InCl3-assisted one-pot synthesis of 1-aminocarbazoles

Article abstract of DOI:10.1016/j.tet.2011.06.091

A novel InCl₃-mediated one-pot reaction leading to 1-aminocarbazoles is reported. Starting from easily available 2-acetyl-1H-indole, the reaction involves the alkylation of C-3 with a prop-2-yn-1-ol followed by a domino aminobenzannulation reac

Full text of DOI:10.1016/j.tet.2011.06.091

Tetrahedron 67 (2011) 6833e6837
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InCl3-assisted one-pot synthesis of 1-aminocarbazoles
*
Diego Facoetti, Giorgio Abbiati, Monica Dell’Acqua, Elisabetta Rossi
ꢀ
Dipartimento di Scienze Molecolari Applicate ai Biosistemi (DISMAB)-Sezione di Chimica Organica ‘A. Marchesini’ Universita degli Studi di Milano, Via G. Venezian 21,
20133 Milano, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 May 2011
Received in revised form 8 June 2011
Accepted 24 June 2011
Available online 30 June 2011
A novel InCl3-mediated one-pot reaction leading to 1-aminocarbazoles is reported. Starting from easily
available 2-acetyl-1H-indole, the reaction involves the alkylation of C-3 with a prop-2-yn-1-ol followed
by a domino aminobenzannulation reaction in the presence of a secondary amine. The indium salt is
most likely involved as catalyst in all three steps of the one-pot reaction. Starting from 2-acetyl-1H-
indole and a series of prop-2-yn-1-ols and secondary amines a small library of products has been
obtained.
Keywords:
Ó 2011 Elsevier Ltd. All rights reserved.
1-Amminocarbazoles
Indium chloride
One-pot reactions
Domino reactions
Lewis acids
1. Introduction
a carbonecarbon triple bond.22 Moreover, in a recent work23 we
reported an indium(III)-promoted domino aminobenzannulation
Carbazole derivatives are widely utilized in medicinal,1 organic,2
and material chemistry.3 In particular,1-aminocarbazoles have been
identified as Bcl-2 protein inhibitors,4 NPY5 antagonists,5 and anion
receptors.6 Duetotheir relevance, in the last decades manysynthetic
approaches have been developed in order to obtain carbazoles
bearing different functionalities. However, only a few reports on the
synthesis of 1-aminocarbazoles have appeared in the literature. The
reported methods involve sequential electrophilic nitration/hydro-
genation reactions on the carbazole nucleus,7 intramolecular Pd(II)-
mediated oxidative coupling of diphenylamine derivatives,8 and
[3þ3]carbocyclisation reactions of C-heteroarylimines with
reaction giving rise to 1-aminocarbazoles 1 starting from 2-acyl-3-
propargyl-1H-indoles 2 and pyrrolidine 3a, Scheme 1, path A.
Also the high-yielding synthesis of 2-acyl-3-propargyl-1H-in-
doles 2 was achieved by InCl3-catalyzed propargylation of 2-acyl-
1H-indole 4 with prop-2-yn-1-ols, or the corresponding acetates,
5,24 Scheme 1, path B.
a
,b
-unsaturated Fischer carbene complexes.9
Our research group has been interested in the development of
domino and multicomponent reactions for the construction of
heterocyclic rings from simple starting materials. Following these
strategies, during the last five years we achieved the synthesis of
pyrazino[1,2-a]indoles,10 4-aminoquinolines, and 4-amino[1,8]na-
phthyridines,11 [1,4]oxazino[4,3-a]indoles,12 2,20-biindolyls,13 pyr-
rolo[1,2-a]indol-2-carbaldehydes,14 quinolines,15 4-substituted-2-
phenylimidazoles,16 isoxazolino[4,5-c]quinolines,17 pyrrolo[1,2-a]
pyrazines,18 pyrimido[1,6-a]indolones,19 dihydroisobenzofurans,20
and isoquinolines.21,18 All reported syntheses proceed under
Lewis acid and/or transition metals catalysis and involve a nucleo-
philic attack of a hetero- or carbon-based nucleophile over
Scheme 1.
With these results in hand, in this work we have explored an
indium(III)-promoted multicomponent reaction (MCR) for the
synthesis of 1-aminocarbazoles 1 starting directly from 2-acyl-1H-
* Corresponding author. E-mail address: elisabetta.rossi@unimi.it (E. Rossi).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.06.091

6834
D. Facoetti et al. / Tetrahedron 67 (2011) 6833e6837
indole 4, propynyl alcohols or propynyl acetates 5 and a secondary
amine 3, Scheme 1, Path C.
overnight in a screwed-cap tube at 75 ꢀC in dry acetonitrile using
the following molar ratios: 4, 5a, 3a, InCl3¼1:1:1.2:0.1.
MCRs allow the coupling of three or more simple and flexible
building blocks in a one-pot operation, giving rise to complex
structures by simultaneous formation of two or more bonds,
according to the domino principle. Multicomponent reactions fulfill
the requirements of an environmentally friendly process by re-
ducing the number of synthetic steps, the energy consumption, and
the waste production. Moreover, over the past 10 years industrial
and academic researchers have transformed this powerful tech-
nology into one of the most efficient and economic tools for com-
binatorial and parallel synthesis, as demonstrated by the increase
in the literature devoted to this research field.25
In a first run (entry 1, method A, multicomponent approach) the
catalyst was added to a solution containing 4, 5a, and 3a, and
the obtained mixture was then heated at reflux. However, under
these conditions, 2-acetyl-1H-indole 4 was recovered unreacted
even after a prolonged reaction time. On the contrary, good yield of
the desired 1-aminocarbazole 1a could be obtained adding up the
reactants as follows: 4 and 5a were dissolved together with the
catalyst in dry acetonitrile and the reaction mixture was stirred for
10 min, then the amine 3a was added and the solution warmed
overnight, (entry 2, method B, one-pot approach). The deferred
addition of the secondary amine to the reaction mixture is probably
required to avoid a Lewis acideLewis base interaction between
InCl3 and pyrrolidine 3 with consequent catalyst deactivation.
Starting from these results a small library of 1-aminocarbazoles
1aeh has been prepared starting from 2-acetyl-1H-indole 4, a se-
ries of propynyl alcohols or propynyl acetates 5aeg and secondary
amines 3a, b under InCl3 catalysis, Table 1.
It is worth to note that indium catalysis has been applied in
MCRs for the synthesis of heterocyclic systems, such as imidaz-
oles,26 piperidines,27 pirazolines,28 tetrahydoquinolines,29 dihy-
dropyrimidines,30 and heterocycle-annulated pyrimidines.31
Compounds 1 have been obtained in moderate to good yields
after flash chromatographic purification over silica gel.
2. Results and discussion
It is worth to note that propynyl alcohols work better than the
corresponding propynyl acetates (cf. entry 2 and 3), so we moved
up our attention to alcohols, which were synthesized avoiding the
tedious acylation steps.
In order to evaluate the generality of our protocol, different
substituted propynyl alcohols were tested. The synthetic strategy
proved to be effective with both electron withdrawing and electron
donating aryl substituent as well as with aliphatic and heterocyclic
substituent.
2-Acylindole 4 was easily prepared in multigram scale starting
from indole-2-carboxylic acid and methyllithium.32 Propynyl al-
cohols 5 could be easily obtained by reaction between the appro-
priate aldehyde and terminal alkyne in the presence of
butyllithium, alcohols were converted into the corresponding ac-
etates with acetic anhydride in pyridine.33
The optimal MCR conditions were investigated using the 2-
acetyl-1H-indole 4, 3-phenyl-1-p-tolylprop-2-ynyl acetate 5a, and
pyrrolidine 3a as model system, Table 1. All reactions were run
Table 1
1-Aminocarbazoles 1aeh
Entry
Propynyl alcohol or acetate 5
Secondary amine 3
Method
Product 1
Yielda (%)
1
A
d
2
3
5a
3a
3a
B
B
1a
1a
63
78
4
3a
B
68
5
3a
B
65

D. Facoetti et al. / Tetrahedron 67 (2011) 6833e6837
6835
Table 1 (continued )
Entry
Propynyl alcohol or acetate 5
Secondary amine 3
Method
Product 1
Yielda (%)
6
7
8
3a
B
61
71
89
3a
B
3a
B
9
5d
B
58
10
5f
3b
B
67
a
Yields are referred to pure isolated compounds after chromatographic purification.
Thethree-stepsreactionpathwaygivingriseto1-aminocarbazoles
1, Scheme 2, involves the In(III)-catalyzed C-3 alkylation of 4 (step 1)
followed by the In(III)-catalyzed enamine formation (step 2) and by
the final 6-exo-dig cyclisation/aromatisation step (step 3).
incipient35) as well as allenyl cations36 has been proposed by sev-
eral authors as possible intermediates. Several mechanistic aspects
connected to steps 2 and 3 and to the dual role exerted by InCl3, for
these and related reactions, have been discussed elsewhere.23
As already stated, the deferred addition of the secondary amine
to the reaction mixture is probably required to avoid catalyst
The exact mechanism of the In(III)-mediated hydroxyl activation
(step 1) is not totally clear. Carbocationic species (free34 or
Scheme 2.

6836
D. Facoetti et al. / Tetrahedron 67 (2011) 6833e6837
deactivation. This hypothesis is supported by the analysis of sev-
eral 1H NMR experiments performed in CD3CN. The 1H NMR
spectrum of pure 5b shows the resonance of the benzylic hydro-
gen at 6.61 ppm. In the presence of 0.1 mol of InCl3 the resonance
at 6.61 decreases progressively and two new peaks appear at 5.88
and 5.56 ppm, Fig. 1. In our opinion these two new resonances
could be attributed to intermediate(s) involving interaction of
both oxygen and triple bond with InCl3. Moreover, when 1 mol of
pyrrolidine is added to the same solution, no change in the
spectrum is observed.
4.2. General procedure for the synthesis of 1-
aminocarbazoles 1aeh
A well stirred solution of 2-acetyl-1H-indole 4 (250 mg,
1.57 mmol), the appropriate propynyl alcohol or acetate
5
(1.57 mmol), and InCl3 (35 mg, 0.16 mmol) in dry acetonitrile (5 ml)
was heated at 75 ꢀC in a screwed-cap tube for 15 min. Then, the
secondary amine 3 (1.88 mmol) was added and the resulting mix-
ture stirred overnight at 75 ꢀC. The reaction was then allowed to
cool at room temperature and the solvent removed under reduced
pressure. The resulting crude product was purified by flash chro-
matography over silica gel to yield the desired 1-aminocarbazole 1.
4.2.1. 3-Benzyl-4-(4-methylphenyl)-1-(pyrrolidin-1-yl)-9H-carba-
zole (1a). Eluent for chromatography: n-hexane/EtOAc, 90:10;
yield (from 5a) 412 mg, 63%. Yield (from 5b) 510 mg, 78%; yellow
oil; nmax 2920, 2244, 1899, 1493; dH (200 MHz, CDCl3) 2.05 (4H, m,
2CH2 pyrrolidine), 2.48 (3H, s, CH3), 3.48 (4H, m, 2NeCH2), 3.93
(2H, s, AreCH2), 6.69e7.59 (14H, m, arom.), 8.18 (1H, s, NH); dC
(50.3 MHz, C6D6) 21.2 (CH3), 39.1 (AreCH2), 24.9, 50.3 (CH2 pyr-
rolidine), 110.7, 113.4, 119.4, 122.9, 125.1, 125.7, 128.3, 129.1, 129.5,
130.4 (Csp2eH), 124.8, 129.0, 130.6, 130.8, 135.4, 136.5, 138.0, 140.0,
143.4 (quat. Csp2); m/z (ESIþ) 417 (100, MHþ); C30H28N2 (416.56):
calcd C 86.50, H 6.78, N 6.72; found C 86.37, H 6.53, N 6.89.
Fig. 1. Resonances of benzylic hydrogen of 5b.
On the contrary, when 5b, InCl3, and pyrrolidine are added to
CD3CN at the same time the benzylic hydrogen at 6.61 ppm remains
unchanged. This supports the existence of an interaction between
InCl3 and pyrrolidine, which inhibits the coordination between
InCl3 and 5b.
4.2.2. 3-Benzyl-4-(4-methoxyphenyl)-1-(pyrrolidin-1-yl)-9H-carba-
zole (1b). Eluent for chromatography: n-hexane/EtOAc, 90:10;
yield 462 mg, 68%; yellow oil; nmax 2924, 1608, 1507, 1240; dH
(200 MHz, CDCl3) 2.06 (4H, m, 2CH2 pyrrolidine), 3.50 (4H, m,
2NeCH2), 3.92 (3H, s, OCH3), 3.96 (2H, s, AreCH2), 6.72 (1H, s,
arom.), 6.76e7.42 (13H, m, arom.), 8.18 (1H, s, NH); dC (50.3 MHz,
CDCl3) 25.3, 50.8 (CH2 pyrrolidine), 39.0 (AreCH2), 55.6 (OCH3),
110.7, 113.0, 114.2, 119.1, 122.5, 125.2, 125.7, 128.3, 129.0, 131.5
(Csp2eH), 123.8, 124.3, 126.9, 130.2, 130.9, 132.8, 135.1, 139.8, 143.1,
158.9 (quat. Csp2); m/z (ESIþ) 433.2 (100, MHþ); C30H28N2O
(432.56): calcd C 83.30, H 6.52, N 6.48; found C 82.96, H 6.45,
N 6.62.
3. Conclusion
In conclusion, this approach leads to an effective synthesis of
a small library of 1-aminocarbazoles with a wide-range of sub-
stituent, in moderate to good yields. The mild conditions and the
high-substrate tolerance represent the main outcomes of this
useful protocol. The reaction is catalyzed by a water-tolerant
Lewis acid as InCl3, and this allows operating under mild condi-
tions, because no anhydrous or inert conditions are strictly
required.
Unfortunately, as already described by other research groups,37
indium(III) salts are able to enhance the electrophilic character in
the carbon atom, and thus to promote the indole alkylation step,
only in aryl substituted secondary (benzylic) propynyl alcohols (or
acetates). Thus, primary or alkyl substituted secondary propynyl
derivatives cannot be used as substrates in these reactions. Further
work is in progress to overcome this drawback and also to extend
the methodology to other heterocyclic systems.
4.2.3. 3-Benzyl-1-(pyrrolidin-1-yl)-4-thien-2-yl-9H-carbazole
(1c). Eluent for chromatography: n-hexane/EtOAc, 90:10; yield:
417 mg, 65%; yellow oil; nmax 2921, 1641, 1592, 1385; dH (200 MHz,
CDCl3) 2.05 (m, 4H, 2CH2 pyrrolidine), 3.53 (m, 4H, 2NeCH2), 4.08
(s, 2H, AreCH2), 6.68 (s, 1H, arom.), 6.83e7.03 (m, 3H, arom.),
7.14e7.46 (m, 9H, arom.), 8.27 (s, 1H, NH); dC (50.3 MHz, CDCl3) 39.1
(AreCH2), 39.1, 50.6 (CH2 pyrrolidine), 110.8, 112.4, 119.4, 122.5,
125.5, 125.8, 126.1, 127.5, 127.8, 128.4, 129.1 (Csp2eH), 119.0, 123.8,
124.8, 129.5, 133.3, 136.3, 139.8, 141.3, 142.9 (quat. Csp2); m/z (ESIþ)
409 (100, MHþ); C27H24N2S (408.56): calcd C 79.37, H 5.92, N 6.86;
found C 79.18, H 5.76, N 6.97.
4. Experimental
4.1. General
All chemicals and solvents are commercially available and were
used after distillation or treatment with drying agents. Silica gel
F254 thin-layer plates were employed for thin-layer chromatogra-
4.2.4. 3-Hexyl-4-(4-methylphenyl)-1-(pyrrolidin-1-yl)-9H-carbazole
(1d). Eluent for chromatography: n-hexane/EtOAc, 90:10; yield:
200 mg, 61%; yellow oil; nmax 2865, 1548, 1321; the 1H and 13C NMR
analysis of the purified compound show the presence of two iso-
mers 1d and 1d0 in a 1:3 ratio.
ꢁ
phy (TLC). Silica gel 40e63 micron/60 A was employed for all flash
column chromatography. Melting points were measured wiꢁth1
a PerkineElmer DSC 6 calorimeter at a heating rate of 5 ꢀC min
and are uncorrected. Infrared spectra were recorded with a Per-
kineElmer FTIR 16 PC spectrometer by using KBr tablets. 1H and 13
C
NMR spectra were determined with a Varian-Gemini 200 or
a Bruker 500 Advance spectrometer at room temperature in CDCl3,
CD3CN, or C6D6 with residual solvent peaks as the internal refer-
ence. The APT sequence was used to distinguish the methyne and
methyl carbon signals from those arising from methylene and
quaternary carbon atoms. Low resolution MS spectra were recorded
with a Thermo-Finnigan LCQ advantage AP electrospray/ion trap
equipped instrument by using a syringe pump device to directly
inject sample solutions.

D. Facoetti et al. / Tetrahedron 67 (2011) 6833e6837
6837
dH (500 MHz, C6D6) 0.91e0.97 (m, 3H, aliph.), 1.33e1.35 (m, 4H,
aliph.), 1.41e1.47 (m, 2H, aliph.), 1.76 (m, 4H, 2CH2 pyrrolidine),
1.84e1.90 (m, 2H, aliph.), 2.35 (s, 3H, CH3), 2.93 (t, J¼7.8 Hz, 2H,
AreCH2), 3.27 (m, 4H, 2NeCH2), 6.78 (s, 1H, arom.), 7.06e7.68 (m,
8H, arom.), 8.23 (s, 1H, NH); the presence of isomer 1d0 with an
exocyclic bond is detectable by the following characteristic signals:
dH (500 MHz, C6D6) 2.24 (s, CH3), 2.25 (s, Csp3eH), 4.55 (t, 3J¼1.5 Hz,
(q, 1JC,F¼272.4 Hz, CF3),129.7 (q, 2JC,F¼31.8 Hz, quat. Csp2); m/z (ESIþ)
499 (100, MHþ); C32H29F3N2 (498.58): calcd C 77.09, H 5.86, N 5.62;
found C 76.95, H 5.82, N 5.66.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.06.091. These data in-
clude MOL files and InChIKeys of the most important compounds
described in this article.
C
sp2eH); dC (125.8 MHz, C6D6) 13.4, 20.4 (CH3), 22.0, 28.8, 31.2, 32.2,
32.7 (CH2), 24.1, 49.8 (CH2 pyrrolidine). The signal splitting in the
aromatic region evidences the presence of the two isomers: dC
(125.8 MHz, C6D6) 109.2, 109.3, 110.0, 111.9, 112.0, 118.4, 120.1, 122.0,
122.3, 124.3, 125.3, 125.4, 128.3, 128.7, 129.7 (Csp2eH), 124.0, 123.1,
127.1, 127.9, 130.0, 131.9, 134.3, 134.8, 135.6, 135.8, 137.1, 139.4, 142.1
(quat. Csp2); isomer 1d0 shows the characteristic signals: dC
(125.8 MHz, C6D6) 13.3, 24.6 (CH3), 22.1, 27.4, 28.8 (CH2), 73.5
(Csp3eH); m/z (ESIþ) 411 (100, MHþ); C29H34N2 (410.59): calcd C
84.83, H 8.35, N 6.82; found C 84.65, H 8.11, N 6.93.
References and notes
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4.2.5. 4-(4-Methylphenyl)-1-(pyrrolidin-1-yl)-3-[3-(trifluoromethyl)
benzyl]-9H-carbazole (1e). Eluent for chromatography: n-hexane/
EtOAc, 99:1; yield: 388 mg, 71%; yellow oil; nmax 2963, 1593, 1450,
1330; dH (500 MHz, CDCl3) 2.07 (4H, m, 2CH2 pyrrolidine), 2.47 (3H,
s, CH3), 3.51 (4H, m, 2NeCH2), 3.97 (2H, s, AreCH2), 6.67 (1H, s,
arom.), 6.71e6.69 (2H, m, arom.), 7.13e7.41 (10H, m, arom.), 8.20
(1H, s, NH); dC (125.8 MHz, CDCl3) 21.4 (CH3), 25.1, 50.6 (CH2 pyr-
rolidine), 38.9 (AreCH2),110.5,112.5,119.0,122.4,125.1,128.4,129.4,
3
130.0, 132.2 (Csp2eH), 122.3 (q, JC,F¼3.8 Hz, Csp2eH), 125.5 (q,
3JC,F¼3.8 Hz, Csp2eH), 123.4, 123.9128.3, 129.6, 130.1, 135.0, 136.8,
136.9,139.6,143.7 (quat. Csp2),124.4 (q,1JC,F¼272.4 Hz, CF3),130.2 (q,
2JC,F¼31.8 Hz, quat. Csp2); m/z (ESIþ): (%)¼485 (100, Mþ); C31H27F3N2
(484.55): calcd C 76.84, H 5.62, N 5.78; found C 76.73, H 5.52, N 5.86.
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4.2.6. 3-Benzyl-4-(4-bromophenyl)-1-(pyrrolidin-1-yl)-9H-carba-
zole (1f). Eluent for chromatography: n-hexane/EtOAc, 90:10,
yield: 673 mg, 89%; yellow oil; nmax 2963, 1596, 1451, 1332; dH
(200 MHz, CDCl3) 2.07 (4H, m, 2CH2 pyrrolidine), 3.52 (4H, m,
2NeCH2), 3.89 (2H, s, AreCH2), 6.73 (2H, d, J¼8.2 Hz, arom.),
6.99e7.03 (1H, m, arom.), 7.12e7.39 (9H, m, arom.), 7.57 (2H, d,
J¼8.3 Hz, arom.), 8.29 (1H, s, NH); (50.3 MHz, CDCl3) 39.0 (AreCH2),
25.3, 50.8 (CH2 pyrrolidine), 110.4, 112.5, 121.2, 122.3, 123.3, 125.8,
126.7, 128.4, 129.0, 131.9 (Csp2eH), 121.4, 123.8, 127.8, 130.2, 130.5,
135.4, 135.7, 137.8, 139.9, 142.7 (quat. Csp2); m/z (ESIþ) 481 (100,
MHþ); C29H25BrN2 (481.43): calcd C 72.35, H 5.23, N 5.82; found C
72.28, H 5.21, N 5.92.
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4.2.7. 3-Benzyl-1-(piperidin-1-yl)-4-(thiophen-2-yl)-9H-carbazole
(1g). Eluent for chromatography: n-hexane/EtOAc, 95:5; yield:
385 mg, 58%; yellow oil; nmax 2930, 1599, 1318, 695; dH (200 MHz,
CDCl3) 1.68 (2H, m, CH2 piperidine), 1.86 (4H, m, CH2 piperidine),
3.12 (4H, m, 2NeCH2), 4.09 (2H, s, AreCH2), 6.85e7.52 (13H, m,
arom.), 8.20 (1H, s, NH); (50.3 MHz, CDCl3) 24.7, 26.9, 39.0, 53.1
(CH2), 110.9, 116.9, 119.5, 122.4, 125.6, 125.8, 126.2, 127.5, 127.6,
128.4, 129.0 (Csp2eH), 123.0, 124.2, 124.3, 132.8, 132.9, 139.3, 139.9,
140.8, 142.8 (quat. Csp2); m/z (ESIþ) 423 (100, MHþ); C28H26N2S
(422.58): calcd C 79.58, H 6.20, N 6.63; found C 79.42, H 6.16, N 6.77.
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4.2.8. 1-(Piperidin-1-yl)-4-p-tolyl-3-(3-(trifluoromethyl)benzyl)-9H-
carbazole (1h). Eluent for chromatography: n-hexane/EtOAc, 95:5;
yield: 524 mg, 67%; yellow oil; nmax 3300, 1642, 1522, 739; dH
(200 MHz, CDCl3) 1.66e1.71 (2H, m, CH2 piperidine), 1.79e1.84 (4H,
m, 2CH2 piperidine), 2.47 (3H, s, CH3), 3.09e3.14 (4H, m, 2NeCH2),
3.99 (2H, s, AreCH2), 6.73e7.70 (13H, m, arom.), 8.22 (1H, s, NH); dC
(50.3 MHz, CDCl3) 24.9, 27.0, 39.2, 53.5 (CH2), 26.3 (CH3), 110.4,
112.7, 119.4, 121.3, 123.5, 125.6, 128.7, 129.7, 130.0 (Csp2eH), 122.7 (q,
3
3JC,F¼3.8 Hz, Csp2eH), 125.8 (q, JC,F¼3.8 Hz, Csp2eH), 124.6, 128.0,
129.7, 133.4, 135.8, 137.0, 137.3, 137.9, 140.1, 144.0 (quat. Csp2), 121.1