TRITHIONES – PRECURSORS OF SYNTHESES
OF TRITHIAPENTALENES AND THEIR OXAANALOGUES
Richard ČMELÍK, Pavel PAZDERA
Masaryk University, Faculty of Science, Department of Organic Chemistry,
Kotlářská 2, CZ–611 37 Brno, Czech Republic; E-mail: pazdera@chemi.muni.cz
Introduction
The syntheses of 5-amino-3-thioxo-3H-1,2-dithiole-4-carboxylic acid functional
derivatives, which represent wide area of trithiones, were originally described in 1963.1 Little
attention1,2 has been given to study of their reactivity in contrast to their simple preparation
from available compounds and presence of convertible functional groups.
The primary aim, to synthesize corresponding heteroannelated pyrimidine systems with
potential biological or pharmaceutical effect3, was not realized. This route started from the
widely used N-ethoxymethylidenamine derivatives.4
However, when 5-amino-3-thioxo-3H-1,2-dithiole-4-carbonitrile reacted with triethyl
orthoformate in presence of acetic anhydride, an unexpected ethoxymethylidene compound
was isolated. The FTIR, 1H and
13
C NMR experiments, elemental analysis and finally X-ray
structure analysis certified the formation of a substance, where the nitrogen atom of starting
substance is acetylated and exocyclic sulfur one is ethylated.5 This observation led us to the
investigation of
the reactivity of this compound class towards alkylation and acylation
reagents.
ORTEP diagram of 2 .(CH3)2NCHO (R = Me, X = CN).
Experimental
The explored reactions, transformation conditions, and products are outlined in Scheme
1 and 2.
We found that alkylations of 1 proceeded entirely on the sulfur atom of the thioxo
group only and the dithiolium salts 2 were formed. On the other hand, the acylation occured
easily on the amino group with starting ester or amide 1 (X = COOEt, CONH2), by heating of
the substrate into the corresponding anhydride or by reaction with acyl chloride in pyridine
solution. In the course of benzoylation or ethoxycarbonylation reaction of the substrate 1 (in
dimethylformamide in presence of a base) amidine 4 was formed together with amide 3. All
attempts to make acylation of the nitrile 1 (X = CN) were unsuccessful.
The amides 3 could be alkylated to salts 5, which led to the free bases 6 by
neutralization of sodium hydrogencarbonate. These compounds were decomposed by action of
the primary amines and elementary sulfur was eliminated. On the other hand, the secondary
amines gave products of alkylsulfanylgroup substitution in 6 and N,N-dialkylamino
compounds 7 were obtained.
Reaction of phosphorus pentasulfide with 6 provided the
trithiazapentalene skleton 8.
If the compound 1 (X = COOEt) reacted with phenylisocyanate the N-substituated urea
9 were formed. Following alkylation under presence of a base led to the generation of 10.
Treatment of isothiocyanate with 1 gave trithiaazapentalene derivative 11. Attempts to isolate
of the reaction intermediate, a sulfur analogue of 9, failed. Substance 12 was prepared by the
reaction of compound 1 with carbon disulfide and two equivalents of alkyl halide in presence
of triethylamine.
The structures of products were supported by the FTIR, NMR-spectra, X-ray structure
analysis and by quantum chemical calculations.
ORTEP diagram of 3 (R’= Me, X = COOEt) and 5 (R = PhCH2, R’= Me, X = COOEt).
X
RS
Y
X
S
S
NH
S
R'
X
+
S
NH2
S
2
S
O
S
N CH N(CH3)2
S
4
3
(a)
(c)
(b)
S
X
X
Y
RS
S
S
NH2
NH
S
S
R'
O
5
1
(e)
(d)
X
RS
N
S
S
R'
O
6
(g)
(f)
X
X
R"2N
N
S
S
R'
RS
O
N
S
7
S
R'
S
8
Scheme 1
(a)
(b)
(c)
(d)
(e)
(f)
(g)
RY / DMF
(RY = MeI, PhCH2I, PhCH2Br; X = CN, COOEt, CONH2)
R’COZ / pyridine; (R’CO)2O
(R’COZ = t-BuCOCl, PhCOCl, EtOCOCl; (R’CO)2O = (MeCO)2O, (EtCO)2O;
X = COOEt, CONH2)
4: X = COOEt
RY / DMF
(RY = MeI, EtBr, n-BuI, PhCH2I, allyl bromide; X = COOEt, CONH2)
B / DMF
(B = Et3N, Na2CO3; X = COOEt, CONH2)
RY, R’COZ
(RY = HC(OEt)3, PhCH2Cl, n-BuI; R’COZ = (MeCO)2O; X = CN)
R2’’NH / CHCl3
(R2’’NH = Et2NH, morpholine; X = CN)
P4S10 / xylene
6: R = Et, PhCH2; X = CN; R’ = Me
X
X
S
NH
S
N HPh
RS
(i)
S
O
S
N
S
N HPh
O
10
9
(h)
S
X
S
(j)
S
NH2
1
(k)
X
X
RS
N
S
S
RS
N HR'''
S
N
S
S
SR
S
12
11
Scheme 2
(h)
(i)
(j)
(k)
PhNCO / pyridine
(X = COOEt)
RY, Et3N / DMF
(RY = MeI, PhCH2I, allyl bromide)
1. R’’’NCS, Et3N / DMF
2. RY
(R’’’ = Me, Ph, allyl; RY = MeI, PhCH2I, allyl bromide; X = COOEt)
1. CS2, Et3N / DMF
2. RY
(RY = MeI, PhCH2I; X = COOEt)
Results and discussion
The structures 6, 7 and 10 were explained best in terms of the reported dipolar
arrangement based on available physical-chemical and computing methods (see below).6
Absence of the carbonyl vibration (=N–)CO(–R') in the IR-spectrum in the range 1660-1690
cm-1 is an important argument for this construction. The closest vibrational band at 1550-1600
cm-1 supports the betain structure existence. The X-ray study of 6 (R=PhCH2, R'=Me, X=CN)
showed the bond lengths C–O 1.249 Å (tabled 1.23 Å for a carbonyl moiety7), S–S 2.127 Å
(2.10 Å in disulfides7) and S…O distance 2.284 Å (1.57 Å for 1,2-oxothiolane skeleton7). The
bond orders in this structure were determined by ab initio quantum-chemical calculations:
C–O 1.704, S–S 0.985, (S–)C–N 1.532, N–C(–O) 1.358 and S–O 0.366. On the other hand,
the existence of 6, a oxadithiapentalene structure with very polar or rather “ionic” S–O bond,
is supported by calculated values of partial charges: + 0.102 for sulfur atom and - 0.450 for
oxygen.
Two different structures, the formula keeping classic carbonyl bond and bicyclic
oxadithiapentalene skeleton2,8, are referred to this structure.
Trithiaazapentalenes 8, 11 and 12 represents so-called “no-bond resonance“ systeme.9
Unexpected prolonged distance of sulfur-sulfur bond (2.184 and 2.522 Å for 8: R=PhCH2,
R'=Me, X=CN) was elucidated earlier by the resonance between the structure of -(1,2dithiole-3-yliden) amide and -(1,2,4-dithiazole-3-yliden) thioketone. Other possible
explanations, mesoionic arrangement9 or structure possessing sulfur d-orbitals10, were
reported too. The calculated bond orders6 (for 8: R=PhCH2, R'=Me, X=CN) S1–S2 0.582, S2–
S3 0.915; S3–C4 1.368, S2–C6 1.204, S1–C8 1.322; C6–C7 1.332, C7–C8 1.376; C4–N5
1.600, N5–C6 1.380 with respect to the planarity of the bicycle indicate the delocalized πsystem preposition and the cooperation of d-orbitals of sulfur atoms.
ORTEP diagram of 8 (R = PhCH2, R’= Me, X = CN) and 11 (R, R’’’= Me, X = COOEt).
References
1. Gewald K.: J. Prakt. Chem. 1966, 31, 214-220.
2. Brois S. J., Scattergood R., Czyzewski J.(Exxon Research and Engineering Co.) Brit. Patent
1,575,202, Chem.Abstr. 1981, 95, P45828d.
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4. Giudice M. R. D., Borini A., Mustazza C., Gatta F.: J. Heterocycl. Chem. 1994, 31, 15031507.
5. Pazdera P., Richter L., Šibor J., Formation and Transformation of 1,2-Chalcogenethiole
Skeleton, Proceedings XXIInd Conference of Organic Chemistry, Častá-Papiernička, June
11-13, 1997, 197.
6. Marek J., Čmelík R., Čajan M., Pazdera P., Structures of 5-R-Sulfanyl-3-acetylimino-3H[1,2]-dithiol-4-carbonitrile and their 3-Thioacetylimino Analogues, 18th European
Crystalographic Meeting, Praha, Czech Republic, August 15-20, 1998, 397.
7. Klingsberg E.: J. Am. Chem. Soc. 1963, 85, 3244-3246 .
8. Allen F. H., Kennard O.: Chemical Design Automation News 8, 1993, 1, 31-37.
9. Pfister-Guillouzo G., Lozac´h N.: Bull. Soc. Chim. France 1963, 153-157.
10. Behringer H., Ruff M., Wiedenmann R.: Chem. Ber. 1964, 97, 1732-1737.