Metallation reactions XXVII. Metallation of (methylthio)anilines

Article abstract of DOI:10.1016/S0022-328X(00)00806-8

The metallation reactions of (methylthio)anilines with organolithium reagents and with the butyllithium-potassium tert-butoxide superbasic mixture are here described. The results show that the para isomer when treated with butyllithium gave a mixture of p

Full text of DOI:10.1016/S0022-328X(00)00806-8

www.elsevier.nl/locate/jorganchem
Journal of Organometallic Chemistry 620 (2001) 263–275
Metallation reactions XXVII.ꢀ
Metallation of (methylthio)anilines
M.G. Cabiddu, S. Cabiddu *, E. Cadoni, R. Cannas, S. De Montis, C. Fattuoni,
S. Melis
Dipartimento di Scienze Chimiche, Complesso Uni6ersitario di Monserrato, SS 554 Bi6io per Sestu, I-09042 Monserrato (CA), Italy
Received 7 July 2000; accepted 18 October 2000
Dedicated to Emeritus Professor Antonio Maccioni
Abstract
The metallation reactions of (methylthio)anilines with organolithium reagents and with the butyllithium–potassium tert-butox-
ide superbasic mixture are here described. The results show that the para isomer when treated with butyllithium gave a mixture
of products with no selectivity. Using tert-butyllithium or superbases we obtained the substitution of the thiomethyl hydrogen.
Moreover, superbase allowed to prepare the disubstituted product with the new groups in the thiomethyl and in ortho to this
group. On the other side, both ortho and meta isomers were lithiated at the thiomethyl carbon by butyllithium and the other
reagents. Starting from the unalkylated amine we prepared through three successive one-pot monometallations N,N-disubstituted
amines with equal or different groups and bearing an alkylthio chain as long as wanted. © 2001 Elsevier Science B.V. All rights
reserved.
Keywords: Metallation; Organolithium; Superbases; Thioethers; (Alkylthio)aminobenzenes
directing groups in metallation reactions. In fact, there
is a unique work by Gilman and Webb published in
1949 [14] describing the monometallation of N,N-
dimethyl-4-(methylthio)aniline that gave, after treat-
ment with carbon dioxide, an arylthioacetic acid in
22.4% yield and the starting compound in 52.1% yield.
In this work we examined the regiochemistry of the
metallation of (methylthio)anilines using organolithium
compounds and superbases.
1. Introduction
In the last years the research on heteroatom pro-
moted metallation has been developed to improve the
synthesis of polysubstituted aromatics and heterocycles
[2–9]. In our recent works we examined the behaviour
of the thioether group as ortho directing group in
metallation reactions and its competition with methoxy
and trifluoromethyl group and fluorine atom [10–12].
Other works in literature examined the competition
between the N,N-dimethylamino group and the alkoxy
and trifluoromethyl group and fluorine atom when both
linked at the same aromatic ring. The results show a
stronger directing power of these last three functions
[10,13].
2. Results and discussion
The starting compounds were reacted with different
metallating reagents: butyllithium, tert-butyllithium, su-
perbasic mixture obtained by mixing butyllithium and
potassium tert-butoxide (LICKOR), in various working
conditions. All metallated compounds were quenched
with iodomethane and analysed by GC/MS.
The metallation reaction was first performed on the
N,N-dimethyl-4-(methylthio)aniline (1a) (Scheme 1) us-
ing butyllithium and hexane as solvent at reflux. We
On the other hand, there are only few reports on the
competition between the amino and the thioether as
ꢀ For Part XXVI, see Ref. [1].
* Corresponding author. Tel.: +39-070-6754387; fax: +39-070-
6754388.
E-mail address: scabiddu@unica.it (S. Cabiddu).
0022-328X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(00)00806-8

264
M.G. Cabiddu et al. / Journal of Organometallic Chemistry 620 (2001) 263–275
recovered only the starting compound (Table 1). The
second step was to introduce the use of N,N,N%,N%-te-
tramethylethylenediamine (TMEDA) in equimolar
amount as butyllithium. After quenching with
iomethane the GC/MS analysis revealed three
monometallation products 2, 3 and 4 in the yield of 15,
12 and 6% derived by metallation in ortho to the
dimethylamino group, in alpha at the thiomethyl group
and in ortho to the sulphur atom, respectively. Using
two moles of the same reagent, unreacted starting mate-
rial was lowered (13%) and we obtained three
monometallated products 2, 3, and 4 (in the yield of 27,
12 and 9%) and three bimetallated 5 (24%), 6 (12%) and
7 (3%): 5 arises from metallation in alpha at the
thiomethyl group and in ortho to the amino group; 6
from lithiation in alpha and ortho to the thiomethyl
group; 7 from substitution in ortho to both dimethy-
lamino and thiomethyl groups. When the reaction was
performed using two molar equivalents of butyllithium,
injecting one mole and after 15 min the second mole,
we obtained five products (2, 3, 4, 5 and 6) in the ratio
of 27:13:22:22:16. The remaining starting material was
18%. We obtained analogous results injecting 2 moles
and after 15 min another 2 moles.
At this point we changed the metallation procedure
treating the organolithium dropwise with the substrate:
we obtained products mixtures as before.
To improve selectivity we tested the more basic tert-
butyllithium and we obtained only the monometallated
product 3: using one molar equivalent of tert-butyl-
lithium we obtained 37% of 3, while with two molar
equivalents of the same reagent we found 54% of 3.
Analogous results were obtained using LICKOR as
metallating reagent (see Table 1).
The ortho isomer 1b gave analogous results (Scheme
2): using one molar equivalent of butyllithium and
TMEDA we obtained only the monometallated
product 10, derived from lithiation at the thiomethyl
carbon, in good yield (82%) (Table 2). Using two molar
equivalents of butyllithium and TMEDA we obtained a
mixture of three mono- 10 (54%), 11 (14%) and 12 (1%)
and two bimetallated products 13 (4%) and 14 (2%).
With 1 molar equivalent of tert-butyllithium we ob-
tained only 10 (44%). Better results derived from the
use of 1 or 2 molecular equivalents of LICKOR that
gave only the monometallated 10 with good yield (81
and 89%, respectively). Increasing this organometallic
(3 molar equivalents) to improve yield of monometal-
lated 10, we obtained a mixture of 10 (50%) and three
bimetallated products 13 (4%), 14 (23%) and 15 (16%).
The metallation of the meta isomer 1c using one
molar equivalent of butyllithium, tert-butyllithium or
superbasic reagent gave only the product 17, derived by
substitution in the alpha position of the thiomethyl
group (Scheme 3), with yields of 67, 46 and 34%,
respectively. Using four molar equivalents of butyl-

M.G. Cabiddu et al. / Journal of Organometallic Chemistry 620 (2001) 263–275
265
lithium, injected in two subsequent times, we revealed
four mono- 17 (37%), 18 (5%), 19 (3%), and 20 (5%)
and three bimetallated products 21 (13%), 22 (9%) and
23 (10%) (Table 3). When 1c was poured onto the same
amount of reagent (four equivalents) we obtained three
products: 17 (66%), 21 (7%) and 22 (8%). Analogously,
to compounds 1a and 1b, even 1c gave an a,a%-dilithi-
ated product 24 (11%), when treated with three molar
equivalents of superbase, beside 17 (65%) and 23 (12%).
In conclusion, these reactions can be used to func-
tionalise the thiomethyl carbon, as proved by the at-
tainment of carboxylic acids 9, 16, 25. Starting from 1a
and LICKOR it is possible to prepare ortho,alpha-SMe-
disubstituted products as proved by attainment of 6.
Using the unsubstituted amine 26 as starting com-
pound, it is possible to obtain N,N-disubstituted
alkylthioamines with equal or different groups on N
and S, through three subsequent one-pot metallations.
This is proved by the attainment of 2-(butylthio)-N-
ethyl-N-methylaniline (29) starting from 2-(methyl-
tio)aniline (26) through a metallation/quenching with
iodomethane, followed by a second metallation/quench-
ing with iodoethane, and a third metallation/quenching
with iodopropane (Scheme 4). This procedure allowed
to prepare even compounds 10 and 30. Moreover, a
monometallation/electrophilic quenching followed by a
bimetallation/electrophilic quenching allowed to intro-
duce two equal and one different groups as showed by
the formation of 31 and 32 (Scheme 4).
The results obtained on the para isomer 1a show that
the regioselectivity of the metallation is dependant on
the structure of the substrate and of the organometallic
(the lithiating power of butyllithium depending on the
coordinating attitude of the substituents on the aro-
matic ring) and on the solvent [2]: when butyllithium–
TMEDA–hexane is used the dimethylamino group is a
better directing group than methylthio. In fact (see
Table 1), the ratio ortho-NMe2/ortho-SMe is between
51/21 and 40/31 for entries 2–5. These results can be
explained by the complexation of butyllithium–
TMEDA preferentially on nitrogen. These data allow
to add new information to the study on the hierarchy of
directing groups in metallation: since it was shown that
the alkoxy is a stronger directing group than alkylthio
and the dimethylamino [2,11], we can write this series
for the directing power:
OMe\NMe2\SMe
On the other side, the metallation with one molar
equivalent of more basic reagents as tert-butyllithium
or superbases have place exclusively at the more acidic
thiomethyl carbon. With more equivalents of superbase
the ratio ortho-NMe2/ortho-SMe is 6/63 and 6/62 for 1a
(see Table 1, entries 10 and 11), 4/23 for 1b (see Table
2 entry 6), 0/12 for 1c (see Table 3, entry 6). These
results can be explained assuming that the determining
factor is the acidity of hydrogens in the substrate
[5,7,15].
The ortho isomer 1b, on the contrary, was lithiated at
the thiomethyl carbon even with one molar equivalent
of butyllithium with good yield and selectivity. These
results can be accounted for by the stabilization of the
thiomethyl carbanion by the adjacent amino group
(Fig. 1). Such an intermediate cannot be formed in 1a.
The formation of products 8, 15, 24, bearing the
isopropylthio function, can be explained by a further
attack of LICKOR on derivatives 3, 10, 17, respectively
[10].
Scheme 1.
The identification of all the products was performed
by interpretation of the mass and NMR spectra or by
comparison with authentic samples.
The product 2 was distinguished from its isomer 4 by
their different retention times, 4 was prepared other
way (see Section 3). Moreover, the mass spectrum of 4
shows the peaks at 121 and 122 more abundant than
for 2. The peak 122 is due to the loss of methyl and CS:
Scheme 2.

Table 2
Metallation of 1-dimethylamino-2-(methylthio)benzene (1b) a
RM (equivalents)
TMEDA (equivalents)
Solvent
T (°C)
t (min)
Starting material (%)
10 (%)
11 (%)
12 (%)
13 (%)
14 (%)
15 (%)
BuLi (1)
1
2
Hexane
Hexane
THF
Hexane
Hexane
Hexane
20“40
20“55
0“20 180
45
60
18
25
56
11
19
7
82
54
44
89
81
50
BuLi (1+1) b
t-BuLi (1)
14
1
4
2
LICKOR (1)
LICKOR (2)
LICKOR (3)
−40“−20
−40“−20
−40“−20
60
60
60
/
4
23
16
a The metallation products were quenched with iodomethane; the yields were determined by GC analyses; LICKOR=equimolar mixture of butyllithium and potassium tert-butoxide.
b The organolithium compound was injected in two subsequent times (the second after 15 min).
Table 3
Metallation of 1-dimethylamino-3-(methylthio)benzene (1c) a
RM (equivalents)
TMEDA (equivalents)
Solvent
T (°C)
t (min)
Starting material (%)
17 (%) 18 (%) 19 (%) 20 (%) 21 (%) 22 (%) 23 (%) 24 (%)
BuLi (1)
BuLi (4)
1
4
4
Hexane
Hexane
Hexane
THF
Hexane
Hexane
Reflux
0“30
30
0“20
−45
150
120
120
120
60
33
19
18
54
66
12
67
66
37
46
34
65
7
13
8
9
620
BuLi (2+2) b
t-BuLi (1)
LICKOR (1)
LICKOR (3)
5
3
5
10
12
(
−45
60
11
263
a The metallation products were quenched with iodomethane; the yields were determined by GC analyses; LICKOR=equimolar mixture of butyllithium and potassium tert-butoxide.
275
b The organolithium compound was injected in two subsequent times (the second after 15 min).

M.G. Cabiddu et al. / Journal of Organometallic Chemistry 620 (2001) 263–275
267
Scheme 3.
Scheme 4. 27, El1=Me; 1b, El1=El2=Me; 10, El1=El2=El3=Me; 28, El1=Me, El2=Et; 29, El1=Me, El2=Et, El3=Pr; 30, El1=El2=Me,
El3=Et; 31, El1=Me, El2=Pr; 32, El1=Me, El2=allyl.
dicarbanion bearing two negative charges on neibouring
carbons (this can not assure the minimization of charge
repulsion between the two lithiums). The consequence is
that these two groups are in para one each other, as
already stated for other substrates [2,18,19,21,22].
For what concerns the products derived from the
ortho isomer 1b, compounds 11 and 12 were distin-
guished assuming these considerations: the peak at 180
(M+−H) is shown by 12 but not by 11. The loss of a
hydrogen atom is difficult (see methyl(methylthio)-
benzenes [23]) and can be observed only when other
concurrent fragmentations are impossible (see N,N-
dimethyltoluidines [20]). These compounds have a very
high (M+−H) peak but in the ortho isomer it has a
lower abundance than in the meta. 12 has a meta
arrangement for the methyl and the amino group. Both
compounds show the peak 148 due to the loss of SH: in
11 it has an abundance of 41.6, in 12 of 24.9. This
fragmentation is favoured when the methyl group is in
meta to the methylthio (compare to 2-methyl- and
3-methyl(methylthio)benzene [17]), while decreases in
the ortho isomer, and even disappears in the 2,6-
dimethyl(methylthio)benzene.
this fragmentation is favoured by a methyl group in
ortho to the SR. The Scheme 5 shows that the structure
derived from 4 is stabilized by the inductive effect of the
ortho methyl (structure 4A).
Thus, 4A is more stable than 2A and the CS bond in
4 has a greater double bond character and it is easier the
elimination of CS [16,17]. Analogously we identified 5
and 6: 6 was prepared other way and its MS spectrum
shows the peak 122 due to the loss of ethyl and CS; this
fragmentation is absent in 5.
The structure of 7 was determined by its molecular ion
(m/e=195) and by the very abundant peak at m/e=180
(M+−CH3). The first datum indicates that 7 is a
bisubstituted derivative, the second shows the presence
of methylthio group: so the reaction leaded to substitu-
tion of two annular hydrogens by two methyl groups.
We can easily exclude that these two methyls are both
in ortho to the amino or to the thiomethyl group,
because these substituents are not able to coordinate
more than one metal atom at time (the first lithiation
diminishing the effectiveness of these groups) [21]. It is
also reasonable to exclude the possibility of two methyls
in ortho one each other: this product should derive by a

268
M.G. Cabiddu et al. / Journal of Organometallic Chemistry 620 (2001) 263–275
14 was distinguished from its isomer 13 because in 14
the loss of ethyl is greater than the loss of ethylene: this
happens when the alkylthio group has a methyl in the
leads for 19 to an ion stabilized by inductive effect by
the ortho methyl, while a such stabilization is impossi-
ble for 20.
ortho
position
(compare
MS
spectra
of
Compounds 22 and 23 bear a methyl in ortho to the
ethylthio group because the fragment 166 (M+−C2H5)
is more abundant than 167 (M+−C2H4) [12,20]. In the
compound 21 the peak 167 is more abundant than 166.
We assigned to the compound 22 the structure with the
methyl in ortho to the amino group by the occurrence
of the peak 180 (M+−CH3) that is absent in 23
(Scheme 6): this in analogy with the MS spectra of
N,N-dimethyltoluidines that show a greater loss of
methyl for the ortho isomer.
(ethylthio)methylbenzenes [23] and [12]). The product
15 was identified by the presence of the peak 153 due to
the loss of an isopropyl group from the SR. If the
isopropyl group would be bonded to the N we should
observe a high peak due to the loss of methyl.
For what concerns the products derived from isomer
1c we identified the compound 17 by the peaks 153 and
152 revealing the ethylthio moiety. It is noteworthy the
abundance of the peak 148 (M+−SH) that is present
in all compounds containing the ethylthio group. This
fragmentation is favoured by the alkylated amino
group in meta to the SC2H5 [17]. Compound 18 was
distinguished from 19 and 20 by the higher intensity of
the peak 166 (M+−CH3): this is due to the greater
steric hindrance; moreover it is useful the comparison
with the MS spectra of 2-methyl(methylthio)benzene
and N,N,2-trimethylaniline which show a peak (M+−
CH3) greater than their isomers. Compound 19 was
distinguished from 20 by the greater intensity of the
peak 150 (M+−CH3–CH4) whose relative intensity
were 22.1 and 9.6, respectively: this can be explained by
a primary loss of methyl from the methylthio group
followed by elimination of CH4 between N(CH3)2 and
the methyl in ortho to this group [23].
3. Experimental
3.1. General
1H-NMR spectra were recorded on a Varian VXR-
300 spectrometer with tetramethylsilane as internal ref-
erence. IR spectra were recorded on a Perkin–Elmer
1310 grating spectrophotometer. The GC-MS analyses
were performed with a Hewlett Packard 5989A GC-MS
system with HP 5890 GC fitted with a capillary column
(50 m×0.2 mm) packed with DH 50.2 Petrocol (0.50 m
film thickness). All flash chromatography was on silica
G60 (Merck) columns. Microanalyses were carried out
with a Carlo Erba 1106 elemental analyser. Melting
points were obtained on a Kofler hot stage microscope
and are uncorrected.
The peak 120, due to the loss of methyl and CH2S, is
more abundant in 19 than in 20: this fragmentation
Commercially available reagent-grade starting mate-
rials and solvents were used. Solutions of butyllithium
in hexane and tert-butyllithium in pentane were ob-
tained from Aldrich Chemical Company and were
analysed by the Gilman double titration method before
use [21]. 1-(Methylthio)-2-(methylthio) and 3-
(methylthio)aniline were purchased (Aldrich).
Fig. 1.
3.2. Starting materials
3.2.1. N,N-Dimethyl-4-(methylthio)aniline (1a)
A solution of 4-(methylthio)aniline (72 mmol) in dry
tetrahydrofuran (100 ml) was blanketed with dry argon
and then treated dropwise at −10°C with a 1.2 M
solution of butyllithium in hexane (79 mmol). When the
addition was complete the mixture was stirred for ca.
30% at 20°C, cooled at −10°C and then treated with
iodomethane (79 mmol). The resulting solution was
successively treated dropwise with a 1.2 M solution of
butyllithium in hexane (79 mmol) and with
iodomethane (79 mmol). The mixture was then kept 12
h at the same temperature with stirring, then poured
into water (250 ml) and the pH adjusted to 5–6 by
addition of 5% hydrochloric acid. The organic layer
was separated, the aqueous layer extracted with diethyl
Scheme 5.

M.G. Cabiddu et al. / Journal of Organometallic Chemistry 620 (2001) 263–275
269
chromatography with light petroleum as eluent. Yield
79%. Pale yellow oil; b.p. 115–117/1.5 mmHg; 1H-
NMR (CDCl3) l: 2.03 (s, 3H, Ar–CH3), 2, 51 (s, 3H
SCH3), 2.97 (s, 6H, NCH3), 6.35 (m, 2H, H-3 and H-5),
7.70 (m, 1H, H-6);13C-NMR (CDCl3) l: 15.95, 21.5,
39.91, 114.09, 115.08, 130.01, 130.63, 142.02, 148.03.
EI-MS: m/e=181 (93.5%, M+), 166 (100%, M+−
CH3), 151 (11.3%, M+−CH3–CH3), 150 (16.7%, M+
−CH3–CH4), 122 (19.3%, M+−CH3–CS), 121
(22.2%, M+−CH3–CS–H), 120 (11.6%, M+−CH3–
CS–2H), 91 (12.9%, C7H+7 ), 65 (4.8%, C5H5+), 45
(5.9%, CHS+). This compound was also identified by
comparison with an authentic sample [25].
Scheme 6.
ether, and the combined organic solutions were dried
(Na2SO4) and concentrated. Yield 78%. Pale yellow oil;
1
b.p. 80–82°C/0.3 mmHg; H-NMR (CDCl3): l 2.30 (s,
3H, SCH3), 2.83 (s, 6H, NCH3), 6.56 (d, 2H, H-2 and
H-6), 7.16 (d, 2H, H-3 and, H-5). 13C-NMR (CDCl3): l
17.51, 41.83, 116.57, 130.15,140.43, 150.07. EI-MS: m/
e=167 (M+, 67.2), 152 (M+−CH3, 100.0), 136 (M+
−CH3–CH4, 14.7), 108 (C6H4S+, 10.1), 77 (C6H5+,
6.5), 65 (C5H+5 , 6.8). This compound was also identified
by comparison with an authentic sample [22].
3.3.2. 4-(Ethylthio)-N,N,3-trimethylaniline (6)
A suspension of 4-nitro-2-methylaniline (33 mmol),
water (60 ml) and concentrated hydrochloric acid (80
ml) was diazotized at 0–5°C with an aqueous solution
of sodium nitrite (36 mmol). The resulting mixture was
added on a solution of potassium ethyl xanthogenate
(69 mmol) in ethanol (30 ml) keeping the reaction at
70–80°C. When the addition was complete the mixture
was stirred for ca.1 h at the same temperature. The
organic layer was separated, the aqueous layer ex-
tracted with diethyl ether, and the combined organic
solutions were concentrated. The residue was refluxed 6
h with a solution of potassium hydroxide (118 mmol) in
ethanol (20 ml) and then treated with diethylsulphate
(33 mmol). When the addition was complete, the mix-
ture was refluxed for ca. 1 h, cooled and poured into
water (200 ml). The organic layer was separated, the
aqueous layer extracted with diethyl ether, and the
combined organic solutions were dried (Na2SO4) and
concentrated. The crude 1-(ethylthio)-2-methyl-4-ni-
trobenzene (25 mmol) was reduced, according to the
literature method [26], to 3-methyl-4-(ethylthio)aniline
using iron (141 mmol), hydrochloric acid (2 ml) and
water (6 ml). The crude product was then methylated
following the method used to prepare 1a. The resulting
6 was purified by flash-chromatography with light
petroleum as eluent. The overall yield was 41%. Pale
yellow viscous oil; b.p. 131–133/2 mmHg; 1H-NMR
(CDCl3) l: 1.25 (t, 3H, SCH2CH3), 2.10 (s, 3H,
ArCH3), 2.65, (q, 2H, SCH2CH3), 2.93 (s, 6H, NCH3),
6.29 (m, 2H, H-2 and H-6), 7.81 (m, 1H, H-5); 13C-
NMR (CDCl3) l: 13.99, 20.85, 28.02, 39.53, 114.85,
115.61, 129.41, 130.03, 141.98, 147.93. EI-MS: m/e=
195 (67.7%, M+), 166 (100%, M+−C2H5), 151 (10.1%,
M+−C2H5–CH3), 150 (13.6%, M+−C2H5–CH4), 134
(4.8%, M+−SC2H5), 122 (16.1%, M+−C2H5–CS),
121 (17.7%, M+−C2H5–CS–H), 120 (9.7%, M+−
C2H5–CS–2H), 91 (7.0%, C7H+7 ), 77 (6.4%, C6H5+), 45
(9.6%, CHS+). Elemental analysis. Found: C, 67.55; H,
8.69; N, 7.11; S, 16.25. C11H17NS (195.3). Calc.: C,
67.65; H, 8.78; N, 7.18; S, 16.39%.
3.2.2. N,N-Dimethyl-2-(methylthio)aniline (1b)
Obtained as above described starting from 2-
(methylthio)aniline. Yield 82%. Pale yellow oil; b.p.
1
91–93°C/0.3 mmHg; H-NMR (CDCl3) l: 2.20 (s, 3H,
SCH3), 2.52 (s, 6H, NCH3), 6.87 (m, 4H, Ar–H);
13C-NMR (CDCl3) l: 17.54, 42.03, 112.61, 114.56,
122.02, 123.98, 131.03, 141.55. EI-MS: m/e=167
(100%, M+), 166 (8.6%, M+−H), 152 (51.7%, M+−
CH3), 151 (20.7%, M+−CH4), 150 (32.7%, M+−
CH4–H), 137 (37.9%, M+−C2H6), 136 (31.0%,
M+−C2H6–H), 134 (24.1%, M+−SH), 118 (20.0%,
M+−CH3–H2S), 109 (19%, C6H5S+), 91 (20.7%,
C7H+7 ), 77 (13.7%, C6H5+), 65 (10.6%, C5H+5 ). This
compound was also identified by comparison with an
authentic sample [23].
3.2.3. N,N-Dimethyl-3-(methylthio)aniline (1c)
Obtained as above described starting from 3-
(methylthio)aniline. Yield 76%. Pale yellow oil; b.p.
1
86–88°C/0.3 mmHg; H-NMR (CDCl3) l: 2.36 (s, 3H,
SCH3), 2.82 (s, 6H, NCH3), 6.65 (m, 4H, Ar–H);
13C-NMR (CDCl3) l: 16.05, 41.81, 114. 54, 119.20,
126.01, 140.02, 141.74, 151.04. EI-MS: m/e=167
(100%, M+), 166 (68.8%, M+−H), 151 (21.3%, M+−
H–CH3), 134 (26.2%, M+−SH), 108 (13.1%, C6H4S+
), 91 (6.5%, C7H7+), 77 (6.9%, C6H+5 ), 65 (7.1%, C5H+5 ).
This compound was also identified by comparison with
an authentic sample [24].
3.3. Authentic samples
N,N-Dimethyl-2-(ethylthio)aniline (10) was prepared
by a published method [23].
3.3.1. 4-(Methylthio)-N,N,3-trimethylaniline (4)
This product was prepared starting from 3-methyl-4-
(methylthio)aniline [25] following the method used to
prepare 1a. The crude product was purified by flash-

270
M.G. Cabiddu et al. / Journal of Organometallic Chemistry 620 (2001) 263–275
3.4. Metallation of 1a
When the reaction was performed with four molar
equivalents of organolithium, injected in two times, the
GC/MS (see Table 1) exhibited five products (2, 3, 4, 5
and 6) in the ratio of 30:9:13:34:14. The remaining
starting material was 10%.
3.4.1. Method A
A 1.2 M solution of butyllithium in hexane (20 mmol)
was gradually added under argon at 20°C to a vigor-
ously stirred solution of 1a (18 mmol) and hexane (15
ml). The resulting mixture was then warmed to reflux
for 1 h. After cooling to room temperature iodomethane
(20 mmol) was added. The mixture was then kept 12 h
with stirring at the same temperature, then poured into
water (100 ml) and the pH was adjusted to 5–6 by
addition of 5% hydrochloric acid. The organic layer was
separated, the aqueous layer extracted with diethyl
ether, and the combined organic solutions were dried
(Na2SO4) and analysed. The GC/MS analyses (see Table
1) exhibited only the starting material.
When the reaction was performed at 0°C pouring 1a
onto four equivalents of butyllithium, the GC/MS (see
Table 1) exhibited six products (2, 3, 4, 5, 6 and 7) in the
ratio of 18:11:14:27:17:13. The remaining starting mate-
rial was 22%.
5. EI-MS: m/e=195 (61.2%, M+), 194 (4.8%, M+−
H), 180 (6.4%, M+−CH3), 166 (100%, M+−C2H5),
151 (7.1%, M+−C2H5–CH3), 150 (12.6%, M+−
C2H5–CH4), 118 (4.2%, M+−SC2H5–CH4), 77 (6.4%,
C6H+5 ), 65 (4.1%, C7H7+), 45 (7.7%, CHS+).
6. EI-MS: m/e=195 (67.7%, M+), 166 (100%, M+−
C2H5), 151 (10.1%, M+−C2H5–CH3), 150 (13.6%, M+
−C2H5–CH4), 134 (4.8%, M+−SC2H5), 122 (16.1%,
M+−C2H5–CS), 121 (17.7%, M+−C2H5–CS–H),
120 (9.7%, M+−C2H5–CS–2H), 91 (7.0%, C7H+7 ), 77
(6.4%, C6H+5 ), 45 (9.6%, CHS+).
3.4.2. Method B
A 1.2 M solution of butyllithium in hexane (20 mmol)
was gradually added under argon at 20°C to a vigor-
ously stirred solution of 1a (18 mmol), anhydrous
TMEDA (20 mmol) and hexane (15 ml). The resulting
mixture was then warmed to 40°C and kept at this
temperature for 1 h. After cooling to room temperature
iodomethane (20 mmol) was added. The mixture was
then worked up in the same manner above described.
The GC/MS analyses (see Table 1) exhibited three
products 2, 3 and 4 in the ratio of 45:37:18. The starting
material remaining was 67%.
7. EI-MS: m/e=195 (93.5%, M+), 194 (9.5%, M+−
H), 180 (100%, M+−CH3), 165 (22.6%, M+−CH3–
CH3), 164 (16.1%, M+−CH3–CH4), 135 (9.3%,
M+−CH3–CHS), 121 (9.7%, M+−CH3–CS–CH3),
91 (11.3%, C7H+7 ), 77 (8.4%, C6H+5 ), 65 (6.7%, C5H+5 ),
45 (7.1%, CHS+).
3.4.3. Method C
2. EI-MS: m/e=181 (91.9%, M+), 180 (16.4%, M+
−H), 166 (100%, M+−CH3), 151 (12.9%, M+−
CH3–CH3), 150 (22.6%, M+−CH3–CH4), 118 (6.4%,
M+−SCH3–CH4), 91 (8.4%, C7H7+), 77 (6.7%, C6H+5 ),
65 (6.4%, C5H+5 ), 45 (10.1%, CHS+).
To a vigorously stirred solution of 1a (18 mmol) and
anhydrous tetrahydrofuran (30 ml) cooled to 0°C, a 1.5
M solution of tert-butyllithium in pentane (22 mmol)
was gradually added under argon. When the addition
was complete the mixture was stirred for ca. 2 h at room
temperature and then treated with iodomethane (22
mmol) at 0°C. The resulting solution was then worked
up in the same manner above described. The GC/MS
analyses (see Table 1) exhibited only the product 3 in
37% yield. The remaining starting material was 63%.
If the reaction was performed with 2 molar equiva-
lents of organolithium we obtained 3 in 54% yield. The
remaining starting material was 46%.
3. EI-MS: m/e=181 (54.8%, M+), 166 (2.4%, M+−
CH3), 153 (5.2%, M+−C2H4), 152 (100%, M+−
C2H5), 136 (9.7%, M+−C2H5–CH4), 109 (4.8%,
M+−C2H5–CH2=N–CH3), 108 (6.4%, M+−C2H5–
CS), 91 (2.3%, C7H7+), 77 (3.1%, C6H5+), 65 (3.8%,
C5H+5 ), 45 (2.5%, CHS+).
4. EI-MS: m/e=181 (93.5%, M+), 166 (100%, M+−
CH3), 151 (11.3%, M+−CH3–CH3), 150 (16.7%, M+
−CH3–CH4), 122 (19.3%, M+−CH3–CS), 121
(22.2%, M+−CH3–CS–H), 120 (11.6%, M+−CH3–
CS–2H), 91 (12.9%, C7H+7 ), 65 (4.8%, C5H+5 ), 45 (5.9%,
CHS+).
From the reaction mixture 4-(ethylthio)-N,N-di-
methylaniline (3) was isolated by distillation. Yield 51%;
b.p. 139–141/4 mmHg. This product was identified by
comparison with an authentic sample.
If the reaction was performed using two molar equiv-
alents of butyllithium, the GC/MS (see Table 1) exhib-
ited six products (2, 3, 4, 5, 6 and 7) in the ratio of
31:14:10:28:14:3. The remaining starting material was
13%.
If the reaction was performed using two molar equiv-
alents of butyllithium, injecting 1 mole and after 15 min
the 2nd mole, the GC/MS (see Table 1) exhibited five
products (2, 3, 4, 5 and 6) in the ratio of 27:13:22:22:16.
The remaining starting material was 18%.
3.4.4. Method D
A 1.2 M solution of butyllithium in hexane (7.2
mmol), was cooled to −40°C under argon and a
solution of 1a (6 mmol) in hexane (5 ml) was added.
Finely powdered potassium tert-butoxide (7.2 mmol)
was added. The mixture was kept for 1 h at −20°C,
then an excess of iodomethane (8.4 mmol) was slowly
added, the cooling bath removed and the reaction
completed by stirring overnight at room temperature.

M.G. Cabiddu et al. / Journal of Organometallic Chemistry 620 (2001) 263–275
271
The resulting solution was then worked up in the same
manner above described. The GC/MS analyses (see
Table 1) exhibited only the product 3 (44%). The
remaining starting material was 56%.
When 2 molar equivalents of superbase were used,
the reaction mixture exhibited four products (3, 4, 5
and 6) in the ratio 21:15:7:57. The remaining starting
material was 13%.
When 3 molar equivalents of superbase were used,
the reaction mixture exhibited four products (3, 5, 6
and 8) in the ratio of 17:6:65:12. The remaining starting
material was 4%.
stituted 13 and 14 in the ratio of 72:19:1:5:3. The
remaining starting material was 25%.
10. EI-MS: m/e=181 (M+, 100.0), 166 (42%, M+−
CH3), 165 (15.5%, M+−CH4), 164 (24.5%, M+−
CH4–H), 151 (49%, M+−C2H6), 150 (50.2%,
M+−CH3–CH4), 148 (41.6%, M+−SH), 134 (9.8%,
M+−SCH3), 132 (11.2%, M+−CH3–H2S), 118
(8.7%, M+−SCH3–CH4), 105 (10.8%, C7H7N+), 91
(16%, C7H+7 ), 77 (11.7%, C6H+5 ), 65 (11%, C5H+5 ).
11. EI-MS: m/e=181 (100%, M+), 166 (4.4%, M+
−CH4), 153 (37.3%, M+−C2H4), 152 (33.3%, M+−
C2H5), 150 (25.3%, M+−C2H6–H), 148 (38.8%,
M+−SH), 137 (49.9%, M+−C2H4–CH4), 136 (50%,
M+−C2H5–CH4), 120 (25.1%, M+−SC2H5), 109
(22.5%, C6H5S+), 91 (18.1%, C7H+7 ), 77 (13.7%, C6H5+
), 65 (15.5%, C5H+5 ).
8. EI-MS: m/e=195 (79%, M+), 153 (55.5%, M+−
C3H6), 152 (100%, M+−C3H7), 136 (12.2%, M+−
C3H7–CH4), 120 (15.9%, M+−SC3H7), 109 (4.5%,
C6H5S+), 108 (6%, C6H4S+), 77 (1.8%, C6H+5 ), 65
(5.4%, C5H+5 ), 43 (5.7%, C3H7+), 42 (8.6%, C3H+6 ).
From the reaction mixture the major component,
4–(ethylthio)-N,N,3-trimethylaniline (6), was isolated
by distillation. Yield 57%; b.p. 143–144°C/4 mmHg.
This product was identified by comparison with an
authentic sample.
12. EI-MS: m/e=181 (100%, M+), 180 (14.6%, M+
−H), 166 (33.3%, M+−CH3), 165 (26.2%, M+−
CH4), 164 (29.9%, M+−CH4–H), 151 (44.8%,
M+−CH3–CH3), 150 (56.3%, M+−CH3–CH4), 148
(24.9%, M+−SH), 132 (15.8%, M+−CH3–H2S), 118
(11.7%, M+−SCH3–CH4), 104 (9.6%, C7H6N+), 91
(14.6%, C7H+7 ), 77 (13.5%, C6H+5 ), 65 (13%, C5H+5 ).
13. EI-MS: m/e=195 (100%, M+), 180 (3.6%, M+
−CH3), 167 (61.4%, M+−C2H4), 166 (32.6%, M+−
C2H5), 164 (26.3%, M+−C2H6–H), 162 (42.9%,
M+−SH), 151 (83.1%, M+−C2H4–CH4), 150 (85.7%,
M+−C2H4–CH4–H), 134 (35.7%, M+−SC2H5), 120
(31.9%, C8H10N+), 105 (13.1%, C7H7N+), 91 (22.1%,
C7H+7 ), 77 (18.9%, C6H5+), 65 (14.4%, C5H+5 ).
3.4.5. Reaction of monometallated 1a with carbon diox-
ide: [4-(dimethylamino)phenylthio]acetic acid (9)
The mixture derived by metallation of 1a, obtained
as described above (Method C, Section 3.4.3) was
poured onto ca. 100 g of crushed solid carbon dioxide.
After 24 h the residue was treated with 10% aqueous
sodium bicarbonate and then with diethyl ether. The
alkali layer was separated, washed with diethyl ether,
and then acidified with cold concentrated hydrochloric
acid, extracted with chloroform, dried (Na2SO4) and
concentrated. The crude product was crystallized from
benzene. Yield 58%; m.p. 84–86°C [13]; IR (CCl4):
14. EI-MS: m/e=195 (100%, M+), 194 (1.1%, M+
−H), 180 (9.9%, M+−CH3), 167 (15.6%, M+−
C2H4), 166 (31.8%, M+−C2H5), 165 (21.9%,
M+−C2H6), 164 (35.8%, M+−C2H6–H), 162 (51.2%,
M+−SH), 151 (68%, M+−C2H4–CH4), 150 (72.8%,
M+−C2H4–CH4–H), 134 (13.3%, M+−SC2H5), 132
(17%, M+−CH3–H2S), 120 (18.8%, C8H10N+), 104
(44.1%, C7H6N+), 91 (16.4%, C7H+7 ), 77 (18.6%, C6H5+
), 65 (17.2%, C5H+5 ).
1
3160 (OH), 1710 cm−1 (CꢀO); H-NMR (CDCl3) l:
2.88 (s, 6H, NCH3), 3.45 (s, 2H, SCH2), 6.35 (d, 2H,
Ar–H), 6.61 (d, 2H, Ar–H), 9.20 (s, 1H, OH); 13C-
NMR (CDCl3) l: 32.57, 42.35, 118.18, 129.06, 140.04,
1502.27, 171.08. EI-MS: m/e=211 (9.5%, M+), 196
(2.3%, M+−CH3), 169 (24.9%, M+−C2H4N), 152
(31.8%, M+−CH2CO2H), 108 (8.1%, C5H4N(CH3)+2 ),
106 (9.1%, C6H5NCH+3 ), 83 (24.1%, C4H3S+), 71
(31.8%, C3H3S+), 59 (100%, C2H3O+2 ), 58 (47.7%,
C2H2O+2 ), 57 (48.1%, C2HO+2 ).
3.5.2. Method B
Using one molar equivalent of 1.5 M solution of
tert-butyllithium in pentane, the reaction mixture
showed only the product 10 (44%). The remaining
starting material was 56%.
3.5.3. Method C
3.5. Metallation of 1b
Using 1 molar equivalent of superbase we obtained
only the product 10 (81%). The remaining starting
material was 19%.
3.5.1. Method A
Using one molar equivalent of 1.2 M solution of
butyllithium in hexane, we obtained a 18% of 1b and a
82% of the monometallated product 10. When we used
two molar equivalents of the same reagent injecting 1
mole and then the 2nd after 15 s, we obtained three
monosubstituted products 10, 11 and 12 and two disub-
When we used two molar equivalents of the same
reagent we obtained 10 in 89% yield. The remaining
starting material was 11%. From the reaction mixture
this product was isolated by distillation. Yield 78%; b.p.
112–114°C/1 mmHg. This product was identified by
comparison with an authentic sample.

272
M.G. Cabiddu et al. / Journal of Organometallic Chemistry 620 (2001) 263–275
The reaction with three molar equivalents of super-
(9.5%, C6H+5 ), 65 (10.1%, C5H+5 ). Elemental analysis.
Found: C, 66.17; H, 8.28; N, 7.65; S, 17.51. C10H15NS
(181.3). Calc.: C, 66.25; H, 8.34; N, 7.73; S, 17.69%.
Using four molar equivalents of the same reagent we
obtained a 66% of 17 and two bisubstituted products 21
and 22 in the ratio of 47:53. The remaining starting
material was 19%.
When 4 equivalents were injected in the reaction flask
in two times (2 equivalents+2 equivalents) we revealed
four monosubstituted products 17, 18, 19 and 20 and
three bisubstituted 21, 22 and 23 in the ratio of
45:6:4:6:16:11:12. The remaining starting material was
18%.
base leaded to a 50% of 10 and a mixture of three
bisubstituted products 13, 14 and 15 in the ratio of
9:54:37. The remaining starting material was 7%.
14. EI-MS: m/e=195 (100%, M+), 162 (17.1%, M+
−SH), 153 (76.1%, M+−C3H6), 152 (46.5%, M+−
C3H7), 138 (38.3%, M+−C3H6–CH3), 137 (69.1%,
M+−C3H6–CH4), 136 (60.9%, M+−C3H7–CH4), 120
(46.1%, M+−SC3H7), 109 (25%, C6H5S+), 91 (16.7%,
C7H+7 ), 77 (14.5%, C6H5+), 65 (16.3%, C5H+5 ), 44
(36.8%, C3H+8 ), 42 (20.9%, C3H+6 ).
3.5.4. Reaction of monometallated 1b with carbon
dioxide: [2-(dimethylamino)phenylthio]acetic acid (16)
The monometallated mixture of 1b, obtained as de-
scribed above (Method C, Section 3.5.3) by reaction
with 2 molar equivalents of superbase was poured onto
ca. 100 g of crushed solid carbon dioxide and worked
up in the same manner above described. Yield 87%.
Viscous yellow oil; IR (neat): 3160 (OH), 1710 cm−1
18. EI-MS: m/e=181 (100%, M+), 166 (87.8%, M+
−CH3), 151 (16%, M+−CH3–CH3), 150 (21.1%, M+
−CH3–CH4), 132 (5.2%, M+−CH3–H2S), 121 (7.1%,
M+−CH3–CS–H), 118 (9.5%, M+−SCH3–CH4),
117 (9.3%, M+−SCH3–CH4–H), 91 (11.8%, C7H+7 ),
77 (9%, C6H+5 ), 65 (5.4%, C5H+5 ).
19. EI-MS: m/e=181 (100%, M+), 166 (42.7%, M+
−CH3), 153 (10.5%, M+−C2H4), 150 (22.1%, M+−
CH3–CH4), 148 (16%, M+−SH), 132 (9.5%,
M+−CH3–H2S), 122 (16.4%, M+−CH3–CS), 120
(22.7%, M+−CH3–CH2S), 118 (12.9%, M+−SCH3–
CH4), 117 (15.7%, C8H7N+), 104 (9.9%, C7H6N+), 91
(12.3%, C7H+7 ), 77 (12.1%, C6H+5 ), 65 (8.5%, C5H+5 ).
20. EI-MS: m/e=181 (100%, M+), 166 (36.9%, M+
−CH3), 165 (13.2%, M+−CH4), 153 (13.8%, M+−
C2H4), 152 (16.4%, M+−C2H4–H), 150 (9.6%,
M+−CH3–CH4), 148 (14.7%, M+−SH), 134 (17.1%,
M+−SCH3), 122 (9.8%, M+−CH3–CS), 120 (4.7%,
M+−CH3–CH2S), 118 (9.7%, M+−CH3–CH4), 109
(4.1%, C6H4S+), 91 (12%, C7H7+), 77 (8.9%, C6H+5 ), 65
(7.6%, C5H+5 ).
1
(CꢀO); H-NMR (CDCl3) l: 2.90 (s, 6H, NCH3), 3.63
(s, 2H, S CH2), 7.40 (m, 4H, Ar–H), 10.26 (s, 1H,
OH); 13C-NMR (CDCl3) l: 36.29, 43.05, 11.03, 119,61,
126.04, 129.83, 141.33, 174.05. EI-MS: m/e=211
(90.9%, M+), 193 (52.3%, M+−H2O), 178 (6.1%, M+
−H2O–CH3), 167 (7.3%, M+−CO2), 166 (7.4%, M+
−CO2H), 152 (50.9%, M+−CH2CO2H), 151 (30.7%,
M+−CH3CO2H), 150 (80.1%, M+−CH3CO2H–H),
137 (99.8%, M+−CO2–CH3–CH3), 136 (100%, M+−
CO2–C2H6–H), 132 (50.3%, M+−CO2H–H2S), 121
(26.7%, M+−SCHCO2H), 120 (29.7%, M+−
SCH2CO2H), 118 (24.3%, M+−SCH2CO2H–2H), 109
(40.5%, C6H5S+), 104 (14.8%, C7H6N+), 91 (28.4%,
C7H+7 ), 77 (27.2%, C6H5+), 65 (23.3%, C2H+5 ). Elemen-
tal analysis. Found: C, 56.78; H, 6.14; N, 6.59; S, 15.05.
C10H13NO2S (211.3). Calc.: C, 56.85; H, 6.20; N, 6.63;
S, 15.17%.
21. EI-MS: m/e=195 (100%, M+), 180 (79.9%, M+
−CH3), 167 (14.2%, M+−C2H4), 166 (11.6%, M+−
C2H5), 165 (11.6%, M+−C2H6), 164 (12.6%,
M+−C2H6–H), 162 (6.6%, M+−SH), 152 (16.9%,
M+−C2H4–CH3), 151 (18.5%, M+−C2H4–CH4), 136
(7.9%, M+−CH3–CS), 123 (7.8%, M+−C2H4–CS),
91 (7.8%, C7H+7 ), 77 (10.4%, C6H+5 ), 65 (4.8%, C5H+5 ).
22. EI-MS: m/e=195 (100%, M+), 180 (15%, M+−
CH3), 167 (11.3%, M+−C2H4), 166 (25.5%, M+−
C2H5), 162 (37.6%, M+−SH), 152 (9.6%,
M+−C2H4–CH3), 151 (9.3%, M+−C2H4–CH4), 150
(11.4%, M+−C2H4–CH4–H), 135 (21.9%, M+−
CH3–CHS), 134 (24.2%, M+−SC2H5), 118 (17%, M+
−SC2H5–CH4), 117 (15.5%, M+−SC2H5–CH4–H),
104 (4.3%, C7H6N+), 91 (10.8%, C7H+7 ), 77 (12.2%,
C6H+5 ), 65 (6.7%, C5H+5 ).
3.6. Metallation of 1c
3.6.1. Method A
The reaction of 1c with one molar equivalent of 1.2
M solution of butyllithium in hexane at reflux tempera-
ture leaded to the monometallated product 17 in a 67%
yield beside a 33% of starting compound 1c. From the
reaction mixture this product was isolated by distilla-
tion. Yield 56%. Pale yellow oil; b.p. 107–108°C/1
1
mmHg; H-NMR (CDCl3) l: 1.19 (t, 3H, SCH2CH3),
2.68 (q, 2H, SCH2CH3), 2.97 (s, 6H, NCH3), 6.55 (m,
2H, Ar–H), 6.95 (m, 2H, Ar–H); 13C-NMR (CDCl3)
l: 14.65, 28.33, 40.81, 116.10, 118.35, 131.63, 138.99,
150.01. EI-MS: m/e=181 (100%, M+), 180 (25.8%,
M+−H), 153 (70.9%, M+−C2H4), 152 (54.8%, M+
−C2H5), 151 (16.1%, M+−C2H5–H), 148 (29%, M+
−SH), 120 (12.9%, M+−SC2H5), 109 (16.1%,
C6H5S+), 108 (19.3%, C6H4S+), 91 (6.1%, C7H+7 ), 77
23. EI-MS: m/e=195 (100%, M+), 167 (33.7%, M+
−C2H4), 166 (72.4%, M+−C2H5), 162 (16%, M+−
SH), 150 (11.5%, M+−C2H4–CH4–H), 134 (26.8%,
M+−SC2H5), 122 (16.1%, M+−C2H5–CS), 121
(9.2%, M+−C2H5–CHS), 106 (4.4%, C7H8N+), 91
(9.9%, C7H+7 ), 77 (8.9%, C6H5+), 65 (5.9%, C5H+5 ).

M.G. Cabiddu et al. / Journal of Organometallic Chemistry 620 (2001) 263–275
273
3.6.2. Method B
was kept for ca. 30 min at 20°C and treated successively
dropwise at −40°C with 1.2 M solution of butyl-
lithium in hexane (15 mmol). Finely powdered potas-
sium tert-butoxide (15 mmol) was added. The mixture
was kept for 1 h at −20°C, then an excess of bromo-
propane was slowly added, the cooling bath removed
and the reaction completed by stirring overnight at
room temperature and worked up in the same manner
above described. Yield 57%. Pale yellow oil; b.p. 132–
135°C/10 mmHg; 1H-NMR (CDCl3) l: 0.89 (t, 3H,
SCH2CH2CH2CH3 or NCH2CH3), 0.94 (t, 3H,
SCH2CH2CH2CH3 or NCH2CH3), 1.50 (m, 2H,
SCH2CH2CH2), 1.69 (m, 2H, SCH2CH2), 2.74 (s, 3H,
NCH3), 2.88 (q, 2H, SCH2), 2.98 (q, 2H, NCH2), 7.05
(m, 4H, Ar–H); 13C-NMR (CDCl3) l: 12.15 13.75,
22.53, 29.98, 32.99, 40.16, 43. 22, 112.37, 115.13, 122.05
123.98, 130.17, 141.63. EI-MS: m/e=223 (39.1%, M+),
208 (100%, M+−CH3), 167 (8.3%, M+−C4H8), 152
(41.5%, M+−CH3–C4H8), 151 (75.4%, M+−CH3–
C4H8–H), 150 (69.7%, M+−CH3–C4H8–2H), 137
(18.8%, C7H7NS+), 136 (20.5%, C7H6NS+), 77 (13.4%,
C6H+5 ). Elemental analysis. Found: C, 69.81; H, 9.41;
N, 6.20; S, 14.22. C13H21NS (223.4). Calcd.: C, 69.90;
H, 9.48; N, 6.27; S, 14.35%.
Using 1 molar equivalent of 1.5 M solution of tert-
butyllithium in pentane, we obtained only the product
17 (46%) The remaining starting material was 54%.
3.6.3. Method C
Using one molar equivalent of superbase we obtained
only the product 17 (34%). The remaining starting
material was a 66%.
When we used 3 molar equivalents of superbase we
revealed a 65% of 17 and two bisubstituted products 23
and 24 in the ratio of 52:48. The remaining starting
material was a 12%.
24. EI-MS: m/e=195 (71.4%, M+), 162 (17.6%,
M+−SH), 153 (89.9%, M+−C3H6), 152 (100%, M+
−C3H7,), 136 (6.7%, M+−C3H7–CH4), 120 (8.2%,
M+−SC3H7), 109 (12.5%, C6H5S+), 108 (13.2%,
C6H4S+), 91 (4.7%, C7H7+), 77 (6.7%, C6H+5 ), 65 (9.3%,
C5H+5 ), 43 (10%, C3H7+), 42 (16.6%, C3H+6 ).
3.6.4. Reaction of monometallated 1c with carbon
dioxide: [3-(dimethylamino)phenylthio]acetic acid (25)
The monometallated mixture of 1c, obtained as de-
scribed above (Method C, Section 3.6.3) by reaction
with 3 molar equivalents of superbase was poured onto
ca. 100 g of crushed solid carbon dioxide and worked
up in the same manner above described. Yield 71%.
Viscous yellow oil; IR (neat): 3400 (OH), 1720 cm−1
3.6.6. N,N-Dimethyl-2-(ethylthio)aniline (10)
Obtained as above described using iodomethane as
first, second and third electrophile. Yield 67%. Pale
yellow oil; b.p. 100–101°C/1.5 mmHg; 1H-NMR
(CDCl3) l: 1.34 (t, 3H, SCH2CH3), 2.73 (s, 6H, NCH3),
2.89 (q, 2H, SCH2CH3), 7.08 (m, 4H, Ar-H); 13C-NMR
(CDCl3) l: 15.97, 28.77, 41.88, 110.94, 113.31, 122.03,
124.99, 132.01, 139. 94. EI-MS: m/e=181 (M+, 100.0),
166 (42%, M+−CH3), 165 (15.5%, M+−CH4), 164
(24.5%, M+−CH4–H), 151 (49%, M+−C2H6), 150
(50.2%, M+−CH3–CH4), 148 (41.6%, M+−SH), 134
(9.8%, M+−SCH3), 132 (11.2%, M+−CH3–H2S),
118 (8.7%, M+−SCH3–CH4), 105 (10.8%, C7H7N+),
91 (16%, C7H+7 ), 77 (11.7%, C6H+5 ), 65 (11%, C5H+5 ).
This compound was also identified by comparison with
an authentic sample [23].
1
(CꢀO); H-NMR (CDCl3) l: 2.90 (s, 6H, NCH3), 3.65
(s, 2H, SCH2), 7.00 (m, 4H, Ar–H), 7.90 (s, 1H, OH);
13C-NMR (CDCl3) l: 33.75, 43.18, 114.08, 116.89,
120.16, 130.97, 141.33, 152.07, 174.21. EI–MS: m/e=
211 (100%, M+), 210 (35.6%, M+−H), 193 (12.1%,
M+−H2O), 178 (72.5%, M+−H2O–CH3), 167 (6.8%,
M+−CO2), 166 (16.3%, M+−CO2H), 152 (32.7%,
M+−CH2CO2H), 151 (37.1%, M+−CH3CO2H), 150
(25.4%, M+−CH3CO2H–H), 137 (31%, M+−CO2–
CH3–CH3), 136 (29.3%, M+−CO2–C2H6–H), 132
(11.6%, M+−CO2H–H2S), 121 (15.5%, M+−
SCHCO2H), 120 (15.7%, M+–SCH2CO2H), 109
(20.3%, C6H5S+), 108 (20%, C6H4S+), 104 (7.2%,
C7H6N+), 91 (12.4%, C7H7+), 77 (15.8%, C6H+5 ), 65
(14.2%, C6H+5 ). Elemental analysis. Found: C, 56.71;
H, 6.16; N, 6.54; S, 15.01. C10H13NO2S (211.3). Calc.:
C, 56.85; H, 6.20; N, 6.63; S, 15.17%.
3.6.7. N,N-Dimethyl-2-(propylthio)aniline (30)
Obtained as above described using iodomethane as
first and second and iodoethane as third electrophile.
Yield 60%. Pale yellow oil; b.p. 115–116°C/5 mmHg;
1H-NMR (CDCl3) l: 1.05 (t, 3H, SCH2CH3), 1.61(m,
2H, SCH2CH2CH3), 1.72 (q, 2H, SCH2CH2CH3), 2.74
(s, 6H, NCH3), 7.05 (m, 4H, Ar–H); 13C-NMR
(CDCl3) l: 14.08, 23.17, 39.53, 41.68, 112.88, 115.77,
122.67, 124.07, 132.01, 141.07. EI-MS: m/e=195
(74.2%, M+), 180 (3.2%, M+−CH3), 162 (16.1%, M+
−SH), 153 (100%, M+−C3H6), 152 (35.5%, M+−
C3H7), 151 (22.5%, M+−C3H6–2H), 150 (35.5%,
M+−C3H7–2H), 138 (32.3%, M+−C3H6–CH3), 137
(48.4%, M+−C3H6–CH4), 136 (51.6%, M+−C3H6–
3.6.5. 2-(Butylthio)-N-ethyl-N-methylaniline (29)
A solution of 26 (14 mmol) in dry hexane (20 ml) was
blanketed with argon and then treated dropwise at
−10°C with 1.2 M solution of butyllithium in hexane
(15 mmol). When the addition was complete the mix-
ture was stirred for ca. 30 min at 20°C, cooled at
−10°C and then treated with iodomethane (15 mmol).
The resulting solution was successively treated dropwise
with 1.2 M solution of butyllithium in hexane (15
mmol) and with iodoethane (15 mmol). The mixture

274
M.G. Cabiddu et al. / Journal of Organometallic Chemistry 620 (2001) 263–275
2H–CH3), 120 (32.4%, M+−SC3H7), 109 (22.6%,
C6H5S+), 77 (12.9%, C6H+5 ). Elemental analysis.
Found: C, 67.69; H, 8.72; N, 7.12; S, 16.31.
C11H17NS (195.3). Calc.: C, 67.64; H, 8.77; N, 7.17;
S, 16.42%.
(37.1%, C10H10N+), 138 (35.8%, C7H8NS+), 136
(64.5%, C7H6NS+), 130 (19.4%, C9H6N+), 109
(30.7%, C6H5S+), 94 (25.8%, C6H8N+), 77 (20.1%,
C6H+5 ). Elemental analysis. Found: C, 71.96; H, 8.27;
N, 6.06; S, 13.60. C14H19NS (233.4). Calc.: C, 72.05;
H, 8.21; N, 6.00; S, 13.74%.
3.6.8. 2-(Butylthio)-N-methyl-N-propyl-aniline (31)
A solution of 26 (14 mmol) in dry hexane (20 ml)
was blanketed with argon and then treated dropwise
at −10°C with 1.2 M solution of butyllithium in
hexane (15 mmol). When the addition was complete
the mixture was stirred for ca. 30 min at 20°C,
cooled at −10°C and then treated with iodomethane
(15 mmol). The mixture was kept for ca. 30 min at
20°C and treated successively dropwise at −40°C
with 1.2 M solution of butyllithium in hexane (30
mmol). Finely powdered potassium tert-butoxide (30
mmol) was added. The mixture was kept for 1 h at
−20°C, then an excess of bromopropane was slowly
added, the cooling bath removed and the reaction
completed by stirring overnight at room temperature
and worked up in the same manner above described.
Yield 65%. Pale yellow oil; b.p. 145–146°C/3 mmHg;
1H-NMR (CDCl3) l: 0.89 (t, 3H, NCH2CH2CH3 or
SCH2CH2CH2CH3), 0.94 (t, 3H, NCH2CH2CH3 or
SCH2CH2CH2CH3), 1.53 (m, 4H, SCH2CH2CH2 and
NCH2CH2), 1.69 (m, 2H, SCH2CH2), 2.70 (s, 3H,
NCH3), 2.87 (t, 2H, SCH2CH2), 2.90 (t, 2H,
NCH2CH2), 7.09 (m, 4H, Ar–H); 13C-NMR (CDCl3)
l: 12.57, 13.69, 21.73, 22.09, 29.97, 41.43, 55.78,
110.65, 114.77, 121.13, 123.83, 130.61, 142.17. EI-MS:
m/e=237 (37%, M+), 208 (100%, M+−C2H5), 181
(7.4%, M+−C4H8), 152 (44.4%, M+−C2H5–C4H8),
151 (74.1%, M+−C2H5–C4H8–H), 150 (70.4%, M+
−C2H5–C4H8–2H), 137 (16.7%, C7H7NS+), 136
(18.5%, C7H6NS+), 77 (11.1%, C6H+5 ). Elemental
analysis. Found: C, 70.71; H, 9.70; N, 5.84; S, 13.38.
C14H23NS (237.4). Calc.: C, 70.83; H, 9.77; N, 5.90;
S, 13.50%.
Acknowledgements
Financial support from the Ministero dell’Univer-
sita` e della Ricerca Scientifica e Tecnologica, Rome
(National Project ‘Stereoselezione in Sintesi Organica.
Metodologie ed Applicazioni’), from the University of
Cagliari and from the C.N.R. (Italy) is gratefully
acknowledged.
References
[1] M.G. Cabiddu, S. Cabiddu, E. Cadoni, S. De Montis, C. Fat-
tuoni, S. Melis, F. Sotgiu, Tetrahedron 55 (1999) 14069.
[2] V. Snieckus, Chem. Rev. 90 (1990) 879.
[3] M. Schlosser, Pure Appl. Chem. 60 (1988) 1627.
[4] M. Schlosser, J.H. Choi, S. Takagishi, Tetrahedron 46 (1990)
5633.
[5] A. Mordini, in: V. Snieckus (Ed.), Advances in Carbanion
Chemistry, Ch. 1, JAI Press, Greenwich CT, 1992.
[6] C.E. Barry, R.B. Bates, W.A. Beavers, F.A. Camou, B. Gor-
don, H.-J. Hsu, N.S. Mills, C.A. Ogle, T.J. Siahaan, K. Su-
vannachut, S.R. Taylor, J.J. White, K.M. Yager, Synlett
(1991) 207.
[7] M. Schlosser, in: R. Scheffold (Ed.), Modern Synthetic Meth-
ods, vol. 6, Verlage HCA/VCH, Basel/Weinheim, 1992, p. 227.
[8] M. Schlosser, Organometallic in Synthesis, Wiley, New York,
1994.
[9] A.M. Sapse, P.v.R. Schleyer, Lithium Chemistry, Wiley, New
York, 1995.
[10] M.G. Cabiddu, S. Cabiddu, E. Cadoni, C. Fattuoni, S. Melis,
J. Fluorine Chem. 98 (1999) 125.
[11] S. Cabiddu, C. Fattuoni, C. Floris, G. Gelli, S. Melis, Tetra-
hedron 49 (1993) 4974, and refs. cited therein.
[12] M.G. Cabiddu, S. Cabiddu, E. Cadoni, R. Corrias, C. Fat-
tuoni, C. Floris, S. Melis, J. Organomet. Chem. 531 (1997)
125.
3.6.9. N-Allyl-2-[(3-butenyl)thio]-N-methylaniline (32)
Obtained as described previously (Section 3.6.8) us-
ing iodomethane as the first and allyl bromide as the
second electrophile. Yield 42%. Pale yellow oil; b.p.
[13] S. Takagishi, G. Katsoulos, M. Schlosser, Synlett (1992) 360,
and refs. cited therein.
[14] H. Gilman, F.J. Webb, J. Am. Chem. Soc. 71 (1949) 4062.
[15] A.C. Knipe, Organic Reactions Mechanism, Wiley, New York,
1992, pp. 337–365.
1
135–136°C/1.5 mmHg; H-NMR (CDCl3) l: 2.44 (m,
2H, SCH2CH2), 2.70 (s, 3H, NCH3), 2.96 (t, 2H,
SCH2CH2), 3.56 (d, 2H, NCH2CH), 5.07 (m, 4H,
CH=CH2), 5.91 (m, 2H, CH=CH2), 7.07 (m, 3H,
Ar–H), 7.18 (m, 1H, Ar–H); 13C-NMR (CDCl3) l:
34.35, 3507, 41.25, 47.98, 112.71, 114.99, 117.63,
121.08, 122.03, 125.02, 125.74, 132.01, 139.02, 140.07.
EI-MS: m/e=233 (16.1%, M+), 204 (7.1%, M+−
CH3), 179 (29%, M+−C4H6), 178 (48.4%, M+−
C4H7), 163 (32.3%, M+−C4H6–CH4), 150 (100%,
M+−C4H7–C2H4), 146 (22.7%, M+−SC4H7), 144
[16] H. Budzikiewicz, C. Djerassi, D.H. Williams, Mass Spectrome-
try of Organic Compounds, Holden–Day Inc, London, 1967,
p. 290.
[17] J.H. Bowie, S.-O. Lawesson, J.Ø. Madson, G. Schroll, D.H.
Williams J. Chem. Soc. B (1966) 951.
[18] G.P. Crowther, R.J. Sundberg, A.M. Sarpeshkar, J. Org.
Chem. 49 (1984) 4657.
[19] S. Cabiddu, C. Fattuoni, C. Floris, G. Gelli, S. Melis, F.
Sotgiu, Tetrahedron 46 (1990) 861.
[20] Hewelett–Packard HP 59943B Wiley 1 Database, Palo Alto,
CA, 1990.

M.G. Cabiddu et al. / Journal of Organometallic Chemistry 620 (2001) 263–275
275
[21] H. Gilman, A.H. Haubein, J. Am. Chem. Soc. 66 (1944) 1515.
[22] V. Baliah, M. Uma, Tetrahedron 19 (1963) 455.
[23] Y. Ohara, K. Akiba, N. Inamoto, Bull. Chem. Soc. Jpn. 56
(1983) 1508.
[24] A. Zweig, J.E. Lehnsen, J. Am. Chem. Soc. 87 (1965) 2647.
[25] V. Baliah, V.M. Kanagasabapathy, Tetrahedron 34 (1978) 3611.
[26] A. Vogel, Textbook of Practical Organic Chemistry, Longman,
London, 1978, p. 660.
.