Mild synthesis of mercaptonitriles from vinyl nitriles and their cyclization reactions

Article abstract of DOI:10.1039/c6ra21948a

Thiol-ene addition of thioacetic acid A is widely used in the synthesis of thiols from vinyl precursors, but so far has not been conducted on non-conjugated vinyl nitriles. The challenge when vinyl nitriles are used is to selectively conduct the thiol-ene addition, while avoiding the nucleophilic addition of A to the nitrile group. We have found that vinyl nitriles give selective UV-induced thiol-ene addition in the presence of photoinitiators as long as a stoichiometric amount of A to the vinyl group and sterically unhindered vinyls are used. In contrast, when a sterically hindered vinyl is used, the nucleophilic addition of the nitrile is favoured. The prepared mercaptonitriles can easily undergo cyclization reactions in basic and acidic conditions as well as in the presence of silica gel. This illustrates the high reactivity of nitriles towards thiol addition. 1,2-Ethanedithiol B is presented as an alternative reagent to A as it allows conversion of vinyl nitriles directly into mercaptonitriles under mild and non-acidic reaction conditions.

Full text of DOI:10.1039/c6ra21948a

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DOI: 10.1039/C6RA21948A
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ARTICLE
Mild synthesis of mercaptonitriles from vinyl nitriles and their
cyclization reactions
Received 00th January 20xx,
Accepted 00th January 20xx
a,b
a,b
c
a
Philip Caspari, Frank A. Nüesch, Antonia Neels, Dorina M. Opris*
DOI: 10.1039/x0xx00000x
Thiol-ene addition of thioacetic acid A is widely used in the synthesis of thiols from vinyl precursor, but so far was not
conducted on non-conjugated vinyl nitriles. The challenge when vinyl nitriles are used is to selectively conduct the thiol-
ene addition, while avoiding the nucleophilic addition of A to the nitrile group. We have found that vinyl nitriles give
selective UV-induced thiol-ene addition in presence of photoinitiators as long as stoichiometric amount of A to the vinyl
group and sterically unhindered vinyls are used. On the contrary, when a sterically hindered vinyl is used, the nucleophilic
addition of the nitrile is favoured. The prepared mercaptonitriles can easily undergo cyclization reactions in basic and
acidic conditions as well as in presence of silica gel. This illustrates the high reactivity of nitriles towards thiol addition. 1,2-
ethanedithiol B is presented as an alternative reagent to A as it allows conversion of vinyl nitriles directly into
mercaptonitriles under mild and non-acidic reaction conditions.
www.rsc.org/
The addition of thioacetic acid
A to alkenes followed by acetyl
Introduction
cleavage is one of the most frequently used synthetic routes to
thiols. Cleavage of the acetyl moiety can be conducted under
6
acidic and basic conditions or by reduction with lithium
22
The radical addition of thiols to carbon-carbon double bonds is
widely known as thiol-ene reaction. This reaction is
regioselective and gives the anti-Markovnikov adduct as major
23
aluminium hydride. Hydrogen sulfide addition to alkenes
leads to formation of significant amount of dialkylsulfides side-
products. Already in 1941 Schjanberg et al. published the
1
product. Due to high conversion, small amount of by-products
selective thiol-ene addition of
A
to non-conjugated pentenoic
acids. Later, Brown et al. reported the selective thiol-ene
addition of to allyl alcohol, allyl acetate, and maleic
anhydride mediated by peroxides. More recently thiol-ene
addition of non-conjugated vinyl amides using BEt and O as
initiator was reported. Thiol-ene addition of aliphatic thiols
and fast reaction time, the thiol-ene reaction is often referred
24
2
to as “thiol click chemistry“ in the literature. The addition is
–5
A
6
mediated by either thermal or by UV radical initiators. Thiol-
25
7
–10
ene reaction is a versatile tool in biochemistry
and polymer
3
2
science. In polymer science, the thiol-ene reaction is a well-
6
26
established process for the preparation of dithiol monomers
1
27,28
to allyl cyanide is known,
however, the formed sulfides
1–13
and in the synthesis of polythioethers
and
cannot be converted into mercaptonitriles. While selective 1,4-
1
polythioesters. Due to its high conversion it was often used
4
29
addition of
the thiol-ene addition of
conjugated vinyl nitrile compounds i.e. allyl cyanide was not
explored so far. The addition of to aliphatic nitriles was
reported to occur under acidic or basic conditions with
A
to acrylonitrile under basic conditions is known,
1
5–21
in
post-polymerization
modifications.
When
A
and 1,2-ethanedithiol to non-
B
photoinitiators are used, the reaction proceeds to completion
7
within few minutes. In their absence thiols can be activated
A
8
by UV irradiation but the reaction rate is considerably lower.
3
0,31
formation of thioamides.
It is also known that
mercaptonitriles can undergo intramolecular reactions under
3
acidic conditions. Given the reactivity of
2
A
to nitriles it was
to various
unclear whether a selective thiol-ene addition of
A
vinyl nitriles followed by the deprotection of the thioester to
thiol can be realized.
In polymer science, mercaptonitriles are attractive
Electronic Supplementary Information (ESI) available: [Full characterization of all new precursor for the functionalization of polyvinylsiloxanes via
1
7
compounds, X-ray crystallographic data for 8, 9, and 17, and the dielectric spectra of
3 and 14 are given. CCDC 1492251 (8), CCDC 1492252 (9) and CCDC 1492250 (17)
contain the supplementary crystallographic data for this paper. The data can be
thiol-ene reaction. We have recently shown that the
dielectric permittivity ( ’) of polysiloxanes modified with polar
1
ε
obtained free of charge from The Cambridge Crystallographic Data Centre via nitrile groups increases linearly with the content of the nitrile
www.ccdc.cam.ac.uk/structures.]. See DOI: 10.1039/x0xx00000x
groups. By increasing the content of nitrile groups on the
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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ARTICLE
Journal Name
polysiloxane, it is to be expected that the permittivity can be (EI) m/z (%): 43.02 (100), 128.02 (10.97), 143.04 (4.38). EA:
further increased. To be attractive precursors for post- calculated: [C] 50.32% [H] 6.33% [N] 9.78% [O] 11.17 [S] 22.39
polymerization reactions, mercaptonitriles must be found: [C] 50.27% [H] 6.54% [N] 9.54% [O] 11.40 [S] 22.22%.
synthesized cost-efficiently on g-scale and have to be stable
during thiol-ene addition to the polyvinylsiloxane.
This work describes the thiol-ene reaction of
4-Mercaptobutanenitrile (2): 4-thioacetic butanenitrile 1 (10 g, 0.07
A
and 1,2- mol), trimethylsilyl chloride (1.8 ml, 0.014 mol), and methanol (150
ethanedithiol
,3,5-tricarbopentanitrile which should allow formation of allowed to cool down to ambient temperature and all volatiles were
thiols with different content of nitrile groups in two steps or removed in vacuo. The residue was dissolved in chloroform and
B to allyl cyanide, allyl malononitrile, and 3-vinyl- ml, 52 mol) were stirred at 65 °C for 18 h. The reaction mixture was
1
directly, respectively.
filtered. After removing all volatiles in vacuo, 4.3 g of crude product
was obtained. The residue was fractionally distilled at 77 °C and 10
1
mbar to give 2 (3 g, 43%) as colourless liquid. H NMR (400 MHz,
3
Experimental Section
CDCl
3
) δ, ppm: 2.68 (dt, J=7.0 Hz, 8.3 Hz, 2H, HS-CH
2
-CH
-CH
-). C NMR (100 MHz, CDCl ) δ, ppm:
-CN), 29.39 (-S-CH -CH -), 23.34 (-S-CH -CH -),
-CN). MS (EI) m/z (%): 54.03 (100), 68.05 (23.84),
2
-), 2.54 (t,
3
3
J=7.0 Hz, 2H, -CH
2
-CH
.38 (t, J=8.3 Hz, 2H, HS-CH
19.10 (-CH -CH
5.90 (-CH -CH
01.03 (97.52).
2
-CN,), 1.96 (q, J=7.0 Hz, 2H, -CH
2
2
-CH -),
2
3
13
1
1
1
1
2
3
General Remarks: All reactions were carried out in dried glassware
under argon atmosphere. Unless otherwise stated, all chemicals
were reagent grade and used as received. Methanol,
dichloromethane (DCM), heptane, ethyl acetate, petroleum ether
and tetrahydrofurane (THF) were purchased from VWR. Anhydrous
methanol was purchased from Sigma Aldrich. Silica gel was
purchased from VWR (‘Normasil 60’ 40-63 μm). Analytical TLC was
carried out on ‘TLC Silica gel 60 F254’ from Merck. TLC plates were
2
2
2
2
2
2
2
2
2
-Iminothiolane hydrochloride (3): 1 (1.4 g, 0.01 mol), trimethylsilyl
chloride (1.3 ml, 0.01 mol), and methanol (20.2 ml, 52 mol) were
stirred at 65 °C for 18 h. The reaction mixture was allowed to cool
down to ambient temperature and all volatiles were removed in
4
visualized with UV light or aqueous KMnO solution. THF was dried
vacuo. The residue was washed with chloroform to give 3 (0.6 g,
over sodium and distilled prior use. All other chemicals were
purchased from Sigma-Aldrich. A mercury vapour UV-light source
UVAHAND 250 GSH1 from Dr. Hönle AG without additional filters
1
4
2
2
5%) as fine powder. H NMR (400 MHz, DMSO-d
6
) δ, ppm: 12.37 (s,
3
3
H, -CH
2
=NH
2
), 3.51 (t, J=6.6 Hz, 2H, -CH
2
-CH
-), 2.56 (q, J=6.8 Hz, 2H, -CH
) δ, ppm: 203.78 (-S-C=NH
)-CH -CH -), 27.55 (-CH -CH -CH
2
2
-S-), 3.18 (t, J=7.1 Hz,
3
13
–2
H, -C(=NH
2
)-CH
2
-CH
2
2
-CH
), 39.38 (-S-
-).
2
-CH
2
-).
C
providing an irradiation intensity of 15 mW cm in the frequency
1
13
NMR (100 MHz, DMSO-d
CH -CH -), 37.61 (-C(=NH
6
2
range between 320 and 600 nm was used. H and C NMR spectra
were recorded on a Bruker Avance III 400 NMR spectrometer using
2
2
2
2
2
2
2
TM
a 5 mm BBO Prodigy CryoProbe at 400.18 and 100.63 MHz,
Allylmalononitrile (5): To a solution of malononitrile (66 g, 1 mol) in
DCM (300 ml), allyl bromide (86 ml, 1 mol) and subsequently
diisopropylethylamine (165 ml, 0.95 mol) were dropped slowly at 0
respectively. Chemical shifts (δ) in ppm are calibrated to residual
3
3
solvent peaks according to literature. Mass spectrometry was
conducted by the laboratory of organic chemistry of ETH Zurich. EI-
MS was measured with Waters' AutoSpec Ultima (EI-triSector-MS),
ESI-MS with Bruker's maXis (ESI/NanoSpray-Qq-TOF-MS). Elemental
analysis was determined with LECO TruSpec Micro, LECO RO-478
and LECO CHNS-932 by the laboratory of organic chemistry of ETH
Zurich. For the broadband dielectric spectroscopy (BDS)
measurements a high impedance Alpha Analyzer combined with a
Quatro temperature controller (both from Novocontrol) has been
employed to cover a broad frequency from 0.1 Hz to 1 MHz. Two
stainless steel discs with a diameter of 20 mm served as electrodes
which were separated by three glass fibers with a diameter of 100
°
C. The solution was allowed to warm up and stirred overnight. The
reaction mixture was washed several times with H
phase was separated and dried over MgSO
2
O. The organic
, filtered and
4
concentrated in vacuo to give 83 g crude product mixture. It was
purified by column chromatography (petroleum ether (40-60 °C)/
ethyl acetate 9:1) to give 5 (35 g, 35%) as colourless viscous liquid.
1
R
F
= 0.4 (heptane/ethyl acetate 2:1). H NMR (400 MHz, CDCl
3
) δ,
ppm: 5.91-5.80 (m, 1H, -CH
2
-CH=CH
2
), 5.43-5.38 (m, 2H, -CH -
2
3
4
CH=CH
2
), 3.78 (t, J=6 Hz, 1H, (NC)
2
-CH-CH
2
-,), 2.75 (dt, J=1 Hz,
) δ, ppm:
), 112.35 (-CN), 34.74 (-CH-CH -),
3
13
2 3
J=6.6 Hz 2H, CH-CH -CH=). C NMR (100 MHz, CDCl
1
2
29.29 (-CH=CH
2
), 122.55 (-CH=CH
2
2
ꢀm.
3.16 (-CH-CH -).
2
S-3-cyanopropyl thioacetate (1): Allyl cyanide (20.0 ml, 0.25 mol),
thioacetic acid (26.6 ml, 0.38 mol), and 2,2-dimethoxy-2-
phenylacetophenone (DMPA) (0.64 g, 0.0025 mol) were dissolved in
THF. The solution was degassed and irradiated for 5 min with a UV
light. All volatiles were removed in vacuo at 60 °C to obtain 36 g
crude product mixture. The residue was fractionally distilled at 117
S-(4,4-dicyanobutyl) thioacetate (6):
A
solution of allyl
malononitrile (1.06 g, 0.01 mol), thioacetic acid (1.2 ml, 0.012 mol)
and DMPA (0.025 g, 0.0002 mol) in THF (15 ml) was carefully
degassed and then irradiated for 5 min with UV light. The volatiles
were removed in vacuo and the crude product mixture (2.6 g) was
-3
F
purified by column chromatography (Heptane/Ethyl acetate 2:1, R =
°
C and 1 x 10 mbar to give 1 (25.4 g, 73%) as pale yellowish liquid.
1
1
3
0
.3). 6 was obtained as colourless viscous liquid (1.35 g, 74%). H
H NMR (400 MHz, CDCl
3
) δ, ppm: 2.97 (t, J=6.9 Hz, 2H, -S-CH
, 2.42 (t, J=8.0 Hz, 2H, -CH -CH -CN,), 2.35 (s, 3H, CH -CO-S-), 1.94
-CH -CN). C NMR (100 MHz, CDCl ) δ,
-CO-S-), 119.09 (-CH -CO-S-),
-), 25.93 (-S-CH -CH -CN). MS
2 2
-CH -
3
3
NMR (400 MHz, CDCl
3
) δ, ppm: 3.87 (t, J=6.8 Hz, 1H, (NC)
2
-CH-CH
2
-
)
(
2
2
3
3
3
13
)
, 2.95 (t, J=6.8 Hz, 2H, CH
2
-CH
-), 1.95-1.84 (m, 2H, CH-CH
) δ, ppm: 195.65 (-S-C=O-CH
2
-SAc), 2.36 (s, 3H, CH
2
-S-CH ), 2.13-
3
q, J=7.1 Hz, 2H, -CH
2
-CH
2
2
3
1
3
2
.06 (m, 2H, CH-CH
2
-CH
2
2
2
-CH -). C NMR
ppm: 195.33 (CH
3
2
2
-CH
2
-CN), 30.77 (CH
-CH
3
(
100 MHz, CDCl
3
3
), 112.53 (-CN), 30.76
28.00 (-S-CH
2
-CH
2
2
-), 16.42 (-CH
2
2
2
| J. Name., 2012, 00, 1-3
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PleaseRd So Cn oA t da vd aj un s ct ems argins
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DOI: 10.1039/C6RA21948A
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ARTICLE
3
3
(
-S-C(=O)-CH
CH -), 22.30 (-CH-CH
EA: calculated: [C] 52.73% [H] 5.53% [N] 15.37% [O] 8.78% [S] CH
3
), 29.55 (CH
2
-CH
2
-CH
2
), 27.22 (CH
2
-SAc), 26.84 (CH- 5.67 (d, J=16 Hz, 1H, CHH=CH-), 5.58 (d, J=11 Hz, 1H, CHH=CH-),
3
3
2
2
-). MS (EI+) m/z (%): 182.05 (5.53), 43.02 (100). 5.44 (dd, J=10.2 Hz, J=16.8 Hz , 1H, CH
-CH -CN), 2.24-2.17 (m, 2H, CHH-CH
7.59% found: [C] 52.53% [H] 5.75% [N] 15.31% [O] 9.05 [S] 17.53%. CHH-CH
22.17 (CH
,4-dicyanobutyl thiol (7): To a degassed solution of 6 (4.7 g, 0.025 34.22 (CH
2
=CH-), 2.57-2.39 (m, 4H,
-CN), 2.00-1.92 (m, 2H,
) δ, ppm: 132.76 (CH =CH-),
=CH-), 117.98 (Cquart-CN), 117.85 (CH -CN), 45.81 (Cquart),
-CH CN), 13.66 (CH -CH -CN). MS (EI) m/z (%): 55.05
2
2
2
13
1
2
-CN). C NMR (100 MHz, CDCl
3
2
1
2
2
4
2
2
2
2
mol) in anhydrous MeOH (43 ml, 1.07 mol) trimethylsilyl chloride (49.53), 80.05 (34.74), 92.05 (70.69), 119.06 (100). EA: calculated:
was added (0.54 ml, 0.0043 mol). The reaction was refluxed for 18 [C] 69.34% [H] 6.40% [N] 24.26% found: [C] 69.21% [H] 6.33% [N]
h. The reaction was allowed to cool down to ambient temperature. 24.16%.
All volatiles were removed in vacuo. The residue was redissolved in
3
CHCl and filtered through a syringe filter. After removing all 4-Cyano-4-vinylheptane bis(thioamide) (12): A solution of 3-
volatiles in vacuo 3.5 g yellowish viscous liquid was obtained. The vinylpentane-1,3,5-tricarbonitrile (0.5 g, 0.0029 mol), thioacetic
residue was fractionally distilled to give 2.5 g pale yellowish liquid acid (4.8 ml, 0.024 mol), and AIBN (0.015 g, 0. 09 mmol) dissolved in
(71%; purity ~ 85%). Further attempts to purify this compound by toluene (30 ml) was carefully degassed. The reaction mixture was
column chromatography were not successful. 7 gives a cyclization stirred for 18 h at 70 °C. After removing all volatiles in vacuo, the
1
reaction to 8 during this purification step. H NMR (400 MHz, CDCl
3
)
mixture was purified by column chromatography (n-heptane/ethyl
-), 2.61-2.67 (m, 2H, acetate 1:1) to give (0.4 g, 58%) of 12. R = 0.2 (heptane/ethyl
) δ, ppm: 8.68 (br s, 4H, -
3
δ, ppm: 3.80 (t, J=6.8 Hz, 1H, (NC)
2
-CH-CH
-CH -), 1.98-1.90 (m, 2H, CH- acetate 1:1). H NMR (400 MHz, acetone-d
-), 1.43 (t, J=8.1 Hz, 1H, -CH -SH). C NMR (100 MHz, CS-NH
), 112.54 (-CN), 29.47 (CH -CH Hz, 1H, CHH=CH-), 5.35 (d, J=10 Hz, 1H, CHH=CH-), 2.77-2.63 (m,
-), 22.46 (-CH-CH -). HRMS (ESI): 4H, CH
S m/z: 141.0481 [M+H]; found 141.0481 [M+H]. MHz, acetone-d6) δ, ppm: 208.12 (-C(S)NH
20.21 (CH =CH-), 117.37 (Cquart-CN), 45.60 (Cquart), 40.14 (CH
CH C(S)NH ), 37.31 (CH -CH -C(S)NH ); MS (ESI): calc. for C10
2
F
1
CH
CH
2
-CH
-CH
2
-SH), 2.23-2.17 (m, 2H, CH-CH
2
2
6
3
13
3
3
3
2
2
2
2 2
), 5.71 (dd, J=10Hz, J=17 Hz, 1H, CH =CH-), 5.42 (d, J=17
3
CDCl
CH ), 30.39 (CH
calc. C
3
) δ, ppm: 195.60 (-S-C=O-CH
3
2
2
-
1
3
2
2
-SH), 23.39 (CH-CH
2
2
2
-CH
2
-C(S)NH
2
), 2.28-2.11 (m, 4H, CH
2
-CH
2
-CN). C NMR (100
=CH-),
6
9
H N
2
2
), 136.79 (CH
2
1
2
2
-
6
-Amino-3,4-dihydro-2H-thiopyran-5-carbonitrile (8): To
a
2
2
2
2
2
16 3 2
H N S
degassed solution of 6 (2.6 g, 0.014 mol) in anhydrous MeOH (24 [M+H] 242.0780; found 242.0779.
ml, 0.593 mol) trimethylsilyl chloride was added (0.03 ml, 0.0024
mol). The reaction was refluxed for 17 h. Then, additional 4-((2-Mercaptoethyl)thio)butanenitrile (13): Allyl cyanide (20 ml,
trimethylsilyl chloride (0.03 ml) was added and the reaction mixture 0.25 mol), 1,2-ethanedithiol (freshly distilled) (168 ml, 2 mol), and
stirred for another 72 h at r.t. All volatiles were removed in vacuo. DMPA (1.3 g, 0.005 mol) were solved in THF. The solution was
The residue was redissolved in CHCl
3
and filtered through a syringe degassed and irradiated for 5 min. All volatiles were removed in
filter. After removing all volatiles in vacuo 1.63 g yellow viscous vacuo at 60 °C to obtain 46 g crude product mixture. The residue
-
3
liquid was obtained. An aliquot of 0.5 g of crude product mixture was fractionally distilled at 105 °C and 1 x 10 mbar to give 13 (26.2
1
H
was purified by column chromatography and recrystallized from n- g, 67%) as colourless liquid (95% Anti-Markovnikov product).
heptane/ ethyl acetate to give 8 (0.3 g, 49%) as colourless solid. R NMR (400 MHz, CDCl ) δ, ppm: 2.76-2.71 (m, 4H, -S-CH -CH -SH),
) δ, ppm: 4.33 (br 2.68 (t, J=7.2 Hz, 2H, -S-CH -CH -), 2.51 (t, 2H, -CH -CH -CN, J= 6.8
-S), 2.35 (t, J=6.4 Hz, Hz), 1.94 (dt, J=7.44 Hz, 2H, -CH -CH -CH -CN), 1.71 (t, J=8.1 Hz,
-SH). C NMR (100 MHz, CDCl ) δ, ppm: 119.27 (CH -CN),
)-S), 120.13 (-CN), 72.94 36.20 (HS-CH -CH -S-), 30.66 (–S-CH -CH -), 25.36 (-CH -CH -CH -),
-), 24.37 (S-CH -CH -CH -), 22.47 24.77 (HS-CH -CH -), 16.14 (-CH -CH -CN). MS [EI+] m/z (%): 114.03
-). HRMS (ESI) calcd. for C S [M+H] 141.0481, (94.2), 161.03 (60.5). EA: calculated: [C] 44.68% [H] 6.87% [N] 8.68%
F
=
3
2
2
1
3
0
.2 (DCM/ heptane 3:1). H NMR (400 MHz, CDCl
3
2
2
2
2
3
3
4
3
s, 2H, -NH
H, -CH -CH
MHz, CDCl ) δ, ppm: 154.19 (C=C(-NH
(NC)-C=C-S), 28.17 (S-CH -CH -CH
-CH -CH -CH
2
), 2.94 (t, J=5.6 Hz, 2H, -CH
2
-CH
-CH
2
2
2
2
1
3
13
2
2
2
-CH -), 2.03-1.96 (m, 2H, -CH
2
2
2
-CH
2
). C NMR (100 1H, -CH
2
3
2
3
2
2
2
2
2
2
2
2
(
(
2
2
2
2
2
2
2
2
2
2
2
2
2
6
H
9
N
2
found 141.0481. EA: calculated: [C] 51.40% [H] 5.74% [N] 19.98% [S] 39.76 found: [C] 44.51% [H] 7.12% [N] 8.58% [S] 39.78.
found: [C] 51.44% [H] 5.83% [N] 19.73%.
2
-(3-((2-Mercaptoethyl)thio)propyl)malononitrile (14): To
a
3-Vinylpentane-1,3,5-trinitrile (9): Allyl cyanide (12.1 ml, 0.15 mol) solution of allyl malononitrile (15 g, 0.14 mol) dissolved in freshly
and vinyl cyanide (21 ml, 0.32 mol) were added dropwise to a distilled THF (500 ml), freshly distilled 1,2-ethanedithiol (52 ml, 0.70
mixture of trimethylbenzylammonium hydroxide (1.2 ml of 40 wt% mol) and DMPA (0.7 g, 0.003 mol) was added under argon
aqueous solution, 0.003 mol) in tert-butanol (25 ml) at 25°C. The atmosphere. The reaction mixture was irradiated for 5 minutes. All
temperature was kept constant by use of an ice bath. After volatiles were removed in vacuo (10 mbar). The residue was
-3
complete addition, the reaction mixture was stirred overnight at fractionally distilled at 145 °C and 9 x 10 mbar to give 14 as
1
ambient temperature. The mixture was acidified with diluted colourless liquid (9 g, 31%). H NMR (400 MHz, CDCl
3
) δ, ppm: 3.83
-), 2.79-2.69 (m, 4H, -S-(CH -SH), 2.64
-S-,), 2.21-2.15 (m, 2H, CH-CH -CH ), 1.96-
3
aqueous HCl and washed several times with DCM. The organic (t, J=6.8 Hz, 1H, (CN)CH-CH
2
2 2
)
3
phase was dried over MgSO
vacuo. The residue was purified by column chromatography (n- 1.88 (m, 2H, CH
heptane/ethyl acetate 2:1) to give a pale yellowish solid (9.0 g). The (100 MHz, CDCl
solid was dissolved in ethyl acetate and precipitated by slow 30.62 (-CH -CH -S-), 29.64 (CH-CH
addition n-heptane to obtain 9 (8.2 g, 31%) as colourless solid. R (CH -CH -SH), 22.48 ((CN)
4
and the volatiles were removed in (t, J=7.1 Hz, 2H, CH
-CH
) δ, ppm: 112.47 ((CN)
-CH ), 26.11 (CH
2
-CH
2
2
2
13
3
2
2
-CH
2
), 1.72 (t, J= 8.0 Hz, 1H, CH
-CH-), 36.11 (-CH
-CH -CH
2
2
-S-H,). C NMR
-CH -SH),
), 24.72
3
2
2
2
2
2
2
2
2
2
F
=
2
2
2
-CH-). MS (ESI) m/z (%): 167 (100), 359.24
1
3
0.5 (heptane/ ethyl acetate 1:1). H NMR (400 MHz, CDCl ) δ, ppm:
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(22.5), 423 (23.8). EA: calculated: [C] 47.97% [H] 6.04% [N] 13.98% within 5 min (Scheme 1). Compound 1 is known in the literature
[S] 32.01%/ found: [C] 47.90% [H] 6.24% [N] 13.74% [S] 31.86%.
and was prepared starting from potassium salt of A and 4-
bromobutyronitrile. Unfortunately, no reaction yield is given for this
3
4,35
3-(2-((2-Mercaptoethyl)thio)ethyl)pentane-1,3,5-tricarbonitrile
reaction.
Cleavage of the acetyl moiety of 1 under acidic
(15): A solution of 9 (0.173 g, 0.001 mol), freshly distilled 1,2- conditions (20 mol% trimethylsilyl chloride (TMSCl) in methanol)
ethanedithiol (0.84 ml, 0.01 mol), and DMPA (0.77 g, 0.003 mol) in proceded at low reaction rate and gave 4-mercaptobutanenitrile 2
THF (20 ml) was carefully degassed and then irradiated for 5 min in moderate yields (43%). When a stoichiometric amount of TMSCl
with
a UV lamp. To the reaction mixture additional 1,2- was used, 2-iminothiolane hydrochloride 3 formed in 60% yield.
ethanedithiol (0.42 ml, 0.004 mol) and DMPA (0.77 g, 0.003 mol) Compound 2 is known and was prepared starting from 4-
were added followed by 10 min irradiation. All volatiles were isothioureidobutyronitrile hydrochloride but the reaction yield was
3
6
removed in vacuo and the product was purified by column very low (15%). Compound 3 is also known in the literature and
chromatography (Heptane/ Ethyl acetate 1:1) to give (0.09 g, 34%) was prepared by nucleophilic substitution starting from 4-
1
37–39
1
5 as yellowish liquid. H NMR (400 MHz, CDCl
m, 4H, HS-CH -CH -S), 2.67 (t, 2H,-S-CH -CH -Cquart, J=8 Hz), 2.57 (t, widely used as thiolation reagent in biochemistry and is referred to
J=8Hz, 4H, -CH -CH -CN), 2.07 (t, J=8 Hz, 4H, -CH
-Cquart), 1.73 (t, 1H, -SH). C NMR (100 MHz, CDCl
-CN), 40.62 (Cquart), 36.65 (-
-Cquart-), 31.63 (CH -CH -CN), 26.79 (S-CH
-CH -S), 13.48 (CH -CN). MS (EI+) m/z (%):
3
) δ, ppm: 2.83-2.72 halogenobutanenitrile and A or thiourea, respectively.
It is
3
(
3
2
2
2
2
3
40-43
2
2
2 2
-CH -CN,), 1.96 (t, as ‘Traut’s reagent’.
3
13
J=8 Hz, 2H, -CH
2
3
)
δ, ppm: 119.96 (Cquart-CN), 117.89 (-CH
2
CH
2
-SH) 35.78 (S-CH
2
-CH
2
2
2
2
-
CH
2
-Cquart-), 24.89 (HS-CH
2
2
2
6
1.01 (100), 69.05 (15.55), 207.08 (17.18), 267.08 (13.02). EA:
calculated: [C] 53.90% [H] 6.41% [N] 15.71% [S] 23.98 found: [C]
3.78% [H] 6.60% [N] 15.43% [S] 23.82%.
5
Compounds16&17: To a solution of allyl malononitrile (53 g,
.5 mol) dissolved in freshly distilled THF (500 ml), 1,2-
Scheme 1 Thiol-ene addition of A to allyl cyanide followed by the
cleavage of the acetyl group to give 2 and 3.
0
ethanedithiol (235 ml, 2.5 mol) and DMPA (2.5 g, 0.002 mol)
was added under argon atmosphere. The reaction mixture was
irradiated for 5 minutes. All volatiles were removed at 80 °C in
Allyl malononitrile 5 was synthesized according to the literature
starting from malononitrile and allyl bromide in one step (Scheme
vacuo (10 mbar). The residue was purified by SiO
2
column
ꢀ DMF)
to give 17 (2 g, 2%) as colourless crystals and 16 (40 g, 40%) as
41
2
). The thiol-ene addition of a slight excess of A to 5 in presence of
chromatography (heptane/ ethyl acetate methanol
ꢀ
DMPA gave S-(4,4-dicyanobutyl) thioacetate 6 in 74% yield within 5
min (Scheme 2). When a large excess of A was used, addition to the
nitrile groups was observed. Acetate cleavage under basic
conditions in presence of butyl amine resulted in quantitative
pale brownish, viscous liquid.
1
1
6: H NMR (400 MHz, N,N-dimethylformamide-d
7
) δ, ppm:
-), 2.79-2.69 (m, 4H, -S-
-SH), 2.64 (t, J=7.1 Hz, 2H, CH -CH -S-,), 2.21-2.15 (m,
H, CH-CH -CH ), 1.96-1.88 (m, 2H, CH -CH -CH ), 1.72 (t,
-S-H,). C NMR (100 MHz, CDCl ) δ, ppm:
-CH-), 36.11 (-CH -CH -SH), 30.62 (-CH -CH -S-),
-CH ), 26.11 (CH -CH -CH ), 24.72 (CH -CH -SH),
-CH-).
7: H NMR (400 MHz, N,N-dimethylformamide-d
.63 (br s, -NH ), 6.37 (br s, -NH ), 3.20-3.30 (m, 2H, -CH
-S-CH -CH ), 2.61-2.68 (m, 2H, CH
-S), 1.69-1.81 (m, 2H, CH -CH -CH
). C NMR (100 MHz, N,N-dimethyformamide-d
)-S), 122.13 (C-CN), 80.72 (C=C(CN)-),
-S-C), 31.21 (CH -CH -S-C), 30.53 (CH -CH -CH
-CH -CH -S), 27.16 (CH -CH -CH -S). HRMS (ESI):
[M+H] 401.0957; found: 401.0957.
3
3
.83 (t, J=6.8 Hz, 1H, (CN)CH-CH
2
3
cyclization of 6 to 6-amino-3,4-dihydro-2H-thiopyran-5-carbonitrile
(CH
2
)
2
2
2
1
8
. The quantitative conversion of 6 to 8 is supported by the H NMR
2
3
2
2
2
2
2
13
spectra where the characteristic signals of 6 disappeared and new
signals appeared which can be easily assigned to 8 (Figure 1). Single
crystals of 8 suitable for x-ray analysis were grown from ethyl
acetate/heptane. The proposed six-membered ring was confirmed
by x-ray structure (Figure 2). The transesterification reaction with
methanol under acidic conditions allowed formation of 4,4-
dicyanobutyl thiol 7, but the reaction did not proceed to
completion. Attempts to purify this compound by vacuum
distillation were only partially successful. The compound still
contained about 15% impurities (Figure 1d). Further attempts to
increase the purity of 7 by column chromatography purification on
silica gel were unsuccessful. The intramolecular cyclization of 7
occurred quantitatively with formation of 8 (Figure 1). The synthesis
of the analog five-membered cycle starting from malononitrile and
ethylene sulfide was already described in the literature, but an
over-stoichiometric amount of a strong base such as sodium
hydride had to be used and the reaction yield was only moderate
J=8.0 Hz, 1H, CH
2
3
1
2
2
1
6
12.47 ((CN)
9.64 (CH-CH
2.48 ((CN)
2
2
2
2
2
2
2
2
2
2
2
2
2
1
7
) δ, ppm:
2
2
2
-CH
2
-
-
S-C), 2.74-2.79 (m, 2H, CH
2
2
2
2
CH
2
-CH
2
2
2
2
), 2.27-2.40 (m, 2H,
) δ,
1
3
C-CH
2
-CH
2
7
ppm: 152.17 ((C=C(NH
1.97 (CH -CH
S), 28.55 (CH
calc. for C16
2
3
2
2
2
2
2
2
2
-
2
2
2
2
2
2
25 4 4
H N S
Results and Discussion
4
5
(
57%).
Allyl cyanide is the simplest aliphatic non-conjugated vinyl nitrile.
The thiol-ene addition of A to allyl cyanide initiated by 1 mol%
DMPA gave S-3-cyanopropyl thioacetate 1 in 73% isolated yield
4
| J. Name., 2012, 00, 1-3
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ARTICLE
3
0,31
CN
occurrs either under acidic or basic catalysis.
At 70 °C the acidity
BuNH
2
NH
2
2
8
of A was sufficient to catalyse its addition to the nitrile of 9.
THF
Br
NC
CN
S
NC
CN
NC
CN
AcSH
DIPEA
DCM
DMPA
5 min, hv
SiO
4
O
NC
NC
TMSCl
MeOH
S
7
O
NC
S
S
5
6
18 h
1
0
SH
AcSH
X
CN
S
Scheme 2 Synthetic route to 4,4-dicyanobutyl thiol
7
.
CN
CN
DMPA
CN
CN
CN
CN
NOH
10-60 min
O
O
BnMe
3
CN
9
S
S
AcSH
AIBN
8h, 70 °C
EtOAc
SiO
CN
HN
NH
H
2
N
NH
2
2
1
11
12
Scheme 3 Synthesis of
9
by cyanoethylation of allyl cyanide and its
reaction with AcSH.
As an alternative to
A
in the transformation of vinyl nitriles to
was tested (Scheme 4). The
is that it allows formation of mercaptonitriles
directly via thiol-ene reaction of vinyl nitriles, even though an
excess of has to be used and the spacer between the thiol and the
mercaptonitriles, 1,2-ethanedithiol
advantage of
B
B
B
nitrile group is prolonged. Intramolecular cyclization reactions of
the formed mercaptonitriles are less favored as five or six-
membered rings cannot form.
SH
NC
HS
SH
NC
S
DMPA
min, hv
13
5
NC
S
n
S
+
1
Fig. 1 H NMR spectra of: a)
6
, b) of the crude reaction mixture
16
NH
2
NH
2
NC
NC
SH
NC
NC
SH
CN
HS
S
S
obtained by reacting
6
with butyl amine, c) of , and d) of
8
7.
S
SiO
2
DMPA
min, hv
5
14
5
S
17
SH
CN 15
S
SH
HS
S
NC
DMPA
15 min, hv
NH
2
NC
CN
NC
CN
CN
9
Scheme 4 Thiol-ene addition of 1,2-ethanedithiol to vinyl nitriles.
Addition of to allyl cyanide gave 4-((2-
B
mercaptoethyl)thio)butanenitrile 13, which did not show any
susceptibility to cyclization. The purification of 13 was done by
distillation and the compound could be easily prepared on 30 g
Fig. 2 ORTEP plot of 8, view perpendicular to the cycle (left) and the
scale. The reaction of
5
with
B
gave 2-(3-((2-
molecular packing down the crystallographic b axis showing the
stacking of the cycles and the hydrogen bonding network (right).
mercaptoethyl)thio)propyl)malononitrile 14. The isolation of 14 by
distillation was possible, but challenging given 14’s high boiling
3
-vinylpentane-1,3,5-trinitrile
literature starting from allyl cyanide (Scheme 3). The vinyl group the intramolecular cyclization with formation of cyclic dimer 17 in
of is sterically hindered due to the bulky –(CH CN moieties in small amounts. The structure of 17 was confirmed by x-ray
alpha position to the vinyl group. This is nicely illustrated by the H
NMR spectrum of where the two protons of the –CH -CH -CN
9
was synthesized according to point. Again, silica gel during chromatography purification catalyzed
4
6
9
2 2
)
1
diffraction analysis on a single crystal (Figure 3). The main product
after chromatography was oligomer 16 which was obtained via
silica gel extraction with DMF and methanol as can be seen in the
9
2
2
group next to the quaternary carbon are not equivalent, as one
would expect (see ESI). This indicates a lack of free rotation of the –
1
H NMR spectrum in the supporting information. No further
(
2 2
CH ) CN moiety. The thiol-ene addition of A to 9 initiated by DMPA
characterizations were conducted on 16 due to its poor solubility.
did not occur even after 60 min UV irradiation. Instead, instability of
the nitriles was observed. When AIBN as thermal radical initiator
and excess of
A was used, the addition of A to the nitrile group was
observed. NMR analysis of the crude product mixture showed the
formation of 11 which hydrolysed to 4-cyano-4-vinylheptane
bis(thioamide) 12 during work-up (60% yield). Formation of 3-(2-
thioacetic)ethylpentane-1,3,5-carbonitrile 10 was not observed. The
conversion of aliphatic nitriles to thioamides is known, however this
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Acknowledgements
We gratefully acknowledge Swiss Federal Laboratories for Materials
Science and Technology (Empa, Dübendorf) for financial support.
Notes and references
1
2
3
4
V. N. Ipatieff and B. S. Friedman, J. Am. Chem. Soc., 1939,
, 71.
C. E. Hoyle and C. N. Bowman, Angew. Chem. Int. Ed.,
010, 49, 1540.
L. Gu, Q. Xue, S. Peng, G. Wang, J. Han and X. Wu,
Polymer, 2016, , 625.
6
1
Fig. 3 ORTEP plot of 17, view perpendicular to the cycle (left) and
the molecular packing down the crystallographic a axis showing the
hydrogen bonding network (right).
2
7
C. Ligeour, L. Dupin, A. Marra, G. Vergoten, A. Meyer, Y.
Dondoni, A. Souteyrand, E. Vasseur, J.-J. Chevolot and F.
Morvan, Eur. J. Org. Chem., 2014, 34, 7621.
Z. Liu, T. Liu, Q. Lin, C. Bao and L. Zhu, Angew. Chem. Int.
Ed., 2015, 54, 174.
In contrast to
of was achieved by using
amount of photoinitiator, and prolonged reaction times. The
difference in the reactivity of and can be explained by the
acidity of the two reagents used. Due to the presence of electron-
withdrawing group, is more acidic as compared to 1,2-
A, selective thiol-ene addition of
B to the vinyl group
9
B
in excess, an over-stoichiometric
5
6
7
A
4
B
Y. Suzuki, T. Higashihara, S. Ando and M. Ueda,
Macromolecules, 2012, 45, 3402.
7
A
N. K. Singha, M. I. Gibson, B. P. Koiry, M. Danial and H.-A.
Klok, Biomacromolecules, 2011, 12, 2908.
ethanedithiol and therefore chemically more reactive towards
nitrile. NMR analysis of the reaction mixture showed product
conversion of approximately 50%. The nitrile groups were
unaffected during reaction and chromatography purification
process. The mercaptonitriles 13-15 did not crystallize. Traces of
Markovnikov addition product were detected in all cases.
8
9
M. H. Stenzel, ACS Macro Lett., 2013,
Y. Chen, G. Chen and M. H. Stenzel, Macromolecules,
010, 43, 8109.
2, 14.
2
1
1
0
1
J. Z. Du, X. J. Du, C. Q. Mao and J. Wang, J. Am. Chem.
Soc., 2011, 133, 17560.
Thiols 13 and 14 were identified as being promising candidates
for the post polymerization modification of polyvinylsiloxanes via
thiol-ene addition. 13 and 14 can be prepared easily on a 20 g scale
and can be purified by distillation. Although the high boiling points
of these thiols may be considered disadvantageous since high
vacuum and high temperatures have to be used for their
distillation, they have the advantage that they are less volatile and
therefore do not have the typical pungent odor characteristic for
thiols. The thiols show a dielectric permittivity at high frequencies
of ε’ = 15.4 and ε’ = 17 for 13 and 14, respectively. Preliminary
results show that 13 and 14 can be successfully used in the selective
thiol-ene addition to polyvinylsiloxane and no side reactions were
observed. Further work in our lab is conducted in this direction.
M. Podgorski, E. Becka, M. Claudino, A. Flores, P. K. Shah,
J. W. Stansbury and C. N. Bowman, Dent. Mater., 2015,
3
1
, 1255.
E. Klemm and S. Sensfuss, Makromol. Chem., 1991, 64
59.
1
1
2
3
,
1
A. S. Quick, J. Fischer, B. Richter, T. Pauloehrl, V. Trouillet,
M. Wegener and C. Barner-Kowollik, Macromol. Rapid
Commun., 2013, 34, 335.
1
1
1
4
5
6
C. S. Marvel and A. Kotch, J. Am. Chem. Soc., 1951, 73
,
1
100.
S. J. Duenki, Y. S. Ko, F. A. Nueesch and D. M. Opris, Adv.
Funct. Mater., 2015, 25, 2467.
S. J. Dünki, M. Tress, F. Kremer, S. Y. Ko, F. A. Nüesch, C.-
D. Varganici, C. Racles and D. M. Opris, RSC Adv., 2015,
0054.
5,
5
Conclusions
1
7
C. Decker and T. Nguyen Thi Viet, Polymer, 2000, 41,
In conclusion, the thiol-ene addition of
malononitrile, and 3-vinylpentane-1,3,5-carbonitrile
investigated. All vinyl nitriles reacted with and as expected
A
and
B
to allyl cyanide, allyl
3905.
was
18 A. Gress, A. Vo and H. Schlaad, Macromolecules, 2007, 40
,
A
B
7928.
except 3-vinylpentane-1,3,5-carbonitrile. This compound with its
sterically hindered vinyl group did not give the thiol-ene addition
19 J. C. Persson, K. Josefsson and P. Jannasch, Polymer, 2006,
47, 991.
product
A
but the addition product to the nitriles. The cleavage of
20 M. Li, P. De, H. Li and B. S. Sumerlin, Polym. Chem., 2010,
the acetyl groups to generate the respective mercaptonitriles must
be conducted under mild acidic conditions due to the high tendency
of the generated thiols to undergo addition to the nitriles under
acidic and basic conditions. Purification of the mercaptonitriles by
column chromatography over silica gel should be avoided. Thiol-ene
1, 854.
21 D. M. Opris, E. Perju and S. J. Duenki, J. Polym. Sci. Part A:
Polym. Chem., 2016, 56, 2940.
22 M. Le Neindre, B. Magny and R. Nicolaÿ, Polym. Chem.,
2013, 4, 5577.
addition of
be a fast and efficient alternative for
mercaptonitriles in one step and mild reaction conditions.
B
to non-conjugated vinyl nitrile compounds proved to
23 J. Polster and P. Schieberle, J. Agric. Food Chem., 2015, 63
,
A
in the synthesis of
1419.
24 E. Schjanberg, Ber. Dtsch. Chem. Ges., 1941, 74, 1751.
2
5 R. Brown, W. E. Jones and A. R. Pinder, J. Chem. Soc, 1951,
6
| J. Name., 2012, 00, 1-3
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Please do not adjust margins

Page 7 of 7
PleaseRd So Cn oA t da vd aj un s ct ems argins
View Article Online
DOI: 10.1039/C6RA21948A
Journal Name
ARTICLE
2
123.
J. Gorges and U. Kazmaier, Eur. J. Org. Chem., 2015, 36
011.
2
6
7
,
8
2
J. W. Lynn, R. L. Roberts and J. R. Kilsheimer, J. Org.
Chem., 1961, 26, 4300.
28
29
30
A. Kjaer and J. Conti, Acta Chem. Scand., 1954, 8, 295.
M. Yunhai and X. Jiaxi, Synthesis, 2012, 44, 2225.
J. Y. Gauthier and H. Lebel, Phosphorus, Sulfur Silicon
Relat. Elem., 1994, 95, 325.
31
32
33
K. A. Mahammed, V. P. Jayashankara, N. Rai, K. Raju, K.
Mohana and P. N. Arunachalam, Synlett, 2009, 14, 2338.
R. Jue, J. M. Lambert, L. R. Pierce and R. R. Traut,
Biochemistry, 1978, 17, 5399.
G. R. Fulmer, A. J. M. Miller, N. H. Sherden, H. E. Gottlieb,
A. Nudelman, B. M. Stoltz, J. E. Bercaw and K. I. Goldberg,
Organometallics, 2010, 29, 2176.
34
35
36
37
N. Park, K. Park, M. Jang and S. Lee, J. Org. Chem., 2011,
7
6
, 4371–4378.
Los, M. (American Cyanamid Co.) Eur. Pat. Appl. EP
33310, 1985.
1
R. R. Traut, A. Bollen, T. T. Sun, J. W. B. Hershey, J.
Sundberg and L. R. Pierce, Biochemistry, 1973, 12, 3266.
M. Wallace, A. J. Allentoff, J. Brailsford, S. Gong, S.
Bonacorsi and F. Rinaldi, J. Label. Compd. Radiopharm.,
2015, 58, 429.
3
8
9
S. F. Carroll and D. A. Goff, 1990, WO 90/06774.
3
T. P. King, Y. Li and L. Kochoumian, Biochemistry, 1978, 17
,
1
499.
T. P. King, Y. Li and L. Kochoumian, Biochemistry, 1986, 25
774.
A. Braden, M. Roner, J. Ganter and K. Nelson, J. Nanosci.
Nanotechnol., 2007, , 925.
40
41
42
,
5
7
T. Tada, K. Mano, E. Yoshide, N. Tanaka and S. Kunugi,
Bull. Chem. Soc. Jpn., 2002, 75, 2247.
4
3
4
T. T. Ngo, Appl. Biochem. Biotechnol., 1986, 13, 213.
4
M. K. Ghorai, R. Talukdar and D. P. Tiwari, Org. Lett., 2014,
, 2204.
16
45
46
47
K. Yamagata, T. Yukihiko, M. Yamazaki, T. Matsuda and K.
Noda, Chem. Pharm. Bull., 1982, 30, 4396.
H. A. Bruson and T. W. Riener, J. Am. Chem. Soc., 1943,
65, 18.
B. Dmuchovsky, F. B. Zienty and W. A. Vredenbur, J. Org.
Chem., 1966, 31, 865.
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