One-pot syntheses of 2-N-Alkylamino-, 2-N-Phenylamino-2-N,N-Dialkylamino-, and 2-N-Alkyl-N-phenylaminothiophenes

Article abstract of DOI:10.1002/(SICI)1099-0690(199802)1998:2<253::AID-EJOC253>3.0.CO;2-E

A number of 2-N-alkylamino- or 2-N-phenylamino-, 2-N,N-dialkylamino-, and 2-N-alkyl-N-phenylaminothiophenes have been prepared in good yields by adding a solution of tert-butylalcohol and potassium tert-butoxide in dimethylsulfoxide to a solution of the adduct from a lithiated 1-alkyne, RCH₂C≡CLi, or the lithiated allene, tBuCH=C=CHLi, and isothiocyanate, R′N=C=S, in tetrahydrofuran and subsequently hydrolyzing the reaction mixture or quenching it with methyl iodide.

Full text of DOI:10.1002/(SICI)1099-0690(199802)1998:2<253::AID-EJOC253>3.0.CO;2-E

FULL PAPER
One-Pot Syntheses of 2-N-Alkylamino-, 2-N-Phenylamino-2-N,N-Dialkylamino-,
and 2-N-Alkyl-N-phenylaminothiophenes
Olga A. Tarasovaa, Ludmila V. Klybaa, Vladimir Yu. Vvedenskya, Nina A. Nedolyaa, Boris A. Trofimova,
Lambert Brandsma*b, and Hermann D. Verkruijsseb
Institute of Organic Chemistry of the Russian Academy of Sciences, Siberian Brancha,
Favorsky Street 1, GUS-664033 Irkutsk, Russia
Department of Preparative Organic Chemistry, Debye Institute, Utrecht Universityb,
Padualaan 8, NL-3584 CH Utrecht, The Netherlands
E-mail: l.brandsma@chem.ruu.nl
Received August 28, 1997
Keywords: Isothiocyanates / Acetylenes / Allenes / Cyclization / Thiophenes
A number of 2-N-alkylamino- or 2-N-phenylamino-, 2-N,N-
dialkylamino-, and 2-N-alkyl-N-phenylaminothiophenes isothiocyanate, RЈN=C=S, in tetrahydrofuran and subse-
have been prepared in good yields by adding a solution of quently hydrolyzing the reaction mixture or quenching it
RCH2CϵCLi, or the lithiated allene, tBuCH=C=CHLi, and
tert-butylalcohol and potassium tert-butoxide in dimethylsu- with methyl iodide.
lfoxide to a solution of the adduct from a lithiated 1-alkyne,
Introduction
Scheme 1
For simple thiophene derivatives having an amino sub-
stituent NRRЈ (Rand RЈ ϭ H, alkyl or aryl) at the 2-posi-
tion only a few efficient synthetic methods have been de-
scribed. About ten years ago we reported in a short paper[1]
the synthesis of 5-substituted 2-N,N-dialkylaminothiophe-
nes from metallated allenic amines or metallated 1-propyn-
ylamines [H2CϭCϭC(M)NR2] with thiocarbonyl com-
pounds such as tert-BuC(ϭS)SCH3 and (C2H5)2NC(ϭS)-
SCH3. A number of 2-N,N-dialkylaminothiophenes have
been obtained by heating the corresponding thiols with a
dialkylamine or a cyclic amine[2]. The N,N-disubstituted
thiophenes have been used[3] for the synthesis of oligothi-
ophenes that show interesting solvatochromatic phenom-
ena.
Having found[4] that lithiated acetylenes RCH2CϵCLi
smoothly add to isothiocyanates RЈNϭCϭS with forma-
tion of the systems RCH2CϵCϪC(SLi)ϭNRЈ, we won-
dered whether it would be possible under suitable con-
ditions to convert the intermediary adducts into allenic in-
termediates RCHϭCϭCHϪC(SLi)ϭNRЈ and sub-
sequently to effect ring closure of the latter systems.
Hydrolysis or N-alkylation finally could afford N-substi-
tuted or N,N-disubstituted thiophenes.
Results and Discussion
tion were investigated separately with propyne, 1-butyne,
methyl propargyl ether, methyl propargyl sulfide, and N,N-
a. Synthesis of 2-Thienylamines from 1-Alkynes
The synthesis of 2-thienylamines was carried out as de- dimethyl propargylamine. Thus, the alkynes 1 were lithiated
picted in Scheme 1. by standard procedures, after which the isothiocyanates
After preliminary experiments with 1-butyne and methyl were added. The efficiency of formation of the adducts 3
isothiocyanate had shown that satisfactory results could be was determined by subsequent quenching with methyl iod-
obtained by a one-pot procedure, the addition and cycliza- ide resulting in the formation of the Schiffs bases
Eur. J. Org. Chem. 1998, 253Ϫ256
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253

L. Brandsma et al.
FULL PAPER
RCH2CϵCϪC(SCH3)ϭNRЈ. With all of the alkynyllithi- rator the solution rapidly turned dark and in the last stage a
ums smooth reactions occurred at 20Ϫ30°C or slightly elev- vigorous decomposition reaction occurred resulting in tarry
ated temperatures. Addition of methyl iodide gave the ex- products. If, instead of hydrolysis, methylation with CH3I
pected Schiffs bases in high yields, except in the cases of was carried out, the stable 2,5-bis-(dimethylamino)thi-
the reaction of the lithiated methyl propargyl sulfide with ophene 8c [R ϭ (CH3)2N, RЈ ϭ CH3] was obtained in a
isothiocyanates. Initially the latter addition reactions good yield. Apparently the corresponding derivative 7 is ex-
seemed to proceed normally, but after a relatively short per- tremely unstable.
iod, during the addition of the isothiocyanate, a sudden
After having obtained generally successful results, we
exothermic reaction took place during which the solution have made some attempts to simplify the one-pot pro-
turned very dark brown. Subsequent methylation afforded cedures by omitting the addition of either tert-butylalcohol
only intractable tarry material. No better results were ob- or potassium tert-butoxide. While in the former case the
tained when the reactions were carried out at temperatures cyclization seemed to proceed somewhat less readily, it was
between 0 and 10°C. tert-Butyl isothiocyanate reacted rela- very slow in the absence of tBuOK.
tively slowly with the lithiated acetylenes. In order to attain
b. Synthesis of Thienylamines from tert-Butylallene
50Ϫ60% conversion, it was necessary to heat the reaction
mixtures for several hours under reflux. The additions were
not noticiably promoted by (catalytic amounts of) copper-
(I)bromide. In a single case (R ϭ CH3, RЈ ϭ iso-C3H7) the
reaction mixture was quenched with an aqueous solution
of ammonium chloride giving the expected thioamide
RCH2CϵCϪC(ϭS)NHRЈ in a good yield. The product de-
composed vigorously during attempted distillation in a high
vacuum, but its identity appeared, except from the IR and
NMR spectra, from its conversion into the Schiffs base
RCH2CϵCϪC(SCH3)ϭNHRЈ in a good yield by addition
to an equivalent amount of potasium tert-butoxide in THF
and subsequent quenching with methyl iodide.
From Scheme I it may be concluded that the intermedi-
ates with the structures 4 can also be generated by metallat-
ing allenes at the terminal carbon atom and subsequently
adding an isothiocyanate. Therefore, similar one-pot pro-
cedures should be possible with allenic hydrocarbons 9 as
starting compounds (Scheme 2).
Scheme 2
In order to effect cyclization of the intermediates 3, an
equivalent amount of tert-butylalcohol and a solution of an
equivalent amount of potassium tert-butoxide in dimeth-
ylsulfoxide were successively added at temperatures between
0 and Ϫ10°C, after which the reaction mixtures were gradu-
ally warmed. The progress of the conversion was followed
by regularly withdrawing samples from the reaction mix-
tures and quenching them with saturated aqueous am-
monium chloride or methyl iodide. The cyclizations were
considered to be complete, when in the GLC the peaks as-
cribed to the methylation products RCH2CϵCϪC(SCH3)ϭ
NRЈ (in the cases of quenching with CH3I), or other peaks,
ascribed to the thioamides RCH2CϵCϪC(CϭS)NHRЈ or
products of hydrolysis of 5 (in the cases of quenching with
an ammonium chloride solution) had vanished and re-
placed by peaks of 8 and 7, respectively. The one-pot pro-
cedures were then terminated by addition of methyl iodide
or aqueous ammonium chloride affording 8 and 7 in satis-
factory yields. The procedure with methyl propargyl ether
and methyl isothiocyanate, however, gave only intractable
tarry products. In the case of phenyl isothiocyanate, good
Allenes 9 (R ϭ alkyl or cycloalkyl) are readily available
by the copper(I)-catalyzed reaction of Grignard compounds
with propargyl halides[5]. tert-Butylallene seemed a suitable
substrate for testing the applicability of Scheme II as its
lithiation (to give 10) proceeds regiospecifically[5]. Primary
alkylallenes are lithiated for 5Ϫ10% at the carbon atom
next to the alkyl group. Performing the same sequence of
operations as had been done with the 1-alkynes afforded
the expected representatives 7 and 8 with R ϭ tBu in fair
to good yields.
results
were
obtained.
Possibly,
the
adduct
CH3OCH2CϵCC(SLi)ϭNCH3, can undergo a tele-elimi-
nation of methanol initiated by removal of a proton from
the ϭNϪCH3 group and resulting in the very unstable cu-
mulenic system H2CϭCϭCϭC(SLi)ϪNϭCH2. Another
limitation of the scope of our synthetic method concerns
the low stability of the product from the reaction of lithi-
c. Stability of the Thienylamines Synthesized
In contrast to the parent compound 2-aminothiophene[6]
,
ated N,N-dimethyl propargylamine 2 [R ϭ (CH3)2N] with the N-monosubstituted thiophenes 7 obtained by our
methyl isothiocyanate (RЈ ϭ CH3) and subsequent hydroly- method seem to be fairly thermostable. Nevertheless, after
sis. During the removal of the solvent on the rotary evapo- storage (under nitrogen) for a few days at room tempera-
254
Eur. J. Org. Chem. 1998, 253Ϫ256

One-Pot Syntheses of Aminothiophenes
FULL PAPER
(Scheme 2) prepared as described in exp. 1 was brought at Ϫ15°C.
tert-Butylalcohol (0.13 mol, in admixture with a few ml of diethyl
ether) and a solution of 0.11 mol of potassium tert-butoxide in 50
ml of DMSO were successively added over a few sec. The reaction
mixtures gradually turned dark-brown upon increasing the tem-
perature. The reactions were followed by withdrawing small ali-
quots (ca. 1 ml), adding them to a mixture of 3 ml of diethyl ether
and 3 ml of saturated aqueous ammonium chloride and making a
gas-liquid chromatogram of the organic layer. After taking a
sample, the reaction mixture was kept at Ϫ15°C during the times
needed for GLC. After GLC had indicated completion of the con-
versions, the reaction mixtures were cooled to 0°C, then 150 ml of
an aqueous solution of 30 g of ammonium chloride was added with
vigorous stirring. The aqueous layer was extracted four times with
small portions of a 1:1 mixture of ether and pentane. The combined
organic solutions were washed twice with aqueous ammonium
chloride (30 g / 150 ml), dried over anhydrous magnesium sulfate
and concentrated under reduced pressure. After one flash distil-
lation at 1 mm Hg or lower pressure through a very short Vigreux
column the products were carefully redistilled. Reaction times and
temperatures, global indications of distillation temperatures in°C/
mm Hg, and spectral data are mentioned below.
ture, or even after some weeks at Ϫ20°C, the refractive in-
dexes had increased considerably, while after redistillation
10Ϫ20% of undistillable material, possibly dimers, re-
mained. Like aminothiophene[6] compounds 7 show a high
sensitivity towards oxygen. Exposure of the compounds to
air caused dark colours within one hour. The N,N-disubsti-
tuted thiophenes 8 are much more stable.
d. Concluding Remarks
Our one-pot procedures give access to a rather wide vari-
ety of 2-N-monosubstituted and 2-N,N-disubstituted thio-
phenes, not or less easily available by other methods.
Experimental Section
The isothiocyanates CH3NϭCϭS, C2H5NϭCϭS, and PhNϭ
CϭS were commercially available, (CH3)2CHϪNϭCϭS was pre-
pared from isopropylamine, acetyl chloride and triethylamine in
chloroform[7]. The preparation of tert-butylallene, methyl propar-
gyl ether, and N,N-dimethyl propargylamine is described in
refs.[4][5]. Tetrahydrofuran was dried by shaking with machine-pow-
dered potassium hydroxide and subsequently distilling the filtered
liquid from sodium sand/benzophenone. For all reactions dimeth-
ylsulfoxide with a water content <1% and potassium tert-butoxide
free from complexed tert-butylalcohol (commercially available)
were used. All reactions were carried out under nitrogen in flame-
dried glass ware. For cooling a bath with liquid nitrogen (oc-
casional cooling) was used. 1H- and 13C-NMR spectra (300 and 75
MHz, respectively) were recorded on a Bruker AC-300F apparatus,
2-N-Methylaminothiophene (7a) (Scheme 1): Reaction time 40
min at 48°C; b.p. 50°C/1 mm Hg, (ref.[8] 88Ϫ92°C/15 mm Hg),
20
1
nD 1.5830, yield 65% (purity 96% GLC). Ϫ H NMR: δ ϭ 2.87
(s, 3 H), 3.80 (br.s, 1 H), 6.01 (dd, J ϭ 3.6 and 1.4, 1 H), 6.46 (dd,
1 H), 6.74 (dd, J ϭ 5.5, 1 H). Ϫ 13C NMR: δ ϭ 34.26, 103.08,
110.11, 126.21, 156.43. Ϫ C5H7NS (113.18): calcd. C 53.06, H 6.23,
N 12.38, S 28.33; found C 53.10, H 6.09, N 12.44, S 28.50.
v
using solutions in deuterochloroform (ca. 20% /v).
2-N-Ethylaminothiophene (7b) (Scheme 1): Reaction time 25 min
at 50°C, b.p. 65°C/15 mm Hg, (ref.[8] 82Ϫ85°C/2Ϫ3 mm Hg),
nD20 1.5630, yield 72% (purity 99.9% GLC). Ϫ 1H NMR: δ ϭ 1.26
(t, 3 H), 3.16 (q, J ϭ 7.2, 2 H), 3.75 (br.s, 1 H), 6.04 (dd, J ϭ 3.6
and 1.4, 1 H), 6.74 (dd, J ϭ 5.5, 1 H), 6.46 (dd, 1 H). Ϫ 13C
NMR: δ ϭ 14.77, 42.66, 103.81, 110.16, 126.11, 155.18. Ϫ C6H9NS
(127.21): calcd. C 56.65, H 7.13, N 11.01, S 25.21; found C 56.54,
H 7.18, N 11.01, S 25.10.
1. Lithiation of 1-Alkynes or tert-Butylallene and Subsequent Re-
action with Isothiocyanates [Preparation of Solutions of 3 (Scheme
1) or 4 (Scheme 2)]: In a 500-ml round-bottomed, three-necked
flask equipped with a gas inlet-thermometer combination, a mech-
anical stirrer and a dropping funnel-outlet combination, was placed
a solution of 0.11 mol of nBuLi in ca. 70 ml of hexane. THF (70
ml) was added with cooling below 0°C. For the lithiation of the
acetylenes the solution was cooled to Ϫ60°C, after which the acety-
lene (0.12 mol, propyne and 1-butyne as a mixture with 30 ml of
THF, cooled at Ϫ50°C) was added within a few seconds. In the
cases of propyne and dimethyl propargylamine suspensions were
formed, the other acetylenes gave clear or almost clear (1-butyne)
solutions. The lithiation of tert-butylallene was carried out by ad-
ding the allene (0.13 mol) in one portion at Ϫ65°C and sub-
sequently stirring the reaction mixture for an additional half hour
at Ϫ25 to Ϫ30°C. A clear solution was formed. Immediately after
the addition of the acetylenes, the solutions or suspensions were
warmed to ϩ10°C and the isothiocyanate (0.10 mol) was added in
one portion (CH3NϭCϭS in admixture with 10 ml of THF). The
temperature of the mixtures was allowed to rise without external
cooling. The reactions with the soluble acetylides proceeded rapidly
within the range 20 to 35°C, in the cases of lithiated propyne and
dimethyl propargylamine smooth conversions were observed after
heating to 35 or 40°C. The reactions were terminated by stirring
for an additional 15 min at 35 to 40°C or 45 to 50°C (lithiated
propyne and dimethyl propargylamine). In all cases yellow or light-
brown (PhNϭCϭS) solutions were formed. Lithiated tert-butylal-
lene is much more reactive, therefore the temperature was kept be-
tween Ϫ85 and Ϫ100°C during the addition of the isothiocyanates
(over 10 min). After the addition the temperature was allowed to
rise (without external cooling) to Ϫ20°C.
2-N-Isopropylaminothiophene (7c) (Scheme 1): Reaction time 40
20
min at 45°C, b.p. 56°C/1 mm Hg, nD 1.5438, yield 78% (purity
1
99.5% GLC). Ϫ H NMR: δ ϭ 1.22 (d, 6 H), 3.45 (m, J ϭ 6.3, 1
H), 3.60 (br.s, 1 H), 6.04 (dd, J ϭ 3.6 and 1.4, 1 H), 6.47 (dd, 1
H), 6.71 (dd, J ϭ 5.5, 1 H). Ϫ 13C NMR: δ ϭ 22.91, 49.40, 105.48,
110.84, 126.06, 154.18.
2-N-Methylamino-5-methylthiophene (7d) (Scheme 1): Reaction
time 30 min at 45°C, b.p. 60°C/1.5 mm Hg, nD20 1.5645, yield 61%
1
(purity 100% GLC). Ϫ H NMR: δ ϭ 2.34 (d, J ϭ 1.1, 3 H), 2.83
(s, 3 H), 3.65 (br.s, 1 H), 5.80 (d, J ϭ 2.6, 1 H), 6.36 (dd, J ϭ 3.6
and 1.1, 1 H). Ϫ 13C NMR: δ ϭ 15.03, 34.23, 102.86, 123.33,
124.81, 154.02. Ϫ C6H9NS (127.21): calcd. C 56.65, H 7.13, N
11.01, S 25.21; found C 56.73, H 7.00, N 11.08, S 25.15.
2-N-Phenylaminothiophene (7e) (Scheme 1): Reaction time 30
min at 42°C, b.p. 110°C/0.5 mm Hg, nD20 1.6555, yield 63% (purity
98.3% GLC). Ϫ 1H NMR: δ ϭ 5.61 (br.s, 1 H), 6.74 (ddd, J ϭ 0.8,
1.4, 3.6), 6.86 (m), 6.89 (m,), 6.90 (dd, J ϭ 5.8), 6.94 (dd), 7.24 (m).
Ϫ
13C NMR: δ ϭ 114.44, 119.00, 119.09, 119.72, 125.77, 129.24,
145.81, 145.89. ϪC10H9NS (175.25): calcd.68.54, H 5.18, N 7.99,
S 18.30; found C 68.35, H 5.20, N 8.00, S 18.41.
2-N-Phenylamino-5-methylthiophene (7f) (Scheme 1): Reaction
20
time 15 min at 40°C, b.p. 120°C/0.5 mm Hg, nD 1.6335, yield
2. Preparation of the 2-N-Alkylamino- and 2-N-Phenylaminothio-
85% (purity 100% GLC). Ϫ 1H NMR (CCl4): δ ϭ 2.44 (d, J ϭ 0.8,
phenes (7) (Schemes 1 and 2): The solution of 3 (Scheme 1) or 4 3 H), 5.2 (br.s, 1 H), 6.53Ϫ6.58 (m), 6.79Ϫ6.86 (m), 7.21 (m). Ϫ
Eur. J. Org. Chem. 1998, 253Ϫ256 255

L. Brandsma et al.
FULL PAPER
13C NMR: δ ϭ 15.69, 114.66, 119.29, 120.56, 123.26, 129.15,
134.47, 142.76, 146.50. Ϫ C11H11NS (189.28): calcd. 69.80, H 5.86, tion time 30 min at 40°C, b.p. 80°C/10 mm Hg, nD 1.5426, yield
N 7.40, S 16.94; found C 69.79, H 5.85, N 7.37, S 16.90.
2-N,N-Dimethylamino-5-methylthiophene (8b) (Scheme 1): Reac-
20
74% (purity 93.1% GLC), (ref.[9] b.p.75°C/10 mm Hg, nD24 1.5425).
1
Ϫ H NMR: δ ϭ 2.3 (d, J ϭ 1.0, 3 H), 2.94 (s, 6 H), 5.80 (d, J ϭ
2-N-Phenylamino-5-methoxythiophene (7g) (Scheme 1): Reaction
3.6, 1 H), 6.36 (dq, 1 H). Ϫ 13C NMR: δ ϭ 14.56, 43.17, 102.71,
123.55, 124.86, 157.37. Ϫ C7H11NS (141.24): calcd. C 59.53, H
7.85, N 9.92, S 22.70; found C 59.41, H 7.75, N 9.97, S 22.65.
20
time 15 min at 45°C, b.p. 155°C/0.5 mm Hg, nD 1.6266, yield
1
55% (purity 99% GLC). Ϫ H NMR: δ ϭ 3.88 (s, 3 H), 5.35 (br.s,
1 H), 5.99 (d, J ϭ 3.9, 1 H), 6.48 (d, 1 H), 6.70Ϫ6.86 (m, 4 H),
7.20 (m, 1 H). Ϫ 13C NMR: δ ϭ 59.81, 101.57, 113.71, 119.16,
121.41, 129.14, 131.58, 147.28, 161.92. Ϫ C11H11NOS (205.28):
calcd. C 64.36, H 5.40, N 6.82, S 15.62; found C 64.21, H 5.40, N
6.84, S 15.67.
2,5-Bis(dimethylamino)thiophene (8c) (Scheme 1): Reaction time
10 min at 15°C, b.p. 80°C/0.7 mm Hg, nD20 1.5561, yield 73% (pu-
rity 97.5% GLC). Ϫ 1H NMR: δ ϭ 2.75 (s, 12 H), 5.69 (s, 2 H). Ϫ
13C NMR: δ ϭ 44.19, 104.28, 149.21. Ϫ C8H14N2S (170.28): calcd.
C 56.43, H 8.29, N 16.45, S 18.83; found C 56.30, H 8.24, N 16.50,
S 18.94.
2-N-Methylamino-5-tert-butylthiophene (7h) (Scheme 2): Reac-
20
tion time 60 min at 45°C, b.p. 90°C/2 mm Hg, nD 1.5323, yield
2-N-Methyl-N-phenylamino-5-methylthiophene (8d) (Scheme 1):
1
43% (purity 99% GLC). Ϫ H NMR: δ ϭ 1.32 (s, 9 H), 2.84 (s, 3
20
Reaction time 15 min at 40°C, b.p. 110°C/1 mm Hg, nD 1.6131,
H), 3.65 (br.s, 1 H), 5.80 (d, J ϭ 3.8, 1 H), 6.41 (d, 1 H). Ϫ 13C
NMR: δ ϭ 32.23, 34.00, 34.21, 102.30, 119.36, 142.34, 153.52. Ϫ
C9H15NS (169.29): calcd. C 63.85, H 8.93, N 8.27, S 18.94; found
C 63.95, H 8.80, N 8.30, S 18.90.
yield 85% (purity 100% GLC). Ϫ 1H NMR: δ ϭ 2.40 (d, 3 H), 3.25
(s, 3 H), 6.47 (d, J ϭ 3.6, 1 H), 6.50 (dq, J ϭ 1.0, 1 H), 6.80 (m),
6.86 (m, 4 H), 7.19 (m, 1 H). Ϫ 13C NMR: δ ϭ 15.85, 41.70, 115.07,
119.05, 120.60, 123.11, 128.77, 134.96, 149.34, 150.48. Ϫ C12H13NS
(203.31): calcd. 70.89, H 6.45, N 6.89, S 15.77; found C 70.90, H
6.35, N 6.94, S 15.78.
2-N-Phenylamino-5-tert-butylthiophene (7i) (Scheme 2): Reac-
tion time 40 min at 48°C, b.p. 135°C/0.5 mm Hg, nD20 1.5948, yield
87% (purity 100% GLC). Ϫ 1H NMR: δ ϭ 1.40 (s, 9 H), 5.30 (br.s,
1 H), 6.58 (d, J ϭ 3.9, 1 H), 6.63 (d, 1 H), 6.82Ϫ6.89 (m, 4 H),
7.23 (m, 1 H). Ϫ 13C NMR: δ ϭ 32.23, 34.00, 34.21, 102.30, 119.36,
142.54, 153.52. Ϫ C14H17NS (231.36): calcd. C 72.768, H 7.41, N
6.05, S 13.86; found C 72.63, H 7.30, N 6.12, S 13.94.
2-N-Methyl-N-phenylamino-5-methoxythiophene (8e) (Scheme
20
1): Reaction time 10 min at 40°C, b.p. 130°C/0.6 mm Hg, nD
1
1.6085, yield 80% (purity 100% GLC). Ϫ H NMR: δ ϭ 3.22 (s, 3
H), 3.82 (s, 3 H), 5.93 (d, J ϭ 3.9), 6.41 (d, 1 H), 6.78 (m, 4 H),
7.19 (m, 1 H). Ϫ 13C NMR: δ ϭ 41.56, 59.68, 101.15, 114.06,
118.56, 120.89, 128.75, 139.19, 149.47, 162.12. Ϫ C12H13NOS
(219.31): calcd. C 65.72, H 5.98, N 6.39, S 14.62; found C 65.75,
H 5.91, N 6.42, S 14.60.
The IR spectra of the N-monosubstituted thiophenes showed in-
ter alia an absorption at approximately 3390 cmϪ1 (NH).
3. Preparation of 2-N,N-Disubstituted Thiophenes (8) (Schemes 1
and 2): For the lithiation of the acetylenes or tert-butylallene, the
addition of the lithio compounds to the isothiocyanates and the
cyclization of the adducts the procedure described in exps. 1 and 2
was followed. The cyclization reaction was monitored by quenching
1-ml samples of the reaction mixtures with aqueous ammonium
chloride, followed by gas liquid chromatography of the organic lay-
ers. In a few cases quenching with methyl iodide gave a clearer
indication of the progress of the cyclizations. After completion of
the cyclization the reaction mixture was cooled to Ϫ5°C and
methyl iodide (30 g, large excess) was added over 10 min while
gradually allowing the temperature of the reaction mixture to rise
to <25°C. After the addition the reaction mixture was stirred for
5 min at 50°C, then 150 ml of an aqueous solution of 30 g am-
monium chloride was added. The products were isolated as de-
scribed for compounds 7 in exp. 2.
2-N,N-Dimethylamino-5-tert-butylthiophene (8f): Reaction time
20
20 min at 60°C, b.p. 70Ϫ75°C/1 mm Hg, nD 1.5242, yield 62%
20
(purity 93.1% GLC), (ref.[1] b.p. 55 °C/0.1 mm Hg, nD 1.5219). Ϫ
1H NMR: δ ϭ 1.31 (s, 9 H), 2.82 (s, 6 H), 5.68 (d, J ϭ 3.6, 1 H),
6.42 (d, 1 H). Ϫ C10H17NS (183.32): calcd. C 65.52, H 9.35, N
7.64, S 17.49; found C 65.38, H 9.30, N 7.70, S 17.53.
[1]
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H. Hartmann, S. Scheithauer, J. Prakt. Chem. 1969, 311,
827Ϫ843.
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F. Effenberger, F. Würthner, F. Steybe, J. Org. Chem. 1995,
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60, 2082Ϫ2091. Ϫ
F. Effenberger, F. Würthner, Angew.
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32, 719Ϫ721.
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1981.
2-N,N-Dimethylaminothiophene (8a) (Scheme 1): Reaction time
1 h at 50Ϫ55°C, b.p. 70°C/10 mm, (ref.[9] 66Ϫ69°C/9 mm Hg),
nD20 1.5560, yield 67% (purity 96.3% GLC). Ϫ 1H NMR: δ ϭ 2.97
(s, 6 H), 5.99 (dd, J ϭ 3.9 and 1.4, 1 H), 6.56 (dd, 1 H), 6.85 (dd,
J ϭ 6.0, 1 H). Ϫ 13C NMR (75 MHz): δ ϭ 43.11, 102.61, 110.22,
126.44, 159.51. Ϫ C6H9NS (127.21): calcd. C 56.65, H 7.13, N
11.01, S 25.21; found C 56.38, H 7.16, N 11.08, S 25.31.
[6]
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D.L. Eck, G.W. Stacy, J. Heterocycl. Chem. 1969, 6, 147Ϫ151.
N.A. Nedolya, to be published; compare B.A. Trofimov, M.G.
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[97254]
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[9]
256
Eur. J. Org. Chem. 1998, 253Ϫ256