Use of Stable Amine-Capped Polyynes in the Regioselective Synthesis of Push-Pull Thiophenes

Article abstract of DOI:10.1021/acs.joc.6b02685

The reactions of a series of 1-halopolyynes with secondary amines led to novel amine end-capped polyynes exhibiting surprisingly high stability toward moisture. The new compounds were characterized by NMR spectroscopy, ESI-MS spectrometry, and X-ray single-crystal diffractometry. The use of amine end-capped polyynes as precursors to substituted push-pull thiophenes was next presented. The results show the first - to the best of our knowledge - transformation of ynamine to thiophene and the first regioselective transformation of a longer polyynes to butadiyne-substituted thiophene. Photophysical studies of the resulting compounds show that some of the substituted thiophenes have high quantum yield photoluminescence upon UV light irradiation.

Full text of DOI:10.1021/acs.joc.6b02685

Subscriber access provided by UB + Fachbibliothek Chemie | (FU-Bibliothekssystem)
Article
Use of stable amine-capped polyynes in the
regioselective synthesis of push-pull thiophenes
Bart#omiej Pigulski, Patrycja M#cik, Jakub Cichos, and Slawomir Szafert
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02685 • Publication Date (Web): 29 Dec 2016
Downloaded from http://pubs.acs.org on December 30, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 34
The Journal of Organic Chemistry
1
2
3
4
Use of stable amineꢀcapped polyynes in the regioselective synthesis of pushꢀpull thiophenes
5
6
7
8
Bartłomiej Pigulski, Patrycja Męcik, Jakub Cichos, Sławomir Szafert*
9
Department of Chemistry, University of Wrocław, 14 F. JoliotꢀCurie, 50ꢀ383 Wrocław,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Poland
R2
R3
R2
N
H
R2
R3
N
Na2S*xH2O
MeCN, 70oC
R3
S
R1
X
R1
31 examples
N
R1
n
n
n-1
THF, rt
n = 1, 2, 3
X = Br, I
9 examples
Abstract
The reactions of a series of 1ꢀhalopolyynes with secondary amines led to novel amine endꢀ
capped polyynes exhibiting surprisingly high stability towards moisture. The new compounds
were characterized by NMR spectroscopy, ESIꢀMS spectrometry, and xꢀray singleꢀcrystal
diffractometry. The use of amine endꢀcapped polyynes as precursors to substituted pushꢀpull
thiophenes was next presented. The results show the first ꢀ to the best of our knowledge ꢀ
transformation of ynamine to thiophene and the first regioselective transformation of a longer
polyynes to butadiyneꢀsubstituted thiophene. Photophysical studies of the resulting
compounds show that some of the substituted thiophenes have high quantum yield
photoluminescence upon UV light irradiation.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 34
1
2
3
4
Introduction
5
6
7
8
Polyynes and cumulenes have attracted an undiminished interest from the scientific
community for more than half a century and a plethora of diverse compounds of this type
have been synthesized to date.1 These linear carbon rods are regarded as model compounds of
hypothetical allotropic form of carbon – carbyne and they have significant application
potential. Such molecules have been explored as molecular wires and switches in
nanoelectronics,2 as materials for optoelectronics (due to their nonlinear optical response),3 or
as precursors for conducting polymers.4 Furthermore, polyynes exist in interstellar matter.5
Although ynamides are widely used as building blocks in organic synthesis,6 ynamines
remain much less explored due to problems with their handling and purification6ꢀ7 owing to
their high moisture sensitivity. In the literature, the hydrolytic instability of ynamines has
even been described as follows: ‘it makes ynamine chemistry inaccessible’.7c However, in situ
generated, they are useful tools in organic synthesis and are used for instance in amide,8
thioamide,9 and substituted naphthalene10 syntheses.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ynamines may be prepared via three general routes: elimination, substitution or
isomerization.7a While the synthesis of ynamines via the reaction of 1ꢀhaloalkynes with
secondary amines is known, the method has hardly been used and to date, the scope of the
reaction has not been explored. A most probable reason for the low interest in this reaction
was that it can give up to three types of unstable products: ynamines, 1,1ꢀdiaminoethenes, and
1,2ꢀdiaminoethenes (see Scheme 1) where the final structure of the main compound is
strongly correlated with the electronic properties of an alkyne, steric bulkiness of an amine
and, of course, reaction conditions.7a,11
Scheme 1. Possible products of a reaction of 1ꢀhaloalkynes with secondary amines.
ACS Paragon Plus Environment

Page 3 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Ynamines or ynamides containing (C≡C)2 or a longer polyyne fragment directly bound
to nitrogen are very rare. Some older works reporting the synthesis of butadiyne,12 hexatriyꢀ
ne,13 and octatetrayneamines14 with the use of perchlorobutenyne precursors and nꢀbutyllithiꢀ
um are known, but usually harsh reaction conditions were needed and characterization of the
final products was very poor. Nevertheless, some butadiyneꢀsubstituted amines were tested in
1,nꢀtopochemical polymerization15 or were used for cyclization reactions.16 Moreover,
interesting pushꢀpull ynamide polyynes with up to four acetylenic units are known.17
As reported above, the structures of products of a reaction between 1ꢀhalopolyynes
and secondary amines were not obvious. Some of the older results suggested that 1ꢀbromobuꢀ
tadiynes react with secondary amines giving products of multiple amination.18 However,
Guillemin and coworkers19 accidentally synthesized a butadiynylꢀsubstituted amine via a
similar reaction and proved that products of a simple substitution are possible. Nevertheless,
there is no detailed investigation on the reactivity of 1ꢀhalopolyynes with secondary amines
and the ultimate goal of this work was to fill this gap.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Our recent research interests have focused on the synthesis and reactivity of 1ꢀ
halopolyynes.20 To date, we have explored their reactivity in the synthesis of organometallic
polyynes21 or in the mechanochemical synthesis of pyrrole endꢀcapped polyynes.22 Herein, we
present a simple and versatile procedure that leads from 1ꢀhalopolyynes to the isolable and
surprisingly stable amine endꢀcapped polyynes. Moreover, the use of the resulting rodꢀlike
amines as substrates for regioselective synthesis of pushꢀpull thiophenes is presented.
Results and Discussion
Synthesis of amine end-capped polyynes
Starting 1ꢀhalopolyynes were obtained according to the procedures previously
developed in our group21b,22a with only 1ꢀbromobutadiyne 1d being newly synthesized (see
the Supporting Information). Literature reports23 and initial studies supported that the reaction
of simple aryl 1ꢀhaloacetylenes with an excess of secondary amines gives diamination
products. Therefore, we expected analogous products for 1ꢀhalopolyynes. Unexpectedly, test
reactions of 1ꢀbromobutadiynes 1aꢀb and analogous iodides with pyrrolidine and piperidine
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 34
1
2
3
4
5
6
7
8
9
gave only pure butadiynamines instead of diaminoenynes. As such, we performed reactions
using a series of 1ꢀhalopolyynes with a variety of secondary amines. Firstly, we observed that
the reaction times are shorter for bromides than iodides, therefore, for further reactions we
used mostly bromides (if it was accessible). Secondly, we usually used THF as a solvent, but
MeCN, CH2Cl2 and nꢀBu2O also gave analogous results. Thirdly, the reactions performed at
elevated temperatures always gave the same ynamine product as those carried out at room
temperature. Fourthly, an excess of amine did not affect the outcome of the reaction (we
tested amounts from 2.0 to 8.0 equivalents with identical result). In conclusion, we did not
find any conditions that gave products of multiple amination instead of ynamine. With the
above in mind, we performed reactions for a series of 1ꢀhalopolyynes to obtain the relevant
amine endꢀcapped polyynes.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. Reaction of 1ꢀbromobutadiynes with secondary amines.
In the first thrust, we performed the reactions for 1ꢀbromobutadiynes (Scheme 2). We
noticed that the reactions with electron withdrawing endgroups (1aꢀc) were faster than those
for electronꢀrich anisole derivative (1d; see Experimental Section). Moreover, 1d did not react
with the less nucleophilic amines (2cꢀe) so the products were obtained only for pyrrolidine
and piperidine. We tested a series of secondary amines in this transformation and it was clear
that the reaction time strongly depended on nucleophilicity of an amine. The most
ACS Paragon Plus Environment

Page 5 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
nucleophilic ones (pyrrolidine 2a and piperidine 2b) gave products within minutes. Reactions
for Nꢀmethylbenzylamine (2e) and 1ꢀ(1,3ꢀdioxolanꢀ2ꢀyl)ꢀNꢀmethylmethaneamine (2c) were
slower and usually took several hours, while reactions with diisopropylamine (2d) typically
needed 24 h for completion. We also tested Nꢀmethylaniline and indoline, but no reaction was
observed. For the working reactions the yields were from 28 to 98%, but in some cases the
yields were further reduced by the purification process. Typically, products were dissolved in
hexanes or a mixture of hexanes and CH2Cl2 and amine hydrobromide was filtered off,
therefore, in case of low soluble products the yields might have been lowered.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Synthesis of amine endꢀcapped hexatriynes and octatetraynes.
Next, the reaction of 1ꢀbromohexatriynes and 1ꢀiodooctatetraynes with a series of
secondary amines was performed (Scheme 3). Since 1ꢀbromooctatetraynes appeared not
enough stable, so for longer chains we used more stable 1ꢀiodooctatetraynes. Products were
obtained with short reaction times (usually few hours), and only the reaction with less
nucleophilic diisopropylamine was slightly slower. Yields obtained for hexatriynes (from 32
to 95%) and octatetraynes (from 48 to 90%) were acceptable.
In the literature ynamines are usually described as ‘highly unstable’ due to their moistꢀ
ure sensitivity but, ynamines with (C≡C)2 or longer carbon chains appeared to be quite stable.
This was tentatively attributed to the CꢀN carbon atom which is less electrophilic than in anaꢀ
logues with single triple bond because of a resonance effect of a polyyne system. The NMR
spectra of the ynamines were measured in wet CDCl3 and no decomposition was observed
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 34
1
2
3
4
5
6
7
8
9
even after few days in solution. Compounds stored for few days in open vials however, showꢀ
ed new signals in the 1H NMR spectra which originated from the corresponding amides. Only
more electron rich 3da and 3db showed much faster decomposition in the presence of moistuꢀ
re and in these cases more careful handling was needed. In the literature ynamides are often
mentioned as more convenient and easier to handle modification of ynamines. As such, the
chemistry of ynamides is far richer than ynamines. Our results show that amine endꢀcapped
polyynes are far more stable than short chained Nꢀethynylamines and may play an important
role as convenient building blocks in organic chemistry.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis of push-pull thiophenes
Next, we utilized the amine endꢀcapped polyynes as substrates for the synthesis of
functionalized thiophenes. Such a transformation for butadiynes is known,24 but to the best
our knowledge, the reaction for butadiynamine has no literature precedence. Moreover, in the
known examples, the presence of a strong base is usually needed.
Scheme 4. Synthesis of substituted thiophenes.
We performed the reaction of nine amine endꢀcapped polyynes with sodium sulfide in
acetonitrile (no base added). Reactions at room temperature turned out to be very slow and
o
were incomplete even after 24 h. The same reactions at 70 C gave pure thiophenes already
ACS Paragon Plus Environment

Page 7 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
after few hours, proving that this simple procedure effectively produced pushꢀpull 2ꢀ
aminothiophenes (4aa, 4ac, 4ae, 4ba, 4ca) from the corresponding butadiynes under very
mild conditions (see Scheme 4). Surprisingly, the reactions for hexatriynes (3ea, 3eb, and
3fb) were regioselective and the only observed products were 2ꢀaminoꢀ5ꢀ
(phenylethynyl)thiophene (A in Scheme 5) with no traces of 2ꢀ(aminoethynyl)ꢀ5ꢀ
phenylthiophene (B in Scheme 5). When octatetrayne 3ga was reacted with one equivalent of
sodium sulfide the reaction was once again regioselective and the only product was 4ga (C in
Scheme 5) and no traces of Eꢀ and Dꢀtype products were observed. The structures of 4ea, 4eb,
4fb, and 4ga derivatives were confirmed with the use of HMQC and HMBC experiments.
Yields were usually from moderate to good (29ꢀ87%).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 5. Possible products for the reaction of amine endꢀcapped polyynes with Na2S.
Interestingly, the reaction of 3ga with excess sodium sulfide gave another product,
which was probably the effect of its twofold reaction with Na2S (F in Scheme 5). Carefully
increasing an excess of Na2S we observed diminishing amount of 4ga and increasing amount
1
of product with four doublets from two thiophene rings in H NMR. However, the product
decomposes very quickly in solution and in solid state, so it was impossible to record its clear
1H and 13C NMR spectrum. Moreover, decomposition of all the resulting thiophenes was
observed during recording of the NMR spectra in CDCl3, probably due to the presence of
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 34
1
2
3
4
5
6
small amounts of HCl in a solvent. Thus, all the NMR spectra for the thiophenes were
recorded in C6D6.
7
8
All the obtained thiophenes were stable in the solid state at room temperature for days
9
but after longer exposure time we observed the decrease of doublets from thiophene moiety
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
(JHH = 4 Hz) in H NMR spectra. Instead, new doublets with higher coupling constant (JHH
=
10 Hz) appeared. According to the literature, decomposition products are probably products
of photoꢀoxidation.25 So, all thiophenes were stored in refrigerator in the dark.
Substituted pushꢀpull 2ꢀaminothiophenes exhibit excellent properties for optoelectronꢀ
ic applications and play an important role in NLO (nonlinear optics) materials.26 Compounds
with 2ꢀaminothiophene moiety exhibit also strong antiꢀAR (androgen receptor) potency,27 are
used as fluorescence biomarkers28 or play an important role as fluorescent dyes.25,29 For insꢀ
tance, DTMꢀ2 and BAPꢀ2 (Figure 1) are used for in vivo fluorescence imaging of βꢀamyloid
(Aβ) plaques that is expected to be a new method for detecting Alzheimer’s disease.28b,28c
Substituted 2ꢀaminoꢀ5ꢀphenylethynylthiophenes or 2ꢀaminoꢀ5ꢀphenylthiophenes (G and H in
Figure 1) have also an influence on A1 adenosine receptor.30 The approach presented so far to
obtain these compounds was different from that shown in this work, so we believe, we have
added a valuable contribution to the synthesis of such thiophenes with high application
potential.
Figure 1. Examples of biologically active 2ꢀaminothiophenes and fluorescent biomarkers
with 2ꢀaminothiophene moiety.
ACS Paragon Plus Environment

Page 9 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Recently, during the preparation of this manuscript, Witulski and coworkers published
the first synthesis of 2ꢀ(tosylamido) and 2,5ꢀbis(tosylamido)thiophenes from butadiyneamides
and butadiyneꢀ1,4ꢀdiamides under similar conditions.31 Our work is the first synthesis of thioꢀ
phenes from polyyneamines and may be considered as a complementary addition to Witulꢀ
ski’s results and is the first synthesis of 2ꢀaminoꢀ5ꢀphenylthiophenes and 2ꢀaminoꢀ5ꢀphenylꢀ
ethynylthiophenes from butadiynes and hexatriynes. Reactions of polyynes higher than butaꢀ
diynes with sodium sulfide are rare and usually mixtures of different products are obtained.32
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Emission spectroscopy
Some of the presented thiophenes exhibit strong photoluminescence upon the UV
irradiation, thus we recorded absorption and emission/excitation spectra for all the new
thiophenes. Arylꢀsubstituted thiophenes 4aa, 4ac, 4ae, and 4ba exhibited the strongest
fluorescence in visible range, whereas for carbonyl 4ca, ethynyl 4ea, 4eb, 4fb and butadiynylꢀ
substituted 4ga compounds no emission was observed. Absorption and emission spectra of all
samples were recorded in a variety of solvents (see the Supporting Information). Stokes shifts
and emission quantum yields of the best emitting samples are summarized in Table 1.
Emission and excitation spectra in Et2O are shown in Figure 2 (for spectra in other solvents
see the Supporting Information). Compounds 4aa, 4ca, and 4ea exhibited very similar
spectroscopic properties with nearly identical blue fluorescence. The highest value of QY was
recorded for 4aa (74%), but compounds 4ac and 4ae exhibited comparable values (67 and
69%, respectively). The presence of a nitro substituent instead of a nitrile (compound 4ba) led
to a lower QY (6%) and the maximum of the emission band shifted from 444 to 579 nm
(orange emission). Moreover, 4ba did not exhibit significant emission in CH2Cl2 and DMF.
Nitroꢀgroupꢀcontaining fluorophores are known to have generally low photoluminescence
quantum yield due to decrease in the radiative rate and the increase in the internal conversion
rate of an exited state.33
Table 1. Emission parameters of substituted thiophenes. All spectra recorded in Et2O.
Emmax [nm]
Exmax [nm]
Stokes shift [cmꢀ1]
Reference sample
QY [%]
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 34
1
2
3
4
5
6
7
8
9
4aa 444
4ac 443
4ae 442
4ba 579
397
393
391
453
2670
2870
2950
4800
Quinine sulfate in 0.1 M H2SO4
74
67
69
6
Quinine sulfate in 0.1 M H2SO4
Quinine sulfate in 0.1 M H2SO4
Rhodamine B in ethanol
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 2. Emission and excitation spectra in Et2O.
Compounds 4aa, 4ac, 4ae, and 4ba exhibited moderate solvatochromism and could be taken
into consideration as solvent polarity probes. Stockes shifts for spectra recorded in solvents
more polar than Et2O were significantly higher (see the Table S1 in the Supporting
Information). Correlation of absorption and emission maxima with solvents π* values34 for
compound 4aa was examined (see Figures S5 and S6 in the Supporting Information).
Correlation parameters were calculated using the equation:
νmax =ν
0 + sπ*
where νmax is the absorption/emission maximum, ν0 shows the absorption/emission maximum
of the compound in nonꢀpolar solvent (π*=0), s describes quantitatively the sensitivity of the
dye to solvent polarity change. In case of compound 4aa the value was ꢀ1200 cmꢀ1, which is
rather low in comparison to the best known solvent polarity probes which are pyridinium
ACS Paragon Plus Environment

Page 11 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
betaines, which are about 8 times more sensitive to solvent polarity changes.35 As the
emission is much slower process than absorption, a larger solvatochromic shifts of emission
7
8
bands are expected. Solvent sensitivity index
s was much higher in case of emission spectra
and its value was ꢀ2800 cmꢀ1 for 4aa. The thorough spectroscopic experiments including
quantum yields measurements in different solvents, the synthesis of larger series of
substituted thiophenes and the theoretical calculations are now under study and will be the
topic of our next publication. Herein, we present preliminary data to indicate possible
application of this group of compounds.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
X-ray Crystallography
According to the literature, a few crystal structures of butadiynamines are known,15,36 and the
only crystal structure of nitrogen endꢀcapped hexatriyne is the structure of hexatriynamide.17
We obtained monocrystals of five ynamines appropriate for single crystal xꢀray analysis.
Monocrystals were obtained from the mixture of CH2Cl2 and hexanes. Compounds 3ad, 3ac,
and 3fd crystallize in monoclinic system,
P21/c space group, whereas 3ec and 3fe crystallize
in triclinic system, ꢀ1 space group (for further details on the structures see the Supporting
P
Information). Molecular views of the two butadiynes 3ad and 3ca and three hexatriynes 3ec,
3fd, and 3fe are presented in the Figure 3. The bond lengths in polyyne chains and the
contraction coefficients are presented in the Table 2. All hexatriynes (3ec, 3fd, 3fe) possess
nearly linear polyyne chains whereas butadiynes were slightly more distorted due to packing
forces. The N1 nitrogen atom in all cases exhibited a typical flat sp2 geometry and the N1ꢀC1
bond length was from 1.311 Å (for 3ca) to 1.322 Å (for 3ad).
Table 2. Bond lengths [Å] in polyyne chains and contraction coefficients.
N1ꢀC1
C1ꢀC2
C2ꢀC3
C3ꢀC4
C4ꢀC5
C5ꢀC6
C6ꢀC7
C1ꢀCxa
0.29%
0.05%
N1ꢀCx+1b
0.35%
3ad
3ca
1.322(3)
1.311(3)
1.221(3)
1.216(3)
1.362(3)
1.356(3)
1.214(3)
1.217(3)
1.420(3)
1.438(3)
ꢀ
ꢀ
ꢀ
ꢀ
0.31%
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 34
1
2
3
4
5
6
7
8
3ec
3fd
3fe
1.319(2)
1.321(2)
1.321(3)
1.204(3)
1.217(2)
1.206(3)
1.364(3)
1.358(2)
1.360(3)
1.212(3)
1.217(2)
1.210(3)
1.371(3)
1.368(2)
1.370(3)
1.204(3)
1.208(2)
1.197(3)
1.432(3)
1.432(2)
1.436(3)
0.06%
0.02%
0.00%
0.08%
0.03%
0.03%
aContraction C1ꢀCx = (C1ꢀCx sum of bond lengths
̶ C1ꢀCx distance)/C1ꢀCx sum of bond
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
b
lengths x 100%. Contraction N1ꢀCx+1 = (N1ꢀCx+1 sum of bond lengths ꢀ N1ꢀCx+1
distance)/N1ꢀCx+1 sum of bond lengths x 100%.
Figure 3. Molecular structures of amine endꢀcapped polyynes. Thermal ellipsoids are drawn
at 50% probability level.
Since aminobutadiynes and diaminobutadiynes are used in topochemical crystalꢀtoꢀ
crystal polymerization,15,36 we analyzed the packing motifs of the presented compounds in
detail. The closest chainꢀchain separation was scrutinized for each structure, which was
ACS Paragon Plus Environment

Page 13 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
understood as the closest carbon–carbon distance from two neighboring polyyne carbon
chains. We found two possible candidates for 1,nꢀtopochemical polymerization: 3ca and 3ec.
In the other cases, the carbonꢀcarbon contacts were not short enough. In case of 3ad and 3fd
bulky diisopropylamine group prevented from close chainꢀchain contacts.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The closest CꢀC contact in 3ca (3.513 Å) was slightly above the sum of the van der
Waals radii for two carbon atoms (3.4 Å), making it a promising candidate for topochemical
polymerization (see Figure 4). The closest carbonꢀcarbon contact in 3ec was longer (3.965 Å)
but still the polymerization could be possible.
Figure 4. Packing motifs for 3ca (top) and 3ec (bottom). Distances in Å. Symmetry
operations for related atoms are: 3ca (i) = x, y, z; (ii) = x, 1.5ꢀy, 0.5+z; 3ec (i) = x, y, z; (ii) = ꢀ
1 +x, y, z.
Moreover, an xꢀray solid state structure of substituted thiophene 4aa was obtained. Its
molecular view is presented in the Figure 5. The whole molecule adopts a nearly planar
geometry, except slightly distorted pyrrolidine moiety. The C1ꢀN1 bond was short (1.351 Å)
and the N1 nitrogen atom adopted a nearly planar sp2 geometry which was similar to the
known structures of 2ꢀamineꢀ5ꢀarylthiophenes.37
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 34
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 5. Molecular structure of 4aa. Thermal ellipsoids are drawn at 50ꢁ% probability level.
Selected bond lengths and angles: C1ꢀN1 = 1.351(4) Å; C15ꢀN1 = 1.465(4) Å; C12ꢀN1 =
1.457(4) Å; C1ꢀS1 = 1.746(3) Å; C4ꢀS1 = 1.759(3) Å; C1ꢀC2 = 1.379(5); C3ꢀC4 = 1.371(4)
Å; C2ꢀC3 = 1.407(5) Å; C4ꢀC5 = 1.448(4) Å; <(C1ꢀN1ꢀC15) = 121.9(3)˚; <(C1ꢀN1ꢀC12)
=125.0(3)˚; <(C12ꢀN1ꢀC15) = 112.6(2)˚.
Conclusions
We showed that the reaction of 1ꢀhalopolyynes with secondary amines is a very
convenient synthetic way to amine endꢀcapped polyynes. The reaction gives products under
very mild conditions and with good yields and selectivity. The resulting Nꢀcapped polyynes
are far more stable towards moisture than short Nꢀethynylamines and may be regarded,
similarly to the ynamides, as a convenient substrate in synthetic organic chemistry. Moreover,
single xꢀray diffraction structures for five amine endꢀcapped polyynes were obtained and the
structural analysis was presented. The reaction of amine endꢀcapped polyynes with sodium
sulfide yielded a series of novel, substituted pushꢀpull thiophenes and, according to our
knowledge, it is the first known direct transformation of ynamines to thiophenes. Moreover,
the reaction of hexatriynes and octatetraynes with sodium sulfide is the first regioselective
example of such transformation. Some of the obtained thiophenes exhibit strong fluorescence
with high quantum yields and may be regarded as solvent polarity probes.
Experimental Section
General
All reactions were conducted under N2 by using standard Schlenk techniques. Glassware was
preꢀdried at 120 °C. Solvents were treated as follows: hexane was distilled from Na, THF was
ACS Paragon Plus Environment

Page 15 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
distilled from Na/benzophenone, CH2Cl2 and CH3CN were distilled from P2O5, Et2O (pure for
analysis) was used as received. 1ꢀHalopolyynes and ((4ꢀmethoxyphenyl)butaꢀ1,3ꢀdiynꢀ1ꢀ
yl)trimethylsilane were obtained according to the known procedures.21, 38 Pyrrolidine (98%),
piperidine (puriss p.a.), diisopropylamine (99.5%), Nꢀmethylbenzylamine (97%), 2ꢀ
methylaminomethylꢀ1,3ꢀdioxolane (98%), Pd(PPh3)2Cl2 (99ꢁ%), Nꢀbromosuccinimide (99ꢁ%),
sodium sulfide hydrate (≥60% of Na2S), AgNO3 (puriss p.a.), KF (puriss p.a.) were used as
received.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1H and 13C NMR spectra were recorded with a 500 MHz spectrometer with an inverse
broadband probe. For all the 1H NMR spectra, the chemical shifts are given in ppm relative to
1
1
the solvent residual peaks (CDCl3, H: 7.26 ppm, 13C: 77.16 ppm; C6D6, H: 7.16 ppm, 13C:
1
128.06 ppm; CD3C(O)CD3, H: 2.05 ppm, 13C: 29.84 ppm). Coupling constants are given in
Hz. HMBC and HMQC techniques were used for peak assignment. HRMS spectra were
recorded using a spectrometer with a TOF mass analyzer and an ESI ion source. Fluorescence
emission and excitation spectra were recorded using an spectrophotometer equipped with a
450 W Xe lamp. Absorption spectra were recorded on a oneꢀbeam spectrometer. Quantum
yields were recorded using comparative method of Williams et al.39 in accordance with the
Jobin Yvon Horiba guide.40 Quinine sulfate in 0.1 M H2SO4 and rhodamine B in ethanol were
used as standard samples with quantum yields of 0.54 and 0.49 QY, respectively.41
Details of X-ray data collection and reduction
XꢀRay diffraction data were collected with the use of ω scan technique. The space groups
were determined from systematic absences and subsequent leastꢀsquares refinement. Lorentz
and polarization corrections were applied. The structures were solved by direct methods and
refined by fullꢀmatrix, leastꢀsquares on F2 by use of the SHELXTL Package.42 Nonꢀhydrogen
atoms were refined with anisotropic thermal parameters. Hydrogen atom positions were
calculated and added to the structure factor calculations, but were not refined.
(1d) 1-(Bromobutadiynyl)-4-methoxybenzene
((4ꢀMethoxyphenyl)butadiynyl)trimethylsilane (391 mg, 2.22 mmol) was dissolved in
acetonitrile and next NBS (474 mg, 2.66 mmol), AgNO3 (377 mg, 2.22 mmol), KF (129 mg,
2.22 mmol), and H2O (75 ꢂL, 4.4 mmol) were added. The flask was wrapped with aluminum
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 34
1
2
3
4
5
6
7
8
9
foil and the mixture was stirred for 24 h at room temperature under N2 atmosphere. Next, the
solvent was evaporated, the solid dissolved in eluent and filtrated through the silica gel plug
(eluent: hexanes/chloroform; v/v; 1:1). Solvent was evaporated under reduced pressure
yielding yellow solid, yield: 28% (0.150 g, 0.638 mmol). 1H NMR (500 MHz, CDCl3) δ 7.46
– 7.43 (m, 2H, HAr), 6.85 – 6.82 (m, 2H, HAr), 3.82 (s, 3H, CH3). 13C NMR (126 MHz,
CDCl3) δ 160.9 (CArO), 134.8 (CArH), 114.5 (CArC≡C), 113.3 (CArH), 74.7 (C≡C), 73.5
(C≡C), 66.0 (C≡C) 55.7 (CH3), 44.0 (C≡C). HRMS(ESI): m/z calcd for C11H8BrO: 234.9759
[M+H+]; found: 234.9753.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis of amine end-capped polyynes
(3aa) 4-(Pyrrolidin-1-ylbutadiynyl)benzonitrile
4ꢀ(Bromobutadiynyl)benzonitrile (1a, 12 mg, 0.052 mmol) was dissolved in a dry and
oxygenꢀfree THF (10 mL) under N2 atmosphere. Next, pyrrolidine (26 ꢂL, 0.32 mmol) was
added and the mixture was stirred for 1 h at room temperature. After this time the solvent was
evaporated, product was dissolved in hexanes, filtrated with the use of the Schlenk technique
and dried under reduced pressure. Product was obtained as a red solid, yield: 60% (6.9 mg,
1
0.031 mmol). H NMR (500 MHz, CDCl3) δ 7.56 – 7.53 (m, 2H, HAr), 7.46 – 7.42 (m, 2H,
HAr), 3.38 – 3.34 (m, 4H, NCH2), 1.90 – 1.87 (m, 4H, CH2). 13C{1H}NMR (126 MHz, CDCl3)
δ 132.0 (CHAr), 131.8 (CHAr), 129.2 (CC≡N), 118.9 (C≡N), 110.4 (CArC≡C), 91.1 (C≡C),
81.3 (C≡C), 79.2 (C≡C), 52.1 (CH2N), 51.7 (C≡C), 25.9 (CH2). HRMS(ESI): m/z calcd for
C15H13N2: 221.1073 [M+H+]; found: 221.1072.
(3ab) 4-(Piperidin-1-ylbutadiynyl)benzonitrile
4ꢀ(Bromobutadiynyl)benzonitrile (1a, 10 mg, 0.043 mmol), piperidine (26 ꢂL, 0.26 mmol),
and THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 1 h, orange
1
solid, yield 44% (4.5 mg, 0.019 mmol). H NMR (500 MHz, CDCl3) δ 7.56 – 7.53 (m, 2H,
HAr), 7.46 – 7.43 (m, 2H, HAr), 3.18 – 3.14 (m, 4H, NCH2), 1.66 – 1.61 (m, 4H, CH2), 1.57 –
1.53 (m, 2H, CH2). 13C{1H}NMR (126 MHz, CDCl3) δ 132.1 (CHAr), 131.9 (CHAr), 129.0
(CC≡N), 118.9 (C≡N), 110.6 (CArC≡C), 92.4 (C≡C), 81.0 (C≡C), 78.8 (C≡C), 52.6 (CH2N),
50.7 (C≡C), 25.1 (CH2), 23.5 (CH2). HRMS(ESI): m/z calcd for C16H15N2: 235.1230 [M+H+];
found: 235.1230.
ACS Paragon Plus Environment

Page 17 of 34
The Journal of Organic Chemistry
1
2
3
4
(3ac) 4-((((1,3-Dioxolan-2-yl)methyl)(methyl)amino)butadiynyl)benzonitrile
5
6
7
8
4ꢀ(Bromorobutadiynyl)benzonitrile (1a, 12 mg, 0.052 mmol), 1ꢀ(1,3ꢀdioxolanꢀ2ꢀyl)ꢀNꢀ
methylmethanamine (17 ꢂL, 0.15 mmol) and THF (10 mL) were reacted according to the
1
9
procedure for 3aa. Reaction time: 3 h, orange solid, yield: 87% (12 mg, 0.045 mmol). H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NMR (500 MHz, CDCl3) δ 7.56 – 7.52 (m, 2H, HAr), 7.46 – 7.43 (m, 2H, HAr), 5.11 (t, J = 4.0
Hz, 1H, OCH2O), 4.05 – 3.97 (m, 2H, OCH2), 3.97 – 3.88 (m, 2H, OCH2), 3.17 (d, J = 4.0
13
Hz, 2H, OCHO), 3.00 (s, 3H, CH3). C{1H}NMR (126 MHz, CDCl3) δ 132.1 (CHAr), 131.9
(CHAr), 129.0 (CC≡N), 118.9 (C≡N), 110.6 (CArC≡C), 102.6 (OCHO), 92.2 (C≡C), 81.0
(C≡C), 79.0 (C≡C), 65.4 (OCH2), 57.5 (NCH2), 50.6 (C≡C), 42.5 (CH3). HRMS(ESI): m/z
calcd for C16H15N2O2: 267.1128 [M+H+]; found: 267.1123.
(3ad) 4-((Diisopropylamino)butadiynyl)benzonitrile
1ꢀ(Bromobutadiynyl)ꢀ4ꢀnitrobenzene (1a, 18 mg, 0.078 mmol), N,Nꢀdiisopropylamine (66
ꢂL, 0.47 mmol) and THF (10 mL) were reacted according to the procedure for 3aa. Reaction
1
time: 24 h, orange solid, yield: 71% (13.8 mg, 0.055 mmol). H NMR (500 MHz, CDCl3) δ
7.54 – 7.52 (m, 2H, HAr), 7.46 – 7.44 (m, 2H, HAr), 3.19 (hept, J = 6.6 Hz, 2H, CH), 1.24 (d, J
13
= 6.6 Hz, 12H, CH3). C{1H}NMR (126 MHz, CDCl3) δ 132.0 (CHAr), 131.7 (CHAr), 129.4
(CC≡N), 119.0 (C≡N), 110.1 (CArC≡C), 88.3 (C≡C), 82.1 (C≡C), 79.0 (C≡C), 57.2 (C≡C),
53.0 (NCH), 21.7 (CH3). HRMS(ESI): m/z calcd for C17H19N2: 251.1543 [M+H+]; found:
251.1539.
(3ae) 4-((Benzyl(methyl)amino)butadiynyl)benzonitrile
4ꢀ(Bromobutadiynyl)benzonitrile (1a, 7.4 mg, 0.032 mmol), Nꢀmethylbenzylamine (13 ꢂL,
0.096 mmol) and THF 10 mL) were reacted according to the procedure for 3aa. Reaction
1
time: 1 h, orange solid, yield: 28% (2.4 mg, 0.0089 mmol). H NMR (500 MHz, CDCl3) δ
7.56 – 7.53 (m, 2H, Hbenzonitrile), 7.47 – 7.44 (m, 2H, Hbenzonitrile), 7.41 – 7.36 (m, 2H, HPh), 7.36
– 7.32 (m, 3H, HPh), 4.19 (s, 2H, CH3), 2.82 (s, 3H, CH3). 13C{1H}NMR (126 MHz, CDCl3) δ
135.8 (CPh), 132.1 (CHbenzonitrile), 131.9 (CHbenzonitrile), 129.0 (CC≡N), 128.9 (CHPh), 128.4
(CHPh), 128.3 (CHPh), 118.9 (C≡N), 110.6 (CArC≡C), 92.7 (C≡C), 80.9 (C≡C), 79.1 (C≡C),
59.6 (C≡C), 51.2 (s), 40.3 (C≡C). HRMS(ESI): m/z calcd for C19H15N2: 271.1229 [M+H+];
found: 271.1225.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 34
1
2
3
4
(3ba) 1-((4-Nitrophenyl)butadiynyl)pyrrolidine
5
6
7
8
1ꢀ(Bromobutadiynyl)ꢀ4ꢀnitrobenzene (1b, 16 mg, 0.064 mmol), pyrrolidine (27 ꢂL, 0.33
mmol) and THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 24
1
9
h, red solid, yield 45% (7.0 mg, 0.029 mmol). H NMR (500 MHz, CDCl3) δ 8.16 – 8.12 (m,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2H, CHAr), 7.52 – 7.45 (m, 2H, CHAr), 3.40 – 3.36 (m, 4H, NCH2), 1.92 – 1.87 (m, 4H, CH2).
13C{1H}NMR (126 MHz, CDCl3) δ 146.2 (CNO2), 131.8 (CArH), 131.4 (CArC≡C), 123.8
(CArH), 92.0 (C≡C), 82.7 (C≡C), 79.4 (C≡C), 52.2 (NCH2), 52.1 (C≡C), 26.0 (CH2).
HRMS(ESI): m/z calcd for C14H13N2O2: 241.0971 [M+H+]; found: 241.0973.
(3bb) 1-((4-Nitrophenyl)butadiynyl)piperidine
1ꢀ(Bromobutadiynyl)ꢀ4ꢀnitrobenzene (1b, 12 mg, 0.048 mmol), piperidine (29 ꢂL, 0.26
mmol) and THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 18
1
h, orange solid, yield 98% (12 mg, 0.047 mmol). H NMR (500 MHz, CDCl3) δ 8.16 – 8.12
(m, 2H, CHAr), 7.51 – 7.48 (m, 2H, CHAr), 3.20 – 3.15 (m, 4H, NCH2), 1.67 – 1.61 (m, 4H,
CH2), 1.59 – 1.51 (m, 2H, CH2). 13C{1H}NMR (126 MHz, CDCl3) δ 146.3 (CNO2), 131.9
(CHA), 131.2 (CArC≡C), 123.8 (CHA), 93.2 (C≡C), 82.3 (C≡C), 79.1 (C≡C), 52.6 (NCH2),
51.1 (C≡C), 25.1 (CH2), 23.5 (CH2). HRMS(ESI): m/z calcd for C15H15N2O2: 255.1128
[M+H+]; found: 255.1124.
(3bc) N-((1,3-dioxolan-2-yl)methyl)-N-methyl-4-(4-nitrophenyl)butadiynamine
1ꢀ(Bromobutadiynyl)ꢀ4ꢀnitrobenzene (1b, 8.0 mg, 0.032 mmol), 1ꢀ(1,3ꢀdioxolanꢀ2ꢀyl)ꢀNꢀ
methylmethanamine (22 ꢂL, 0.19 mmol) and THF (10 mL) were reacted according to the
1
procedure for 3aa. Reaction time: 2 h, yellow solid, yield 91% (8.1 mg, 0.029 mmol). H
NMR (500 MHz, CDCl3) δ 8.15 – 8.11 (m, 2H, CHAr), 7.51 – 7.47 (m, 2H, CHAr), 5.11 (t, J =
4.0 Hz, 1H, OCHO), 4.04 – 4.01 (m, 2H, OCH2), 3.93 – 3.90 (m, 2H, OCH2), 3.18 (d, J = 4.0
13
Hz, 2H, NCH2), 3.01 (s, 3H, CH3). C{1H}NMR (126 MHz, CDCl3) δ 146.4 (CNO2), 131.9
(CHAr), 131.1 (CArC≡C), 123.7 (CHAr), 102.5 (OCHO), 93.0 (C≡C), 82.3 (C≡C), 79.2 (C≡C),
65.4 (OCH2), 57.5 (NCH2), 50.9 (C≡C), 42.6 (CH3). HRMS(ESI): m/z calcd for C15H15N2O4:
287.1026 [M+H+]; found: 287.1024.
(3bd)
N
,
N-diisopropyl-4-(4-nitrophenyl)butadiynamine
ACS Paragon Plus Environment

Page 19 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1ꢀ(Bromobutadiynyl)ꢀ4ꢀnitrobenzene (1b, 10 mg, 0.040 mmol), diisopropylamine (17 ꢂL,
0.12 mmol) and THF (10 mL) were reacted according to the procedure for 3aa. Reaction
time: 24 h, yellow solid, yield 88% (9.8 mg, 0.035 mmol). 1H NMR (500 MHz, CDCl3) δ 8.16
– 8.10 (m, 2H), 7.51 – 7.48 (m, 2H), 3.21 (hept, J = 6.6 Hz, 2H), 1.25 (d, J = 6.6 Hz, 12H).
13C{1H}NMR (126 MHz, CDCl3) δ 146.0 (CNO2), 131.7 (CHAr), 131.6 (CArC≡C), 123.7
(CHAr), 89.2 (C≡C), 83.5 (C≡C), 79.4 (C≡C), 57.6 (C≡C), 53.1 (CH), 21.7 (CH3).
HRMS(ESI): m/z calcd for C16H19N2O2: 271.1441 [M+H+]; found: 271.1442.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(3be) N-benzyl-N-methyl-4-(4-nitrophenyl)butadiynamine
1ꢀ(Bromobutadiynyl)ꢀ4ꢀnitrobenzene (1b, 12 mg, 0.048 mmol), Nꢀmethylbenzylamine (19
ꢂL, 0.14 mmol) and THF (10 mL) were reacted according to the procedure for 3aa. Reaction
time: 4 h, yellow solid, yield 67% (9.3 mg, 0.032 mmol). 1H NMR (500 MHz, CDCl3) δ 8.16
– 8.12 (m, 2H, C6H4NO2), 7.52 – 7.49 (m, 2H, C6H4NO2), 7.41 – 7.37 (m, 2H, C6H5), 7.36 –
7.32 (m, 3H, C6H5), 4.20 (s, 2H, CH2), 2.83 (s, 3H, CH3). 13C{1H}NMR (126 MHz, CDCl3) δ
146.3 (CNO2), 135.6 (CPh), 131.8 (CHnitrobenzene), 131.0 (Cnitrobenzene), 128.8 (CHPh), 128.2 (two
overlapped signals, CHPh), 123.6 (CHnitrobenzene), 93.4 (C≡C), 82.1 (C≡C), 79.2 (C≡C), 59.5
(CH2), 51.4 (C≡C), 40.1 (CH3). HRMS(ESI): m/z calcd for C18H14N2O2Na: 313.0947
[M+Na+]; found: 313.0950.
(3ca) Methyl 5-(pyrrolidin-1-yl)penta-2,4-diynoate
Methyl 5ꢀbromopentaꢀ2,4ꢀdiynoate (1c, 27 mg, 0.14 mmol), pyrrolidine (36 ꢂL, 0.42 mmol)
and THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 1 h, yellow
solid, yield 93% (23 mg, 0.13 mmol). 1H NMR (500 MHz, CDCl3) δ 3.75 (s, 3H, CH3), 3.40 –
3.36 (m, 4H, NCH2), 1.90 – 1.85 (m, 4H, CH2). 13C{1H}NMR (126 MHz, CDCl3) δ 154.8
(C=O), 92.5 (C≡C), 77.7 (C≡C), 75.0 (C≡C), 54.0 (C≡C), 52.5 (CH3), 52.0 (NCH2), 25.9
(CH2). HRMS(ESI): m/z calcd for C10H12NO2: 178.0863 [M+H+]; found: 178.0867.
(3cb) Methyl 5-(piperidin-1-yl)penta-2,4-diynoate
Methyl 5ꢀbromopentaꢀ2,4ꢀdiynoate (1c, 27 mg, 0.144 mmol), piperidine (25 ꢂL, 0.26 mmol)
and THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 1 h, yellow
solid, yield 36% (10 mg, 0.052 mmol). 1H NMR (500 MHz, CDCl3) δ 3.75 (s, 3H, CH3), 3.21
– 3.14 (m, 4H, NCH2), 1.66 – 1.60 (m, 4H, CH2), 1.51 – 1.57 (m, 2H, CH2). 13C{1H}NMR
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 34
1
2
3
4
5
6
7
8
(126 MHz, CDCl3) δ 154.8 (C=O), 93.7 (C≡C), 77.4 (C≡C), 74.8 (C≡C), 52.9 (C≡C), 52.5
(CH3), 52.3 (NCH2), 25.1 (CH2), 23.3 (CH2). HRMS(ESI): m/z calcd for C11H14NO2:
192.1019 [M+H+]; found: 192.1023.
9
(3cc) Methyl 5-(((1,3-dioxolan-2-yl)methyl)(methyl)amino)penta-2,4-diynoate
Methyl 5ꢀbromopentaꢀ2,4ꢀdiynoate (1c, 16 mg, 0.086 mmol), 1ꢀ(1,3ꢀdioxolanꢀ2ꢀyl)ꢀNꢀ
methylmethanamine (29 ꢂL, 0.25 mmol) and THF (5 mL) were reacted according to the
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
procedure for 3aa. Reaction time: 1 h, yellow solid, yield: 53% (10 mg, 0.045 mmol). H
NMR (500 MHz, CDCl3) δ 5.08 (t, J = 3.9 Hz, 1H, OCH2O), 4.01 – 3.99 (m, 2H, OCH2), 3.92
– 3.89 (m, 2H, OCH2), 3.75 (s, 3H, CH3), 3.16 (d, J = 3.9 Hz, 2H, OCHO), 3.00 (s, 3H, CH3).
13C{1H}NMR (126 MHz, CDCl3) δ 154.7 (C=O), 102.3 (OCHO), 93.6 (C≡C), 77.1 (C≡C),
74.6 (C≡C), 65.4 (OCH2), 57.2 (NCH2), 52.5 (OCH3), 52.4 (C≡C), 42.4 (CH3). HRMS(ESI):
m/z calcd for C11H14NO4: 224.0917 [M+H+]; found: 224.0915.
(3cd) Methyl 5-(diisopropylamino)penta-2,4-diynoate
Methyl 5ꢀbromopentaꢀ2,4ꢀdiynoate (1c, 9.9 mg, 0.052 mmol), N,Nꢀdiisopropylamine (23 ꢂL,
0.15 mmol) and THF (5 mL) were reacted according to the procedure for 3aa. Reaction time:
1
2.5 h, yellow solid, yield: 75% (8.2 mg, 0.39 mmol). H NMR (500 MHz, CDCl3) δ 3.76 (s,
3H, CH3), 3.19 (hept, J = 13.1, 6.6 Hz, 2H, CH), 1.22 (d, J = 6.5 Hz, 12H, CH3).
13C{1H}NMR (126 MHz, CDCl3) δ 155.0 (C=O), 90.4 (C≡C), 78.8 (C≡C), 75.3 (C≡C), 59.7
(C≡C), 53.3 (OCH3), 52.4 (NCH), 21.6 (CH3). HRMS(ESI): m/z calcd for C12H17NO2Na:
230.1151 [M+Na+]; found: 230.1149.
(3da) 1-((4-Methoxyphenyl)butadiynyl)pyrrolidine
1ꢀ(Bromobutadiynyl)ꢀ4ꢀmethoxybenzene (1d, 9.6 mg, 0.041 mmol), pyrrolidine (10 ꢂL, 0.12
mmol) and THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 4 h,
1
yellow solid, yield: 89% (8.9 mg, 0.037 mmol). H NMR (500 MHz, CDCl3) δ 7.38 – 7.36
(m, 2H, HAr), 6.81 – 6.80 (m, 2H, HAr), 3.79 (s, 3H, CH3), 3.32 (t, J = 6.8 Hz, 4H, NCH2 ),
1.88 – 1.82 (m, 4H, CH2). 13C{1H}NMR (126 MHz, CDCl3) δ 159.5 (OCAr), 133.7 (CHAr),
115.9 (CArC≡C), 114.1 (CHAr), 87.5 (C≡C), 79.7 (C≡C), 74.3 (C≡C), 55.4 (OCH3), 52.2
(NCH2), 50.7 (C≡C), 25.9 (CH2). HRMS(ESI): m/z calcd for C15H17NNaO2: 266.1151
[M+H2O+Na+]; found: 266.1163.
ACS Paragon Plus Environment

Page 21 of 34
The Journal of Organic Chemistry
1
2
3
4
(3db) 1-((4-Methoxyphenyl)butadiynyl)piperidine
5
6
7
8
1ꢀ(Bromobutadiynyl)ꢀ4ꢀmethoxybenzene (1d, 12 mg, 0.051 mmol), piperydine (15 ꢂL, 0.15
mmol) and THF (5 mL) were reacted according to the procedure for 3aa. Reaction time: 4 h,
1
9
yellow solid, yield: 74% (9.1 mg, 0.038 mmol). H NMR (500 MHz, CDCl3) δ 7.38 – 7.37
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(m, 2H, HAr), 6.81 – 6.80 (m, 2H, HAr), 3.80 (s, 3H, CH3), 3.13 – 3.11 (m, 4H, NCH2), 1.64 –
1.59 (m, 4H, CH2), 1.55 – 1.51 (m, 2H, CH2). 13C{1H}NMR (126 MHz, CDCl3) δ 159.6
(CArO), 133.7 (CHAr), 115.7 (CHAr), 114.1 (CArC≡C), 88.8 (C≡C), 79.4 (C≡C), 74.0 (C≡C),
55.4 (CH3), 52.8 (NCH2), 49.9 (C≡C), 25.1 (CH2), 23.6 (CH2). HRMS(ESI): m/z calcd for
C16H18NO: 240.1343 [M+H+]; found: 240.1352.
(3ea) 4-(Pyrrolidin-1-ylhexatriynyl)benzonitrile
4ꢀ(Bromohexatriynyl)benzonitrile (1e, 9.0 mg, 0.035 mmol), pyrrolidine (22 ꢂL, 0.21 mmol)
and THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 1 h, red
1
solid, yield 57% (5.0 mg, 0.020 mmol). H NMR (500 MHz, CDCl3) δ 7.59 – 7.56 (m, 2H,
HAr), 7.54 – 7.51 (m, 2H, HAr), 3.38 (ddd, J = 6.7, 4.3, 2.6 Hz, 4H, NCH2), 1.90 – 1.85 (m,
4H, CH2). 13C{1H}NMR (126 MHz, CDCl3) δ 133.1 (CHAr), 132.2 (CHAr), 127.7 (CC≡N),
118.7 (C≡N), 111.9 (CArC≡C), 86.9 (C≡C), 80.5 (C≡C), 76.8 (C≡C), 72.2 (C≡C), 66.4 (C≡C),
54.6 (C≡C), 52.1 (NCH2), 26.0 (CH2). HRMS(ESI): m/z calcd for C17H13N2: 245.1073
[M+H+]; found: 245.1076.
(3eb) 4-(Piperidin-1-ylhexatriynyl)benzonitrile
4ꢀ(Bromohexatriynyl)benzonitrile (1e, 13 mg, 0.051 mmol), piperidine (30 ꢂL, 0.30 mmol)
and THF (5 mL) were reacted according to the procedure for 3aa. Reaction time: 2 h, yellow
1
solid, yield 76% (10 mg, 0.039 mmol). H NMR (500 MHz, CDCl3) δ 7.59 – 7.56 (m, 2H,
HAr), 7.53 (d, J = 8.5 Hz, 2H, HAr), 3.20 – 3.15 (m, 4H, NCH2), 1.66 – 1.60 (m, 4H, CH2),
1.56 – 1.51 (m, 2H, CH2). 13C{1H}NMR (126 MHz, CDCl3) δ 133.0 (CHAr), 132.1 (CHAr),
127.6 (CC≡N), 118.6 (C≡N), 111.8 (CArC≡C), 88.1 (C≡C), 80.3 (C≡C), 76.6 (C≡C), 71.9
(C≡C), 66.1 (C≡C), 53.3 (C≡C), 52.4 (NCH2), 25.1 (CH2), 23.4 (CH2). HRMS(ESI): m/z
calcd for C18H15N2: 259.1230 [M+H+]; found: 259.1225.
(3ec) 4-((((1,3-Dioxolan-2-yl)methyl)(methyl)amino)hexatriynyl)benzonitrile
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 34
1
2
3
4
4ꢀ(Bromohexatriynyl)benzonitrile (1e, 5.0 mg, 0.020 mmol), 1ꢀ(1,3ꢀdioxolanꢀ2ꢀyl)ꢀNꢀ
5
6
methylmethanamine (7 ꢂL, 0.06 mmol) and THF (5 mL) were reacted according to the
7
8
1
procedure for 3aa. Reaction time: 1.5 h, yellow solid, yield 90% (5.1 mg, 0.018 mmol). H
9
NMR (500 MHz, CDCl3) δ 7.59 – 7.56 (m, 2H, HAr), 7.54 – 7.51 (m, 2H, HAr), 5.10 (t, J = 3.9
Hz, 1H, OCHO), 4.05 – 3.98 (m, 2H, OCH2), 3.95 – 3.88 (m, 2H, OCH2), 3.16 (d, J = 3.9 Hz,
2H, NCH2), 3.00 (s, 3H, CH3). 13C{1H}NMR (126 MHz, CDCl3) δ 133.0 (CHAr), 132.1
(CHAr), 127.5 (CC≡N), 118.6 (C≡N), 111.9 (CArC≡C), 102.5 (OCHO), 88.0 (C≡C), 80.2
(C≡C), 76.5 (C≡C), 71.7 (C≡C), 66.1 (C≡C), 65.4 (CH3), 57.3 (NCH2), 53.1 (C≡C), 42.4
(CH3). HRMS(ESI): m/z calcd for C18H15N2O2: 291.1128 [M+H+]; found: 291.1119.
(3ed) 4-((Diisopropylamino)hexatriynyl)benzonitrile
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4ꢀ(Bromohexatriynyl)benzonitrile (1e, 24 mg, 0.088 mmol), diisopropylamine (37 ꢂL, 0.26
mmol) and THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 24
1
h, yellow solid, yield 95% (23 mg, 0.084 mmol). H NMR (500 MHz, CDCl3) δ 7.58 – 7.56
(m, 2H), 7.53 – 7.50 (m, 2H), 3.17 (hept, J = 6.6 Hz, 2H), 1.23 (d, J = 6.6 Hz, 12H).
13C{1H}NMR (126 MHz, CDCl3) δ 132.8 (CHAr), 132.1 (CHAr), 127.8 (CC≡N), 118.6 (C≡N),
111.6 (CArC≡C), 84.4 (C≡C), 80.6 (C≡C), 77.1 (C≡C), 72.8 (C≡C), 66.5 (C≡C), 59.9 (C≡C),
53.1 (CH), 21.6 (CH3). HRMS(ESI): m/z calcd for C19H19N2:275.1543 [M+H+]; found:
275.1541.
(3ee) 4-((Benzyl(methyl)amino)hexatriynyl)benzonitrile
4ꢀ(Bromohexatriynyl)benzonitrile (1e, 18 mg, 0.071 mmol), Nꢀmethylbenzylamine (23 ꢂL,
0.17 mmol) and THF (10 mL) were reacted according to the procedure for 3aa. Reaction
time: 24 h, yellow solid, yield 76% (16 mg, 0.054 mmol). 1H NMR (500 MHz, CDCl3) δ 7.58
(d, J = 8.6 Hz, 2H, C6H4CN), 7.53 (d, J = 8.6 Hz, 2H, C6H4CN), 7.41 – 7.34 (m, 3H, C6H5),
7.33 – 7.30 (m, 2H, C6H5), 4.18 (s, 2H, CH2), 2.82 (s, 3H, CH3). 13C{1H}NMR (126 MHz,
CDCl3) δ 135.4 (CPh), 133.0 (CHbenzonitrile), 132.1 (CHbenzonitrile), 129.0 (CHPh), 128.4 (CHPh),
128.4 (CHPh), 127.5 (CC≡N), 118.5 (C≡N), 111.9 (CArC≡C), 88.5 (C≡C), 80.2 (C≡C), 76.7
(C≡C), 71.7 (C≡C), 66.3 (C≡C), 59.4 (CH2), 53.8 (C≡C), 40.1 (CH3). HRMS(ESI): m/z calcd
for C21H15N2: 295.1230 [M+H+]; found: 295.1232.
(3fa) 1-((4-Nitrophenyl)hexatriynyl)pyrrolidine
ACS Paragon Plus Environment

Page 23 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1ꢀ(Bromohexatriynyl)ꢀ4ꢀnitrobenzene (1f, 7.0 mg, 0.026 mmol), pyrrolidine (4 ꢂL, 0.052
mmol) and THF (5 mL) were reacted according to the procedure for 3aa. Reaction time: 1 h,
orange solid, yield 65% (4.4 mg, 0.017 mmol). 1H NMR (500 MHz, CDCl3) δ 8.16 (d, J = 9.0
Hz, 2H, HAr), 7.59 (d, J = 9.0 Hz, 2H, HAr), 3.40 – 3.37 (m, 4H, NCH2), 1.91 – 1.84 (m, 4H,
CH2). 13C{1H}NMR (126 MHz, CDCl3) δ 147.1 (CNO2), 133.2 (CHAr), 129.7 (CArC≡C),
123.8 (CHAr), 87.2 (C≡C), 81.4 (C≡C), 76.7 (C≡C), 72.8 (C≡C), 66.5 (C≡C), 54.6 (C≡C),
52.0 (NCH2), 25.9 (CH2). HRMS(ESI): m/z calcd for C16H13N2O2: 265.0972 [M+H+]; found:
265.0968.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(3fb) 1-((4-Nitrophenyl)hexatriynyl)piperidine
1ꢀ(Bromohexatriynyl)ꢀ4ꢀnitrobenzene (1f, 6.0 mg, 0.022 mmol), piperidine (13 ꢂL, 0.13
mmol) and THF (5 mL) were reacted according to the procedure for 3aa. Reaction time: 1.5
1
h, orange solid, yield: 73% (4.4 mg, 0.016 mmol). H NMR (500 MHz, CDCl3) δ 8.19 – 8.15
(m, 2H, HAr), 7.61 – 7.57 (m, 2H, HAr), 3.23 – 3.13 (m, 4H, NCH2), 1.67 – 1.61 (m, 4H, CH2),
1.58 – 1.52 (m, 2H, CH2). 13C{1H}NMR (126 MHz, CDCl3) δ 147.2 (CNO2), 133.2 (CHAr),
129.7 (CArC≡C), 123.8 (CHAr), 88.5 (C≡C), 81.3 (C≡C), 76.5 (C≡C), 72.5 (C≡C), 66.2 (C≡C),
53.5 (C≡C), 52.4 (NCH2), 25.1 (CH2), 23.4 (CH2). HRMS(ESI): m/z calcd for C17H15N2O2:
279.1128 [M+H+]; found: 279.1126.
(3fc) N-((1,3-dioxolan-2-yl)methyl)-N-methyl-6-(4-nitrophenyl)hexatriynamine
1ꢀ(Bromohexatriynyl)ꢀ4ꢀnitrobenzene (1f, 28.0 mg, 0.10 mmol), 1ꢀ(1,3ꢀdioxolanꢀ2ꢀyl)ꢀNꢀ
methylmethanamine (35 ꢂL, 0.31 mmol) and THF (5 mL) were reacted according to the
1
procedure for 3aa. Reaction time: 1.5 h, orange solid, yield: 32% (9.9 mg, 0.032 mmol). H
NMR (500 MHz, CDCl3) δ 8.17 – 8.15 (m, 2H, HAr), 7.60 – 7.58 (m, 2H, HAr), 5.10 (t, J = 3.9
Hz, 1H), 4.02 (dd, J = 8.8, 5.2 Hz, 2H), 3.92 (dd, J = 4.4, 2.3 Hz, 2H), 3.17 (d, J = 3.9 Hz,
2H), 3.00 (s, 3H, CH3). 13C{1H}NMR (126 MHz, CDCl3) δ 147.2 (CNO2), 133.2 (CHAr),
129.6 (CArC≡C), 123.8 (CHAr), 102.4 (OCHO), 88.4 (C≡C), 81.2 (C≡C), 76.4 (C≡C), 72.3
(C≡C), 66.2 (C≡C), 65.4 (OCH2), 57.3 (C≡C), 53.2 (NCH2), 42.4 (CH3). HRMS(ESI): m/z
calcd for C17H15N2O4: 311.1026 [M+H+]; found: 311.1021.
(3fd)
N,
N
-diisopropyl-6-(4-nitrophenyl)hexatriynamine
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 34
1
2
3
4
5
6
7
8
9
1ꢀ(Bromohexatriynyl)ꢀ4ꢀnitrobenzene (1f, 12 mg, 0.041 mmol), N,Nꢀdiisopropylamine (18
ꢂL, 0.13 mmol) and THF (5 mL) were reacted according to the procedure for 3aa. Reaction
time: 4 h, orange solid, yield: 59% (7.0 mg, 0.024 mmol). 1H NMR (500 MHz, CDCl3) δ 8.17
– 8.15 (m, 2H, HAr), 7.58 – 7.56 (m, 2H, HAr), 3.18 (hept, J = 6.6 Hz, 2H, CH), 1.24 (d, J =
6.5 Hz, 12H, CH3). 13C{1H}NMR (126 MHz, CDCl3) δ 147.0 (CNO2), 133.0 (CHAr), 129.9
(CArC≡C), 123.8 (CHAr), 84.8 (C≡C), 81.7 (C≡C), 77.0 (C≡C), 73.5 (C≡C), 66.6 (C≡C), 60.2
(C≡C), 53.2 (NCH), 21.7 (CH3). HRMS(ESI): m/z calcd for C18H19N2O2: 295.1441 [M+H+];
found: 295.1446.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(3fe) N-benzyl-N-methyl-6-(4-nitrophenyl)hexatriynamine
1ꢀ(Bromohexatriynyl)ꢀ4ꢀnitrobenzene (1f, 22 mg, 0.080 mmol), Nꢀmethylbenzylamine (31
ꢂL, 0.24 mmol) and THF (5 mL) were reacted according to the procedure for 3aa. Reaction
1
time: 1.5 h, orange solid, yield: 48% (12 mg, 0.038 mmol). H NMR (500 MHz, CDCl3) δ
8.18 – 8.16 (m, 2H, C6H4NO2), 7.60 – 7.58 (m, 2H, C6H4NO2), 7.40 – 7.31 (m, 5H, C6H5),
4.19 (s, 2H, CH2), 2.82 (s, 3H, CH3). 13C{1H}NMR (126 MHz, CDCl3) δ 147.2 (CNO2),
135.4 (CPh), 133.2 (CHnitrobenzene), 129.6 (CnitrobenzeneC≡C), 129.0 (CHPh), 128.4 (CHPh), 128.5
(CHPh), 123.8 (CHnitrobenzene) 88.1 (C≡C), 81.2 (C≡C), 76.6 (C≡C), 72.3 (C≡C), 66.4 (C≡C),
59.5 (CH2), 53.9 (C≡C), 40.1 (CH3). HRMS(ESI): m/z calcd for C20H15N2O2: 315.1128
[M+H+]; found: 315.1132.
(3ga) 4-(Pyrrolidin-1-yloctatetraynyl)benzonitrile
4ꢀ(Iodooctatetrayl)benzonitrile (1g, 31 mg, 0.095 mmol), pyrrolidine (24 ꢂL, 0.29 mmol) and
THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 2 h, red solid,
1
yield 94% (24 mg, 0.089 mmol). H NMR (500 MHz, CDCl3) δ 7.61 – 7.55 (m, 4H, HAr),
3.39 (ddd, J = 6.8, 4.3, 2.6 Hz, 4H, NCH2), 1.90 – 1.86 (m, 4H), CH2). 13C{1H}NMR (126
MHz, CDCl3) δ 133.4 (CHAr), 132.2 (CHAr), 126.7 (CC≡N), 118.4 (C≡N), 112.5 (CArC≡C),
85.4 (C≡C), 79.6 (C≡C), 75.7 (C≡C), 71.3 (C≡C), 68.7 (C≡C), 68.3 (C≡C), 63.9 (C≡C), 55.8
(C≡C), 52.0 (NCH2), 25.9 (CH2). HRMS(ESI): m/z calcd for C19H13N2: 269.1073 [M+H+];
found: 269.1073.
(3gb) 4-(Piperidin-1-yloctatetraynyl)benzonitrile
ACS Paragon Plus Environment

Page 25 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
4ꢀ(Iodooctatetraynyl)benzonitrile (1g, 10 mg, 0.031 mmol), piperidine (11 ꢂL, 0.11 mmol)
and THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 1.5 h, red
7
8
1
solid, yield: 48% (4.3 mg, 0.015 mmol). H NMR (500 MHz, CDCl3) δ 7.61 – 7.54 (m, 4H,
9
HAr), 3.20 – 3.16 (m, 2H, NCH2), 1.66 – 1.60 (m, 4H, CH2), 1.57 – 1.50 (m, 2H, CH2).
13C{1H}NMR (126 MHz, CDCl3) δ 133.4 (CHAr), 132.2 (CHAr), 126.7 (CC≡N), 118.4 (C≡N),
112.5 (CArC≡C), 86.6 (C≡C), 79.5 (C≡C), 75.6 (C≡C), 71.2 (C≡C), 68.5 (C≡C), 68.1 (C≡C),
63.7 (C≡C), 54.6 (C≡C), 52.3 (NCH2), 25.1 (CH2), 23.3 (CH2). HRMS(ESI): m/z calcd for
C20H15N2: 283.1230 [M+H+]; found: 283.1231.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(3gc) 4-((((1,3-Dioxolan-2-yl)methyl)(methyl)amino)octatetraynyl)benzonitrile
4ꢀ(Iodooctatetraynyl)benzonitrile (1g, 10 mg, 0.031 mmol), 1ꢀ(1,3ꢀdioxolanꢀ2ꢀyl)ꢀNꢀ
methylmethanamine (11 ꢂL, 0.095 mmol) and THF (5 mL) were reacted according to the
1
procedure for 3aa. Reaction time: 5 h, red solid, yield: 90% (8.9 mg, 0.028 mmol). H NMR
(500 MHz, CDCl3) δ 7.61 – 7.59 (m, 2H, HAr), 7.57 – 7.56 (m, 2H, HAr), 5.09 (t, J = 3.9 Hz,
1H, OCH2O), 4.01 (dd, J = 4.4, 2.3 Hz, 2H, OCH2), 3.92 (dd, J = 4.4, 2.3 Hz, 2H, OCH2O),
3.16 (d, J = 3.9 Hz, 2H, OCHO), 3.00 (s, 3H, CH3). 13C{1H}NMR (126 MHz, CDCl3) δ 133.4
(CHAr), 132.2 (CHAr), 126.6 (CC≡N), 118.4 (C≡N), 112.6 (CArC≡C), 102.4 (OCHO), 86.6
(C≡C), 79.4 (C≡C), 75.6 (C≡C), 71.1 (C≡C), 68.4 (C≡C), 67.9 (C≡C), 65.4 (OCH2), 63.6
(C≡C), 57.2 (NCH2), 54.2 (C≡C), 42.4 (CH3). HRMS(ESI): m/z calcd for C20H14N2O2Na:
337.0947 [M+Na+]; found: 337.0946.
(3gd) 4-((Diisopropylamino)octatetraynyl)benzonitrile
4ꢀ(Iodooctatetrayl)benzonitrile (1g, 10 mg, 0.031 mmol), diisopropylamine (14 ꢂL, 0.10
mmol) and THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 24
1
h, red solid, yield 84% (7.7 mg, 0.026 mmol). H NMR (500 MHz, CDCl3) δ 7.61 – 7.54 (m,
4H, CHAr), 3.17 (hept, J = 6.5 Hz, 2H, CH), 1.23 (d, J = 6.6 Hz, 12H, CH3). 13C{1H}NMR
(126 MHz, CDCl3) δ 133.3 (CHAr), 132.2 (CHAr), 126.8 (CC≡N), 118.4 (C≡N), 112.4
(CArC≡C), 82.9 (C≡C), 79.7 (C≡C), 75.9 (C≡C), 71.5 (C≡C), 69.0 (C≡C), 68.9 (C≡C), 64.3
(C≡C), 61.3 (C≡C), 53.2 (CH), 21.7 (CH3). HRMS(ESI): m/z calcd for C21H19N2: 299.1543
[M+H+]; found: 299.1546.
(3ge) 4-((Benzyl(methyl)amino)octatetraynyl)benzonitrile
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 34
1
2
3
4
5
6
7
8
9
4ꢀ(Iodooctatetrayl)benzonitrile (1g, 7.0 mg, 0.022 mmol), Nꢀmethylbenzylamine (9 ꢂL, 0.072
mmol) and THF (10 mL) were reacted according to the procedure for 3aa. Reaction time: 24
h, red solid, yield: 91% (6.4 mg, 0.020 mmol). 1H NMR (500 MHz, CDCl3) δ 7.62 – 7.55 (m,
4H, C6H4CN), 7.41 – 7.28 (m, 5H, C6H5), 4.18 (s, 2H. CH2), 2.82 (s, 3H, CH3). 13C{1H}NMR
(126 MHz, CDCl3) δ 135.1 (CPh), 133.3 (CHbenzonitrile), 132.1 (CHbenzonitrile), 128.9 (CHPh),
128.4 (CHPh), 128.2 (CHPh), 126.5 (CC≡N), 118.2 (C≡N), 112.4 (CArC≡C), 86.9 (C≡C), 79.3
(C≡C), 75.6 (C≡C), 71.0 (C≡C), 68.5 (C≡C), 67.8 (C≡C), 63.7 (C≡C), 59.3 (CH2), 54.8
(C≡C), 39.9 (CH3). HRMS(ESI): m/z calcd for C23H15N2: 319.1230 [M+H+]; found:
319.1243.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis of push-pull thiophenes
(4aa) 4-(5-(Pyrrolidin-1-yl)thiophen-2-yl)benzonitrile
4ꢀ(Pyrrolidinꢀ1ꢀylbutadiynyl)benzonitrile (3aa, 19 mg, 0.086 mmol) was dissolved in MeCN
o
(10 mL) and the mixture was heated to 70 C under N2 atmosphere. Next, Na2S•xH2O (60%
of Na2S, 0.10 mmol) was added and the mixture was stirred for 2.5 h. After this time water
(100 mL) was added and the product was extracted with Et2O (3 x 30 mL). Combined organic
layers were washed twice with H2O (2 x 20 mL), dried over MgSO4, filtered and the solvent
was evaporated under reduced pressure yielding 19 mg (0.075 mmol) of yellow solid. Yield:
1
87%. H NMR (500 MHz, C6D6) δ 7.10 – 7.07 (m, 2H, Hbenzonitrile), 7.05 – 7.02 (m, 2H,
Hbenzonitrile), 6.97 (d, J = 4.0 Hz, 1H, Hthiophene), 5.58 (d, J = 4.0 Hz, 1H, Hthiophene), 2.86 – 2.81
(m, 4H, NCH2), 1.38 – 1.33 (m, 4H, CH2). 13C{1H}NMR (126 MHz, C6D6) δ 157.2
(CthiopheneN), 139.8 (Cbenzonitrile), 132.6 (CHbenzonitrile), 126.4 (CHthiophene), 124.0 (Cthiophene),
123.5 (CHbenzonitrile), 119.5 (C≡N), 108.0 (CC≡N), 101.7 (CHthiophene), 50.4 (NCH2), 25.7
(CH2). HRMS(ESI): m/z calcd for C15H15N2S: 255.0950 [M+H+]; found: 255.0949.
(4ac) 4-(5-(((1,3-Dioxolan-2-yl)methyl)(methyl)amino)thiophen-2-yl)benzonitrile
4ꢀ((((1,3ꢀDioxolanꢀ2ꢀyl)methyl)(methyl)amino)butadiynyl)benzonitrile (3ac, 0.083 mmol),
Na2S•xH2O (60% of Na2S, 12 mg, 0.10 mmol) and MeCN (10 mL) were reacted according to
1
the procedure for 4aa. Yellow solid (18 mg, 0.060 mmol), yield: 72% H NMR (500 MHz,
C6D6) δ 7.01 (s, 4H, Hbenzonitrile), 6.86 (d, J = 4.1 Hz, 1H, Hthiophene), 5.73 (d, J = 4.1 Hz, 1H,
Hthiophene), 4.89 (t, J = 3.9 Hz, 1H, OCH), 3.44 – 3.37 (m, 2H, OCH2), 3.28 – 3.20 (m, 4H,
ACS Paragon Plus Environment

Page 27 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
OCH2, NCH2), 2.74 (s, 3H, CH3). 13C{1H}NMR (126 MHz, C6D6) δ 160.1 (CthiopheneN), 139.5
(Cbenzonitrile), 132.6 (CHbenzonitrile), 126.2 (CHthiophene), 124.9 (Cthiophene), 123.7 (CHbenzonitrile),
119.4 (C≡N), 108.4 (CC≡N), 103.1 (OCHO), 102.4 (CHthiophene), 65.0 (OCH2), 58.2 (NCH2),
41.0 (CH3). HRMS(ESI): m/z calcd for C16H17N2O2S: 301.1005 [M+H+]; found: 301.1010.
(4ae) 4-(5-(Benzyl(methyl)amino)thiophen-2-yl)benzonitrile
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4ꢀ((Benzyl(methyl)amino)butadiynyl)benzonitrile (3ae, 15 mg, 0.055 mmol), Na2S•xH2O
(60% of Na2S, 6.4 mg, 0.08 mmol) and MeCN (10 mL) were reacted according to the
1
procedure for 4aa. Yellow solid (13 mg 0.043 mmol), yield: 78% H NMR (500 MHz, C6D6)
δ 7.13 – 7.09 (m, 2H, C6H5), 7.07 – 7.01 (m, 3H, C6H5), 7.00 (s, 4H, C6H4CN), 6.83 (d, J =
4.1 Hz, 1H, Hthiophene), 5.66 (d, J = 4.1 Hz, 1H, Hthiophene), 4.02 (s, 2H, CH2), 2.47 (s, 3H, CH3).
13C{1H}NMR (126 MHz, C6D6) δ 160.3 (CthiopheneN), 139.4 (Cbenzonitrile), 137.4 (CPh), 132.6
(CHbenzonitrile), 129.0 (CHPh), 127.8 (CHPh), 127.5 (CHPh), 126.2 (CHthiophene), 125.2 (Cthiophene),
123.8 (CHbenzonitrile), 119.4 (C≡N), 108.5 (CC≡N), 103.5 (CHthiophene), 59.1 (CH2), 39.5 (CH3).
HRMS(ESI): m/z calcd for C19H16N2NaS: 327.0930 [M+Na+]; found: 327.0931.
(4ba) 1-(5-(4-Nitrophenyl)thiophen-2-yl)pyrrolidine
1ꢀ((4ꢀNitrophenyl)butadiynyl)pyrrolidine (3ba, 14 mg, 0.058 mmol), Na2S•xH2O (60% of
Na2S, 14 mg, 0.12 mmol) and MeCN (10 mL) were reacted according to the procedure for
4aa. Yellow solid (9.0 mg, 0.033 mmol), yield: 57% 1H NMR (500 MHz, C6D6) δ 7.95 – 7.90
(m, 2H, Hnitrobenzene), 7.09 – 7.05 (m, 2H, Hnitrobenzene), 6.99 (d, J = 4.1 Hz, 1H, Hthiophene), 5.58
(d, J = 4.1 Hz, 1H, Hthiophene), 2.84 – 2.80 (m, 4H, NCH2), 1.37 – 1.32 (m, 4H, CH2).
13C{1H}NMR (126 MHz, C6D6) δ 157.9 (CthiopheneN), 144.8 (CNO2), 141.9 (Cnitrobenzene), 127.5
(CHthiophene), 124.7 (CHnitrobenzene), 123.5 (Cthiophene), 122.9 (CHnitrobenzene), 102.1 (CHthiophene),
50.4 (NCH2), 25.7 (CH2). HRMS(ESI): m/z calcd for C14H15N2O2S: 275.0849 [M+H+]; found:
275.0850.
(4ca) Methyl 5-(pyrrolidin-1-yl)thiophene-2-carboxylate
Methyl 5ꢀ(pyrrolidinꢀ1ꢀyl)pentaꢀ2,4ꢀdiynoate (3ca, 14.7 mg, 0.083 mmol), Na2S•xH2O (60%
of Na2S, 9.7 mg, 0.12 mmol) and MeCN (10 mL) were reacted according to the procedure for
4aa. Yellow solid (6.9 mg, 0.033 mmol), yield: 40% 1H NMR (500 MHz, C6D6) δ 7.85 (d, J =
4.2 Hz, 1H, Hthiophene), 5.44 (d, J = 4.2 Hz, 1H, Hthiophene), 3.58 (s, 3H, CH3), 2.65 (t, 4H,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 34
1
2
3
4
1
NCH2), 1.21 – 1.19 (m, 4H, CH2). H NMR (500 MHz, Acetone) δ 7.48 (d, J = 4.2 Hz, 1H,
5
6
7
8
1H, Hthiophene), 5.79 (d, J = 4.3 Hz, 1H, 1H, Hthiophene), 3.72 (s, 3H, CH3), 3.34 – 3.30 (m, 4H
NCH2), 2.09 – 2.07 (m, 4H CH2). 13C{1H}NMR (126 MHz, C6D6) δ 163.2 (C=O), 161.2
(CthiopheneN), 135.8 (CHthiophene), 101.5 (CHthiophene), 51.1 (CH3), 50.1 (NCH2), 25.5 (CH2) (one
signal under solvent). 13C{1H}NMR (126 MHz, Acetoneꢀd6) δ 163.4 (C=O),), 162.2
(CthiopheneN), 136.3 (CHthiophene), 126.1 (CHthiophene), 101.9 (CHthiophene), 51.3 (CH3), 51.2
(NCH2), 26.4 (CH2). HRMS(ESI): m/z calcd for C10H14NO2S: 212.0740 [M+H+]; found:
212.0751.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(4ea) 4-((5-(Pyrrolidin-1-yl)thiophen-2-yl)ethynyl)benzonitrile
4ꢀ(Pyrrolidinꢀ1ꢀylhexatriynyl)benzonitrile (3ea, 17 mg, 0.070 mmol), Na2S•xH2O (60% of
Na2S, 12 mg, 0.10 mmol) and MeCN (10 mL) were reacted according to the procedure for
4aa. Yellow solid (15 mg, 0.054 mmol), yield: 77% 1H NMR (500 MHz, C6D6) δ 7.20 (d, J =
4.0 Hz, 1H, Hthiophene), 7.00 – 6.97 (m, 2H, Hbenzonitrile), 6.80 – 6.77 (m, 2H, Hbenzonitrile), 5.42 (d,
J = 4.0 Hz, 1H, Hthiophene), 2.72 – 2.68 (m, 4H, NCH2), 1.28 – 1.24 (m, 4H, CH2).
13C{1H}NMR (126 MHz, C6D6) δ 157.9 (CthiopheneN), 135.2 (CHthiophene), 132.0 (CHbenzonitrile),
130.8 (CHbenzonitrile), 128.8 (CC≡N), 118.8 (C≡N), 110.6 (CbenzonitrileC≡C), 104.3 (Cthiophene),
100.7 (CHthiophene), 91.4 (C≡C), 90.7 (C≡C), 50.3 (NCH2), 25.6 (CH2). HRMS(ESI): m/z calcd
for C17H15N2S: 279.0950 [M+H+]; found: 279.0953.
(4eb) 4-((5-(Piperidin-1-yl)thiophen-2-yl)ethynyl)benzonitrile
4ꢀ(Piperidinꢀ1ꢀylhexatriynyl)benzonitrile (3eb, 14 mg, 0.052 mmol), Na2S•xH2O (60% of
Na2S, 7.0 mg, 0.059 mmol) and MeCN were reacted according to the procedure for 4aa.
1
Yellow solid (11 mg, 0.038 mmol), yield: 73% H NMR (500 MHz, C6D6) δ 7.12 (d, J = 4.1
Hz, 1H, Hthiophene), 6.97 – 6.94 (m, 2H, Hbenzonitrile), 6.79 – 6.76 (m, 2H, Hbenzonitrile), 5.67 (d, J
= 4.1 Hz, 1H, Hthiophene), 2.77 – 2.73 (m, 4H, NCH2), 1.23 – 1.17 (m, 4H, CH2), 1.10 – 1.04
(m, 2H, CH2). 13C{1H}NMR (126 MHz, C6D6) δ 162.4 (CthiopheneN), 134.5 (CHthiophene), 131.9
(CHbenzonitrile), 131.0 (CHbenzonitrile), 128.4 (CC≡N), 118.7 (C≡N), 111.0 (CbenzonitrileC≡C), 106.8
(Cthiophene), 104.1 (CHthiophene), 91.4 (C≡C), 89.8 (C≡C), 51.5 (NCH2), 25.1 (CH2), 23.6 (CH2).
HRMS(ESI): m/z calcd for C18H16N2NaS: 315.0926 [M+Na+]; found: 315.0925.
(4fb) 1-(5-((4-Nitrophenyl)ethynyl)thiophen-2-yl)piperidine
ACS Paragon Plus Environment

Page 29 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1ꢀ((4ꢀNitrophenyl)hexatriynyl)piperidine (3fb 19 mg, 0.068 mmol), Na2S•xH2O (60% of
Na2S, 8.6 mg, 0.10 mmol) and MeCN (10 mL) were reacted according to the procedure for
4aa. Yellow solid (5.7 mg, 0.020 mmol), yield: 29% 1H NMR (500 MHz, C6D6) δ 7.67 – 7.64
(m, 2H, Hbenzonitrile), 7.14 (d, J = 4.1 Hz, 1H, Hthiophene), 7.01 – 6.98 (m, 2H, Hbenzonitrile), 5.67
(d, J = 4.1 Hz, 1H, Hthiophene), 2.78 – 2.73 (m, 4H, NCH2), 1.23 – 1.17 (m, 4H, CH2).
13C{1H}NMR (126 MHz, C6D6) δ 162.6 (CthiopheneN), 146.6 (CNO2), 134.9 (CHthiophene), 131.0
(CHnitrobenzene), 130.5 (CnitrobenzeneC≡C), 123.7 (CHnitrobenzene), 106.6 (CthiopheneC≡C), 104.1
(CHthiophene), 91.5 (C≡C), 91.0 (C≡C), 51.5 (NCH2), 25.0 (CH2). HRMS(ESI): m/z calcd for
C17H17N2O2S: 313.1005 [M+H+]; found: 313.1007.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(4ga) 4-((5-(Pyrrolidin-1-yl)thiophen-2-yl)butadiynyl)benzonitrile
4ꢀ(Pyrrolidinꢀ1ꢀyloctatetraynyl)benzonitrile (3ga, 14 mg, 0.043 mmol), Na2S•xH2O (60% of
Na2S, 5.4 mg, 0.046 mmol) and MeCN (10 mL) were reacted according to the procedure for
4aa. Yellow solid (6.8 mg, 0.022 mmol), yield: 51% 1H NMR (500 MHz, C6D6) δ 7.15 (d, J =
4.2 Hz, 1H, Hthiophene), 6.85 – 6.82 (m, 2H, Hbenzonitrile), 6.69 – 6.67 (m, 2H, Hbenzonitrile), 5.26 (d,
J = 4.1 Hz, 1H, Hthiophene), 2.63 – 2.58 (m, 4H, NCH2), 1.23 – 1.19 (m, 4H, CH2).
13C{1H}NMR (126 MHz, C6D6) δ 158.4 (CthiopheneN), 137.7 (CHthiophene), 132.3 (CHbenzonitrile),
131.8 (CHbenzonitrile), 127.1 (CC≡N), 118.4 (C≡N), 112.0 (CbenzonitrileC≡C), 103.2 (Cthiophene),
100.7 (CHthiophene), 82.9 (CbenzonitrileC≡C), 81.3 (CthiopheneC≡C), 80.1 (C≡C), 78.0 (C≡C), 50.2
(NCH2), 25.5 (CH2). HRMS(ESI): m/z calcd for C19H17N2OS: 321.1056 [M+H3O+]; found:
321.1057.
Author Information
Corresponding Author
slawomir.szafert@chem.uni.wroc.pl
Notes
The authors declare no competing financial interest.
Acknowledgements
The authors would like to thank the National Science Centre Poland (Grants UMOꢀ
2015/19/B/ST5/02917) for support of this research. The authors would like to thank Grzegorz
Wołczański for the help with HRMS spectra.
ACS Paragon Plus Environment