A highly effective and mild protocol for the production of 1-thioamidoalkyl-2-naphthols using 1,3-disulfonic acid imidazolium trifluoroacetate as a dual-functional catalyst

Article abstract of DOI:10.1515/znb-2018-0001

A solvent-free protocol for the production of 1-thioamidoalkyl-2-naphthols via a one-pot multi-component reaction of arylaldehydes with 2-naphthol and thioacetamide using the ionic liquid 1,3-disulfonic acid imidazolium trifluoroacetate ([Dsim][TFA]) is described. Furthermore, a plausible and attractive mechanism based on the dual functionality of the catalyst is proposed. Because of the dual functionality of [Dsim][TFA] (possessing acidic and basic sites), it is found to be generally highly effective, affording the products in high yields and short reaction times under mild conditions. We claim that this is one of the best protocols for the synthesis of 1-thioamidoalkyl-2-naphthols (in terms of yield, temperature, conditions, and/or the reaction time).

Full text of DOI:10.1515/znb-2018-0001

Z. Naturforsch. 2018; aop
Mostafa Karami and Abdolkarim Zare*
A highly effective and mild protocol for the production
of 1-thioamidoalkyl-2-naphthols using 1,3-disulfonic acid
imidazolium trifluoroacetate as a dual-functional catalyst
https://doi.org/10.1515/znb-2018-0001
and consequently used for monitoring the binding of thio-
amide-containing peptides to proteins [8], (v) utilization
in medicinal chemistry [9], (vi) application as catalysts for
organic transformations [10, 11], and others [12, 13]. The
practical method for the synthesis of 1-thioamidoalkyl-
2-naphthols involves the one-pot multi-component reac-
tion of arylaldehydes with 2-naphthol and thioacetamide
promoted by a catalyst [14–21]. However, the reported
catalysts possess at least one of the following drawbacks:
long reaction time, moderate yield, harsh conditions, uti-
lization of volatile and toxic organic solvents as reaction
media, nonsystematic approach to the synthesis (only a
few 1-thioamidoalkyl-2-naphthols have been synthesized
besides other products), and the use of large amounts of
the catalyst. In addition, only a few catalysts have been
reported for this synthesis in the literature. Hence, intro-
ducing a new catalyst for the reaction which does not have
Received January 1, 2018; accepted February 26, 2018
Abstract: A solvent-free protocol for the production of
1-thioamidoalkyl-2-naphthols via a one-pot multi-com-
ponent reaction of arylaldehydes with 2-naphthol and
thioacetamide using the ionic liquid 1,3-disulfonic acid
imidazolium trifluoroacetate ([Dsim][TFA]) is described.
Furthermore, a plausible and attractive mechanism based
on the dual functionality of the catalyst is proposed.
Because of the dual functionality of [Dsim][TFA] (pos-
sessing acidic and basic sites), it is found to be generally
highly effective, affording the products in high yields and
short reaction times under mild conditions. We claim that
this is one of the best protocols for the synthesis of 1-thio-
amidoalkyl-2-naphthols (in terms of yield, temperature,
conditions, and/or the reaction time).
Keywords: 1-thioamidoalkyl-2-naphthol; 1,3-disulfonic these disadvantages is of importance.
acid imidazolium trifluoroacetate ([Dsim][TFA]); dual-
During the last decade, ionic liquids (ILs) have been
functional catalyst; ionic liquid; multi-component reac- introduced into nearly all fields of chemistry (organic,
tion; solvent-free reaction.
inorganic, analytical, electrochemistry, and catalysis).
Their extensive use is based on the outstanding properties
of ILs, e.g. high chemical, electrochemical, and thermal
stability, broad liquid range, very low vapor pressure,
capacity to modify their physical and chemical proper-
ties by changing the cation and anion structures, non-
flammability, capability to dissolve numerous kinds of
materials, and the ability to act as catalysts, reagents,
and solvents in organic transformations. Organic chem-
ists have designed a variety of acidic ILs to be utilized
as catalysts (or reagents) in organic reactions [22–29].
1,3-Disulfonic acid imidazolium trifluoroacetate ([Dsim]
[TFA]) is an acidic IL that has been applied as catalyst
for the preparation of 14H-dibenzo[a,j]xanthenes and
1,8-dioxo-decahydroacridines [25].
One-pot multi-component reactions are of importance
in organic and pharmaceutical chemistry, where three or
more starting materials are made to react in one pot and
one step to afford a complex product that has the main
elements of the all reactants. Consequently, this technique
increases the yield, decreases the reaction time, saves
energy and time, minimizes the use of volatile organic sol-
vents, and reduces the generation of side products, which
are in accordance with green chemistry protocols [30–32].
1 Introduction
1-Thioamidoalkyl-2-naphthol derivatives are of sig-
nificance, as they can be readily hydrolyzed to the bio-
logically important compounds 1,3-amino alcohols.
Notch-sparing, secretase-inhibitory, antibacterial, anti-
pain, bradycardiac, and hypotensive activities have been
reported for 1,3-amino alcohols [1–4]. On the other hand,
1-thioamidoalkyl-2-naphthols contain N-alkyl thioamide
or thioamide moieties, which are the bases for a variety
of uses, including (i) luminescent activity when com-
plexed with palladium [5], (ii) selective complexation of
copper, silver, cadmium, and lead [6], (iii) application
in peptide chemistry [7], (iv) quenching tryptophan and
tyrosine fluorescence in a distance-dependent manner,
*Corresponding author: Abdolkarim Zare, Department of Chemistry,
Payame Noor University, PO Box 19395-3697, Tehran, Iran,
e-mail: abdolkarimzare@pnu.ac.ir; abdolkarimzare@yahoo.com
Mostafa Karami: Department of Chemistry, Payame Noor University,
PO Box 19395-3697, Tehran, Iran
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2ꢀ ꢀM. Karami and A. Zare: Effective catalytic synthesis of 1-thioamidoalkyl-2-naphthols
Table 1:ꢀSynthesis of 1-thioamidoalkyl-2-naphthols catalyzed by
Another important green technique in synthetic
[Dsim][TFA].
chemistry is carrying out reactions under solvent-free
conditions. This technique has usually many advantages
with respect to shorter reaction time, higher yield, easier
work-up, safer reaction conditions, higher selectivity, pre-
venting or decreasing byproducts/waste generation, and
lower energy requirement [33–35].
S
O
S
CH3
NH
H2N
CH3
Ar
H
Ar
[Dsim][TFA] (15 mol%)
Solvent-free, 60 °C
+
OH
OH
Considering the above issues, we introduce here the
ionic liquid [Dsim][TFA] as a highly effective, mild, and
dual-functional catalyst for the synthesis of 1-thioam-
idoalkyl-2-naphthols by the one-pot multi-component
reaction of arylaldehydes with 2-naphthol and thioaceta-
mide under solvent-free conditions. Interestingly, this
catalyst has none of the mentioned drawbacks.
It should be mentioned that we had previously used
[Dsim][HSO4] and [Dsim][Cl] for the preparation of 1-car-
bamatoalkyl-2-naphthols and 1-amidoalkyl-2-naphthols
at 80 and 120°C; however, during those investigations,
we did not synthesize 1-thioamidoalkyl-2-naphthols
[28, 29]. According to our experience, the production of
1-thioamidoalkyl-2-naphthols is more difficult than that of
1-carbamatoalkyl/amidoalkyl-2-naphthols.
Productꢁ Ar
no.
ꢁ
Timeꢁ Yieldꢁ
(min) (%)aꢁ
M.p. (°C)
Foundꢁ Reported [ref.]
1
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
C6H5
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
35ꢂ
25ꢂ
25ꢂ
75ꢂ
55ꢂ
55ꢂ
35ꢂ
25ꢂ
40ꢂ
55ꢂ
80ꢂ
30ꢂ
25ꢂ
50ꢂ
96ꢂ 192–194ꢂ 190–193 [19]
97ꢂ 231–233ꢂ 234–236 [16]
97ꢂ 245–247ꢂ 243–245 [15]
88ꢂ 228–231ꢂ 229–231 [20]
95ꢂ 222–224ꢂ 219–221 [18]
93ꢂ 257–259ꢂ 256–258 [18]
95ꢂ 244–246ꢂ 243–245 [18]
94ꢂ 173–175ꢂ 174–176 [20]
95ꢂ 206–208ꢂ 208–210 [16]
93ꢂ 234–236ꢂ
86ꢂ 180–182ꢂ 181–182 [18]
91ꢂ 248–250ꢂ
94ꢂ 183–185ꢂ 180–183 [19]
92ꢂ 238–240ꢂ 240–242 [16]
2
3
3-O2NC6H4
4-O2NC6H4
2-O2NC6H4
4
5
2,4-Cl2C6H3
3-ClC6H4
6
7
4-ClC6H4
8
2-ClC6H4
4-FC6H4
3-CH3OC6H4
4-CH3OC6H4
2,5-(CH3O)2C6H3ꢂ
4-CH3C6H4
4-HOC6H4
9
10
11
12
13
14
–
–
ꢂ
ꢂ
aIsolated yield.
2 Results and discussion
To obtain the appropriate amount of the catalyst and the shows, [Dsim][TFA] was highly effective and general for the
suitable reaction temperature, the reaction of 3-nitroben- synthesis. The corresponding 1-thioamidoalkyl-2-naphthols
zaldehyde (1 mmol), 2-naphthol (1 mmol), and thioaceta- were produced in high to excellent yields and short reaction
mide (1.3 mmol) for the production of compound 2 was times when the arylaldehydes were bearing electron-with-
examined using various amounts of [Dsim][TFA] (10– drawing and electron-releasing substituents in the ortho,
17 mol%) in the temperature range 50–65°C under sol- meta, or para positions. Furthermore, aldehydes possess-
vent-free conditions (Scheme 1). Higher yields and shorter ing two substituents afforded the relevant products in high
reaction times resulted when the reaction was carried out yields and relatively short times (products 5 and 12).
in the presence of 15 mol% of the IL at 60°C (yieldꢀ=ꢀ97%,
timeꢀ=ꢀ25 min).
The IL functions as a dual-functional catalyst, because
it has both acidic and basic sites (SO3H group as the acid,
Then, the effectiveness and generality of use of [Dsim] and trifluoroacetate as the base). Altogether, there are
[TFA] was appraised by reacting miscellaneous aromatic three acidic sites and one basic site in the catalyst (Fig. 1).
aldehydes with 2-naphthol and thioacetamide under the
optimized reaction conditions. The optimized reaction
times and yields are displayed in Table 1. As the table
O
F3C
O
H
Basic site
Acidic site
O
S
S
CH3
NH
OH
O
S
O
O
H2N
OH
CH3
H
O
[Dsim][TFA]
Solvent-free
O2N
N
+
H
Acidic site
Acidic site
NO2
N
O
S
O
H
Scheme 1:ꢀModel reaction.
Fig. 1:ꢀAcidic and basic sites of [Dsim][TFA].
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ꢁꢀꢀꢀ
M. Karami and A. Zare: Effective catalytic synthesis of 1-thioamidoalkyl-2-naphtholsꢃ ꢃ3
Thus, [Dsim][TFA] can act as a highly effective and general The mechanism is supported by reports in the literature
catalyst for reactions that need both acidic and basic sites [14–16, 18].
simultaneously, e.g. the production 1-thioamidoalkyl-
2-naphthols. This is shown in the reaction mechanism with the reported catalysts, we have tabulated the results
(Scheme 2). and the reaction conditions for the synthesis of compound
To highlight the merit of our catalyst in comparison
At first, the basic anion (trifluoroacetate) assists 1 in the presence of these catalysts in Table 2. As can be
2-naphthol for the addition to the activated aldehyde (by seen in this table, [Dsim][TFA] afforded better results than
the acidic hydrogen of [Dsim][TFA]) to produce the inter- the other catalysts (in terms of the reaction yield, time and
mediate I. The removal of a H2O molecule from I through temperature). Moreover, we have performed the synthesis
the assistance of both the cation and the anion of the IL under solvent-free conditions.
gives the intermediate II. Finally, a Michael-type addition
of thioacetamide to II affords the product; this step is also
accelerated by the acidic and basic sites of [Dsim][TFA].
3 Conclusion
In summary, we have introduced an IL catalyst for the
synthesis of 1-thioamidoalkyl-2-naphthols. The advan-
O
F3C
O
H
O
tages of the presented protocol include high effective-
ness, generality, high yields, short reaction times,
cleaner reaction profile, simplicity, low cost, easy prepa-
ration of the catalyst, mild conditions, and good com-
pliance with the green chemistry protocols. We claim
that this is one of the best protocols for the synthesis of
1-thioamidoalkyl-2-naphthols.
O
S
N
N
HO3S
Ar
H
OH
O
O
H
H
O
O
[Dsim][TFA]
[Dsim][TFA]
Ar
O
Ar
H
N
(I)
O
CF3
O
SO3H
O
N
O
H
S
N
O
N
S
O
H
HN
CH3
S
HO3S
F3C
O
O
Ar
O
Ar
Ar
O
H
O
H
O
O
O
[Dsim][TFA]
4 Experimental
_
H2O
(II)
S
CH3
NH
4.1 General
Ar
HO
All starting materials and solvents were bought from
Merck, Fluka, or Acros. [Dsim][TFA] was prepared accord-
ing to the reported protocol (Scheme 3) [25]. Known com-
pounds were identified by comparing their melting points/
spectroscopic data with those reported in the literature.
The product
Scheme 2:ꢀProposed mechanism for the synthesis of
1-thioamidoalkyl-2-naphthols.
Table 2:ꢀComparison of the merit of [Dsim][TFA] with other reported catalysts for the synthesis of compound 1 in terms of the reaction yield,
time, and temperature.
Catalyst
ꢁ
Conditions
ꢁ
Time (min)
ꢁ Yield (%)ꢁ
Ref.
[Dsim][TFA]
ꢂ
Solvent-free, 60°C
Solvent-free, 120°C
Solvent-free, 120°C
ꢂ
ꢂ
ꢂ
35
25
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
96ꢂ
80ꢂ
73ꢂ
88ꢂ
93ꢂ
78ꢂ
80ꢂ
80ꢂ
95ꢂ
88ꢂ
This work
[14]
Trichloro-1,3,5-triazinane-2,4,6-trioneꢂ
1,3-Dichloro-5,5-dimethylhydantoin
Fe(HSO4)3
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
35
[14]
1,2-Dichloroethane, 60°C ꢂ
390
200
12
[15]
1,3-Dibromo-5,5-dimethylhydantoin
Trityl chloride
Solvent-free, 130°C
Solvent-free, 70°C
Solvent-free, 80°C
Solvent-free, 70°C
1,2-Dichloroethane, refluxꢂ
Solvent-free, 110°C
ꢂ
ꢂ
ꢂ
ꢂ
[16]
[17]
DCDBTSDa
25
[18]
Saccharin sulfonic acid
p-Toluenesulfonic acid
[Et3N–SO3H]Cl
50
[19]
60
[20]
ꢂ
30
[21]
aN,2-dibromo-6-chloro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide.
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4ꢀ
ꢀM. Karami and A. Zare: Effective catalytic synthesis of 1-thioamidoalkyl-2-naphthols
[4] A. Y. Shen, C. T. Tsai, C. L. Chen, Eur. J. Med. Chem. 1999, 34, 877.
HCl
+
[5] M. Akaiwa, T. Kanbara, H. Fukumoto, T. Yamamoto, J. Organomet.
Chem. 2005, 690, 4192.
CH2Cl2
r. t.
CF3COOH
CH2Cl2, r. t.
2
ClSO3H
Cl
+
N
NH
N
N
HO3S
SO3H
[6] F. Arnaud-Neu, G. Barrett, D. Corry, S. Cremin, G. Ferguson,
J. F. Gallagher, S. J. Harris, M. A. McKervey, M.-J. Schwing-Weill,
J. Chem. Soc., Perkin Trans. 1997, 2, 575.
[7] J. H. Miwa, A. K. Patel, N. Vivatrat, S. M. Popek, A. M. Meyer,
Org. Lett. 2001, 3, 3373.
[8] J. M. Goldberg, R. F. Wissner, A. M. Klein, E. J. Petersson, Chem.
Commun. 2012, 48, 1550.
[CF3COO]
+
HCl
N
N
HO3S
SO3H
[Dsim][TFA]
Scheme 3:ꢀSynthesis of [Dsim][TFA].
[9] F. Wang, R. Langley, G. Gulten, L. G. Dover, G. S. Besra,
W. R. Jacobs Jr., J. C. Sacchettini, J. Exp. Med. 2007, 204, 73.
[10] P. W. Tan, A. M. Mak, M. B. Sullivan, D. J. Dixon, J. Seayad,
Angew. Chem. Int. Ed. 2017, 56, 16550.
Progress of the reactions was monitored by thin-layer
chromatography (TLC). The melting points were recorded
on a Büchi B-545 apparatus in open capillary tubes.
Spectra were recorded on the following apparatuses:
[11] Y. Singjunla, M. Pigeaux, R. Laporte, J. Baudoux, J. Rouden, Eur.
J. Org. Chem. 2017, 2017, 4319.
[12] M. N. Xanthopoulou, S. K. Hadjikakou, N. Hadjiliadis,
E. R. Milaeva, J. A. Gracheva, V. Y. Tyurin, N. Kourkoumelis,
K. C. Christoforidis, A. K. Metsios, S. Karkabounas,
K. Charalabopoulos, Eur. J. Med. Chem. 2008, 43, 327.
[13] C. Jiang, P. J. Young, S. Brown-Xu, J. C. Gallucci, M. H. Chisholm,
Inorg. Chem. 2017, 56, 1433.
13
1H NMR (400 or 500 MHz) and C NMR (100 or 125 MHz)
on Bruker Avance DPX, FT-NMR spectrometers, and the
mass spectra on spectrometer 5975C VL MSD model with a
triple axis detector.
[14] A. Khazaei, F. Abbasi, A. R. Moosavi-Zare, M. Khazaei,
M. H. Beyzavi, J. Chin. Chem. Soc. 2015, 62, 850.
[15] H. Eshghi, G. H. Zohuri, S. Damavandi, Synth. Commun. 2012,
42, 516.
[16] A. Ghorbani-Choghamarani, S. Rashidimoghadam, Res. Chem.
Intermed. 2015, 41, 6271.
[17] A. Khazaei, M. A. Zolfigol, A. R. Moosavi-Zare, F. Abi, A. Zare,
H. Kaveh, V. Khakyzadeh, M. Kazem-Rostami, A. Parhami,
H. Torabi-Monfared, Tetrahedron 2013, 69, 212.
[18] A. Khazaei, F. Abbasi, A. R. Moosavi-Zare, J. Sulfur Chem. 2015,
36, 364.
[19] A. Zare, H. Kaveh, M. Merajoddin, A. R. Moosavi-Zare,
A. Hasaninejad, M. A. Zolfigol, Phosphorus Sulfur Silicon Relat.
Elem. 2013, 188, 573.
[20] A. Hassanabadi, M. R. Hosseini-Tabatabaei, J. Chem. Res. 2012,
36, 510.
[21] A. Zare, S. Akbarzadeh, E. Foroozani, H. Kaveh,
A. R. Moosavi-Zare, A. Hasaninejad, M. Mokhlesi,
M. H. Beyzavi, M. A. Zolfigol, J. Sulfur Chem. 2012, 33, 259.
[22] A. S. Amarasekara, Chem. Rev. 2016, 116, 6133.
[23] R. L. Vekariya, J. Mol. Liq. 2017, 227, 44.
[24] A. A. Marzouk, A. A. Abdelhamid, S. K. Mohamed, J. Simpson,
Z. Naturforsch. 2017, 72b, 23.
4.2 General procedure for the synthesis
of 1-thioamidoalkyl-2-naphthols
A mixture of arylaldehyde (1 mmol), 2-naphthol (1 mmol,
0.144 g), thioacetamide (1.3 mmol, 0.097 g) and [Dsim]
[TFA] (0.15 mmol, 0.051) was stirred at 60°C. Progress of
the reaction was monitored by TLC. When the reaction
was completed, the resulting precipitate was recrystal-
lized from ethanol (95%) to afford the pure product.
5 Supporting information
Selected spectral data and spectra of the 1-thioami-
doalkyl-2-naphthols have been given in the Supporting
Information available online (https://doi.org/10.1515/
znb-2018-0001).
[25] A. K. Dutta, P. Gogoi, R. Borah, RSC Adv. 2014, 4, 41287.
[26] M. A. Zolfigol, A. Khazaei, A. R. Moosavi-Zare, A. Zare,
H. G. Kruger, Z. Asgari, V. Khakyzadeh, M. Kazem-Rostami,
J. Org. Chem. 2012, 77, 3640.
Acknowledgment: We thank Research Council of Payame
Noor University for providing the necessary research facil-
ities and financial support for carrying out this work.
[27] A. Zare, Z. Nasouri, J. Mol. Liq. 2016, 216, 364.
[28] A. Zare, T. Yousofi, A. R. Moosavi-Zare, RSC Adv. 2012, 2, 7988.
[29] M. A. Zolfigol, A. Khazaei, A. R. Moosavi-Zare, A. Zare, V.
Khakyzadeh, Appl. Catal. A 2011, 400, 70.
[30] A. R. Moosavi-Zare, M. A. Zolfigol, V. Khakyzadeh, C. Böttcher,
M. H. Beyzavi, A. Zare, A. Hasaninejad, R. Luque, J. Mater.
Chem. A 2014, 2, 770.
[31] J. Safaei-Ghomi, S. H. Nazemzadeh, H. Shahbazi-Alavi,
Z. Naturforsch. 2017, 72b, 927.
[32] E. Lamera, S. Bouacida, M. L. Borgne, Z. Bouaziz, A. Bouraiou,
Tetrahedron Lett. 2017, 58, 1305.
References
[1] H.-X. Wei, D. Lu, V. Sun, J. Zhang, Y. Gu, P. Osenkowski, W. Ye,
D. J. Selkoe, M. S. Wolfe, C. E. Augelli-Szafran, Bioorg. Med.
Chem. Lett. 2016, 26, 2133.
[2] M. Kidwai, R. Chauhan, Asian J. Org. Chem. 2013, 2, 395.
[3] N. Gyemant, H. Engi, Z. Schelz, I. Szatmari, D. Toth, F. Fulop,
J. M. Nar, P. D. Witte, Br. J. Cancer 2010, 103, 178.
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M. Karami and A. Zare: Effective catalytic synthesis of 1-thioamidoalkyl-2-naphtholsꢃ ꢃ5
[33] M. Himaja, D. Poppy, K. Asif, Int. J. Res. Ayurveda Pharm. 2011,
2, 1079.
[34] G. B. D. Rao, S. Nagakalyanb, G. K. Prasad, RSC Adv. 2017, 7,
3611.
[35] A. Zare, A. R. Moosavi-Zare, M. Merajoddin, M. A. Zolfigol,
T. Hekmat-Zadeh, A. Hasaninejad, A. Khazaei, M. Mokhlesi,
V. Khakyzadeh, F. Derakhshan-Panah, M. H. Beyzavi, E. Rostami,
A. Arghoon, R. Roohandeh, J. Mol. Liq. 2012, 167, 69.
Supplemental Material: The online version of this article offers
supplementary material (https://doi.org/10.1515/znb-2018-0001).
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