Microwave-activated synthesis of thiazolo[5,4-d]thiazoles by a condensation/oxidation sequence

Article abstract of DOI:10.1039/c3ra45015e

A microwave-assisted preparation of symmetrical thiazolo[5,4-d]thiazoles from the corresponding aldehydes is presented. The two-step reaction sequence comprises the condensation of aldehydes with dithiooxamide followed by oxidation/aromatization with 1,4-

Full text of DOI:10.1039/c3ra45015e

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Microwave-activated synthesis of thiazolo[5,4-d]-
thiazoles by a condensation/oxidation sequence†‡
Cite this: RSC Adv., 2014, 4, 1322
Alessio Dessı,ab Massimo Calamante,ab Alessandro Mordini,ab Lorenzo Zani,bc
`
d
b
*
Maurizio Taddei and Gianna Reginato
A
microwave-assisted preparation of symmetrical thiazolo[5,4-d]thiazoles from the corresponding
aldehydes is presented. The two-step reaction sequence comprises the condensation of aldehydes with
dithiooxamide followed by oxidation/aromatization with 1,4-benzoquinone derivatives. The new
procedure provides the desired products in good yields and in most cases allows reduction of the excess
of aldehyde employed in the process compared to previous methodologies. For the first time,
application of the reaction both on aromatic and aliphatic aldehydes is demonstrated.
Received 11th September 2013
Accepted 23rd October 2013
DOI: 10.1039/c3ra45015e
www.rsc.org/advances
their potential biological activity,7 but recently the interest in
their properties has increased spectacularly due to their inclu-
Introduction
sion in functional materials with several applications. In
particular, they have been used as spacer units in semicon-
ducting materials for polymer and organic light-emitting
diodes,8 organic eld-effect transistors,9 as well as uorescent
sensors and emitters.10 Moreover, they have been incorporated
in donor/acceptor polymers for organic bulk heterojunction
solar cells,11 and introduced in organic sensitizers for dye-
sensitized solar cells.12 Finally, thiazolo[5,4-d]thiazoles might
represent an innovative class of ligands for coordination
chemistry.13
The rst compound of this class was prepared in 1891 by
Ephraim,14 but its correct structure was established only in 1960
by Johnson et al.,15 who were the rst to prepare a large number of
analogues.16 These were obtained by reaction of dithiooxamide
with an excess of the appropriate aromatic aldehydes, a reaction
which was oen affected by some limitations, such as high
temperatures, long reaction times, large excess of aldehyde
required and, frequently, low to moderate yields.8–11,13,15,16 A few
alternative synthetic procedures have been reported based on the
stepwise elaboration of different starting materials.6,17–20 More
recently, milder conditions for the condensation of dithiooxamide
with aldehydes have been described,21 however, a systematic study
to nd optimal and more general conditions, tolerant to different
functional groups, has not been reported so far.
Thiazole derivatives, either of natural or synthetic origin, are
known to possess a range of interesting properties: for example,
the thiazole ring is present in thiopeptide antibiotics,1 and
some natural thiazole-containing macrocycles have shown
cytotoxic and antimicrobial activities.2 In addition, they have
found use in materials science since they exhibit strong uo-
rescence3 as well as non-linear optical4 and semiconducting
properties.5
Among thiazole derivatives, thiazolo[5,4-d]thiazoles (1) are a
class of compounds characterized by a rigid and coplanar
bicyclic scaffold giving rise to an extended p-electron system
(Fig 1).6 These substances were also initially investigated for
Fig. 1 The thiazolo[5,4-d]thiazole ring system.
a
`
Universita degli Studi di Firenze, Dipartimento di Chimica “Ugo Schiff”, Via della
Lastruccia 13, 50019 Sesto Fiorentino, Italy
bCNR – Istituto di Chimica dei Composti Organometallici (CNR-ICCOM), Via Madonna
del Piano 10, 50019 Sesto Fiorentino, Italy. E-mail: gianna.reginato@iccom.cnr.it;
The advent of microwave-assisted organic synthesis has
contributed signicantly to the development of mild and
sustainable procedures for the preparation of organic
compounds as it oen leads to a remarkable decrease in reac-
tion times and chemical waste, an increase in yields, and an
easier product workup.22 This technique has also found useful
application in the synthesis of heterocycles,23 which led us to
think it could also be exploited for thiazolothiazole synthesis.
Indeed, during our studies on the preparation of new organic
Fax: +39 044 5225203; Tel: +39 055 5225255
c
`
CNR – Istituto per la Sintesi Organica e la Fotoreattivita (CNR-ISOF), Via Piero Gobetti
101, 40129 Bologna, Italy
d
`
Universita degli Studi di Siena, Dipartimento di Biotecnologie, Chimica e Farmacia,
Via A. Moro 2, 53100 Siena, Italy
† This paper is dedicated to the memory of Prof. Alessandro Degl’Innocenti.
‡ Electronic Supplementary Information (ESI) available: Copies of 1H-and
13C-NMR spectra of compounds 1b, 1c, 1d, 1e, 1f, 1i, 1j, 1k, 1l, 1m, 1o, 1p, 1q,
1r, 4, 1H-NMR spectrum of compound 1n, 1H-NMR spectrum of the crude 1b/3
mixture. See DOI: 10.1039/c3ra45015e
1322 | RSC Adv., 2014, 4, 1322–1328
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sensitizers for dye-sensitized solar cells,12a,c we observed that the dithiooxamide was irradiated under solventless conditions at
yield of thiazolo[5,4-d]thiazole 1a, stemming from aldehyde 2a 150 ꢀC for 30 min, 2,5-bis(2-methoxyphenyl)-thiazolo[5,4-d]-
(Scheme 1), could be signicantly enhanced if the reaction was thiazole 1b was obtained in 48% yield aer recrystallization
carried out in solvent-free conditions and under MW-irradia- (entry 1). The aldehyde/dithiooxamide 4 : 1 ratio was selected to
tion. Thus, the efficiency of the reaction was improved ensure complete dissolution of dithiooxamide under solvent-
compared to the usual thermal process;8a moreover, the reac- free conditions. Such result was already comparable to that
tion time was notably shortened to just 15 minutes.24
obtained with the classical thermal procedure by employing a
Prompted by this result and in consideration of the much larger amount of aldehyde 2b (47% yield, 8.0 eq.).15
1
demonstrated utility of thiazolo[5,4-d]thiazoles, we decided to However, analysis of the H-NMR spectrum of the crude reac-
study in more detail the effect of microwave activation in the tion mixture revealed the presence of a byproduct, which we
condensation of dithioxoamide with aromatic aldehydes, aim- identied as symmetrical compound 3 (Fig 2), based on the
ing to nd a general and mild synthetic procedure.
assignment of the relevant spectral peaks (see ESI‡). Such
compound is a likely intermediate in the cyclization pathway;6
formation of a similar species was already observed in the
thermal reaction of salicylaldehyde with dithiooxoamide,15 and
in that case it was shown that it could be converted to the
desired product by heating at 250–270 ꢀC, with or without
addition of a mild oxidant like sulfur. Therefore, we reasoned
that the yield of our reaction could be further improved by
addition of an oxidant, in order to facilitate the last dehydro-
genation step and achieve full aromatization to product 1b.
Indeed, when the crude mixture was directly dissolved in
THF and reacted with 0.25 eq. of DDQ (Table 1, entry 2) at reux
for 10 min the yield was improved to 61%. Use of 0.5 eq. of DDQ
led to a further increase to 70% (entry 3), and employment of a
cheaper, structurally related oxidant such as chloranil gave
practically the same result (68%, entry 4). Importantly, when the
same conditions were applied using conventional thermal
heating a lower yield of the desired compound was obtained
(48%, entry 5) showing that MW activation is benecial for the
reaction outcome. A reasonable yield could be still obtained
when lowering the amount of aldehyde to 3.0 eq. (entry 6), while
further experiments showed that variation of the temperature
(entries 7 and 8) or employment of a longer reaction time were
not productive in this case.
Results and discussion
Optimization of the reaction conditions was carried out using
2-methoxybenzaldehyde 2b as the model substrate (Table 1) to
generate thiazolo[5,4-d]thiazole 1b.
This substrate was chosen because it is inexpensive and
readily available, and the corresponding product could be easily
obtained in high purity by a simple precipitation followed by
recrystallization. When a (4 : 1) mixture of aldehyde and
Scheme 1 MW-assisted synthesis of thiazolo[5,4-d]thiazole 1a.
Table 1 Optimization of reaction conditions for the preparation of
thiazolothiazole 1b from 2-methoxybenzaldehyde 2b
Microwave reactions under solvent-free conditions are
attractive since they are usually characterized by reduced waste,
low costs and simplicity in processing and handling. However,
in the case of solid reaction partners or when a large excess of
one reagent should be avoided, use of a solvent can be advan-
tageous. For this reason we decided to investigate also the
reaction outcome using nitrobenzene as the reaction medium, a
solvent previously employed in thermal procedures.21
Entry
2ba
T (ꢀC)
DDQa
Yieldb
Although we found that the reaction was less efficient (entry 9),
we observed that in the presence of solvent it was possible to
obtain a reasonable yield of the product even using a strict stoi-
chiometric amount of aldehyde (2.0 eq. entry 11), proving these as
the best conditions to be used with valuable or solid substrates.
1
2
3
4.0
4.0
4.0
4.0
4.0
3.0
4.0
4.0
4.0
3.0
2.0
150
150
150
150
150
150
100
180
150
150
150
—
48%
61%
70%
68%
48%
61%
—
52%
59%
63%
55%
0.25
0.50
0.50c
0.50
0.75
0.50
0.75
0.50
0.50
0.50
4
5d
6
7
8
9e
10e
11e
a
b
Equivalents used in the reaction relative to dithiooxamide. Yield of
isolated compound. Reaction time was 30 min for all entries.
c
d
Chloranil was used instead of DDQ as the oxidant. Reaction
e
performed without MW activation. Nitrobenzene (C6H5NO2) was
used as the solvent.
Fig. 2 Structure of intermediate 3 and of the oxidants used in this work.
RSC Adv., 2014, 4, 1322–1328 | 1323
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Having found two sets of efficient reaction conditions, the characterization (entries 6–7). In the case of compound 1h, it
scope of the MW-assisted procedures was assessed by reacting a was possible to detect the corresponding molecular peaks by
range of aldehydes both under solvent-free conditions (method direct infusion mass spectrometry, which showed the typical
A) and in solution (method B). The results obtained are reported distribution pattern of a tetrachloro-substituted compound. On
in Table 2, together with the best results previously described in the other hand, in order to conrm indirectly the formation of
the literature for known compounds.
1g, we reasoned that a more soluble compound could be
The two methods gave in most of the cases the expected obtained by introduction of long alkyl chains. Therefore, the
product in good yield (up to 81%) and high purity. Solvent-free solid obtained aer crystallization was reacted with 1-octyne,
conditions generally provided better results, except in the cases under heterogeneous Pd-catalyzed Sonogashira conditions,27
of products 1d,e (entries 3, 4). The procedure was suitable both and the soluble tetraalkyl-substituted bisaryl-thiazolothiazole 4
for substituted aromatic (entries 1–7) and heteroaromatic was isolated aer ash column chromatography (Scheme 2). It
(entries 8–13) aldehydes.
should be pointed out that this reaction was carried out under
With these substrates, superior yields compared to the substantially heterogeneous conditions, and at the end four
literature were oen obtained (up to 76%, entries 1, 3, 8, 9, 11). new carbon–carbon bonds were formed. Preparation of
In some other cases, similar yields were obtained but a much compound 4, besides proving the actual formation of 1g,
smaller excess of aldehyde (entries 2, 4) was required. Finally, demonstrates the synthetic utility of the present procedure
only for two substrates this methodology afforded results when starting from halo-substituted aryl aldehydes. Indeed,
comparable to the literature (entries 5, 10). The best result was thiazolothiazoles such as 1g, being able to undergo further
obtained with EDOT-aldehyde 2n, which gave the correspond- synthetic manipulation, constitute useful building blocks for a
ing product in 81% yield (entry 13). Unfortunately, compounds series of applications such as those already outlined, where
1g and 1h were almost completely insoluble in a wide range of compounds featuring extended p-structures are oen
organic solvents, which hampered their full spectroscopic required.8–13
Table 2 Scope of MW activated condensation/oxidation sequence to thiazolo[5,4-d]thiazoles
Entry
R
Product
1b
Methoda,b
Isolated yield
Lit. yield (eq. of 2)
47% (ref. 15) (8)
78% (ref. 15) (10)
35% (ref. 25) (10)
52% (ref. 26) (3.5)
45% (ref. 25) (2)
1
2
3
4
5
2-CH3O-Ph (2b)
Ph (2c)
A
B
A
B
A
B
A
B
A
B
B
B
A
B
B
B
B
B
B
A
B
A
B
B
A
B
68%
55%
73%
66%
35%
58%
46%
47%
46%
30%
69%c
72%c
72%
49%
66%
66%
76%
75%
81%
54%d
40%d
40%
21%
33%
6%
1c
2-Br-Ph (2d)
4-tBu-Ph (2e)
2-OH-Ph (2f)
1d
1e
1f
6
7
8
3,5-Br2-Ph (2g)
2,4-Cl2-Ph (2h)
2-Thienyl (2i)
1g
1h
1i
—
—
36% (ref. 11a) (2)
9
2-Furyl (2j)
4-Pyridyl (2k)
2-Pyridyl (2l)
5-Thiazolyl (2m)
2-(3,4-Ethylendioxy)thienyl (2n)
n-Hexyl (2o)
1j
1k
1l
1m
1n
1o
40% (ref. 15) (13)
60% (ref. 21) (2)
60% (ref. 21) (2)
—
—
—
10
11
12
13
14
15
Cyclohexyl (2p)
1p
—
16
17
tert-Butyl (2q)
Styryl (2r)
1q
1r
—
7% (ref. 15) (9)
9%
a
b
Method A: aldehyde 2 (4.0 eq.), dithioxamide (1.0 eq.), MW, 150 ꢀC, 300, neat. Method B: aldehyde 2 (2.0 eq.), dithioxamide (1.0 eq.),
c
nitrobenzene, MW, 150 ꢀC, 300. Due to the almost complete insolubility in a wide range of organic solvents, full characterization was not
possible. d Puried by ash column chromatography.
1324 | RSC Adv., 2014, 4, 1322–1328
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ꢀ
60 C boiling fraction. Thin layer chromatography was carried
out on aluminum-supported Merck 60 F254 plates; detection
was carried out using UV light and permanganate or molybdo-
phosphoric acid solutions followed by heating. Flash column
chromatography was performed using Merck Kieselgel 60 (300–
400 mesh) as the stationary phase. 1H-NMR spectra were
recorded at 300 or 400 MHz, and 13C-NMR spectra were recor-
ded at 75.5 or 100.6 MHz. Chemical shis were referenced to the
residual solvent peak (CDCl3, d 7.26 ppm for 1H-NMR and d
77.16 ppm for 13C-NMR; pyridine-d5, d 7.22, 7.58 and 8.74 ppm
for 1H-NMR, d 123.9, 135.9 and 150.4 ppm for 13C-NMR; DMSO-
d6, d 2.50 ppm for 1H-NMR). FT-IR spectra were recorded in the
range 4000–400 cmꢁ1 with a 2 cmꢁ1 resolution. ESI-MS spectra
were obtained by direct injection of the sample solution and are
reported in the form m/z. Melting points are uncorrected.
Scheme 2 Elaboration of compound 1g by means of a Pd-catalyzed
Sonogashira reaction.
Remarkably, product formation occurred also with chal-
lenging substrates such as primary, secondary and tertiary
aliphatic aldehydes 2o–q, albeit with moderate yields (33–54%,
entries 14–16). Conversion of such substrates was usually
unsuccessful under classic conditions, due to the formation of
aldol-type byproducts (for enolizable aldehydes) and difficult
nal aromatization (formation of a shorter and less stabilized
p-system); employment of the present methodology allowed to
overcome such obstacles. Moreover, this was the rst time that
a synthetic procedure for the preparation of thiazolo[5,4-d]-
thiazoles was reported to work both on aromatic and aliphatic
substrates. Indeed, to date the preparation of only one aliphatic
product was described.7a,b,26 Finally, the method found a
limitation in the use of a-b-unsaturated aldehydes as, when
cinnamaldehyde 2r was subjected to the reaction conditions,
the corresponding product could be isolated only in low yields
(entry 17).
General procedure A
In a microwave vial equipped with a magnetic stirrer were
introduced aldehyde 2 (8.0 mmol, 4.0 eq.) and dithiooxamide
(2.0 mmol, 1.0 eq.). The resulting mixture was heated under
microwave irradiation at 150 ꢀC for 30 min, then allowed to cool
down to room temperature. The reaction mixture was diluted
with THF (ca. 5 mL) and transferred in a ask, then chloranil
(1.0 mmol, 0.5 eq.) was added to the reaction mixture, which
was heated to reux and stirred for 10 min. Aer this time
heating was interrupted and methanol (ca. 10 mL) was added to
the reaction mixture, which was cooled down to 0 ꢀC. The
precipitated solid was ltered and washed with methanol, and
recrystallized from THF to give pure thiazolo[5,4-d]thiazole 1.
General procedure B
In a microwave vial equipped with a magnetic stirrer were
placed aldehyde
2 (2.0 mmol, 2.0 eq.), dithiooxamide
Conclusions
(1.0 mmol, 1.0 eq.) and nitrobenzene (1 mL). The resꢀulting
mixture was heated under microwave irradiation at 150 C for
30 min, aer which it was allowed to cool down to room
temperature. THF (ca. 5 mL) and chloranil (0.5 mmol, 0.5 eq.)
were added to the reaction mixture, which was transferred to a
ask, heated to reux and stirred for 10 min. Aer this time
heating was interrupted and methanol (ca. 10 mL) was added to
the reaction mixture, which was cooled down to 0 ꢀC. The solid
was ltered, washed with methanol and recrystallized from THF
to give pure thiazolo[5,4-d]thiazole 1.
In summary, we have developed a rapid and simple procedure
for the synthesis of thiazolo[5,4-d]thiazoles through microwave
activation of the condensation of dithioxoamide with aromatic
aldehydes, followed by oxidation (aromatization). These useful
products were obtained in good yields, using mild conditions
and oen reducing the excess of aldehydes employed in the
process. Application of the reaction both on aromatic and
aliphatic aldehydes, as well as further elaboration of the reac-
tion products by cross-coupling chemistry, was demonstrated.
2,5-Bis(2-methoxyphenyl)-thiazolo[5,4-d]thiazole(1b).15 Alde-
hyde 2b (1.09 g, 8.00 mmol) was reacted with dithiooxamide
(240 mg, 2.00 mmol) following general procedure A. Aer
purication, compound 1b (482 mg, 68% yield) was obtained as
Experimental section
General remarks
All reactions were performed under an inert nitrogen atmo- a pale brown solid; mp ¼ 260–261 ꢀC (lit.15 253–254 ꢀC); 1H-NMR
sphere in a ame- or oven-dried apparatus. Microwave-assisted (300 MHz, CDCl3) dH 8.45 (2H, dd, J ¼ 7.9 and 1.7 Hz), 7.42 (2H,
transformations were carried out using a CEM Discover Bench- td, J ¼ 7.4 and 1.7 Hz), 7.12 (2H, t, J ¼ 8.2 Hz), 7.06 (2H, d, J ¼ 8.3
Mate reactor at xed temperature (surface sensor monitoring) Hz), 4.08 (6H, s); 13C-NMR (100 MHz, CDCl3) dC 163.5, 156.6,
and variable power (max. power 300 W). Liquid aldehydes were 152.1, 131.1, 128.6, 123.1, 121.4, 111.8, 55.9; IR (KBr) cmꢁ1 3078,
distilled under vacuum before use. 3,4-Ethylenedioxythiophene- 2832, 1582; MS (ESI) m/z 355 (M + H+, 100%).
2-carboxaldehyde28 was prepared according to a published
2,5-Diphenylthiazolo[5,4-d]thiazole (1c).15 Aldehyde 2c
procedure. All other chemicals employed were commercially (849 mg, 8.00 mmol) was reacted with dithiooxamide (240 mg,
available and used as received. Petroleum ether was the 40– 2.00 mmol) following general procedure A. Aer purication,
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compound 1c (430 mg, 73% yield) was obtained as a yellow (75 MHz, CDCl3) dC 162.7, 149.9, 137.7, 128.8, 128.3, 126.9; IR
1
solid; mp ¼ 196–198 C (lit.15 209–210 C); H-NMR (300 MHz, (KBr) cmꢁ1 3116, 1571; MS (ESI) m/z 307 (M + H+, 100%).
ꢀ
ꢀ
CDCl3) dH 7.99–8.02 (4H, m), 7.47–7.50 (6H, m); 13C-NMR (75
2,5-Bis(fur-2-yl)-thiazolo[5,4-d]thiazole (1j).15,29 Aldehyde 2j
MHz, CDCl3) dC 169.3, 151.0, 134.1, 130.8, 129.3, 126.5; IR (KBr) (192 mg, 2.00 mmol) was reacted with dithiooxamide (120 mg,
cmꢁ1 3059, 1570; MS (ESI) m/z 295 (M + H+, 100%).
1.00 mmol) in 1.0 mL of nitrobenzene, following general
2,5-Bis(2-bromophenyl)-thiazolo[5,4-d]thiazole (1d).25 Alde- procedure B. Aer purication, 181 mg (0.66 mmol) of
hyde 2d (370 mg, 2.00 mmol) was reacted with dithiooxamide compound 1j (181 mg, 66% yield) was obtained as a dark green
(120 mg, 1.00 mmol) in 1.0 mL of nitrobenzene, following solid; mp ¼ >250 ꢀC (dec.) (lit.15 238–240 ꢀC); 1H-NMR (300 MHz,
general procedure B. Aer purication, compound 1d (262 mg, CDCl3) dH 7.56 (2H, d, J ¼ 1.5 Hz), 7.08 (2H, d, J ¼ 3.3 Hz), 6.59
58% yield) was obtained as a pale green solid; mp ¼ 228–229 ꢀC; (2H, dd, J ¼ 3.6 and 2.1 Hz); 13C-NMR (75 MHz, CDCl3) dC 158.8,
1H-NMR (300 MHz, CDCl3) dH 8.06 (2H, dd, J ¼ 8.0 and 1.6 Hz), 150.7, 148.8, 144.4, 112.8, 110.3; IR (KBr) cmꢁ1 3111, 1497; MS
7.75 (2H, dd, J ¼ 8.0 and 1.2 Hz), 7.46 (2H, td, J ¼ 7.6 and 1.2 (ESI) m/z 275 (M + H+, 100%).
Hz), 7.33 (2H, td, J ¼ 8.0 and 1.6 Hz); 13C-NMR (100 MHz, CDCl3)
2,5-Bis(pyridine-4-yl)-thiazolo[5,4-d]thiazole (1k).21,30 Alde-
dC 166.8, 151.9, 134.5, 134.4, 132.1, 131.3, 127.9, 121.7; IR (KBr) hyde 2k (214 mg, 2.00 mmol) was reacted with dithiooxamide
cmꢁ1 3055, 1570, 1026; MS (ESI) m/z 453 (M + H+, 100%), 455 (120 mg, 1.00 mmol) in 1.0 mL of nitrobenzene, following
(50%), 451 (50%).
general procedure B. Aer purication, compound 1k (196 mg,
2,5-Bis(4-tert-butylphenyl)-thiazolo[5,4-d]thiazole (1e).26 Alde- 66% yield) was obtained as a light brown solid; mp ¼ 301–304
hyde 2e (324 mg, 2.00 mmol) was reacted with dithiooxamide ꢀC (lit.21 300–302 ꢀC); 1H-NMR (300 MHz, CDCl3) dH 8.78 (4H, d,
(120 mg, 1.00 mmol) in 1.0 mL of nitrobenzene, following J ¼ 6.6 Hz), 7.87 (4H, d, J ¼ 6.9 Hz); 13C-NMR (100 MHz, CDCl3)
general procedure B. Aer purication, compound 1e (187 mg, dC 167.6, 152.5, 151.0, 140.6, 120.2; IR (KBr) cmꢁ1 3038, 1596;
47% yield) was obtained as a pale yellow solid; mp ¼ 285–287 ꢀC; MS (ESI) m/z 297 (M + H+, 100%).
1H-NMR (300 MHz, CDCl3) dH 7.92 (4H, d, J ¼ 8.1 Hz), 7.49 (4H, d,
2,5-Bis(pyridine-2-yl)-thiazolo[5,4-d]thiazole (1l).13b,21 Alde-
J ¼ 8.4 Hz), 1.37 (18H, s); 13C-NMR (75 MHz, CDCl3) dC 169.1, hyde 2l (214 mg, 2.00 mmol) was reacted with dithiooxamide
154.3, 150.7, 131.5, 126.3, 126.2, 35.1, 31.3; IR (KBr) cmꢁ1 3058, (120 mg, 1.00 mmol) in 1.0 mL of nitrobenzene, following
2962, 1517; MS (ESI) m/z 407 (M + H+, 100%).
general procedure B. Aer purication, compound 1l (225 mg,
2,5-Bis(2-hydroxyphenyl)-thiazolo[5,4-d]thiazole (1f).15,21 Alde- 76% yield) was obtained as a brown solid; mp ¼ 334–335 ꢀC
hyde 2f (977 mg, 8.00 mmol) was reacted with dithiooxamide (lit.21 325–326 ꢀC); 1H-NMR (300 MHz, CDCl3) dH 8.66 (2H, d, J ¼
(240 mg, 2.00 mmol) following general procedure A. Aer puri- 4.5 Hz), 8.24 (2H, d, J ¼ 7.5 Hz), 7.85 (2H, td, J ¼ 7.7 and 1.7 Hz),
cation, compound 1f (300 mg, 46% yield) was obtained as a 7.37 (2H, dd, J ¼ 7.5 and 4.8 Hz); 13C-NMR (75 MHz, CDCl3) dC
light brown solid; mp ¼ 303–305 ꢀC (lit.15 300–302 ꢀC); 1H-NMR 171.0, 153.4, 151.6, 149.8, 137.3, 125.2, 120.1; IR (KBr) cmꢁ1
(300 MHz, CDCl3) dH 11.39 (2H, s), 7.65 (2H, d, J ¼ 7.9 Hz), 7.38 3056, 1570; MS (ESI) m/z 297 (M + H+, 100%).
(2H, t, J ¼ 8.3 Hz), 7.10 (2H, d, J ¼ 8.3 Hz), 6.98 (2H, t, J ¼ 8.1 Hz);
2,5-Bis(1,3-thiazol-5-yl)-thiazolo[5,4-d]thiazole (1m). Alde-
13C-NMR (75 MHz, pyridine-d5) dC 166.7, 157.2, 151.3, 132.2, hyde 2m (226 mg, 2.00 mmol) was reacted with dithiooxamide
128.6, 121.2, 120.4, 117.9; IR (KBr) cmꢁ1 3212, 3038, 1576; MS (120 mg, 1.00 mmol) in 1.0 mL of nitrobenzene, following
(ESI) m/z 327 (M + H+, 100%).
general procedure B. Aer purication, compound 1m (231 mg,
ꢀ
2,5-Bis(3,5-dibromophenyl)-thiazolo[5,4-d]thiazole (1g). Alde- 75% yield) was obtained as a brown solid; mp ¼ 295–297 C;
hyde 2g (528 mg, 2.01 mmol) was reacted with dithiooxamide 1H-NMR (300 MHz, CDCl3) dH 8.91 (2H, s), 8.37 (2H, s); 13C-NMR
(120 mg, 1.00 mmol) in 1.0 mL of nitrobenzene, following (100 MHz, CDCl3) dC 160.0, 155.2, 150.6, 142.5, 133.4; IR (KBr)
general procedure B. Aer purication, compound 1g (419 mg, cmꢁ1 3048, 1533; MS (ESI) m/z 309 (M + H+, 100%). HRMS (ESI,
69% yield) was obtained as a pale brown solid, which was ion trap) m/z calcd for C10H5N4S4 [M + 1]+ 308.9392. Found
insoluble in all the organic solvents tested. IR (KBr) cmꢁ1 3074, 308.9395.
1580, 1038.
2,5-Bis(2,3-dihydrothieno[3,4-b][1,4]-dioxin-5-yl)-thiazolo
2,5-Bis(2,4-dichlorophenyl)-thiazolo[5,4-d]thiazole (1h). Alde- [5,4-d]thiazole (1n). Aldehyde 2n (340 mg, 2.00 mmol) was
hyde 2h (350 mg, 2.01 mmol) was reacted with dithiooxamide reacted with dithiooxamide (120 mg, 1.00 mmol) in 1.0 mL of
(120 mg, 1.00 mmol) in 1.0 mL of nitrobenzene, following nitrobenzene, following general procedure B. Aer purication,
general procedure B. Aer purication, compound 1h (311 mg, compound 1n (341 mg, 81% yield) was obtained as a brown
72% yield) was obtained as a brown solid, which was insoluble in solid. mp ¼ >350 ꢀC (dec.); 1H-NMR (400 MHz, DMSO-d6) dH
all the organic solvents tested. IR (KBr) cmꢁ1 3071, 1582, 1065; 6.94 (2H, s), 4.50–4.53 (4H, m), 4.33–4.36 (4H, m); IR (KBr) cmꢁ1
MS (ESI) m/z 431 (75%), 433 (M + H+, 100%), 435 (50%), 437 3107, 2926, 1507, 1065; MS (ESI) m/z 423 (M + H+, 100%). HRMS
(11%), 439 (1%).
(ESI, ion trap) m/z calcd for C16H11O4N2S4 [M + 1]+ 422.9596.
2,5-Bis(thiophen-2-yl)-thiazolo[5,4-d]thiazole (1i).11a,29 Alde- Found 422.9596. Due to the low solubility of compound 1n in
hyde 2i (897 mg, 8.01 mmol) was reacted with dithiooxamide most organic solvents it was not possible to record a suitable
(240 mg, 2.00 mmol) following general procedure A. Aer 13C-NMR spectrum.
purication, compound 1i (441 mg, 72% yield) was obtained as
2,5-Dihexyl-thiazolo[5,4-d]thiazole (1o). Aldehyde 2o (228
1
a yellow solid; mp ¼ 244–245 ꢀC (lit.29 246 ꢀC); H-NMR (400 mg, 2.00 mmol) was reacted with dithiooxamide (120 mg, 1.00
MHz, CDCl3) dH 7.58 (2H, dd, J ¼ 3.7 and 1.1 Hz), 7.47 (2H, dd, mmol) in 1.0 mL of nitrobenzene, following general procedure
J ¼ 5.0 and 1.1 Hz), 7.12 (2H, dd, J ¼ 5.0 and 3.7 Hz); 13C-NMR B. Purication by ash column chromatography (SiO2; PE/
1326 | RSC Adv., 2014, 4, 1322–1328
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Et2O ¼ 10/1) afforded compound 1o (124 mg, 40%yield) as a
pale yellow oil; 1H-NMR (300 MHz, CDCl3) dH 3.04 (4H, t, J ¼ 7.6
Hz), 1.82 (4H, q, J ¼ 7.4 Hz), 1.25–1.47 (12H, m), 0.83–0.92 (6H,
m); 13C-NMR (75 MHz, CDCl3) dC 172.6, 148.4, 35.1, 31.6, 29.9,
28.8, 22.6, 14.2; IR (KBr) cmꢁ1 2927, 1467; MS (ESI) m/z 311 (M +
H+, 100%). HRMS (ESI, ion trap) m/z calcd for C16H27N2S2 [M +
1]+ 311.1610. Found 311.1615.
2,5-Dicyclohexyl-thiazolo[5,4-d]thiazole (1p). Aldehyde 2p
(897 mg, 8.01 mmol) was reacted with dithiooxamide (240 mg,
2.00 mmol) following general procedure A. Aer purication,
compound 1p (245 mg, 40% yield) was obtained as a light brown
solid; mp ¼ 140–141 ꢀC; 1H-NMR (300 MHz, CDCl3) dH 3.03 (2H,
tt, J ¼ 11.4 and 3.2 Hz), 2.14–2.19 (4H, m), 1.84–1.89 (4H, m),
1.72–1.77 (2H, m), 1.52–1.66 (4H, m), 1.26–1.47 (6H, m);
13C-NMR (75 MHz, CDCl3) dC 178.0, 148.0, 44.1, 33.6, 26.1, 25.9;
IR (KBr) cmꢁ1 2923, 1465; MS (ESI) m/z 307 (M + H+, 100%);
anal. calcd for C16H22N2S2: C, 62.70; H, 7.24; N, 9.14. Found: C,
62.94; H, 7.59; N, 9.13%.
Acknowledgements
M.C. is grateful to Regione Toscana within the POR-FSE 2007-
2013 program for a post-doctoral fellowship (FOTOSENSORG
project).
Notes and references
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1328 | RSC Adv., 2014, 4, 1322–1328
This journal is © The Royal Society of Chemistry 2014