Effective synthesis of ortho-substituted trithiophenol amines by Miyazaki-Newman-Kwart rearrangement

Article abstract of DOI:10.1002/ejoc.201100977

An efficient synthesis of ortho-substituted trithiophenol amines from commercially available salicaldehydes by Miyazaki-Newman-Kwart rearrangement/threefold reductive amination is reported. The rearrangement has been carried out on salicaldehyde-O-thiocarbamates using microwave induced heating, which furnishes a series of thiosalicaldehyde-S-carbamates in high yield. The thiocarbamate has three roles: it enables effective S-O rearrangement, acts as a protecting group during the threefold reductive amination and can be easily removed under reductive conditions. The three-step synthesis has an overall yield ranging from 30-35 %, and it enables access to a series of increasingly important C_3v symmetric ligands in a structurally systematic way.

Full text of DOI:10.1002/ejoc.201100977

FULL PAPER
DOI: 10.1002/ejoc.201100977
Effective Synthesis of ortho-Substituted Trithiophenol Amines by Miyazaki–
Newman–Kwart Rearrangement
Blerina Gjoka,[a] Francesco Romano,[a] Cristiano Zonta,*[a] and Giulia Licini*[a]
Dedicated to Professor Gianfranco Scorrano on the occasion of his 72nd birthday
Keywords: Rearrangement / Amines / Thiophenols / Microwave chemistry
An efficient synthesis of ortho-substituted trithiophenol
amines from commercially available salicaldehydes by Miya-
zaki–Newman–Kwart rearrangement/threefold reductive
amination is reported. The rearrangement has been carried
out on salicaldehyde-O-thiocarbamates using microwave in-
duced heating, which furnishes a series of thiosalicaldehyde-
S-carbamates in high yield. The thiocarbamate has three
roles: it enables effective S–O rearrangement, acts as a pro-
tecting group during the threefold reductive amination and
can be easily removed under reductive conditions. The three-
step synthesis has an overall yield ranging from 30–35%, and
it enables access to a series of increasingly important C3v
symmetric ligands in a structurally systematic way.
of ligands with a wide variety of transition metals and main
group elements.
Introduction
The use of highly symmetric polydentate ligands, in par-
ticular, ligands presenting one C3 symmetry axis, is emerg-
ing as a possible strategy for the formation of catalytically
robust complexes.[1] These ligands can be used to (i) control
the coordination chemistry and the environment of the
metal centre, (ii) modulate the electronic and steric proper-
ties of the corresponding complexes and (iii) control their
catalytic properties. We have been interested in the study of
the synthesis and coordination chemistry of triphenol
amine ligands (TPA, Scheme 1), and we have tested the
catalytic activity of their early transition metal complexes.[2]
A substantial number of publications deal with the coordi-
nation chemistry[3] and catalytic performance[4] of this class
Although the synthesis of TPA is usually performed by
a one-step Mannich reaction of ortho-para-disubstituted
phenols with hexamethylenetetramine, we recently reported
an original synthesis based on the reductive amination of
protected salicaldehydes.[5] This synthetic strategy is an ef-
ficient methodology to build a large variety of ligands with
various functionalities on a multigram scale. In this regard,
we are interested in taking advantage of our synthetic ap-
proach for the preparation of the analogous trithiophenol
amines (TTA, Scheme 1). Inspired by the trigonal FeS3 co-
ordination sites present in the FeMo-cofactor of nitroge-
nase, TTA (R = H) was first synthesized by Koch et al. and
used for the preparation of the corresponding iron(II) and
iron(III) complexes.[6] More recently, gallium(III) and in-
dium(III) complexes have been obtained, which show inter-
esting applications in radiolabelling.[7] Although extensive
theoretical studies have been carried out on TTA (R = H)
complexes with iron,[8] ortho-substituted TTA derivatives
and their coordination chemistry with different metals have
not been intensively investigated. Therefore, the develop-
ment of a general and efficient synthesis for TTAs is desir-
able and will offer the opportunity to extend their applica-
tion in catalysis.
Scheme 1. TPA and TTA ligands.
In view of our experience in TPA synthesis and in their
use as ligands for catalysis, we planned to prepare TTA li-
gands in a similar fashion. This translates into the use of
reductive amination as key step for the preparation of the
amino skeleton and Miyazaki–Newman–Kwart (MNK) re-
arrangement for the preparation of the thiophenol salical-
[a] Department of Chemical Sciences, University of Padova,
Via Marzolo 1, 35131 Padova, Italy
Fax: +39-049-8275248
E-mail: giulia.licini@unipd.it
cristiano.zonta@unipd.it
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Eur. J. Org. Chem. 2011, 5636–5640

Effective Synthesis of ortho-Substituted Trithiophenol Amines
dehyde monomers (Scheme 2). MNK rearrangement allows
the migration of the aryl group of an O-aryl thiocarbamate
from the oxygen to the sulfur atom, which forms an S-aryl
thiocarbamate.[9]
Scheme 2. Retrosynthetic approach for the synthesis of TTA from
salicaldehydes.
Moreover, whereas the reported synthesis for TTA re-
quires a multistep synthetic sequence,[6,7] this approach of-
fers an easy modular synthesis. Furthermore, the opportu-
nity for introducing groups in the ortho position will expand
the knowledge of the coordination chemistry of TTAs and
offer new applications in metal complexation and catalysis.
Herein we report a series of ortho-substituted TTAs,
which can be easily and effectively prepared by reductive
amination of the corresponding MNK rearranged S-thio-
carbamoyl salicaldehydes. This synthetic approach allows
easy access to ortho-substituted TTAs 1a–c (R = H, Me,
Ph, respectively) in high purity by a three step procedure
from commercially available salicaldehydes. The synthesis is
characterized by a satisfactory final chemical yield, easy
and efficient purifications and fast reactions. The key issue
that makes this method successful is the use of the thio-
carbamoyl group both as a rearranging agent and protect-
ing group during the reductive amination carried out in the
presence of NaBH(AcO)3 and NH4AcO.[10] This strategy
allows the effective construction of the ligand skeleton and
differently substituted TTAs.
Scheme 3. Synthetic procedure for the synthesis of 1a–c.
Treatment of 2a–d with N,N-dimethylthiocarbamoyl
chloride (DMTCl) in acetonitrile in the presence of potas-
sium carbonate gave the desired O-thiocarbamates 3a–d in
good yields after purification (75–77%). The compounds
can be either purified by column chromatography or crys-
tallisation. Alternative procedures with different bases, such
as 1,4-diazabicyclo[2.2.2]octane or NaH in N,N-dimethyl-
formamide, did not furnish satisfactory yields for all of the
products.
Reaction conditions for the MNK rearrangement were
optimized for 3a (R = H, Table 1). The rearrangement was
performed initially using the Lewis acid catalyst BF3·OEt2
as reported by Brooker et al.[11] Even if the reaction pro-
ceeds smoothly in high yield, it requires very long reaction
times (3 d) and strictly anhydrous reaction conditions. To
obtain a more reliable method we tried the classical thermal
rearrangement (Table 1, Entry 2). The reaction carried out
Table 1. Optimisation of MNK rearrangement reaction conditions
for 3a.
Results and Discussion
Our initial attempts in preparing TTAs were focused on
the use of the MNK rearrangement directly on the threefold
O-thiocarbamoyl TPAs. Although the threefold introduc-
tion of the thiocarbamoyl groups proceeded smoothly, the
rearrangement did not take place. For this reason, we exam-
ined a different strategy, which consisted of the preliminary
derivatization of the OH group of substituted salical-
dehydes 2a–d (R = H, Me, Ph, tBu, respectively) followed
by MNK rearrangement of the resulting O-thiocarbamate
esters 3a–d, a threefold reductive amination of the thiosal-
icaldehyde S-thiocarbamates 4a–d, and finally the reductive
removal of the protecting carbamoyl groups, yielding 1a–c
(Scheme 3). The starting materials are commercially avail-
able (2a–c) or easily accessible from the corresponding phe-
nol using paraformaldehyde and MgCl2 (2d).[5]
Entry Method[a] Solvent[b] Temp. Time Conv.[c]
4a:2a:6a[c]
[°C]
[min] [%]
1
2
3
4
5
6
BF3·OEt2 DCE
85
72 h
5
10
5
10
15
95
80
30
95
99
99
90:10:0
30:70:0
Ͼ99:1:0
Ͼ99:1:0
Ͼ99:1:0
90:0:10
thermal
MW
neat
300
200
230
230
230
NMP
NMP
NMP
NMP
MW
MW
MW
[a] BF3·OEt2: Lewis acid rearrangement using the conditions de-
scribed in ref.[11], thermal: rearrangement induced by conventional
heating, MW: rearrangement induced by microwave heating
(200 W). [b] DCE: 1,2-dichloroethane. [c] Data obtained from H
NMR analysis of the crude mixture.
1
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B. Gjoka, F. Romano, C. Zonta, G. Licini
FULL PAPER
at 300 °C gives 25% of the desired product, 4a, in a very 4d (25%) with an increased amount of 6d (48%). As a con-
short time. However, under these conditions, extensive hy- sequence of the low yields of 4d, the synthesis of TTA 1d
drolysis of the reagent to 2a (56%) is observed. On the con- was not further investigated. However, we must point out
trary, the reaction performed using microwave (MW) in- that the MNK rearrangement is effective (60% of re-
duced heating, after dissolving the sample in N-methylpyr- arranged product as 4d + 6d) and can still be synthetically
rolidone (NMP), enables the tuning and optimization of the useful. Moreover, 2b and 2d can be recycled.
reaction conditions and the maximization of conversion of
S-Thiocarbamoyl aldehydes 4a–c could be purified by
3a into 4a without reagent or product hydrolysis (Table 1, column chromatography after removal of the solvent by dis-
Entries 3–6).[12] The best reaction conditions use anhydrous tillation at low pressure. The resulting S-thiocarbamoyl al-
NMP at 230 °C for 10 min (Table 1, Entry 5). Shorter reac- dehydes 4a–c were used for reductive amination in the pres-
tion times do not permit complete conversion of the rea- ence of NaBH(AcO)3/NH4AcO. The yields of 5a–c after
gent, and longer reaction times result in the partial hydroly- purification are satisfactory (ca. 50%). The only byproduct
sis of the S-thiocarbamoyl group yielding thiosalicaldehyde of the reactions is the benzylic alcohol arising from the re-
(6a, 10%, Table 1, Entry 6). The product can be purified duction of the corresponding aldehyde. The final step can
either by column chromatography or crystallisation.
be carried out to completion under reductive conditions
The best reaction conditions for 3a were applied to 3b–d (lithium aluminium hydride), whereas hydrolytic methods
(Table 2). The presence of an ortho substituent is known to (KOH/EtOH) gave only partial deprotection. The desired
strongly influence the MNK rearrangement.[9a] Preliminary 1a–c were obtained in satisfactory yields after aqueous
tests showed that, although a clean and quantitative re- work up (60–65%). These compounds are known to have
arrangement was obtained for the phenyl-substituted alde- low stability under oxidative or basic conditions (formation
hyde 4c, the presence of an aliphatic group in the ortho posi- of disulfides and dibenzo[1,5]dithiocines)[13] and, for these
tion, as in the methyl 3b or tert-butyl 3d systems, results in reasons, they were usually used directly for the synthesis of
extensive reagent and/or product hydrolysis, lowering the the corresponding metal complexes without further purifi-
final yield of 4. Therefore, irradiation times were decreased cation.[14]
to 5 min and a good yield of 3c was obtained (95% conver-
The synthesis can be further optimized by carrying out
sion, Table 2, Entry 4), whereas 3b, with 97% conversion, the reductive amination and deprotection in a one-pot pro-
gave a rearrangement yield of 78% for S-thiocarbamate 4b cedure (Scheme 4). This strategy has been tested on 4c af-
(54%) and the hydrolyzed 6b (24%, Table 2, Entry 2 and fording the product in satisfactory yields. Therefore, only
4). For 3d, reagent and product hydrolysis was even more three steps are required to obtain the TTA ligands from the
important. The MNK rearrangement furnished 10% yield commercially available salicaldehydes.
of 4d and 50% of 6d. It seems likely that the aliphatic sub-
stituent is not responsible for the scarce yield in the re-
arrangement step, but it gives a lower stability towards hy-
drolysis of the starting material and rearranged product.
Further variation of the reaction times and reaction tem-
peratures under MW induced heating conditions or the use
of BF3·OEt2 did not result in better yields. Compounds 3b
and 3d were also irradiated without solvent and an in-
creased yield of rearranged product was obtained for 3b
Scheme 4. One-step synthesis of 1a from 4a.
(90%, Table 2 Entry 3), whereas 3d gave a higher yield of
Conclusions
Our new method allows the synthesis of ortho-substi-
Table 2. MNK rearrangement for 3a–d.
tuted trithiophenol amines 1a–c (R = H, Me, Ph) with satis-
factory yields in a three-step procedure starting from com-
mercially available aldehydes. This approach allows access
to this increasingly important class of ligands in a structur-
ally systematic way using either commercially available or
easily synthesized building blocks. Moreover, the synthesis
of 4a–d is important for the preparation of thio analogues
of salan, salen and salalen ligands. We are currently em-
ploying this methodology for the synthesis of a larger li-
brary of sulfur-containing ligands for application in coordi-
nation chemistry and catalysis.
Entry Substrate
Conditions
Time Conv.[a] 4:6:2[a]
[min] [%]
1
2
3
4
5
6
3a R = H
NMP (0.4 m) 10
99
97
97
95
99
99
100:0:0
54:24:22
59:31:10
99:0:1
10:50:40
25:27:48
3b R = Me NMP (0.4 m)
5
2
5
5
2
3b R = Me neat[b]
3c R = Ph
NMP (0.4 m)
3d R = tBu NMP (0.4 m)
Experimental Section
3d R = tBu neat[b]
[a] Data obtained from 1H NMR analysis of the crude mixture. [b]
Neat 0.1 mmol.
General Methods: Chemicals and solvents were purchased from
commercial suppliers and used as supplied. Compounds 2a, 2b and
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Eur. J. Org. Chem. 2011, 5636–5640

Effective Synthesis of ortho-Substituted Trithiophenol Amines
2d are commercially available (Sigma–Aldrich). Compound 2c is
easily accessible from the corresponding phenol.[15] 1H NMR spec-
tra were recorded with a Bruker AC 250 (250.18 MHz) or Bruker
Avance DRX 300 (300.13 MHz) spectrometer, using partially deu-
terated solvent or TMS as internal references (TMS δ = 0.00 ppm,
CHCl3 δ = 7.26 ppm). ESI-MS experiments were performed with
an ESI-TOF Mariner TM, Applied Biosystems by flow injection
analysis using acetonitrile as the mobile phase. Microanalyses were
performed with a Perkin–Elmer 2400 CHN Elemental Analyser.
either directly by aqueous drown-out from NMP solutions or by
extraction into EtOAc followed by flash silica gel chromatography.
S-(2-Formylphenyl) N,N-Dimethylthiocarbamate (4a): Irradiation
time at 230 °C, 5 min. After extraction into EtOAc, the crude mate-
rial was purified by flash chromatography (SiO2, petroleum ether:-
EtOAc 8:2). Bright yellow oil; yield 85%. 1H NMR (250 MHz,
CDCl3): δ = 10.35 (s, 1 H), 8.02 (d, J = 5.7 Hz, 1 H), 7.55 (m, 3
H), 3.16 (s, 3 H), 3.03 (s, 3 H) ppm. 13C NMR (62.9 MHz, CDCl3):
δ = 191.82, 165.23, 148.24, 140.08, 138.58, 135.31, 129.58, 127.75,
37.09 ppm. C10H11NO2S (209.26): calcd. C 57.39, H 5.30; found C
57.20, H 5.26.
Synthesis of Substituted O-(2-Formylphenyl) N,N-Dimethylthiocarb-
amates 3a–d: Substituted salicaldehydes 2a–d, (0.05 mol) were dis-
solved in dry acetonitrile (20 mL) under nitrogen at room tempera-
ture. K2CO3 (26.25 g, 0.2 mol) was added to the stirring solution.
After 10 min, solid dimethylthiocarbamoyl chloride (7.4 g,
0.06 mol) was added and the mixture heated to 80 °C. After 24 h
the mixture was cooled to room temperature, the solid residue was
collected by filtration and dissolved in EtOAc (25 mL). The organic
layer was washed with water (3ϫ15 mL), dried with Na2SO4 and
concentrated under reduced pressure. The product was purified by
flash chromatography (SiO2, petroleum ether:EtOAc 8:2).
S-(2-Formyl-6-methylphenyl) N,N-Dimethylthiocarbamate (4b): Ir-
radiation time at 230 °C, 2 min. After extraction into EtOAc, the
crude material was purified by flash chromatography (SiO2, petro-
1
leum ether:Et2O 7:3). Orange oil; yield 52%. H NMR (250 MHz,
CDCl3): δ = 10.42 (s, 1 H), 7.80 (d, J = 7.5 Hz, 1 H), 7.40 (m, 2
H), 3.13 (s, 3 H), 2.95 (s, 3 H), 2.43 (s, 3 H) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 192.06, 164.61, 143.97, 138.39, 135.47,
131.60, 129.65, 126.20, 37.04, 20.84 ppm. C11H13NO2S (223.29):
calcd. C 59.17, H 5.87; found C 59.29, H 5.92.
O-(2-Formylphenyl) N,N-Dimethylthiocarbamate (3a): White solid;
yield 75%. H NMR (250 MHz, CDCl3): δ = 10.07 (s, 1 H), 7.91
S-(3-Formylbiphenyl-2-yl) N,N-Dimethylthiocarbamate (4c): Irradi-
ation time at 230 °C, 5 min. After extraction into EtOAc, the crude
material was purified by flash chromatography (SiO2, petroleum
ether:EtOAc 8:2). Bright yellow oil; yield 94%. 1H NMR
(250 MHz, CDCl3): δ = 10.36 Hz (s, 1 H), 8.0 (m, 1 H), 7.52 (m, 2
H), 7.34 (m,3 H), 7.2 (m,2 H), 2.97 (s, 6 H) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 191.69, 165.10, 148.26, 140.10, 138.59,
135.34, 130.75, 129.60, 127.77, 127.55, 36.96 ppm. C16H15NO2S
(285.36): calcd. C 67.34, H 5.30; found C 67.36, H 5.12.
1
(d, J = 9.0 Hz, 1 H), 7.89 (t, J = 9.0 Hz 1 H), 7.4 (t, J = 13.0 Hz,
1 H), 7.13 (d, J = 13.0 Hz 1 H), 3.48 (s, 3 H), 3.43 (s, 3 H) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 187.92, 154.81, 134.43, 129.23,
128.69, 126.00, 123.96, 111.49, 43.40, 38.92 ppm. C10H11NO2S
(209.26): calcd. C 57.39, H 5.30; found C 57.50, H 5.28.
O-(2-Formyl-6-methylphenyl) N,N-Dimethylthiocarbamate (3b):
1
Orange oil; yield 77%. H NMR (250 MHz, CDCl3): δ = 10.02 (s,
1 H), 7.74 (d, J = 7.5 Hz, 1 H), 7.49 (d, J = 7.2 Hz, 1 H), 7.30 (t,
J = 7.5 Hz, 1 H), 3.40 (s, 3 H), 3.31 (s, 3 H), 2.43 (s, 3 H) ppm.
Synthesis of Tris[2-(N,N-dimethylthiocarbamoyl)benzyl]amines 5a–
c: Rearranged aldehydes 4a–c (3 mmol) were mixed with ammo-
13C NMR (62.9 MHz, CDCl3): δ = 188.77, 153.45, 136.70, 132.38, nium acetate (80 mg, 1 mmol) in THF (20 mL) under a nitrogen
129.13, 127.55, 126.12, 111.84, 43.33, 38.69, 15.51 ppm.
C11H13NO2S (223.29): calcd. C 59.17, H 5.87; found C 59.01, H
5.91.
atmosphere. After 2 h sodium triacetoxy borohydride (920 mg,
4 mmol) was added. The mixture was stirred overnight at room
temperature and the solvents evaporated to dryness. The residue
was dissolved in EtOAc and washed twice with ammonium chlo-
ride and brine. The organic layer was dried with Na2SO4 and con-
centrated under reduced pressure. The product was purified by
flash chromatography. (SiO2, petroleum ether:EtOAc:Et3N,
8:2:0.01).
O-(3-Formylbiphenyl-2-yl) N,N-Dimethylthiocarbamate (3c): White
1
solid; yield 75%. H NMR (250 MHz, CDCl3): δ = 10.09 (s, 1 H),
7.94 (d, J = 7.5 Hz, 1 H), 7.62 (d, J = 7.5 Hz, 1 H), 7.49 (s, 1 H),
7.41 (m, 5 H), 3.30 (s, 3 H), 3.12 (s, 3 H) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 188.49, 152.45, 136.44, 130.19, 129.17,
128.39, 127.85, 126.47, 43.40, 38.63 ppm. C16H15NO2S (285.36):
calcd. C 67.34, H 5.30; found C 67.66, H 5.32.
Tris[2-(N,N-dimethylthiocarbamoyl)benzyl]amine (5a): Bright yel-
1
low oil; yield 55%. H NMR (250 MHz, CDCl3): δ = 7.53 Hz (d,
J = 7.5 Hz, 3 H), 7.42 (d, J = 5.0 Hz, 3 H), 7.31 (t, J = 5.0 Hz, 3
H), 7.21 (t, J = 7.5 Hz, 3 H), 3.69 (s, 6 H), 2.98 (s, 18 H) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 166.50, 142.82, 136.93, 130.96,
129.02, 128.74, 126.96, 56.95, 36.72 ppm. ESI-MS: m/z = 596.2 [M
+ H]+.
O-(2-Formyl-6-tert-butylphenyl) N,N-Dimethylthiocarbamate (3d):
Yellow solid; yield 75%, H NMR (250 MHz, CDCl3): δ = 9.92 (s,
1
1 H), 7.75 (d, J = 7.5 Hz, 1 H), 7.67 (d, J = 7.5 Hz, 1 H), 7.30 (t,
J = 7.5 Hz, 1 H), 3.48 (s, 6 H) 1.40 (s, 9 H) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 188.52, 153.30, 142.51, 133.20, 130.64,
128.53, 125.98, 126.47, 43.40, 39.10, 35.05, 30.83 ppm.
C14H19NO2S (265.37): calcd. C 63.36, H 7.22; found C 63.55, H
7.26.
Tris[2-(N,N-dimethylthiocarbamoyl)-3-methylbenzyl]amine
(5b):
Bright yellow oil; yield 50%. 1H NMR (250 MHz, CDCl3): δ =
7.80 (d, J = 7.5 Hz, 3 H), 7.40 (m, 6 H), 3.73 (s, 6 H), 3.04 (s, 18
H), 2.43 (s, 9 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 165.70,
147.97, 140.39, 138.30, 133.70, 131.44, 128.30, 37.04, 20.84 ppm.
ESI-MS: m/z = 639.2 [M + H]+.
Synthesis of Substituted S-(2-Formylphenyl) Dimethylthiocarb-
amates 4a–d: Microwave reactions were performed in 10 mL sealed
tubes with a regularly calibrated CEM Discover focused 300 W mi-
crowave reactor with IR temperature monitoring and noninvasive
pressure transducer. In a typical procedure, O-thiocarbamate 3a–d
(1 mmol) was dissolved in NMP (2.5 mL) and heated to the re-
quired temperature with stirring for a fixed time. The heating time
to reach the set temperature was typically 60 s, depending on the
scale, the maximum wattage supplied (100–300 W) and the tem-
perature required. The heating time is not included in the quoted
hold time for any given procedure. The products 4a–c were isolated
Tris[2-(N,N-dimethylthiocarbamoyl)-3-phenylbenzyl]amine (5c): Yel-
1
low oil; yield 53% H NMR (250 MHz, CDCl3): δ = 7.80 Hz (d, J
= 7.5 Hz, 3 H), 7.30 (m, 3 H), 7.27 (m, 15 H), 7.20 (m, 3 H), 3.96
(s, 6 H), 2.85 (s, 18 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ =
166.29, 147.85, 144.74, 142.12, 129.53, 129.37, 129.04, 128.89,
127.32, 126.72, 57.65, 37.19 ppm. ESI-MS: m/z = 825.3 [M + H]+.
Synthesis of Tris(2-mercaptobenzyl)amines 1a–c: To a solution of
5a–c (0.16 mmol) in dry THF (2 mL) was slowly added LiAlH4
Eur. J. Org. Chem. 2011, 5636–5640
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B. Gjoka, F. Romano, C. Zonta, G. Licini
FULL PAPER
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(3 mL) at 0 °C followed by H2SO4 (10% water, 2 mL). The mixture
was extracted into EtOAc (5 mL), washed with water and dried
with Na2SO4. The resulting solution was concentrated under re-
duced pressure. The ligands the products were not purified because
of their instability.
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1
Tris(2-mercaptobenzyl)amine (1a): Bright yellow oil; yield 60%. H
NMR (250 MHz, CDCl3): δ = 7.33 Hz (d, J = 7.5 Hz, 3 H), 7.3 (d,
J = 5.0 Hz, 3 H), 7.17 (t, J = 5.0 Hz, 3 H), 7.21 (t, J = 7.5 Hz, 3
H), 3.69 (s, 6 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 142.82,
136.93, 130.76, 129.02, 128.74, 126.96, 56.95 ppm. HRMS (ESI):
calcd. for C21H21NS3 [M + H]+ 384.0914; found 384.0898.
Tris(2-mercapto-3-methylbenzyl)amine (1b): Bright yellow oil; yield
1
60%. H NMR (250 MHz, CDCl3): δ = 7.60 (d, J = 7.5 Hz, 3 H),
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128.30, 57.04, 21.84 ppm. HRMS (ESI): calcd. for C33H42N4O3S3
[M + H]+ 426.1384; found 426.1334.
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This approach has been used recently for the synthesis of a
thiophenolate ligand for copper, see: S. Torelli, M. Orio, J.
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Tris(2-mercapto-3-phenylbenzyl)amine (1c): Bright yellow oil; yield
65%. 1H NMR (250 MHz, CDCl3): δ = 7.38 Hz (m, 3 H), 7.35
(m,3 H), 7.30 (m,15 H), 7.10 (m, 3 H), 3.80 (s, 6 H), ppm. 13C
NMR (62.9 MHz, CDCl3): δ = 147.85, 144.74, 142.12, 129.53,
129.37, 129.04, 128.89, 127.32, 126.72, 57.65, ppm. HRMS (ESI):
calcd. for C39H33NS3 [M + H]+ 612.1853; found 612.1897.
[8]
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Acknowledgments
The Ministero dell’Università e della Ricerca (MIUR) (Progetto
Dottorati di Ricerca Fondazione, CARIPARO) (to F. R.) and the
Università di Padova (Progetti Eccellenza 2009/10, NANO-MOD-
ule, Fondazione CARIPARO, PRIN 2008 and PRAT 2009) are
acknowledged for financial support.
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Received: July 5, 2011
Published Online: August 31, 2011
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