The synthesis and characterization of solvatochromic maleimide-fused N-allyl- and N-alkyl-substituted 1,4-dithiines and diels-alder reactions with anthracene

Article abstract of DOI:10.1002/jhet.305

(Chemical Equation Presented) A simple and facile access to new solvatochromic maleimide-fused N-allyl- and N-alkyl-substituted 1,4-dithiines from the corresponding N-substituted succinamic acid derivatives in one-pot with oxidation by thionyl chloride is described. The Diels-Alder reaction of these 1,4-dithiines with anthracene has been investigated. The 1,4-dithiine derivatives react smoothly with anthracene via charge-transfer complexes to form the Diels-Alder adducts in excellent yields.

Full text of DOI:10.1002/jhet.305

188
The Synthesis and Characterization of Solvatochromic
Maleimide-Fused N-Allyl- and N-Alkyl-Substituted 1,4-Dithiines
and Diels–Alder Reactions with Anthracene
Vol 47
Sꢀirin Gu¨lten*
˘
Department of Chemistry, Faculty of Arts and Sciences, Terzioglu Campus, C¸ anakkale Onsekiz
Mart University, C¸ anakkale 17020, Turkey
*E-mail: siringulten@hotmail.com
Received July 1, 2009
DOI 10.1002/jhet.305
Published online 8 January 2010 in Wiley InterScience (www.interscience.wiley.com).
A simple and facile access to new solvatochromic maleimide-fused N-allyl- and N-alkyl-substituted
1,4-dithiines from the corresponding N-substituted succinamic acid derivatives in one-pot with oxidation
by thionyl chloride is described. The Diels–Alder reaction of these 1,4-dithiines with anthracene has
been investigated. The 1,4-dithiine derivatives react smoothly with anthracene via charge-transfer com-
plexes to form the Diels–Alder adducts in excellent yields.
J. Heterocyclic Chem., 47, 188 (2010).
INTRODUCTION
more than 100 years, although the correct stuctures were
assigned recently [1,6,7]. Many polycyclic 1,4-dithiine
derivatives are useful as pigments and functional materi-
als for electrooptical applications [7].
Sulfur-containing heterocyclic compounds have held
the focus of researchers along decades of historical de-
velopment of organic synthesis. Their biological activ-
ities and unique structures allow several applications in
different parts of pharmaceutical and agrochemical
research or in material science [1].
For 80 years, the Diels–Alder reaction has remained
as one of the best and most powerful methods of synthe-
sis of six-membered rings and bicyclic molecules [8].
Many factors, such as its versatility, its high regio- and
stereoselectivity, and its ability to rapidly give polyfunc-
tionality have contributed to the popularity of this reac-
tion in organic syntheses.
The synthesis of 1,4-dithiines has recevied much
attention because of their biological activity, particularly
as fungicides and antibacterials [2], their application in
synthetic organic and medicinal chemistry, their struc-
tural and electronic properties, their ability to act as
electron donors [3], and the wide variety of synthetic
transformation they undergo [3]. Some derivatives of
1,4-dithiines show activities as nonpeptide antagonists
of the human Galanin hGAL-1 receptors [4], and some
1,4-dithiine-2,3,5,6-tetracarboxydiimides have been used
as anthelmintics [5]. Detailed research of 1,4-dithiines
has been limited by a lack of suitable synthetic
approaches. Some 1,4-dithiines have been known for
Anthracene and its derivatives are among the most
useful polycyclic aromatic compounds and efficient pho-
tochromic systems. In view of their fluorescent proper-
ties, they are of practical interest as sensors and markers
in biological or supramolecular systems [9]. Anthracenes
are well-known as fairly reactive dienes that easily
undergo both thermal and photochemical Diels–Alder
cycloadditions with a variety of dienophiles [10]. In the
thermal [4þ2] cycloaddition reaction mechanism, new
C
V
2010 HeteroCorporation

January 2010
The Synthesis and Characterization of Solvatochromic Maleimide-Fused
N-Allyl- and N-Alkyl-Substituted 1,4-Dithiines and Diels–Alder Reactions with Anthracene
189
dithiines (9a–d) from succinamic acid derivatives (8a–
d) in one-pot with oxidation by thionyl chloride and
their subsequent Diels–Alder cycloaddition reactions
with anthracene.
Maleimide-fused N-allyl- and N-alkyl-substituted
1,4-dithiines. The initial study began with the reaction
between succinic anhydride 7 and the appropriate
amines to give N-substituted succinamic acid deriva-
tives. Maleimide-fused N-allyl [18] and N-alkyl 1,4-
dithiines were prepared in high yields from correspond-
ing N-substituted succinamic acid derivatives using
SOCl2 according to the earlier reported procedure (Table
Figure 1. 1,4-Dithiine and its derivatives.
sigma bonds are formed simultaneously, either by direct
addition or via intermediate charge-transfer (CT) com-
plex (electron donor-acceptor molecular complex).
Many studies have indicated the observation of transient
color that disappears as the thermal Diels–Alder reaction
proceeds. This has been shown to be due to the forma-
tion of a CT complex during the course of the reaction
[11].
¨
1) by Michaılidis et al. [19], who reported without ex-
perimental details. 1,4-Dithiines 9a–d are green and
deep green crystals, but their solutions in various sol-
vents (diethyl ether, ethanol, chloroform, acetone, and
benzene) are coloured yellow (9a in diethyl ether, etha-
nol, and acetone; 9c in ethanol), green (9a in benzene;
9c in acetone; 9d in ethanol), deep geen (9a in chloro-
form; 9c in diethyl ether and chloroform), deep blue (9c
in benzene; 9d in diethyl ether), purple (9b in acetone),
deep blue-green (9d in benzene and chloroform), deep
blue-purple (9b in benzene and chloroform; 9d in ace-
tone); thus, products 9a–d are higly solvatochromic.
Maleimide-fused N-allyl 1,4-dithiine 9a is partly soluble
in diethyl ether and ethanol, whereas 9b is insoluble in
diethyl ether and ethanol.
Very few articles deal with the synthesis, characteri-
zation, reactions, and properties of maleimide-fused 1,4-
dithiines [7,12–15]. Hayakawa et al. [12] and Kim et al.
[13] have reported the preparation of the methyl, ethyl,
propyl, and t-butyl derivatives of maleimide-fused 1,4-
dithiine with short experimental details. The mechanistic
pathway was not suggested in these reports. Valla et al.
[14] and Zentz et al. [15] have reported the preparation
of the propyl, isopropyl, butyl, and benzyl derivatives of
maleimide-fused 1,4-dithiine with experimental details
and investigated the mechanistic pathway by using a
Pummerer rearrangement-like reaction. 1,4-Dithiines 2,
3, 4, and 5 were used as a dienophile for Diels–Alder
reactions by Hayakawa et al. [12] and Kim et al. [13]
(Fig. 1).
The conjugation of double bond with carbonyl groups
in 1,4-dithiines 9a–d leads to both the n ! p* and the
p ! p* transitions being shifted to longer wavelengths.
The absorptions are found between 300 and 310 nm for
p ! p* transition and between 378 and 389 nm for n
! p* transition in 9a–d. The n ! p* transitions are
much less intense (fi ¼ 1271–1803) than p ! p* transi-
tion (fi ¼ 1657–2439).
1,4-Dithiine 1 and its derivatives undergo thermal
elimination of sulfur to produce corresponding thiophene
derivatives [16]. Nevertheless, thermal stability of N,N0-
dimethyl-dipyrrole-fused dithiine 2 and the dianhydride
6 was observed by Draber [17], along with the forma-
tion of cycloadducts with anthracene (Fig. 1).
The reaction is straightforward and requires simple
and inexpensive starting materials. We have, thus, intro-
duced a highly efficient methodology for the synthesis
of maleimide-fused N-allyl- and N-alkyl-substituted 1,4-
dithiines. It may be widely applicable for the prepara-
tion of a variety of 1,4-dithiines.
Draber [17] has suggested the planar structure of 2
and 6 based on strong ultraviolet absorptions at long
wavelenghts, thermal stability, and the ability to form
CT complexes. Indeed, various molecular orbital calcu-
lations have indicated 2 and 6 to be nearly planar [12].
1,4-Ditihiine 3 exhibits a planar structure that makes
easy the formation of CT crystals with anthracene in
alternate donor-acceptor stacks [13].
Diels–Alder cycloaddition reactions. When anthra-
cene was allowed to react with 1,4-dithiines 9a–d in
refluxing benzene, the characteristic green, deep blue,
deep blue-green, and deep blue-purple colors of 9a–d
disappeared, and the corresponding Diels–Alder cyclo-
adducts 10a–d were obtained in 95, 89, 94, and 90%
yields, respectively (Table 1). Much longer reaction
times were needed for 9c and 9d than for the reaction
of 9a and 9b, probably, because of the increased steric
bulk. Anthracene and 9a–b in CHCl3 underwent a slow
reaction at room temperature in the dark in 2 weeks,
giving the Diels–Alder cycloadducts 10a and 10b in 99
and 94% yield, respectively. The same reaction was
RESULTS AND DISCUSSION
This study describes synthesis of new solvatochromic
maleimide-fused N-allyl- and N-alkyl-substituted 1,4-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

190
Sꢀ. Gu¨lten
Vol 47
Table 1
Formation of 1,4-dithiines and the Diels-Alder cycloadducts.
Entry
1,4-Dithiine
Yield (%)
63
Diels-Alder cycloadduct
Time
Yield (%)
1
2
3
24 h
2 weeks
95[a]
99[b]
60
88
22 h
2 weeks
89[a]
94[b]
5 days
4 weeks
94[a]
74[b]
4
87
3 days
4 weeks
90[a]
79[b]
The Diels–Alder reaction conditions: [a]: benzene, reflux; [b]: CHCl3, rt, in the dark.
carried out using 9c and 9d under the same reaction
conditions but over a time of 4 weeks, giving 10c and
10d in 74 and 79% yield, respectively (Table 1). The
Diels–Alder cycloadducts 10a–d were bright yellow
crystals, which were reasonably soluble in dichlorome-
thane, chloroform, and ethanol. Only endo-cycloadducts
10a and 10b were obtained, while the Diels–Alder
cycloadducts 10c and 10d were shown to be a mixture
of two diastereoisomers in a 1:1 ratio as shown by inte-
geometry that leads to endo- rather than exo-product.
The kinetically favorable endo-Diels–Alder cycloadduct
is formed faster (lowest activation energy), even though
the thermodynamically favorable exo-product is more
stable. Secondary orbital overlap in the transition state
between the orbitals on the carbonyl groups in the 1,4-
dithiine and the orbitals in the anthracene not directly
involved in bonding. These interactions do not lead to
bond formation, but they do lower the energy of the
transition state (Scheme 1).
1
gration of signals in the H NMR spectrum. The struc-
ture of these adducts 10a–d were determined on the ba-
sis of 1H and 13C NMR spectroscopy, mass spectros-
copy, and elemental analysis.
The IR spectra exhibited characteristic imide bands at
1771 and 1707 cmꢀ1 for 10a, at 1776 and 1708 cmꢀ1
for 10b, at 1773 and 1706 cmꢀ1 for 10c, and at 1767
1
When anthracene and 1,4-dithiine approach each other
in the Diels–Alder reaction, the best overlap is achieved
when the reactants lie directly on top of one another, a
and 1703 cmꢀ1 for 10d. H NMR spectra showed two
N-allyl or N-alkyl proton signals for one isomer, one of
them being shifted upfield as a result of shielding effect
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2010
The Synthesis and Characterization of Solvatochromic Maleimide-Fused
N-Allyl- and N-Alkyl-Substituted 1,4-Dithiines and Diels–Alder Reactions with Anthracene
191
Scheme 1. Formation of the endo-Diels–Alder cycloadduct.
of the anthracene ring. Characteristic absorptions of an-
thracene have disappeared, indicating destruction of the
anthracene conjugated system by the Diels–Alder cyclo-
additon. The UV–vis spectroscopic analysis of the
Diels–Alder cycloadducts 10a–d revealed the appear-
ance of new absorption bands at 405, 412, 410, and 411
nm, respectively.
and all Diels–Alder cycloadducts 10a–d are new com-
pounds. To the best of our knowledge, this method is
the first example of a one-step synthesis of maleimide-
fused N-allyl- and sterically-bulky N-alkyl-substituted
1,4-dithiines directly from succinamic acid derivatives
by thionyl chloride oxidation. This one-pot reaction con-
verts various succinamic acid derivatives to solvatochro-
mic 1,4-dithiines, which underwent the Diels–Alder
reactions with anthracene in excellent yields.
In accordance with the reported early experimental
results [13], there are two pathways for the formation of
the Diels–Alder cycloadducts of 1,4-dithiines 9a–d and
anthracene (Fig. 2). The choice of these reaction path-
ways only depends on the electronic properties of dieno-
phile (1,4-dithiine) and diene (anthracene). Electron-rich
dienes (anthracene, 9-methylanthracene, 9,10-dimethy-
lanthracene) give a cycloadduct via pathway I, modestly
electron-deficient diene (9-anthracenecarboxaldehyde)
give a cycloadduct via pathway II, and no reaction
occurs to the strongly electron-deficient diene (9-nitroan-
thracene) [12]. 1,4-Dithiine derivatives 9a–d act as
strong acceptors in CT complex formation and possess
high reactivity as planar electron-rich dienes.
EXPERIMENTAL
The melting points were measured on an Electrothermal
9100 melting point apparatus and are uncorrected. The UV–vis
absorption spectra were determined with a Perkin Elmer
Lamda 25 spectrophotometer in chloroform solutions using 10-
mm quartz cells. The IR spectra were recorded on a One FTIR
1
ATR Perkin Elmer spectrometer. The H and 13C NMR spec-
tra were taken with a Varian NMR Gemini 300 and Bruker
400 Ultra Shield spectrometers and chemical shifts were
recorded as ppm downfield from internal tetramethylsilane.
The mass spectra were taken on a Waters ZQ Micromass LC/
MS spectrometer. Elemental analyses were performed on a
Leco 932 CHNS instrument. All chemicals were purchased
from commercial suppliers and used directly without any fur-
ther purification. Organic solvents were dried by standard
methods and were distilled before use. All the reactions were
performed under a nitrogen atmosphere. Reaction progress was
monitored by TLC on precoated aluminum-backed plates
(Merck SIL G/UV254), and chromophoric compounds were
visualised by UV light and subsequent staining with alkaline
potassium permanganate solution or iodine. Petroleum ether
refers to light petroleum (bp 40–60ꢁC).
According to the preliminary investigation by Draber
[17], the reaction of 1,4-dithiines 9a–d with the elec-
tron-rich anthracene occurred via CT complexes, as evi-
denced by unusual color change during the reaction.
We, herein, report new 1,4-dithiine derivatives and
their Diels–Alder cycloadducts. The oxidation reaction
by thionyl chloride was succesfully applied to 8a–d,
which gave the corresponding ring-closed 1,4-dithiines
9a–d in good yields. To the best of our knowledge,
three of the synthesized 1,4-dithiines, 9a, 9c, and 9d,
General procedure for the preparation of N-substituted
succinamic acids (8a–d). Reaction of succinic anhydride 7
(16 mmol) with the appropriate amine (20 mmol) in the pres-
ence of the dry appropriate solvent (10 mL, THF, MeCN, ace-
tone, or 1,4-dioxane) at room temperature with stirring for a
few hours generated the corresponding N-substituted succi-
namic acids 8a–d. After the reaction was completed, the sol-
vent was removed under reduced pressure and recrystallized
from the appropriate solvent (Et2O, 1,4-dioxane, or water).
4-Oxo-4-(prop-2-enylamino)butanoic acid (8a). White crys-
tals; 70% yield (1.76 g); mp 93–94ꢁC; IR-ATR (mmax, cmꢀ1):
3500–2600, 3302, 1690, 1639, 1618, 1544; 1H NMR (400
MHz, DMSO-d6): 2.54 (t, J ¼ 6.9 Hz, 2H, CH2CONH), 2.72
(t, J ¼ 6.9 Hz, 2H, CH2COOH), 3.90 (m, 2H, CONHCH2),
5.20–5.15 (skew dq, 2H, CH¼¼CH2), 5.80 (m, 1H, CH¼¼CH2),
Figure 2. Pathway I: The cycloaddition via CT complex, pathway II:
Direct cycloaddition.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

192
Sꢀ. Gu¨lten
Vol 47
5.97–6.34 (br s, 1H, NH), 7.34–10.45 (br s, 1H, OH); 13C
NMR (100 MHz, DMSO-d6): 29.70 (CH2CONH), 30.64
(CH2COOH), 41.55 (CONHCH2), 115.37 (CH¼¼CH2), 135.04
(CH¼¼CH2), 171.63 (CONH), 174.35 (COOH); MS (ESIþ): m/
z (%): 158 (44, [M þ H]þ), 152 (14), 140 (100); Anal. Calcd.
for C7H11NO3: C, 53.49; H, 7.05; N, 8.91. Found: C, 53.55;
H, 7.19; N, 8.94.
1657), 378 (1271), 600 (29); IR-ATR (mmax, cmꢀ1): 1777,
1710, 1661, 1566; 1H NMR (400 MHz, DMSO-d6): 4.02
(skew dt, 4H, CH2CH¼¼CH2), 5.17 (dt, J ¼ 1.22, 18.6 Hz, 4H,
CH¼¼CH2), 5.80 (m, 2H, CH¼¼CH2); 13C NMR (100 MHz,
DMSO-d6): 40.86 (CH2CH¼¼CH2), 117.30 (CH¼¼CH2), 131.08
(CH¼¼CH2), 132.20 (Q), 164.39 (CO); MS (APIꢀ): m/z (%):
334 (100, [Mþ]); Anal. Calcd. for C14H10N2O4S2ꢂ1.07H2O: C,
47.55; H, 3.46; N, 7.92; S, 18.18. Found: C, 47.42; H, 3.21;
N, 7.52; S, 18.16.
4-Oxo-4-(phenylmethylamino)butanoic acid (8b). White
crystals; 83% yield (2.75 g); mp 132–133ꢁC (lit. [20] mp
137.7–138.2ꢁC; lit. [14,15] mp 144ꢁC ); IR-ATR (mmax, cmꢀ1):
3300–2500, 3296, 1689, 1639, 1540; 1H NMR (400 MHz,
DMSO-d6): 2.61 (m, 2H, CH2), 2.46 (m, 2H, CH2), 3.4 (br s,
1H, NH), 4.36 (d, J ¼ 5.71 Hz, 2H, CH2NH), 6.02 (br s, 1H,
OH), 7.3–7.2 (m, 5H, Ar); 13C NMR (100 MHz, CDCl3):
30.17 (CH2), 31.03 (CH2), 43.84 (CH2), 127.78 (CH), 128.71
(CH), 128.84 (CH), 137.77 (Q), 172.43 (CONH), 174.66
(COOH); MS (ESIꢀ): m/z (%): 206 (100, [M ꢀ H]ꢀ); MS
(ESIþ): m/z (%): 208 (35, [M þ H]þ), 230 (100, [M þ Na]þ).
4-[(6-Methylheptan-2-yl)amino]-4-oxobutanoic acid (8c). White
2,6-Dibenzyl-1H,5H-[1,4]dithiino[2,3-c:5,6-c0]dipyrrole-1,3,5,
7(2H,6H)-tetrone (9b). Dark green pellets; 60% yield (500
mg); mp 216–218ꢁC (lit. [14,15] mp 224ꢁC); UV (CHCl3)
k
max: 301 nm sh (fi 1980), 387 (1300), 594 (40); IR-ATR
(mmax, cmꢀ1): 1775, 1707, 1693, 1596; 1H NMR (400 MHz,
DMSO-d6): 4.6 (s, 4H, CH2), 7.34–7.45 (m, 10H, Ar); 13C
NMR (100 MHz, DMSO-d6): 42.53 (CH2), 128.36 (CH),
128.67 (CH), 128.88 (CH), 131.65 (Q), 135.03 (Q), 163.66
(CO); MS (APIꢀ): m/z (%): 434 (100, [Mþ]).
2,6-Di(6-methylheptan-2-yl)-1H,5H-[1,4]dithiino[2,3-c:5,6-
c0]dipyrrole-1,3,5,7(2H,6H)-tetrone (9c). Green solid; 88%
yield (800 mg); mp 99–100ꢁC; UV (CHCl3) kmax: 310 nm sh
(fi 1955), 388 (1636), 595 (45); IR-ATR (mmax, cmꢀ1): 1771,
1692, 1573; 1H NMR (400 MHz, CDCl3): 0.77 (d, J ¼ 6.6
Hz, 6H, CH3), 0.79 (d, J ¼ 6.6 Hz, 6H, CH3), 1.07–1.13 (m,
8H, CH2), 1.26 (d, J ¼ 6.93 Hz, 6H, CH3), 1.41–1.53 (m, 4H,
CH2), 1.73–1.79 (m, 2H, CH), 3.84–4.19 (m, 2H, CH); 13C
NMR (100 MHz, CDCl3): 18.54 (CH3), 22.45 (CH3), 22.61
(CH3), 24.39 (CH2), 27.75 (CH), 33.81 (CH2), 38.32 (CH2),
48.89 (CH), 131.35 (Q), 164.21 (CO); MS (APIꢀ): m/z (%):
478 (100, [Mþ]); Anal. Calcd. for C24H34N2O4S2ꢂ0.8H2O: C,
58.46; H, 7.28; N, 5.68; S, 13.00. Found: C, 58.15; H, 7.19;
N, 5.62; S,12.87.
crystals; 93% yield (3.40 g); mp 79–80ꢁC; IR-ATR (mmax
,
cmꢀ1): 3200–2500, 3287, 1714, 1648, 1550; 1H NMR (300
MHz, CDCl3): 0.84 (d, J ¼ 6.44 Hz, 6H, CH3), 1.09 (d, J ¼
6.44 Hz, 3H, CH3), 1.10–1.16 (m, 1H, CH), 1.2–1.3 (m, 2H,
CH2), 1.38–1.42 (m, 2H, CH2), 1.44–1.53 (m, 2H, CH2), 2.49
(skew t, 2H, CH2), 2.67 (skew t, 2H, CH2), 3.30–3.95 (m, 1H,
CH), 5.95 (d, J ¼ 8.5 Hz, 1H, NH); 13C NMR (75.5 MHz,
CDCl3): 20.96 (CH3), 22.78 (CH3), 22.81 (CH3), 23.99 (CH2),
28.07 (CH), 30.29 (CH2), 31.12 (CH2), 37.16 (CH2), 38.92
(CH2), 45.99 (CH), 172 (CONH), 176.81 (COOH); MS
(ESIꢀ): m/z (%): 228 (100, [M ꢀ H]ꢀ); MS (ESIþ): m/z (%):
230 (100, [M þ H]þ), 252 (98, [M þ Na]þ); Anal. Calcd. for
C12H23NO3: C, 62.85; H, 10.11; N, 6.11. Found: C, 62.59; H,
9.71; N, 6.30.
2,6-Di(2-ethylhexyl)-1H,5H-[1,4]dithiino[2,3-c:5,6-c0]dipyrrole-
1,3,5,7(2H,6H)-tetrone (9d). Dark green solid; 87% yield (790
mg); mp 57–58ꢁC; UV (CHCl3) kmax: 310 nm sh (fi 2439),
389 (1803), 601 (45); IR-ATR (mmax, cmꢀ1): 1776, 1703,
1571; 1H NMR (400 MHz, CDCl3): 0.78–0.84 (skew t, 12H,
CH3), 1.10–1.22 (m, 16H, CH2) 1.60 (m, 2H, CH), 3.30 (d, J
¼ 7.12 Hz, 4H, CH2); 13C NMR (100 MHz, CDCl3): 10.23
(CH3), 14.03 (CH3), 22.93 (CH2), 23.65 (CH2), 28.37 (CH2),
30.30 (CH2), 38.19 (CH), 42.79 (CH2), 131.42 (Q), 164.42
(CO); MS (APIꢀ): m/z (%): 478 (100, [Mþ]); Anal. Calcd. for
C24H34N2O4S2ꢂ0.4H2O: C, 59.33; H, 7.22; N, 5.77; S, 13.20.
Found: C, 59.04; H, 6.89; N, 5.84, S, 13.20.
General procedure for the Diels–Alder cycloadditions
(10a–d). To a solution of anthracene (0.49 mmol) in benzene
(15 mL) was added 1,4-dithiines 9a–d (0.45 mmol), and the
reaction mixture was refluxed until the green, deep blue, deep
blue-green, and deep blue-purple colors of 9a–d faded away,
indicating the complete consumption of 9a–d. The solution
was concentrated in vacuo, purification by column chromatog-
raphy on silica, eluting with petroleum ether-EtOAc (9:1) gave
the corresponding endo-cycloadducts 10a and 10b and a 1:1
mixture of diastereoisomers of 10c and 10d.
4-[(2-Ethylhexyl)amino]-4-oxobutanoic acid (8d). White crys-
tals; 80% yield (2.92 g); mp 65–67ꢁC; IR-ATR (mmax, cmꢀ1):
3310–2500, 3318, 1691, 1631, 1544; 1H NMR (300 MHz,
CDCl3): 0.85–0.88 (m, 6H, CH3), 1.22–1.32 (m, 8H, CH2),
1.35–1.45 (m, 1H, CH), 2.5 (skew t, 2H, CH2), 2.66 (skew t,
2H, CH2), 3.16 (dt, J ¼ 1.46, 4.7 Hz, 2H, CH2), 6.00 (br s,
1H, NH); 13C NMR (75.5 MHz, CDCl3): 11.01 (CH3), 14.29
(CH3), 23.20 (CH2), 24.30 (CH2), 29.01 (CH2), 30.20 (CH2),
31.01 (CH2), 31.09 (CH2), 39.40 (CH), 42.87 (CH2), 172.75
(CONH), 176.89 (COOH); MS (ESIꢀ): m/z (%): 228 (100, [M
ꢀ H]ꢀ); MS (ESIþ): m/z (%): 230 (95, [M þ H]þ), 252 (100,
[M þ Na]þ); Anal. Calcd. for C12H23NO3: C, 62.85; H, 10.11;
N, 6.11. Found: C, 62.50; H, 9.81; N, 6.45.
General procedure for the preparation of maleimide-fused
N-allyl- and N-alkyl-substituted 1,4-dithiines (9a–d). To a solu-
tion of N-substituted succinamic acid 8a–d (3.82 mmol) in dry
1,4-dioxane (10 mL) was added dropwise a solution of thionyl
chloride (30.56 mmol) in dry 1,4 dioxane (2 mL) at room
temperature with stirring. The solution was heated at 50ꢁC for
6 h. After the reaction was completed, the solution was con-
centrated in vacuo, column chromatography of the residue
over silica eluting with petroleum ether-EtOAc (9:1) furnished
9a–d.
The same reactions of 9a–d were conducted at room tem-
perature in CHCl3 and in the dark for 2 and 4 weeks.
The same reactions of 8a–d were conducted at room tem-
perature with stirring overnight.
2,6-Di(prop-2-en-1-yl)-1H,5H-[1,4]dithiino[2,3-c:5,6-c0]dipyrrole-
1,3,5,7(2H,6H)-tetrone (9a). Dark green crystals; 63% yield
(400 mg); mp 225–227ꢁC; UV (CHCl3) kmax : 300 nm sh (fi
5,10-Dihydro-2,13-di(prop-2-en-1-yl)-5,10[10,20]-benzeno-4a,10a-
(methaniminomethano)-1H-naphtho[20,30:5,6][1,4]dithiino[2,3-
c]pyrrole-1,3,12,14(2H)-tetrone (10a). Bright yellow solid;
95% yield (218 mg); mp 258–260ꢁC (melts with dec.); UV
(CHCl3) kmax: 292 nm sh (fi 2060), 405 (440); IR-ATR (mmax
,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2010
The Synthesis and Characterization of Solvatochromic Maleimide-Fused
N-Allyl- and N-Alkyl-Substituted 1,4-Dithiines and Diels–Alder Reactions with Anthracene
193
cmꢀ1): 1771, 1707, 1650, 1579; H NMR (400 MHz, CDCl3):
3.76 (d, J ¼ 3.7 Hz, 2H, CH2), 3.88 (d, J ¼ 3.7 Hz, 2H, CH2),
4.68 (s, 2H, CH), 4.80–4.85 (m, 2H), 5.12–5.15 (m, 2H, CH),
5.60–5.75 (m, 2H, CH), 7.03–7.05 (m, 2H, Ar), 7.08–7.10 (m,
2H, Ar), 7.20–7.23 (m, 2H, Ar), 7.26–7.29 (m, 2H, Ar); 13C
NMR (100 MHz, CDCl3): 40.60, 41.76, 55.84, 68.80, 118.64,
119.43, 125.76, 127.22, 127.88, 128.04, 128.79, 131.11,
136.99, 137.50, 137.66, 164.14, 172.57; MS (APIþ): m/z (%):
513 (38, [M þ H]þ); Anal. Calcd. for C28H20N2O4S2ꢂ1.7H2O:
C, 61.91; H, 4.34; N, 5.16; S, 11.81. Found: C, 61.54; H, 4.67;
N, 5.29; S,12.20.
Ar), 7.09 (m, 4H, Ar), 7.22 (m, 4H, Ar), 7.27 (m, 4H, Ar);
1
13C NMR (100 MHz, CDCl3): 10.31,10.34, 14.03, 14.09,
22.88, 23.01, 23.33, 23.64, 28.03, 28.41, 30.02, 30.30, 37.55,
38.47, 42.23, 43.75, 55.64, 68.54, 68.60, 125.63, 125.68,
127.11, 127.14, 127.49, 127.54, 128.04, 128.06, 136.50,
136.52, 136.57, 137.76, 137.77, 137.79, 165.04, 173.47,
173.49; MS (APIþ): m/z (%): 657 (38, [M þ H]þ); Anal.
Calcd. for C38H44N2O4S2ꢂ0.4H2O: C, 68.79; H, 6.81; N, 4.22;
S, 9.66. Found: C, 68.39; H, 6.46; N, 4.26; S, 9.40.
¨
Acknowledgment. The author is indebted to Prof. H. Goker,
5,10-Dihydro-2,13-dibenzyl-5,10[10,20]-benzeno-4a,10a-(methani-
minomethano)-1H-naphtho[20,30:5,6][1,4]dithiino[2,3-c]pyrrole-
1,3,12,14(2H)-tetrone (10b). Bright yellow crystals; 89% yield
(244 mg); mp 278–280ꢁC (melts with dec.); UV (CHCl3)
Central Laboratory of Pharmacy, Ankara University, for the mea-
surement of the mass spectra and elemental microanalyses. The
author is grateful to Prof. I. Kaya, Department of Chemistry, C¸ an-
akkale Onsekiz Mart University, for the FT-IR and UV-vis spec-
trometers facilities. The author also thanks NMR Analysis
Laboratory of Hacettepe University for recording NMR spectra.
k
max: 290 nm sh (fi 2583), 412 (569); IR-ATR (mmax, cmꢀ1):
1776, 1708, 1581; 1H NMR (400 MHz, CDCl3): 4.33 (s, 2H,
CH), 4.42 (s, 2H, CH2), 4.6 (s, 2H, CH2), 6.50–6.54 (m, 2H,
Ar), 6.79–6.81 (m, 4H, Ar), 7.02–7.09 (m, 7H, Ar), 7.25–7.35
(m, 5H, Ar); 13C NMR (100 MHz, CDCl3): 42.10, 43.43,
55.67, 68.87, 125.32, 126.93, 127.66, 127.93, 127.99, 128.22,
128.44, 128.60, 128.64, 129.46, 133.63, 135.42, 136.77,
137.11, 137.40, 164.24, 172.75; MS (APIþ): m/z (%): 613 (85,
[M þ H]þ); Anal. Calcd. for C36H24N2O4S2: C, 70.57; H,
3.95; N, 4.57; S, 10.47. Found: C, 70.69; H, 3.96; N, 4.55; S,
10.02.
REFERENCES AND NOTES
´
[1] Garcıa-Valverde, M.; Torroba, T. Eur J Org Chem 2006,
849.
[2] Guillaumet, G. In Comprehensive Heterocyclic Chemistry
II; Boulton, A. J., Ed.; Pergamon: Oxford, 1996; Vol. 6, p 448.
´
[3] (a) Andreu, R.; Garın, J.; Orduna, J.; Royo, J. K. Tetrahe-
dron Lett 2001, 42, 875; (b) Murru, S.; Kavala, V.; Singh, C. B.; Patel,
B. K. Tetrahedron Lett 2007, 48, 1007.
5,10-Dihydro-2,13-di(6-methylheptan-2-yl)-5,10[10,20]-benzeno-
4a,10a-(methaniminomethano)-1H-naphtho[20,30:5,6][1,4]
dithiino[2,3-c]pyrrole-1,3,12,14(2H)-tetrone (10c). Yellow oil
slowly crystallized to bright yellow crystals; 94% yield (277
mg); mp 99–101ꢁC; UV (CHCl3) kmax: 284 nm sh (fi 1895),
[4] Scott, M. K.; Ross, T. M.; Lee, D. H. S.; Wang, H.-Y.;
Shank, R. P.; Wild, K. D.; Davis, C. B.; Crooke, J. J.; Potocki, A. C.;
Reitz, A. B. Bioorg Med Chem 2000, 8, 1383.
[5] Draber, W.; Korte, F. U.S. Pat. 3,364,229 (1968).
[6] Link, T.; Oberjat, M.; Klar, G. J Chem Res S 1997, 435.
[7] (a) Matsuoka, M.; Iwamoto, A.; Furukawa, N.; Kitao, T. J
Heterocycl Chem 1992, 29, 439; (b) Katrizky, A. R.; Fan, W.-Q. J
Heterocycl Chem 1993, 30, 1679.
410 (313); IR-ATR (mmax, cmꢀ1): 1773, 1706, 1580; H NMR
1
(400 MHz, CDCl3): 0.71 (d, J ¼ 6.5 Hz, 6H, CH3), 0.73 (d, J
¼ 6.7 Hz, 6H, CH3), 0.76 (d, J ¼ 6.6 Hz, 6H, CH3), 0.77 (d, J
¼ 6.6 Hz, 6H, CH3), 0.94–0.97 (m, 8H, CH2), 1.03–1.08 (m,
8H, CH2), 1.20 (d, J ¼ 6.9 Hz, 12 H, CH3), 1.33–1.44 (m, 8H,
CH2), 1.63–1.68 (m, 4H, CH), 3.75–3.84 (m, 2H, CH), 3.86–
3.95 (m, 2H, CH), 4.67 (s, 4H, CH), 7.04–7.06 (m, 4H, Ar),
7.08–7.11 (m, 4H, Ar), 7.22–7.24 (m, 4H, Ar), 7.28–7.30 (m,
4H, Ar); 13C NMR (100 MHz, CDCl3): 16.85, 18.29, 22.49,
22.57, 23.89, 24.43, 25.52, 27.74, 29.70, 30.94, 32.31, 33.91,
38.17, 38.45, 48.22, 49.33, 55.89, 55.91, 67.94, 67.96, 125.73,
125.79, 126.98, 127.25, 127.87, 127.90, 134.14, 135.98,
136.28, 137.64, 137.67, 137.91, 137.93, 164.68, 164.74,
173.23, 173.33; MS (APIþ): m/z (%): 657 (100, [M þ H]þ);
Anal. Calcd. for C38H44N2O4S2: C, 69.48; H, 6.75; N, 4.26; S,
9.76. Found: C, 69.22; H, 6.58; N, 3.88; S, 9.55.
[8] Diels, O.; Alder, K. Liebigs Ann 1928, 460, 98.
[9] Ihmels, H. Eur J Org Chem 1999, 1595, and references
therein.
[10] Atherton, J. C. C.; Jones, S. Tetrahedron 2003, 59, 9039.
[11] Atherton, J. C. C.; Jones, S. Tetrahedron 2003, 59, 9039,
and references therein.
¯
[12] Hayakawa, K.; Mibu, N.; Osawa, E.; Kanematsu, K. J. Am
Chem Soc 1982, 104, 7136.
[13] Kim, J. H.; Hubig, S. M.; Lindeman, S. V.; Kochi, J. K.
J Am Chem Soc 2001, 123, 87.
[14] Valla, A.; Cartier, D.; Zentz, F.; Labia, R. Synth Commun
2006, 36, 3591.
[15] Zentz, Z.; Labia, R.; Sirot, D.; Faure, O.; Grillot, R.; Valla,
A. II Farmaco 2005, 60, 944.
5,10-Dihydro-2,13-di(2-ethylhexyl)-5,10[10,20]-benzeno-4a,10a-
(methaniminomethano)-1H-naphtho[20,30:5,6][1,4]dithiino[2,3-
c]pyrrole-1,3,12,14(2H)-tetrone (10d). Bright yellow crystals;
90% yield (265 mg); mp 188–189ꢁC; UV (CHCl3) kmax: 288
nm sh (fi 4328), 411 (852); IR-ATR (mmax, cmꢀ1): 1767,
¯
[16] Hayakawa, K.; Mibu, N.; Osawa, E.; Kanematsu, K. J Am
Chem Soc 1982, 104, 7136, and references therein.
[17] Draber, W. Chem Ber 1967, 100, 1559.
[18] Gu¨lten, S. Drugs Fut 2007, 32(Suppl A), 14.
1
1703, 1581; H NMR (400 MHz, CDCl3): 0.62–0.66 (t, J ¼ 7
¨
[19] Michaılidis, A.; Giraud, M.; Molho, D. In Organic Sulphur
Hz, 6H, CH3), 0.77–0.84 (m, 18H, CH3), 1.06–1.21 (m, 24H,
CH2), 1.48 (m, 4H, CH), 3.07 (d, J ¼ 6.97 Hz, 4H, CH2), 3.16
(d, J ¼ 6.97 Hz, 4H, CH2), 4.68 (s, 4H, CH), 7.03 (m, 4H,
Chemistry; Stirling, C. J., Ed.; Butterworths: London, 1975; p 466.
[20] Pressman, D.; Bryden, J. H.; Pauling, L. J. Am Chem Soc
1948, 70, 1352.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet