Palladium-Catalyzed Cyclocarbonylation Approach to Thiadiazafluorenones: A Correction

Article abstract of DOI:10.1021/acs.joc.9b01043

The palladium-catalyzed carbonylation of 2-(propynylthio)benzimidazoles bearing a terminal triple bond leads to 2-methyl-1-thia-4a,9-diazafluoren-4-ones instead of the previously reported 3-methyl isomers, as unequivocally established by XRD analysis of a representative product. A correction is therefore provided here in order to rectify the previous erroneous assignment of the position of the methyl group. Moreover, the process has been generalized to substrates bearing an internal triple bond, which lead to 3-alkyl-2-methyl-1-thia-4a,9-diazafluoren-4-ones, whose structure was confirmed by XRD analysis of two representative derivatives.

Full text of DOI:10.1021/acs.joc.9b01043

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Note
A Palladium-Catalyzed Cyclocarbonylation
Approach to Thiadiazafluorenones. A Correction
Lucia Veltri, Roberta Amuso, Corrado Cuocci, Paola Vitale, and Bartolo Gabriele
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01043 • Publication Date (Web): 11 Jun 2019
Downloaded from http://pubs.acs.org on June 17, 2019
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A Palladium-Catalyzed Cyclocarbonylation Approach to Thiadiazafluorenones.
A Correction
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Lucia Veltri,*† Roberta Amuso,† Corrado Cuocci,§ Paola Vitale,‡ and Bartolo Gabriele*†
†
Laboratory of Industrial and Synthetic Organic Chemistry (LISOC), Department of Chemistry and Chemical
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Technologies, University of Calabria, Via Pietro Bucci 12/C, 87036 Arcavacata di Rende (CS), Italy
§ Institute of Crystallography, CNR, Via Amendola 122/O, 70124 Bari, Italy
‡
Department of Pharmacy - Pharmaceutical Sciences, University of Bari “Aldo Moro”, Via E. Orabona 4, Bari, 70125,
Italy
lucia.veltri@unical.it; bartolo.gabriele@unical.it
R1
R1
O
Me
N
N
N
Pd cat
R2
R2
S
S
+ CO
N
H
(50-74%)
CO
Pd(0)
PdI2
H2O
Pd(0)
O
R1
R1
Me
R1
Pd
Pd
CO
R2
Pd+
N
Me
N
R2
N
S
+
R2
C
S
S
N
H
N
N
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Abstract
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The palladium-catalyzed carbonylation of 2-(propynylthio)benzimidazoles bearing a terminal triple bond
leads to 2-methyl-1-thia-4a,9-diazafluoren-4-ones, instead of the previously reported 3-methyl isomers, as
unequivocally established by XRD analysis of a representative product. A correction is therefore provided
here in order to rectify the previous erroneous assignment of the position of the methyl group. Moreover,
the process has been generalized to substrates bearing an internal triple bond, which led to 3-alkyl-2-methyl-
1-thia-4a,9-diazafluoren-4-ones, whose structure was confirmed by XRD analysis of two representative
derivatives.
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1-Thiadiazafluoren-4-one derivatives are polyheterocyclic compounds of particular interest, as they are
known to possess significant pharmacological activities,1,2 including cardiotonic activity.2 Their importance
justifies the continuous interest in developing novel synthetic approaches starting from relatively simple and
available substrates.3
In the course of our studies on carbonylation reactions leading to polyheterocyclic compounds, we
investigated the reactivity of 2-(propynylthio)benzimidazoles bearing a terminal triple bond (1a-f) with
carbon monoxide in the presence of the PdI2/KI catalytic system under non-oxidative conditions. We
published the results obtained, and assigned the structure of the products as 3-methyl-1-thia-4a,9-
diazafluoren-4-ones (Scheme 1).4 We here reassign the structure of those products as the corresponding 2-
methyl isomers, based on the results obtained with 2-(propynylthio)benzimidazoles bearing an internal triple
bond and X-ray structural determination of representative products.
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Scheme
1.
Previously
Reported
Palladium-Catalyzed
Cyclocarbonylation
of
2-
4
5
6
(Propynylthio)benzimidazoles Bearing a Terminal Triple Bond 1a-f4
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9
Me
S
O
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Pd cat
N
N
N
+ CO
S
R
R
N
H
1a-f
(not correct)
We originally optimized the reactivity of 1a-f and carried out the carbonylation reactions in EtOH at 100
°C for 3 h, under a 5/2 mixture of CO‒CO2 at 70 atm, in the presence of PdI2 (2 mol%) and KI (1 equiv).4
Methyl-substituted 1-thia-4a,9-diazafluoren-4-ones were obtained, as confirmed by spectrometric and
spectroscopic data, by an additive carbonylation process. A relatively simple mechanism, involving N-
palladation followed by CO insertion, triple bond insertion, protonolysis, and isomerization, seemed in
agreement with the formation of 3-methyl-substituted thiadiazafluorenones, as shown in Scheme S1
(Supporting Information).4
To further expand the synthetic scope of the process, we have investigated the reactivity of substrates
bearing an internal triple bond. Surprisingly, however, the carbonylation reaction of 2-(pent-2-yn-1-ylthio)-
1H-benzo[d]imidazole 3a did not lead to the expected 3-propyl-substituted derivative, but to
thiadiazofluorenone 4a bearing a methyl group at C-2 and an ethyl group at C-3 (Scheme 2),5 as confirmed
by XRD analysis (Figure 1).6
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Scheme 2. Formation of 3-Ethyl-2-methyl-1-thia-4a,9-diazafluoren-4-one 4a from 2-(Pent-2-yn-1-ylthio)-
1H-benzo[d]imidazole 3a
7
8
9
Et
Et
O
PdI2 (2 mol%)
KI (1 equiv)
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Me
N
N
+ CO
N
S
CO (30 atm)
S
N
MeOH, 80 °C, 20 h
4a
(60%)
H
3a
IPd
O
Pr
O
Et
Et
O
N
HI
PdI2
N
N
N
N
S
S
S
N
(not formed)
Figure 1. X-Ray Structure of 3-Ethyl-2-methyl-1-thia-4a,9-diazafluoren-4-one 4a, Showing the Atom Labelling
Scheme6
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This unexpected result prompted us to reinvestigate the structure of the methyl-substituted products
obtained starting from substrates bearing a terminal triple bond, which, by analogy to 4a, could actually have
corresponded to the 2-methyl-substituted isomers rather than the originally proposed4 3-methyl-substituted
compounds. A single crystal X-ray analysis of the product obtained from the carbonylation of 2-(prop-2-
ynylthio)-1H-benzo[d]imidazole 1a4 indeed confirmed that the methyl group occupies the C-2 rather than the
C-3 position, and thus corresponds to 2-methyl-1-thia-4a,9-diazafluoren-4-one 2a, as shown in Figure 2. This
means that the structures of all products obtained in our original publication (with the methyl group at C-3)4
should be corrected to the corresponding 2-methyl-substituted isomers 2a‒f, as shown in Table S1
(Supporting Information).
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Figure 2. X-Ray Structure of 2-Methyl-1-thia-4a,9-diazafluoren-4-one 2a, Showing the Atom Labelling
Scheme6
The process has then been generalized to other differently substituted substrates 3b‒i, bearing various
alkyl groups on the triple bond and electron-withdrawing as well as -donating groups on the aromatic ring.
As can be seen from the results shown in Table 1, the reaction was quite general, and the corresponding 3-
alkyl-2-methyl-1-thia-4a,9-diazafluoren-4-ones 4 were isolated in fair yields (50-60 %). The C-2 position of
the methyl group was further confirmed by the XRD analysis of product 4f, bearing two methoxy substituents
of the aromatic ring (Figure 3).
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Figure 3. X-Ray Structure of 3-Ethyl-6,7-Dimethoxy-2-methyl-1-thia-4a,9-diazafluoren-4-one 4f, Showing the
Atom Labelling Scheme6
Table 1. Synthesis 3-Alkyl-2-methyl-1-thia-4a,9-diazafluoren-4-ones 4a-i by Palladium-Catalyzed Carbonylation of 2-
(Alkynylthio)benzimidazoles 3a-i Bearing an Internal Triple Bonda
R1
R1
O
PdI2 (2 mol%)
KI (1 equiv)
Me
N
N
R2
S
R2
+ CO
S
CO (30 atm)
MeOH, 80 °C, 20 h
N
N
H
4
3
Entry
3
4
Yield of 4b (%)
Et
Et
1
2
O
60
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Me
N
N
S
N
S
4a
N
H
3a
Me
N
Me
O
Me
N
N
S
S
4b
N
H
3b
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Pr
Pr
3
4
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9
O
N
57
Me
S
N
S
N
4c
N
H
3c
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C5H11
C5H11
Me
55
O
N
S
N
S
N
4d
N
H
3d
Et
Et
O
56
Me
Me
Me
Me
Me
Me
N
N
Me
Me
S
N
S
4e
N
H
3e
Et
Et
O
50
MeO
MeO
N
N
MeO
MeO
S
N
S
4f
N
H
3f
57[c]
Et
Et
O
N
N
MeO
S
N
MeO
S
N
H
4g
3g
Et
Et
O
59
Cl
Cl
N
N
Cl
Cl
S
N
S
4h
N
H
3h
O
57[d]
Et
Et
Me
N
N
F
S
N
F
S
N
4i
H
3i
a All reactions were carried out at 80 °C under 30 atm (at 25 °C) of CO, in MeOH as the solvent (substrate concentration:
b
0.2 mmol of 1 per mL of solvent), and in the presence of 2 mol% of PdI2 and 1 equiv of KI. Isolated yield, based on
starting material 1. c Mixture of regioisomers (3/1 by 1H NMR). d Mixture of regioisomers (1.1/1 by 1H NMR).
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Mechanistically, formation of 2-methyl-substituted products 2a‒f (Table S1, Supporting Information) and
4a-i (Table 1) must imply some kind of structural rearrangement. Most likely, this takes place by Pd(0)-
promoted propargyl-allene rearrangement,7 occurring through formal Pd(0) attack to the terminal carbon of
the triple bond, with elimination of a thiolate I and formation of the allenylpalladium intermediate II (Scheme
3). Formation of an iodide-stabilized palladium(0) species under our conditions may take place by the water-
gas shift reaction between PdI2, CO and traces of water present in the reaction mixture, as already observed
by us under similar conditions.8 Addition of the thiolate I to the allenic moiety of II then leads to palladacycle
intermediate III. The latter undergoes carbon monoxide insertion to give IV, from which the final product is
formed by reductive elimination (Scheme 3).
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Scheme 3. Proposed Mechanistic Pathway for the Palladium-Catalyzed Cyclocarbonylation of 2-(Prop-2-
ynylthio)-1H-benzo[d]imidazoles 1a-f and 3a-i Leading to 2-Methyl-1-thia-4a,9-diazafluoren-4-ones 2a-f
and 4a-i, respectively
PdI2 + CO + H2O
R1
Pd(0) + 2 HI + CO2
Pd(0)
R1
S
R1
C
Pd
N
Pd+
N
Me
N
R2
+
S
R2
S
R2
N
II
N
H
I H
N
III
CO
O
R1
O
R1
Me
Pd
Me
N
N
N
R2
R2
S
S
Pd(0)
N
IV
1
2a-f
4a-i
(R = H)
1
(R = alkyl)
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To corroborate this mechanistic hypothesis, we carried out a cross-over experiment, by allowing to react
an equimolar mixture of substrates 3d and 3e under the optimized conditions (Scheme 4). The GLC-MS
analysis of the reaction mixture evidenced the formation of four products (4a, 4d, 4e, and 5) (Scheme 4),
deriving from the addition of the two different thiolates to the two different allenylpalladium complexes
deriving from 3d and 3e, which is clearly in agreement with the proposed mechanism (Scheme 3).9
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Scheme 4. Cross-over Experiment: Formation of a Mixture of Thiadiazafluorenones 4a, 4d, 4e, and 5 from
Carbonylation of a Mixture of Substrates 3d and 3e
C5H11
Me
O
PdI2 (2 mol %)
KI (1 equiv)
Me
Me
N
N
4a 4d 4e
+
+
+
S
3d 3e
+
+ CO
CO (30 atm)
MeOH, 80 °C, 20 h
5
We also verified if free allenes (possibly deriving from protonolysis of complex II) were involved as
intermediates in the formation of final bicyclic products. However, as shown in Scheme 5, the carbonylation
of 3d together with commercially available cyclohexylallene 6 only gave the diazafluorenone 4d (49% yield)
without any formation of the mixed product resulting from allene incorporation.10 This result strongly
suggests that protonolysis of complex II to give a free allene does not occur in our process, and that, according
to Scheme 3, this intermediate preferentially undergoes direct attack by thiolate I.
Scheme 5. Carbonylation of 3d in the presence of cyclohexylallene 6
PdI2 (2 mol %)
KI (1 equiv)
4d
6
(49%) + unreacted (46%)
3d
+
C
CO (30 atm)
MeOH, 80 °C, 20 h
6
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In conclusion, in this Note we have corrected the structure of the products obtained from PdI2/KI-
catalyzed carbonylation of 2-(propynylthio)benzimidazoles bearing a terminal triple bond 1. In fact, as
confirmed by XRD analysis, 2-methyl-1-thia-4a,9-diazafluoren-4-ones 2 are formed, instead of the previously
reported4 3-methyl isomers. We have also extended the process to the use of substrates bearing an internal
triple bond 3, which, in a similar way, led to the corresponding 3-alkyl-2-methyl-1-thia-4a,9-diazafluoren-4-
ones 4, as confirmed by XRD analysis. Product formation must ensue from some unexpected kind of structural
rearrangement, most likely occurring through palladium-promoted propargyl-allene rearrangement to give
a thiolate and an allenylpalladium intermediate, followed by thiolate addition to the central allenic carbon
and cyclocarbonylation.
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EXPERIMENTAL SECTION
General Experimental Methods. Solvents and chemicals were reagent grade and used without further
purification. All reactions were analyzed by TLC on silica gel 60 F254 and by GLC using capillary columns with
polymethylsilicone +5% phenylsilicone as the stationary phase. Column chromatography was performed on
silica gel 60 (70‒230 mesh) or alumina gel 90 (70‒230 mesh). Evaporation refers to the removal of solvent
under reduced pressure. Melting points are uncorrected. 1H NMR and 13C NMR spectra were recorded at 25
°C on a 300 or 500 MHz spectrometers in CDCl3, DMSO-d6, or CD3OD solutions with Me4Si as the internal
standard. 19F NMR spectra were recorded at 25 °C on a 500 MHz spectrometer in CDCl3 solutions at 471 MHz
with CF2Br2 or CFCl3 as the internal standard. Chemical shifts (δ) and coupling constants (J) are given in ppm
and Hz, respectively. IR spectra were taken with an FT-IR spectrometer. Mass spectra were obtained using a
GC-MS apparatus at 70 eV ionization voltage. The HRMS spectra were taken on Q-TOF-MS mass
spectrometer, equipped with an electrospray ion source (ESI) operated in dual ion mode. 10 L of the sample
solutions (CH3OH) were introduced by continuous infusion at a flow rate of 200 L min-1 with the aid of a
syringe pump. Experimental conditions were performed as following: capillary voltage, 4000 V; nebulizer
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pressure, 20 psi; flow rate of drying gas, 10 L/min; temperature of sheath gas, 325 C; flow rate of sheath gas,
10 L/min; skimmer voltage, 60 V; OCT1 RF Vpp, 750 V; fragmentor voltage, 170 V. The spectra data were
recorded in the m/z range of 100–1000 Da in a centroid pattern of full-scan MS analysis mode. The MS/MS
data of the selected compounds were obtained by regulating diverse collision energy (18–45 eV).
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Preparation of Substrates 3a-i. 2-(Prop-2-ynylthio)-1H-benzo[d]imidazoles 3a-i, bearing an internal triple
bond, were prepared with the following procedure. To a solution of the 1H-imidazole-2-thione derivative
(16.7 mmol) [1,3-dihydrobenzoimidazole-2-thione (commercially available): 2.50 g; 5,6-dimethyl-1,3-
dihydrobenzoimidazole-2-thione (commercially available): 2.97 g; 5,6-dichloro-1,3-dihydrobenzoimidazole-
2-thione (commercially available): 3.65 g; 5.6-dimethoxy-1,3-dihydrobenzoimidazole-2-thione:4 3.51 g; 5-
methoxy-1,3-dihydrobenzoimidazole-2-thione
(commercially
available):
3.00
g;
5-fluoro-1,3-
dihydrobenzoimidazole-2-thione:4 2.81 g] in anhydrous acetone (100 mL), was added, under nitrogen, K2CO3
(2.3 g , 16.7 mmol,) and the 1-bromoalk-2-yne derivative (25.1 mmol) [1-bromopent-2-yne (commercially
available): 3.69 g; 1-bromobut-2-yne (commercially available): 3.34 g; 1-bromohex-2-yne:11 4.04 g; 1-
bromooct-2-yne:12 4.75 g]. The mixture was stirred at room temperature for 20 h. After evaporation of the
solvent, dichloromethane (30 mL) and water (30 mL) were sequentially added, and phases were separated.
The aqueous phase was extracted again with dichloromethane (20 mL) and finally the collected organic
phases were dried over Na2SO4. After filtration and evaporation of the solvent, products 3a-i were purified
by column chromatography on silica gel using as eluent: 9:1 hexane-AcOEt for 3b, 3d, 3h; 8:2 hexane-AcOEt
for 3c; 7:3 hexane-AcOEt for 3a, 3e, 3f, 3g, 3i.
2-(Pent-2-yn-1-ylthio)-1H-benzo[d]imidazole (3a). Yield: 2.75 g, starting from 2.50 g of 1,3-
dihydrobenzoimidazole-2-thione (76%). Colorless solid, mp = 139 – 141 °C. IR (KBr);  = 2972 (s), 2181 (vw),
1445 (s), 1402 (s), 1270 (m), 1228 (m), 980 (m), 737 (s) cm-1. 1H NMR (300 MHz, DMSO-d6): δ = 12.74 (s, br, 1
H), 7.63 – 7.40 (m, 2 H), 7.24 – 7.13 (m, 2 H), 4.16 (t, J = 2.3 , 2 H), 2.16 (qt, J = 7.5, 2.3, 2 H), 1.00 (t, J = 7.5, 3
H); 13C{1H}NMR (75 MHz, DMSO-d6): δ = 149.0, 143.4 (br), 135.7 (br), 122.0, 117.6 (br), 111.0 (br), 85.5, 75.2,
20.8, 13.9, 12.0. GC/MS: m/z = 216 (M+, 77), 201 (100), 187 (27), 150 (27), 122 (42). HRMS (ESI-TOF) m/z: [M
+ Na]+ Calcd for C12H12N2SNa+ 239.0613; Found 239.0609.
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2-(But-2-yn-1-ylthio)-1H-benzo[d]imidazole (3b). Yield: 2.70 g, starting from 2.50 g of 1,3-
dihydrobenzoimidazole-2-thione (80%). Colorless solid, mp = 169 – 171 °C; IR (KBr):  = 2972 (m, br), 2239
(vw), 1445 (m), 1402 (s), 1269 (m), 1229 (m), 980 (m) cm-1. 1H NMR (300 MHz, DMSO-d6): δ = 12.59 (s, br, 1
H), 7.51 – 7.41 (m, 2 H), 7.18 – 7.09 (m, 2 H), 4.12 (q, J = 2.5, 2 H), 1.77 (t, J = 2.5, 3 H); 13C{1H}NMR (75 MHz,
DMSO-d6): δ = 148.8, 121.5, 79.4, 74.8, 20.3, 3.2 (Note: the signals of quaternary carbons were too broad to
be detected). GC-MS: m/z = 202 (M+, 100), 201 (72), 187 (31), 169 (81), 149 (42), 122 (77). HRMS (ESI-TOF)
m/z: [M + Na]+ Calcd for C11H10N2SNa+ 225.0457; Found: 225.0451.
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2-(Hex-2-yn-1-ylthio)-1H-benzo[d]imidazole (3c). Yield: 2.00 g, starting from 2.50 g of 1,3-
dihydrobenzoimidazole-2-thione (52%). Colorless solid, mp = 140 – 142 °C. IR (KBr):  = 2959 (m, br), 2234
(vw), 1441 (m), 1400 (m), 1269 (m), 1242 (m), 737 (s) cm-1; 1H NMR (300 MHz, CD3OD): δ = 7.54 – 7.44 (m, 2
H), 7.24 – 7.15 (m, 2 H), 4.98 (s, br, 1 H), 4.03-3.98 (m, 2 H), 2.13 -2.02 (m, 2 H), 1.46 -1.29 (m, 2 H), 0.81 (t, J
= 7.3, 3 H); 13C{1H}NMR (75 MHz, CD3OD): δ = 150.3, 140.4 (br), 123.5, 115.0 (b), 85.4, 75.7, 23.0, 22.5, 21.4,
13.6. GC–MS: m/z = 230 (M+, 60), 201 (100), 187 (24), 169 (28), 150 (28), 122 (29). HRMS (ESI-TOF) m/z: [M
+ Na]+ Calcd for C13H14N2SNa+ 253.0770; Found: 253.0769.
2-(Oct-2-yn-1-ylthio)-1H-benzo[d]imidazole (3d). Yield: 3.45 g, starting from 2.50 g of 1,3-
dihydrobenzoimidazole-2-thione (80%). Colorless solid, mp = 108 – 111 °C. IR (KBr):  = 2957 (m br), 2234
(w), 1445 (m), 1402 (s), 1267 (m), 1227 (m), 980 (m), 739 (s) cm-1. 1H NMR (500 MHz, DMSO-d6): δ = 12.61 (s,
br, 1 H), 7.50 – 7.41 (m, br, 2 H), 7.15 – 7.10 (m, 2 H), 4.12 (t, J = 2.3, 2 H), 2.12 (tt, J = 7.0, 2.3, 2 H), 1.36-1.31
(m, 2 H), 1.25 – 1.13 (m, 4 H), 0.77 (t, J = 7.0, 3 H); 13C{1H}NMR (125 MHz, DMSO-d6): δ = 148.6, 121.5, 83.7,
75.7, 30.2, 27.7, 21.5, 20.5, 17.9, 13.7 (Note: the signals of two quaternary carbons were too broad to be
detected); GC-MS: m/z = 258 (M+, 100), 202 (97), 201 (100), 187 (14), 169 (14), 143 (41). HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C15H18N2SNa+ 281.1083; Found: 281.1085.
5,6-Dimethyl-2-(pent-2-yn-1-ylthio)-1H-benzo[d]imidazole (3e). Yield: 2.45 g, starting from 2.97 g of 5,6-
dimethyl-1,3-dihydrobenzoimidazole-2-thione (60%). Colorless solid, mp = 164 – 166 °C. IR (KBr):  = 2974
(m), 2232 (vw), 1449 (m), 1391 (s), 1227 (m), 982 (m); 1H NMR (300 MHz, DMSO-d6): δ = 7.26 (s, 2 H), 4.12 (t,
J = 2.2, 2 H), 2.28 (s, 6 H), 2.14 (qt, J = 7.5, 2.2, 2 H), 0.99 (t, J = 7.5, 3 H) (Note: the NH signal was too broad
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to be detected). 13C{1H}NMR (75 MHz, DMSO-d6): δ = 147.1, 137.4, 130.2, 114.1, 85.2, 75.0, 20.8, 19.9, 13.6,
11.7 (Note: the signals of two quaternary carbons were too broad to be detected); GC-MS: m/z = 244 (M+,
100), 243 (23), 229 (53), 171 (6). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C14H16N2SNa+ 267.0926; Found:
267.0925.
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5,6-Dimethoxy-2-(pent-2-yn-1-ylthio)-1H-benzo[d]imidazole (3f). Yield: 3.46 g, starting from 3.51 g of 5.6-
dimethoxy-1,3-dihydrobenzoimidazole-2-thione (75%). Colorless solid, mp = 102 – 105 °C; IR (KBr):  = 2950
(m), 2234 (vw), 1393 (s), 1331 (s), 1200 (s), 1138 (s), 1007 (m), 849 (m) cm-1; 1H NMR (300 MHz, CD3OD): δ =
7.05 (s, 2 H), 4.95 (s, br); 3.90 (t, J = 2.4, 2 H), 3.85 (s, 6 H), 2.10 (qt, J = 7.5, 2.4, 2 H), 0.98 (t, J = 7.5, 3 H);
13C{1H}NMR (75 MHz, CD3OD): δ = 148.6, 146.9, 97.8 (br), 86.9, 75.0, 56.8, 23.4, 14.1, 13.0 (Note: the signal
of a quaternary carbon was too broad to be detected); GC-MS: m/z = 276 (M+, 100), 261 (43), 243 (26), 209
(14), 174 (5). HRMS (ESI-TOF) m/z : [M + Na]+ Calcd for C14H16N2O2SNa+ 299.0825; Found: 299.0825.
6-Methoxy-2-(pent-2-yn-1-ylthio)-1H-benzo[d]imidazole (3g). Yield: 3.29 g, starting from 3.00 g of 5-
methoxy-1,3-dihydrobenzoimidazole-2-thione (80%). Colorless solid, mp = 112 – 116 °C; IR (KBr):  = 2875
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(m), 2230 (vw), 1628 (m), 1393 (s), 1204 (s), 1161 (s), 1034 (m), 980 (m), 806 (s) cm-1; H NMR (300 MHz,
CDCl3): δ = 7.48 (d, J = 8.8, 1 H), 7.08 (d, J = 2.3, 1 H), 6.87 (dd, J = 8.8, 2,3, 1 H), 4.01 (t, J = 2.4, 2 H), 3.82 (s, 3
H), 2.12 (qt, J = 7.5, 2.4, 2 H), 1.04 (t, J = 7.5, 3 H) (Note: the NH signal was too broad to be detected);
13C{1H}NMR (75 MHz, CDCl3); δ = 156.4, 148.1, 139.5 (br), 134.3 (br), 115.3, 111.9, 97.2, 86.5, 74.1, 55.8, 22.5,
13.6, 12.5; GC-MS: m/z = 246 (M+, 100), 231 (51), 217 (25), 174 (15), 120 (18). HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C13H14N2OSNa+ 269.0719; Found: 269.0717.
5,6-Dichloro-2-(pent-2-yn-1-ylthio)-1H-benzo[d]imidazole (3h). Yield: 3.33 g, starting from 3.65 g of 5,6-
dichloro-1,3-dihydrobenzoimidazole-2-thione (70%). Yellow solid. mp = 188 – 193 °C. IR (KBr):  = 2920 (m),
2234 (vw), 1377 (s), 1319 (m), 1096 (m), 961 (m), 868 (m) cm-1; 1H NMR (300 MHz, DMSO-d6): δ = 7.74 (s, 2
H), 4.15 (t, J = 2.4, 2 H), 2.16 (qt, J = 7.5, 2.4, 2 H), 1.00 (t, J = 7.5, 3 H) (Note: the NH signal was too broad to
be detected); 13C{1H}NMR (75 MHz, DMSO-d6): δ = 152.5, 124.0, 114.8 (br), 85.3, 74.8, 20.4, 13.6, 11.8 (Note:
the signal of a quaternary carbon was too broad to be detected); GC-MS: m/z = 288 [(M+4)+, 13], 286 [(M+2)+,
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69], 285 [(M+1)+, 21)], 284 (M+, 100), 271 (27), 269 (39), 257 (55), 255 (76), 220 (39), 167 (32). HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C12H11Cl2N2S+ 285.0015; Found: 285.0015.
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6-Fluoro-2-(pent-2-yn-1-ylthio)-1H-benzo[d]imidazole (3i). Yield: 1.56 g, starting from 2.81 g of 5-fluoro-
1,3-dihydrobenzoimidazole-2-thione: 2.81 (40%). Colorless solid, mp = 175 – 177 °C; IR (KBr):  = 2914 (m,
br), 2237 (vw), 1397 (s), 1142 (s), 988 (m), 845 (s), 799 (s) cm-1; 1H NMR (300 MHz, DMSO-d6): δ = 12.79 (s,
br, 1 H), 7.62-7.20 (m, 2 H), 7.01 (t, J = 9.7, 1 H), 4.18-4.12 (m, 2 H), 2.22 – 2.11 (m, 2 H), 1.01 (t, J = 7.5, 3 H).
13C{1H}NMR (75 MHz, DMSO-d6): δ = 158.2 (d, J = 233.9, C-6 bonded to F), 150.7 (tautomer A), 149.5
(tautomer B), 144.0 (tautomer A or B), 140.2 (tautomer B or A), 135.5 (tautomer A or B), 132.1 (tautomer B
or A), 118.1 (tautomer A or B), 110.9 (tautomer B or A), 109.7 (d, J = 25.3, C-5 or C-7, tautomer A or B), 109.3
(d, J = 25.3, C-5 or C-7, tautomer B or A), 103.3 (d, J = 24.3, C-7 or C-5, tautomer A or B), 97.2 (d, J = 25.5, C-7
or C-6, tautomer B or A), 85.1, 74.9, 20.4, 13.6, 11.7 (Note: some carbon signals were doubled owing to slow
tautomerization of the imidazole ring). 19F NMR (471 MHz, DMSO-d6):  = ‒120.0 (s, tautomer A or B), ‒121.4
(s, tautomer B or A). GC-MS: m/z = 234 (M+, 76), 219 (100), 205 (32), 168 (27), 140 (47), 108 (37). HRMS (ESI-
TOF) m/z: [M + Na]+ Calcd for C12H11FN2SNa+ 257.0519; Found: 257.0513.
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General Procedure for the Synthesis of Thiadiazafluorenones 4a‒i (Table 1). A 35 mL stainless steel
autoclave was charged in the presence of air with PdI2 (5.8 mg, 1.61  10–2 mmol), KI (133 mg, 0.81 mmol),
MeOH (4 mL), and the 2-prop-2-ynylthiobenzimidazole (0.81 mmol; 3a: 175 mg; 3b: 164 mg; 3c: 187 mg; 3d:
209 mg; 3e: 198 mg; 3f: 224 mg; 3g: 200 mg; 3h: 231 mg; 3i: 190 mg). The autoclave was purged at room
temperature several times with CO under stirring (5 atm) and eventually pressurized with CO2 (30 atm). After
being stirred at 80 °C for 3 h, the autoclave was cooled, degassed and opened. After evaporation of the
solvent, products 4 were purified by column chromatography on neutral alumina using 98:2 hexane-AcOEt
as eluent.
3-Ethyl-2-methyl-1-thia-4a,9-diazafluoren-4-one (4a). Yield: 119 mg, starting from 175 mg of 3a (60%)
(Table 1, entry 1). Colorless solid, mp = 132 – 134°C. IR (KBr):  = 1675 (s), 1475 (s), 1432 (s), 1358 (m), 1313
(m), 1148 (m), 760 (m) cm-1. 1H NMR (500 MHz, CDCl3): δ = 8.57 (d, J = 8.1), 7.74 (d, J = 8.1), 7.50-7.44 (m, 1
H), 7.44-7.38 (m, 1 H), 2.76 (q, J = 7.5, 2 H), 2.43 (s, 3 H), 1.18 (t, J = 7.5, 3 H); 13C{1H}NMR (125 MHz, CDCl3):
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δ = 160.4, 146.2, 142.4, 140.7, 131.6, 127.8, 125.7, 123.8, 118.4, 116.1, 21.3, 20.6, 13.0. GC-MS: m/z = 244
(M+, 100), 229 (51), 211 (16), 201 (16). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C13H12N2OSNa+ 267.0563;
Found: 267.0557.
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2,3-Dimethyl-1-thia-4a,9-diazafluoren-4-one (4b). Yield: 103 mg, starting from 164 mg of 3b (55%) (Table
1, entry 2). Colorless solid, mp = 178 – 183°C. IR (KBr).  = 1674 (s), 1474 (m), 1435 (m), 1354 (w), 1312 (m),
1150 (m), 768 (s) cm-1. 1HNMR (300 MHz, CDCl3): δ = 8.59 (d, J = 8.0), 7.73 (d, J = 7.7), 7.50-7.30 (m, 2 H), 2.36
(s, 3 H), 2.21 (s, 3 H). 13C{1H}NMR (75 MHz, CDCl3): δ = 160.7, 146.1, 142.3, 140.6, 131.4, 125.7, 123.8, 121.8,
118.3, 116.0, 21.3, 13.4. GC-MS: m/z = 230 (M+, 100), 201 (27), 169 (15), 150 (15). HRMS (ESI-TOF) m/z: [ M
– H]- Calcd for [C12H9N2OS]‒ 229.0441; Found: 229.0452.
2-Methyl-3-propyl-1-thia-4a,9-diazafluoren-4-one (4c). Yield: 119 mg, starting from 187 mg of 3c (57%)
(Table 1, entry 3). Colorless solid, mp = 111 – 112°C. IR (KBr):  = 1684 (s), 1466 (s), 1431 (s), 1350 (s), 1311
(s), 1152 (m), 746 (s) cm-1. 1HNMR (300 MHz, CDCl3): δ = 8.57 (d, J = 8.0), 7.74 (d, J = 7.8, 1 H), 7.52-7.35 (m,
2 H), 2.70 (t, J = 7.6, 2 H), 2.43 (s, 3 H), 1.59 (sext, J = 7.6, 2 H), 1.03 (t, J = 7.6, 3 H). 13C{1H}NMR (125 MHz,
CDCl3): δ = 160.5, 146.2, 142.3, 141.0, 131.5, 126.4, 125.7, 123.8, 118.4, 116.1, 29.8, 22.0, 20.9, 14.1. GC-MS:
m/z = 258 (M+, 96), 243 (14), 229 (100), 201 (16), 143 (12). HRMS (ESI-TOF) m/z: [M – H]- Calcd for C14H13N2OS‒
257.0754; Found: 257.0764.
2-Methyl-3-pentyl-1-thia-4a,9-diazafluoren-4-one (4d). Yield: 128 mg, starting from 209 mg of 3d (55%)
(Table 1, entry 4). Colorless solid, mp = 56 – 58°C. IR (KBr):  = 1684 (s), 1474 (s), 1443 (s), 1383 (s), 1315 (m),
1225 (m), 1155 (m), 760 (s) cm-1. 1HNMR (300 MHz, CDCl3): δ = 8.51 (d, J = 7.6, 1 H), 7.68 (d, J = 7.9), 7.44-
7.28 (m, 2 H), 2.62 (t, J = 7.8, 2 H), 2.34 (s, 3 H), 1.57-1.22 (m, 6 H), 0.87 (t, J = 6.5, 3 H). 13C{1H}NMR (125 MHz,
CDCl3): δ = 160.4, 146.1, 142.3, 140.8, 131.4, 126.5, 125.6, 123.7, 118.3, 116.0, 31.8, 28.4, 27.9, 22.5, 20.8,
14.0. GC-MS: m/z = 286 (M+, 47), 229 (37), 202 (31), 137 (100). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C16H18N2OSNa+: 309.1032; Found: 309.1036.
2,6,7-Trimethyl-3-ethyl-1-thia-4a,9-diazafluoren-4-one (4e). Yield: 124 mg, starting from 198 mg of 3e
(56%) (Table 1, entry 5). Colorless solid, mp = 154 – 158°C. IR (KBr):  = 1667 (s), 1477 (m), 1442 (s), 1350 (s),
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1169 (m), 883 (m), 768 (m) cm-1; 1H NMR (300 MHz, CDCl3): δ = 8.27 (s, 1 H), 7.43 (s, 1 H), 2.70 (q, J = 7.4, 2
H), 2.38 (s, 3 H), 2.36 (s, 6 H), 1.15 (t, J = 7.4, 3 H). 13C{1H}NMR (75 MHz, CDCl3): δ = 160.2, 144.9, 140.8, 140.4,
134.7, 132.9, 129.7, 127.4, 118.3, 116.1, 21.2, 20.52, 20.46, 13.0. GC/MS: m/z = 272 (M+, 100), 257 (44), 239
(13), 229 (19). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C15H16N2OSNa+ 295.0876; Found: 295.0871.
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3-Ethyl-6,7-dimethoxy-2-methyl-1-thia-4a,9-diazafluoren-4-one (4f). Yield: 123 mg, starting from 224 mg
of 3f (50%) (Table 1, entry 6). Colorless solid, mp = 167 – 169°C. IR (KBr):  = 1667 (s), 1462 (s), 1427 (s), 1373
(m), 1318 (s), 1007 (m), 841 (m), 756 (m) cm-1; 1H NMR (300 MHz, CDCl3): δ = 8.13 (s, 1 H), 7.20 (s, 1 H), 4.01
(s, 3 H), 3.97 (s, 3 H) 2.76 (q, J = 7.5, 2 H), 2.44 (s, 3 H), 1.18 (t, J = 7.5, 3 H). 13C{1H}NMR (75 MHz, CDCl3): δ =
160.5, 148.6, 147.1, 143.6, 140.8, 136.3, 127.2, 125.1, 100.1, 98.7, 56.4, 56.2, 21.3, 20.6, 13.1. GC/MS: m/z =
304 (M+, 100), 289 (60), 261 (9), 167 (32). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C15H16N2O3SNa+ 327.0774;
Found: 327.0767.
Mixture of Regioisomers 3-Ethyl-7-methoxy-2-methyl-1-thia-4a,9-diazafluoren-4-one (A) and 3-Ethyl-6-
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methoxy-2-methyl-1-thia-4a,9-diazafluoren-4-one (B) (4g; A/B ratio about 3.0, by HNMR). Yield: 127 mg,
starting from 200 mg of 3g (57%) (Table 1, entry 7). Colorless solid, mp = 114 – 119°C. IR (KBr):  = 1670 (s),
1477 (s), 1431 (s), 1358 (m), 1018 (m), 845 (m), 764 (m) cm-1; 1H NMR (300 MHz,CDCl3): δ = 8.40 (d, J = 8.9, 1
H, B), 8.09 (d, J = 2.4, 1 H, A), 7.59 (d, J = 8.8, 1 H, A), 7.17 (d, J = 2.3, 1 H, B), 7.05 (dd, J = 8.8, 2.4, 1 H, A), 6.97
(dd, J = 8.9, 2.3, 1 H, B), 3.90 (s, 3 H, A), 3.87 (s, 3 H, B), 2.72 (q, J = 7.4, 2 H, A+B), 2.40 (s, 3 H, A+B), 1.16 (t, J
= 7.4, 3 H, A+B); 13C{1H}NMR (75 MHz, CDCl3): δ = 160.6 (A), 160.0 (B), 158.3 (B), 157.0 (A), 146.4 (B), 144.2
(A), 143.6 (B), 141.0 (A), 140.3 (B), 136.6 (A), 132.1 (A), 127.6 (B), 127.3 (A), 125.8 (B), 118.7 (A), 116.4 (B),
115.3 (A), 112.7 (B), 101.1 (B), 99.4 (A), 55.92 (A), 55.89 (B), 21.3 (A+B), 20.6 (A+B), 13.1 (A+B); GC/MS [A]:
m/z = 274 (M+, 100), 259 (55), 231 (18), 180 (10), 165 (11). GC/MS [B]: m/z = 274 (M+, 100), 259 (56), 231
(17), 180 (10), 165 (11). HRMS (ESI - TOF) m/z: [M + Na]+ Calcd for C14H14N2O2SNa+ 297.0668; Found: 297.0663.
6,7-Dichloro-3-ethyl-2-methyl-1-thia-4a,9-diazafluoren-4-one (4h). Yield: 150 mg, starting from 231 mg of
3h (59%) (Table 1, entry 8). Colorless solid, mp = 200 – 202°C. IR (KBr):  = 1670 (s), 1466 (m), 1427 (s), 1350
(m), 914 (m), 872 (m) cm-1. 1H NMR (300 MHz, CDCl3): δ = 8.63 (s, 1 H), 7.75 (s, 1 H), 2.75 (q, J = 7.5, 2 H), 2.46
(s, 3 H), 1.17 (t, J = 7.5, 3 H). 13C{1H}NMR (75 MHz, CDCl3): δ = 159.7, 148.1, 141.5, 141.4, 130.3, 129.9, 127.84,
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127.82, 119.4, 117.3, 21.3, 20.7, 12.9. GC/MS: m/z = 316 [(M+4)+, 13], 314 [(M+2)+, 65], 312 (M+, 100), 299
(22), 297 (30), 279 (17), 277 (18), 271 (11), 269 (16). HRMS (ESI-TOF) m/z: [M + H]+ calcd for C13H11Cl2N2OS+
312.9964; Found: 312.9949.
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Mixture of Regioisomers 3-Ethyl-6-fluoro-2-methyl-1-thia-4a,9-diazafluoren-4-one (A) and 3-Ethyl-7-
fluoro-2-methyl-1-thia-4a,9-diazafluoren-4-one (B) (4i; A/B ratio about 1.1, by 1HNMR).Yield: 121 mg, starting
from 190 mg of 3i (57%) (Table 1, entry 9). Colorless solid, mp = 107 – 109°C. IR (KBr):  = 1670 (s), 1468 (s),
1437 (s), 1358 (m), 1130 (m), 845 (m), 814 (m) cm-1; 1H NMR (300 MHz, CDCl3): δ = 8.46 (dd, J = 8.9, 5.0, 1 H,
A), 8.24 (dd, J = 8.9, 2.4, 1 H, B), 7.63 (dd, J = 8.9, 4.8, 1 H, B), 7.36 (dd, J = 8.9, 2.3, 1 H, A), 7.18 (td, J = 8.9,
2.4, 1 H, B), 7.09 (dd, J = 8.9, 2.3, 1 H, A), 2.79-2.67 (m, 2 H, A+B), 2.43 (s, 3 H, A), 2.43 (s, 3 H, B), 1.22-1.12
(m, 3 H, A+B); 13C{1H}NMR (75 MHz, CDCl3): δ = 160.9 (d, J = 242.6, A), 160.09 (B), 159.95 (A), 159.6 (d, J =
241.6, B), 147.8 (A+B), 146.2 (B), 143.2 (d, J = 12.8, A), 141.0 (d, J = 28.9, B), 138.67 (A or B), 138.65 (B or A),
131.4 (d, J = 14.2, B), 128.8 (A), 127.6 (d, J = 22.0, A), 118.9 (d, J = 9.9, B), 116.7 (d, J = 9.9, A), 113.8 (d, J =
25.1, B), 111.7 (d, J = 25.2, A), 104.5 (d, J = 24.8, A), 103.3 (d, J = 29.6, B), 21.28 (A+B), 20.64 (A), 20.60 (B),
12.99 (A+B). 19F NMR (471 MHz, CD3Cl):  = ‒115.8 (s, A), ‒117.4 (s, B); GC/MS (A + B): m/z = 262 (M+, 100),
247 (52), 229 (16), 219 (21), 168 (9). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C13H11FN2OSNa+ 285.0468;
found: 285.0468.
Cross-over Experiment (Scheme 4). A 35 mL stainless steel autoclave was charged in the presence of air
with PdI2 (11.6 mg, 3.22  10–2 mmol), KI (267 mg, 1.61 mmol), MeOH (8 mL), 3d (208.7 mg, 0.81 mmol) and
3e (197.6 mg, 0.81 mmol). The autoclave was purged at room temperature several times with CO under
stirring (5 atm) and eventually pressurized with CO2 (30 atm). After being stirred at 80 °C for 20 h, the
autoclave was cooled, degassed and opened. The resulting crude inseparable mixture was analyzed by GLC
and LC-MS, which evidenced the formation of 4a, 4d, 4e and 5 in a ratio 4a: 4d: 4e: 5 = 1: 1.2: 3: 1.9
(determined by GLC).9 GC/MS (5): m/z = 314 (M+, 100), 271 (14), 257 (46), 230 (48), 178 (16), 137 (73).
Carbonylation of 3d in the Presence of Cyclohexylallene (Scheme 5). A 35 mL stainless steel autoclave
was charged in the presence of air with PdI2 (8.3 mg, 2.30  10–2 mmol), KI (191.24 mg, 1.15 mmol), MeOH
(5.8 mL), 3d (148.8 mg, 0.58 mmol) and cyclohexylallene 6 (commercially available; 70.4 mg, 0.58 mmol). The
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autoclave was purged at room temperature several times with CO under stirring (5 atm) and eventually
pressurized with CO2 (30 atm). After being stirred at 80 °C for 20 h, the autoclave was cooled, degassed and
opened. The crude mixture was analyzed in GLC to determinate the cyclohexylallene conversion (54%). After
evaporation of the solvent, the crude mixture was purified by column chromatography on neutral alumina
(98:2 hexane-AcOEt as eluent) affording 4d in 49% yield (81.8 mg).10
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Supporting Information. Scheme S1, Table S1, X-Ray data for compounds 2a, 4a, and 4f. Copy of HRMS, 1H
NMR, 13C{1H}NMR, and 19F NMR spectra for Substrates 3a-i and Products 4a-i.
Acknowledgments
The X-ray laboratory for single-crystal diffraction at the Dipartimento di Scienze della Terra and
Geoambientali, University of Bari “Aldo Moro”, was funded by Fondo Europeo per lo Sviluppo Regionale
(FESR), Fondo di rotazione (FDR) Programma Operativo Nazionale per le Regioni dell’Obiettivo 1 – Ricerca
Scientifica, Sviluppo Tecnologico, Alta Formazione 2000-2006.
The XRPD laboratory at the Dipartimento di Scienze della Terra and Geoambientali, University of Bari “Aldo
Moro”, was funded by Potenziamento Strutturale PONa3_00369 “Laboratorio per lo Sviluppo Integrato delle
Scienze e delle Tecnologie dei Materiali Avanzati e per dispositivi innovativi (SISTEMA)”.
References
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alkylthiobenzo[d]imidazoles on the Action, Potential Duration and Isometric Contraction in Guinea Pig Atrium
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Activated by Carbachol and in Guinea Pig Heart Papillary Muscles. Drug Res. 2006, 56, 282-287. (b) Brukshtus,
A. B.; Garalene, V. N.; Sirvidite, A. R.-R.; Daukshas, V. K. Synthesis and Cardiotonic Activity of 2-Alkylthio-1-
acyl-5, 6-dimethoxybenzimidazoles and their Cyclic Analogs. Pharm. Chem. J. 1994, 28, 392-395. (c)
Brukshtus, A. B.; Garalene, V. N.; Sirvidite, A. R.-R.; Daukshas, V. K. Synthesis and Cardiotonic activity of 2-
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(2) Crossley, R. (John Wyeth & Brother Limited, Maidemhead, England). Preparation of 2,3-
Dihydrothiazolo- and Thiazinobenzimidazoles as Antiulcer and Antihypersecretion Agents. US Pat. 4,873,237
(1989).
(3) See, for examples: (a) Khalil, A. K. Phosphorus Sulfur Silicon Relat. Elem. Phase-Transfer Catalyzed
Alkylation and Acylation of 2-Mercapto-5-Methyl-1H-Benzimidazole. 2007, 182, 815-823. (b) Britsun, V. N.;
Lozinskii, M. O. Synthesis of 2-Aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-Aryl-
2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones. Chem. Heterocycl. Compds. 2003, 39, 960-964. (c)
Bell, S. C.; Wei, P. H. L. Syntheses of Heterocyclic Fused Thiazole Acetic Acids. J. Med. Chem. 1976, 19, 524-
530.
(4) Veltri, L.; Paladino, V.; Plastina, P.; Gabriele, B. A Palladium Iodide-Catalyzed Cyclocarbonylation
Approach to Thiadiazafluorenones. J. Org. Chem. 2016, 81, 6106−6111.
(5) The conditions reported in Scheme 3 ensued from an optimization study of the operative parameters
(data not shown).
(6) Detailed X-ray structural determination data as well as the CIFs can be found in the Supporting
Information.
(7) For a recent example, see: Li, Q.-H.; Jeng, J.-Y.; Gau, H.-M. Highly Efficient Synthesis of Allenes from
Trimethylaluminum Reagent and Propargyl Acetates Mediated by a Palladium Catalyst. Eur. J. Org. Chem.
2014, 7916-7923.
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(8) Chiusoli, G.P.; Costa, M.; Cucchia, L.; Gabriele, B.; Salerno, G.; Veltri, L. Carbon Dioxide Effect on
Palladium-Catalyzed Sequential Reactions with Carbon Monoxide, Acetylenic Compounds and Water. J. Mol.
Catal. A:Chem. 2003, 204, 133-142.
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(9) The relative amounts of products 4d, 4e, 4a, and 5 were 1: 1.2: 3: 1.9 (determined by GLC). All attempts
to isolate at the pure state mixed product 5 failed, owing to the complexity of the reaction mixture; however,
its GLC-MS spectrum was compatible with the assigned structure. We thank the Associate Editor, Prof. Scott
D. Rychnovsky, for suggesting us to carry out this experiment.
(10) The cyclohexylallene conversion was 54% (determined by GLC analysis of the reaction mixture);
partial decomposition occurred with formation of chromatographically immobile materials, which were not
investigated further). We thank the Associate Editor and a referee for suggesting us to carry out such an
experiment.
(11) Carless, H. A. J.; Batten, R. J. Photosensitized Oxidation of Model Unsaturated Lipid System – (4Z, 7Z)-
Undeca-4,7-diene and (4Z)-Undec-4-en-7-yne. J. Chem. Soc., Perkin Trans. 1 1987, 1999-2007.
(12) Rosenberger, M. (Hoffmann-La Roche Inc.). Synthesis of SRS-Active Compounds. U.S. Pat. US4311645
(1982).
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