHz,
CDCl3): d = 2.43 (3H, s), 6.89 (1H, t, J = 7.5 Hz), 7.02
(1H, d, J = 8.3 Hz), 7.18 (1H, d, J = 8.0 Hz), 7.29 (2H, d,
J = 8.3 Hz), 7.44 (1H, t, J = 7.8 Hz), 7.66 (2H, d,
J = 8.3 Hz), 8.04 (1H, s), 12.55 (1H, s) ppm; 13C NMR
(62.9 MHz, CDCl3): d = 21.20, 117.03, 119.19, 120.40,
121.60, 129.85, 132.80, 134.49, 140.52, 140.93, 143.87,
159.89 ppm.
1458.4, 2866.4, 2927.4, 3040.4 cm-1
.
N,N0-[Oxybis[(ethane-2,1-diyl)oxy(2,1-phenylene)(methy-
lylidene)]]bis[4-methylaniline oxide] (6b, C32H32N2O5)
Yield 62%; yellow solid; m.p.: 133–134 °C; 1H NMR
(400 MHz, CDCl3): d = 2.37 (s, 6H), 3.93 (t, J = 4.4 Hz,
4H), 4.21 (t, J = 4.4 Hz, 4H), 6.92 (d, J = 7.6 Hz, 2H),
6.94–7.19 (m, 6H), 7.38–7.43 (m, 2H), 7.63 (d,
J = 8.8 Hz, 4H), 8.41 (s, 2H), 9.47 (dd, J1 = 8 Hz,
J2 = 1.6 Hz, 2H) ppm; 13C NMR (100.6 MHz, CDCl3):
d = 21.2, 68.4, 69.7, 111.9, 120.8, 121.4, 121.6, 128.7,
128.9, 129.5, 131.9, 139.9, 147.3, 156.5 ppm; IR (neat):
C-(4-Chlorophenyl)-N-(4-chlorophenyl)nitrone
(5e, C14H11Cl2NO)
Yield 90%; m.p.: 194–196 °C; 1H NMR (250 MHz,
CDCl3):d = 4.74 (2H, s), 7.3–7.6 (4H, m), 7.69 (2H, d,
J = 8.3 Hz), 7.88 (1H, s), 8.34 (2H, d, J = 8.7 Hz) ppm;
13C NMR (62.9 MHz, CDCl3): d = 64.16, 121.67, 127.27,
128.98, 130.29, 133.63, 136.57, 143.49 ppm.
ꢀ
m = 756.1, 815.8, 945.2, 1072.0, 1242.1, 1285.4, 1456.0,
2879.7 cm-1
.
N,N0-[Ethane-1,2-diylbis[oxy(ethane-2,1-diyl)oxy(2,1-
phenylene)(methylylidene)]]bis[4-methylaniline oxide]
(6c, C34H36N2O6)
Yield 72%; brown solid; m.p.: 123–125 °C; 1H NMR
(400 MHz, CDCl3): d = 2.39 (s, 6H), 3.69 (s, 4H), 3.84 (t,
C-(4-Chlorophenyl)-N-(2-methylphenyl)nitrone
(5h, C14H12ClNO)
Yield 76%; oil; 1H NMR (250 MHz, CDCl3):d = 2.39
(3H, s), 7.10–7.50 (6H, m), 7.54 (1H, s), 8.30 (2H, d,
123

F. Kazemi et al.
J = 4.8 Hz, 4H), 4.18 (t, J = 4.4 Hz, 4H), 6.92 (d,
J = 8.4 Hz, 2H), 7.10–7.14 (m, 2H), 7.25 (d,
J = 8.4 Hz, 4H), 7.39–7.43 (m, 2H), 7.68 (d,
J = 8.4 Hz, 4H), 7.42 (s, 2H), 9.48 (dd, J1 = 8 Hz,
J2 = 1.2 Hz, 2H) ppm; 13C NMR (100.6 MHz, CDCl3):
d = 21.2, 68.2, 69.6, 70.8, 111.6, 120.5, 121.3, 121.5,
128.9, 129.6, 132.0, 139.9, 147.3, 156.7 ppm; IR (neat(:
IR (neat): mꢀ = 764.1, 1050.4, 1114.9, 1158.7, 1240.9,
1296.09, 1391.9, 1459.5, 1591.6, 2870.9, 3060.0 cm-1
.
Acknowledgements This work was supported by Institute for
Advanced Studies in Basic Sciences (IASBS).
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ꢀ
m = 746.5, 809.9, 1063.2, 1126.7, 1174.6, 1248.5, 1449.5,
2860.8 cm-1
.
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131.9, 139.8, 147.4, 156.7 ppm; IR (neat): m = 758.3,
823.1, 942.8, 1113.4, 1245.1, 1289.4, 1457.3, 1593.4,
1684.1, 2870.9, 3046.4 cm-1
.
N,N0-[Ethane-1,2-diylbis[oxy(ethane-2,1-diyl)oxy(2,1-
phenylene)(methylylidene)]]bis[4-aminoaniline oxide]
(6e, C32H34N4O6)
Yield 73%; brown solid; m.p.: 82–83 °C; 1H NMR
(400 MHz, CDCl3): d = 3.63 (br, 4H), 3.90 (s, 4H), 3.89
(t, J = 4.4 Hz, 4H), 4.19 (t, J = 4.8 Hz, 4H), 6.69 (d,
J = 8.4 Hz, 3H), 6.94 (d, J = 8 Hz, 2H), 7.04–7.08 (m,
2H), 7.16 (d, J = 8.4 Hz, 3H), 7.37–7.41 (m, 2H), 8.148
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compositions
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a-phenyl-N-phenylnitrone
compounds (US patent 4,224,340, 23 Sep 1980). Chem Abstr
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(dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 2H), 8.97 (s, 2H) ppm; 13
C
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NMR (100.6 MHz, CDCl3): d = 68.2, 69.7, 70.9, 112.6,
115.6, 116.7, 121.3, 122.0, 122.4, 122.5, 127.3, 132.0,
ꢀ
153.1, 158.5 ppm; IR (neat): m = 754.2, 826.8, 1046.1,
1108.4, 1247.5, 1287.7, 1449.8, 1507.3, 1612.9, 2871.4,
3353.4, 3431.1 cm-1
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Yield 63%; yellow oil; 1H NMR (400 MHz, CDCl3):
d = 3.31 (t, J = 5.2 Hz, 4H), 3.43 (t, J = 5.2 Hz, 4H),
3.70 (t, J = 4.8 Hz, 4H), 4.12 (t, J = 4.8 Hz, 4H), 6.93 (d,
J = 8 Hz, 2H), 7.15–7.19 (m, 2H), 7.29–7.62 (m, 10H),
7.87–7.91 (m, 4H), 8.18 (d, J = 7.6 Hz, 2H), 8.29 (s, 2H),
9.65 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 2H) ppm; 13C NMR
(100.6 MHz, CDCl3): d = 68.1, 69.3, 70.4, 70.5, 111.5,
120.1, 120.8, 121.2, 123.0, 125.0, 127.0, 127.7, 128.0,
128.9, 129.7, 132.4, 133.7, 136.0, 134.2, 146.4, 156.6 ppm;
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