Desulfurization of 4-nitro-N,2-diphenyl-3-(phenylamino)isothiazol- 5(2h)-imine: Formation of a 3-imino-2-nitroprop-2-enamidine

Article abstract of DOI:10.1002/(SICI)1522-2675(19981216)81:12<2388::AID-HLCA2388>3.0.CO;2-H

The course of the desulfurization reaction of 4-nitro-N,2-diphenyl-3- (phenylamino)isothiazol-5(2H)-imine (3) is investigated and the formation of the unstable 3-imino-2-nitroprop-2-enamidine (A) as intermediate is discussed. Addition of amines and thioph

Full text of DOI:10.1002/(SICI)1522-2675(19981216)81:12<2388::AID-HLCA2388>3.0.CO;2-H

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Helvetica Chimica Acta ± Vol. 81 (1998)
Desulfurization of 4-Nitro-N,2-diphenyl-3-(phenylamino)isothiazol-
5(2H)-imine: Formation of a 3-Imino-2-nitroprop-2-enamidine1)
2
by Dally Moya Argilagos ), Roland W. Kunz, Anthony Linden, and Heinz Heimgartner*
Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich
The course of the desulfurization reaction of 4-nitro-N,2-diphenyl-3-(phenylamino)isothiazol-5(2H)-imine
(3) is investigated and the formation of the unstable 3-imino-2-nitroprop-2-enamidine (A) as intermediate is
discussed. Addition of amines and thiophenol to the reaction mixture yielded the amidine derivatives 5 and the
thioimidate 6, respectively, via nucleophilic addition of the respective reagent to A (Scheme 2). Benzoic acid
and thiobenzoic acid afforded the amide 7 and the thioamide 8, respectively, as secondary products of the
expected adducts 7a and 8a (Schemes 3 and 4). The presence of (benzylidene)(methyl)amine in the reaction
mixture of the desulfurization of 3 led to the 1,2,4-oxadiazole derivative 10, together with the quinoxaline N-
oxide 4 as a minor product. Reaction mechanisms involving an intermediate ketene imine and participation of
the NO2 group in the reaction leading to 1,2,4-oxadiazole 10 are proposed. Ab initio calculations of model
structures for the nitroketene imine were performed and the results correlated with the experimental results.
The structures of 8 and 10 were established by X-ray crystal-structure analysis.
1. Introduction. ± Ketene imines 1 have attracted considerable interest as substrates
in organic synthesis [1 ± 3], especially for the synthesis of heterocycles [4 ± 7], where
cycloaddition reactions are mainly involved [8 ± 13]. Moreover, recent studies of the
rearrangement of intermediate N-allylketene imines (1, R3 ˆ CH2ˆCHCH2) to give
the isomeric nitriles 2 have indicated new applications of the ketene-imine chemistry
[14 ± 16].
Ketene imines were first prepared by Staudinger in unspecified yield by the
interaction of a phosphinimine with a ketene [17]. Since then, several methods for their
preparation have been described [18] such as alkylation of nitrile derivatives, addition
of isocyanides to alkynes and to carbenes, reaction of nitrile oxides with phosphor-
ylides, dehydration of amides [19], and reaction of nitrilium salts with an organic base
[20], among others. The desulfurization of S-containing compounds such as thioureas
[21][22], thioamides [5][23][24], thioimidates [25][26], dithioles [27], thiadiazoles,
and isothiazoles [28][29] leads also to the formation of ketene imines. Recently, we
have reported on the desulfurization of 3,3-diamino-2-nitroprop-2-enethioamides
which yields nitroketene imines as reactive intermediates [26][30][31].
1
)
)
Presented in part at the 36th IUPAC Congress, Geneva, Switzerland, August 1997.
Part of the Ph.D. thesis of D.M.A., Universität Zürich, 1998.
2

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The synthesis of alkene-diimines (1, R2 ˆ RC(NR')) by S-extrusion from isothiazole
derivatives with Ph3P [28][29] prompted us to investigate the desulfurization of the
nitroisothiazol derivative 3, which was expected to yield 3-imino-2-nitroprop-2-
enamidine A as a useful intermediate for the synthesis of NO2-substituted compounds.
However, upon treatment of 3 with Ph3P, the quinoxaline N-oxide 4 (Scheme 1) and
numerous decomposition compounds were obtained (cf. [32]).
Scheme 1
Taking into account the formation of 4 and the occurrence of two bands at 2337 and
2261 cm 1 in the IR spectra of the crude reaction mixture, which disappeared under the
reaction conditions (cf. [32]), the presence of a highly reactive intermediate ketene
imine, which undergoes cyclization and decomposition could be suggested. In the
present paper, we report on the attempts to confirm this proposal by trapping the
reactive intermediate with nucleophiles. In addition, ab initio calculations of model
structures of A were carried out to evaluate the influence of the NO2 group (cf. A;
Scheme 1) and the contribution of a mesomeric nitrilium form to the ketene-imine
structure, which could explain the shift of the observed IR bands compared with those
1
of known ketene imines (ca. 2000 cm ).
2. Results. ± 2.1. Formation of 2-Nitro-N2-phenyl-3,3-bis(phenylamino)prop-2-
enamidines 5. The desulfurization of 4-nitroisothiazol-5(2H)-imine 3 with Ph3P at 08
[31][32] in the presence of different amines (Method A) led to the corresponding 2-
nitro-propenamidines 5 in good yields (Scheme 2 and Table 1). On the other hand,
when morpholine and pyrrolidine were added after completion of the reaction of 3
with Ph3P (TLC monitoring), derivatives 5a and 5b were isolated (Method B) as well as
4% quinoxaline N-oxide 4 (cf. [32]), but some decomposition products were also
formed. The proposed mechanism of the reaction involves the formation of an
intermediate ketene imine A followed by nucleophilic attack by the amine. Thus, the
presence of an amine in the reaction mixture led only to the adduct 5, while amine
addition, after the desulfurization step, resulted in the additional formation of

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Helvetica Chimica Acta ± Vol. 81 (1998)
quinoxaline N-oxide 4 and decomposition products of intermediate A. Therefore,
Method B led to lower yields of 5 compared with Method A. Moreover, the IR bands
observed in the reaction mixture of the desulfurization of 3 were only detected in the
absence of amines (Method B), disappearing immediately after amine addition.
Scheme 2
Table 1. Prepared 2-Nitro-N2-phenyl-3,3-bis(phenylamino)prop-2-enamidines 5
Compound
R,R
Yield [%]a)
Method A
Method B
5a
b
c
(CH2)2O(CH2)2
(CH2)4
Et, Et
PhCH2, H
99
93
90
72b)
±
91
d
76b)
±
a) With respect to 3. b) Isolation of the compounds was particularly difficult.
The 2-nitro-N2-phenyl-3,3-bis(phenylamino)prop-2-enamidines 5 were purified by
flash column chromatography and characterized by their spectroscopic data. Although,
according to TLC, the reactions following Method A led exclusively to the formation of
5 and Ph3PS, the yield of isolated 5 was only 72 ± 93%. As an exception, 5a was obtained
quantitatively (Table 1).
The 1H- and 13C-NMR spectra of compounds 5 in (D6)DMSO as well as in CDCl3 at
room temperature show, in general, quite broad signals for the H- and C-atoms. This
1
observation, in addition to the equivalence of the two NH groups in the H-NMR
spectra, indicate a slow interconversion of conformers by rotation around the
C
N(amino) bonds, as is usually found for similar push-pull compounds [26][33].
In addition, a rotation around the formal C(2)ˆC(3) bond must also take place
(cf. [30]).

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Surprisingly, aniline and 4-methoxyaniline did not react in the expected fashion,
and the reaction behavior in these cases was analogous to that observed when no
amines were added to the mixture3). To evaluate the influence of the nucleophilic
reagent, the reactions were carried out with other nucleophiles.
2.2. Formation of Phenyl 2-Nitro-N-phenyl-3,3-bis(phenylamino)prop-2-enethio-
imidate (6). In accordance with the results mentioned in Sect. 2.1, the addition of PhSH
after the desulfurization of 3 (Method B) yielded the phenyl thioimidate 6 via
nucleophilic attack of PhSH to the intermediate A (Scheme 2). IR Monitoring of the
reaction showed again the disappearance of the characteristic IR absorptions assigned
to A after the addition of PhSH. Very surprisingly, BuSH, PrSH, and i-PrSH did not
yield any addition products; the reactions led only to decomposition compounds and
quinoxaline N-oxide 4, as in the absence of nucleophilic reagents.
The phenyl thioimidate 6 was isolated, after column chromatography, in 62% yield
as well as quinoxaline N-oxide 4 (4%) and Ph3PS (95%), and characterized
1
spectroscopically. The broad signals in the H- and 13C-NMR spectra of 6 in CDCl3
at room temperature point once more to slow interconversion of the conformers4).
1
Indeed, the H-NMR spectrum in (D6)DMSO at room temperature shows, besides
signals for the aromatic H-atoms, the presence of three down-field-shifted signals
corresponding to the NH-atoms of different conformers. In the 13C-NMR spectrum in
(D6)DMSO at room temperature, only very broad signals were observed.
2.3. Formation of N-[2-Nitro-1-(phenylamino)-2-(N-phenylcarbamoyl)ethenyl]-N-
phenylbenzamide (7). Addition of PhCOOH to the reaction mixture from the
desulfurization of 3 led to the unexpected benzamide 7 (Scheme 3). A reaction
mechanism via nucleophilic addition of PhCOOH to the intermediate A yielding the
unstable benzoate 7a, and subsequent intramolecular N-acylation could explain the
formation of the more stable 7.
Scheme 3
The amide 7 was obtained in 67% yield after purification by column chromatog-
raphy, and it was characterized by its spectroscopic data using principally 2D-NMR
spectroscopy.
1
The H-NMR spectrum in CD3CN at 220 K exhibits, besides the signals for the
aromatic H-atoms, two down-field-shifted signals at 9.11 and 11.29 ppm assigned to the
3
)
)
The same results were observed by carrying out the reaction in MeOH: Ph3PS and quinoxaline N-oxide 4
precipitated from the reaction mixture, but no adduct of the ketene imine with MeOH was detected.
A possible rotation around the formal C(2)ˆC(3) bond is supported by the bond lengths in the crystal
structure of a corresponding methylthio derivative reported in [26].
4

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Helvetica Chimica Acta ± Vol. 81 (1998)
NH-atom of the PhNH and that of the carbamoyl group, respectively. The HMBC
spectrum recorded under the same conditions shows for both NH groups correlation
peaks, which are in accordance with the proposed structure. The NH appearing at
9.11 ppm exhibits a cross-peak with the ortho-C-atoms of a Ph ring (3J(C,H)) and, in
2
addition, shows a J(C,H) correlation with the corresponding aromatic C(1)-atom,
confirming the presence of the PhNH group. A second 2J(C,H) cross-peak indicates a
further coupling of this NH with C(3). The NH arising at 11.29 ppm displays two cross
3
2
peaks, indicating the corresponding J(C,H) and J(C,H) correlation with a Ph ring.
Additionally, a 3J(C,H) cross-peak to the C-atom bearing the NO2 group and a 2J(C,H)
cross-peak to a CˆO group appeared. These data confirmed that the two PhNH groups
are not attached to the same C-atom and indicated the presence of benzamide structure
7, ruling out the alternative structure 7a. In addition, the low-field shift of one of the NH
resonances could be explained due to the deshielding effect of the CˆO group of the
benzamide group.
Broad signals in the 1H- and 13C-NMR spectra of 7 in CD3CN at room temperature
hint again at an equilibrium between several conformers. This assumption was
confirmed by low-temperature NMR experiments which clearly exhibited splitting of
the NH signal at 9.11 ppm due to the freezing of the conformations.
2.4. Formation of 2-Nitro-N-phenyl-3,3-bis(phenylamino)prop-2-enethioamide (8).
In contrast to the results described in Sect. 2.3, addition of PhCOSH to the reaction
mixture from the desulfurization of 3 led to the isolation of the thioamide 8, instead of
the expected adduct 8a or the N-acylated product 8b (Scheme 4). The formation of 8
can be explained by the hydrolysis of 8a, formed by the nucleophilic addition of
PhCOSH to A, in analogy to the already described addition of amines and PhCOOH
(cf. Sect. 2.1 and 2.3, resp.). Since the reaction was performed under anhydrous
conditions, hydrolysis of 8a must have resulted from the column chromatography on
silica gel during workup.
The thioamide 8 was isolated in 75% yield and characterized spectroscopically. Its
properties were identical with those of 8 obtained by another route [34]. After
Scheme 4

Helvetica Chimica Acta ± Vol. 81 (1998)
2393
crystallization from MeOH, the structure of 8 was established by X-ray crystallography
(Fig. 1).
The crystal structure of 8 revealed that the asymmetric unit contains two molecules
(A and B) and a partially occupied site for a H2O molecule. The molar amount of H2O
in the structure is ca. 10%. The two independent molecules differ most significantly in
Fig. 1. ORTEP Plot [35] of the molecular structures of the two independent molecules A and B of 8 (arbitrary
numbering of the atoms, with 50% probability ellipsoids)

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the orientation of one PhNH group, which is rotated by ca. 1758, but there are also
slight differences in the orientations of the other Ph rings. The structure shows the usual
non-planarity across the C(2) C(3)5) bond (cf. [26][30]), with the planes on either
side of the C(2) C(3) bond making angles of 81.5(3) and 83.1(3)8 for molecules A and
B, respectively. Note that all atoms in each of the regions C(4) to N(2), and C(10) to
C(16) form highly planar systems, which suggest p-bonding delocalization in these
regions (cf. [30]). This is supported by the corresponding bond lengths, which again
show the usual patterns (Table 2).
Table 2. Selected Bond Lengths [Š] and Torsion Angles [8] for Molecules A and B of 8 (cf. Fig. 1)
Molecule A
Molecule B
S(1) C(1)
C(1) C(2)
C(2) C(3)
N(4) C(3)
1.690(4) N(1) C(1)
1.436(5) N(2) C(2)
1.490(5) N(3) C(3)
1.313(5)
1.330(5)
1.360(4)
1.317(5)
S(31) C(31)
C(31) C(32)
C(32) C(33)
N(34) C(33)
1.671(4) N(31) C(31)
1.457(5) N(32) C(32)
1.486(5) N(33) C(33)
1.320(5)
1.348(4)
1.339(4)
1.321(5)
S(1) C(1) N(1) C(4)
C(2) C(1) N(1) C(4)
N(1) C(1) C(2) C(3)
N(1) C(1) C(2) N(2)
S(1) C(1) C(2) C(3)
S(1) C(1) C(2) N(2)
O(1) N(2) C(2) C(1)
O(1) N(2) C(2) C(3)
O(2) N(2) C(2) C(1)
O(2) N(2) C(2) C(3)
C(1) C(2) C(3) N(3)
C(1) C(2) C(3) N(4)
C(2) C(3) N(4) C(16)
C(2) C(3) N(3) C(10)
N(2) C(2) C(3) N(3)
N(2) C(2) C(3) N(4)
N(3) C(3) N(4) C(16)
N(4) C(3) N(3) C(10)
0.1(6)
179.1(4)
176.4(4)
4.7(6)
2.9(5)
176.0(3)
0.6(6)
179.6(3)
179.1(3)
1.9(5)
99.4(4)
80.2(5)
0.9(6)
S(31) C(31) N(31) C(34)
C(32) C(31) N(31) C(34)
N(31) C(31) C(32) C(33)
N(31) C(31) C(32) N(32)
S(31) C(31) C(32) C(33)
S(31) C(31) C(32) N(32)
O(31) N(32) C(32) C(31)
O(31) N(32) C(32) C(33)
O(32) N(32) C(32) C(31)
O(32) N(32) C(32) C(33)
C(31) C(32) C(33) N(33)
C(31) C(32) C(33) N(34)
C(32) C(33) N(34) C(46)
C(32) C(33) N(33) C(40)
N(32) C(32) C(33) N(33)
N(32) C(32) C(33) N(34)
N(33) C(33) N(34) C(46)
N(34) C(33) N(33) C(40)
1.1(6)
179.6(4)
173.1(3)
0.9(6)
6.3(5)
178.5(3)
1.8(6)
174.3(3)
179.0(3)
6.6(5)
93.4(4)
86.3(5)
0.9(6)
179.4(4)
79.8(5)
100.5(4)
179.5(4)
0.9(7)
4.8(6)
79.7(5)
100.7(4)
178.7(4)
174.8(4)
In molecule A, H N(1) of the thioamide group forms an intramolecular H-bond
with O(1) of the NO2 group (graph set: S(6) [36]; N ´´´ O 2.637(4) Š, N H ´´´ O
141(3)8), forming a six-membered ring. Molecule B forms an identical intramolecular
H-bond (N ´´´ O 2.634(4) Š, N H ´´´ O 142(4)8). Additionally, H N(3) of molecule A
forms weak bifurcated intermolecular H-bonds with both of the O-atoms of the NO2
group of molecule B (N ´´´ O 3.346(4) and 3.087(4) Š, N H ´´´ O 165(3)8 and 134(3)8,
resp.), and H N(33) of molecule B interacts, in an identical fashion, with a different
molecule A (N ´´´ O 3.147(4) and 3.007(4) Š, N H ´ ´ ´ O 151(4)8 and 146(4)8, resp.).
This links the molecules into cyclic ´ ´ ´ A ´ ´ ´ B ´´´ A ´´´ B ´´´ centrosymmetric tetramers;
graph sets: R21(4) for the local interaction and R44(24) for the tetramer. H N(4) of
molecule A also forms bifurcated intermolecular H-bonds, one being with O(32) of the
NO2 group (N ´´´ O 2.802(4) Š, N H ´´´ O 156(3)8) of the same molecule B as above;
graph set: D, while the other weaker interaction is with O(2) of the NO2 group (N ´´´ O
5
)
The arbitrary numbering of the atoms in the ORTEP diagram (Fig. 1) is used.

Helvetica Chimica Acta ± Vol. 81 (1998)
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2.923(4) Š, N H ´´´ O 108(3)8) of a neighboring molecule A. This latter interaction
forms centrosymmetric ´´´ A ´´´ A ´´´ dimers; graph set: R22(12) [36]. Molecule B does
not have the latter two interactions. Instead, H N(34) forms an intermolecular H-
bond with the S-atom of the CˆS group (N ´´´ S 3.220(4) Š, N H ´´´ S 152(3)8) of
molecule A; graph set: D. This difference is presumably brought about by the 1758
difference in the torsion angles about the C(3) N(3) and the C(33) N(33) bonds
(Table 2). The combination of all intermolecular interactions links the molecules into
Å
an infinite two-dimensional network which lies perpendicular to the [101] direction.
2.5. Formation of 4-Nitrophenyl 2-Nitro-N-phenyl-3,3-bis(phenylamino)prop-2-
enimidate (9). Addition of 4-nitrophenol to the reaction mixture from the desulfur-
ization of 3 induced a similar reaction course (TLC and IR monitoring) as already
observed by the addition of amines (cf. Sect. 2.1). TLC indicated the presence of a main
product besides Ph3PS and traces of the quinoxaline N-oxide 4. Nevertheless, the
expected adduct 9 could not be isolated since it decomposed during workup via flash
column chromatography. Attempts to isolate 9 under different conditions led only to a
small amount of impure 9 which was characterized by mass spectrometry. The ESI-MS
exhibits a strong peak corresponding to [M ‡ H] of the expected product, but the
molecular weight and the similarity of the reaction courses of the formation of 5 and 6
with that of 9 were the only evidences for structure 9.
2.6. Formation of 4,5-Dihydro-4-methyl-N1,N2,5-triphenyl-1,2,4-oxadiazole-3-carb-
amidine (10). In the presence of (benzylidene)(methyl)amine (Method A), the
desulfurization of 3 afforded a new addition product characterized as the 1,2,4-
oxadiazole derivative 10. A completely novel and unprecedented reaction mechanism
for its formation is proposed in Scheme 5: after nucleophilic attack of an O-atom of the
NO2 group at the electrophilic C-atom of A, a formal 1,3-dipolar cycloaddition with the
(benzylidene)(methyl)amine leads to a bicyclic adduct which, by elimination of
phenylisocyanate, yields 10. A retro-cycloaddition of the oxazetine N-oxide to give
phenyl isocyanate and a nitrile oxide, which then undergoes a 1,3-dipolar cycloaddition
with the imine, is conceivable as well. The participation of the NO2 group in this
mechanism is in accordance with the reaction pattern of the nitroketene imine
observed in the desulfurization of 4-nitroisothiazol-5(2H)-imines 3 in the absence of
trapping reagents [32]. As a side product, the quinoxaline N-oxide 4 was detected in
minor amounts.
The 1,2,4-oxadiazole 10 was obtained in 36% yield after purification by MPLC.
Attempts to elucidate the structure by 2D-NMR spectroscopy failed due to the absence
3
of J(C,H) correlation peaks to the nonaromatic sp2 C-atoms in the HMBC spectrum.
Therefore, the assignment of the signals could be achieved only partially. After
crystallization of the material from MeOH, the structure of 10 was established by X-ray
crystallography (Fig. 2).
The molecules of 10 crystallize in a chiral space group. However, the asymmetric
unit contains two symmetry-independent molecules (A and B) which are enantio-
morphs. Therefore, the crystals are racemic, and the direction of the polar axis in the
crystal lattice has been chosen arbitrarily. The two molecules are practically mirror
images of one another, although the Ph ring at C(2)6) in molecule A is rotated by ca.
6
)
The arbitrary numbering of the atoms in the ORTEP diagram (Fig. 2) is used.

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Helvetica Chimica Acta ± Vol. 81 (1998)
Scheme 5
138 with respect to its orientation in molecule B. Tests showed that the molecules were
not related by any additional symmetry from a higher symmetry space group. The
pseudo-mirror relating the molecules is also not parallel to any of the unit cell axes.
The amino group of each symmetry independent molecule forms an intermolecular
H-bond with the unsubstituted N-atom of the oxadiazole ring (N ´´´ N 2.935(6) and
2.968(6) Š, N H ´´´ N 154(4)8 and 156(5)8, in molecules A and B, resp.) of a
neighboring symmetry unrelated molecule. The interactions link the molecules into
infinite one-dimensional ´ ´ ´ A ´ ´ ´ B ´´´ A ´´´ B ´´´ chains which run parallel to the x-axis;
graph set: C22(10).
3. Molecular-Structure Calculations. ± Ab initio calculations at the 6-31G*/MP2
level of the ketene-imine structure I and the nitrilium structure II indicate that they
represent mesomeric forms from which only I exists. This is clearly shown by the
optimized geometry of the I.
As a starting geometry for the calculations, the structure of the nitrilium derivative
II was assumed. Optimization of the geometry of different conformations (torsion
angle of the C(2) C(3) bond and (E)/(Z) variation of the N(1) C(2) bond) afforded
stable gas-phase conformations within an energy range of 3.5 kcal/mol. They all possess
the ketene-imine structure I with the lowest energy. The geometrical properties of I are
summarized in Table 3.

Helvetica Chimica Acta ± Vol. 81 (1998)
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Fig. 2. ORTEP Plot [35] of the molecular structures of the two independent molecules A and B of 10 (arbitrary
numbering of the atoms, with 50% probability ellipsoids)
Table 3. Calculated Bond Lengths [Š], and Bond and Torsion Angles [8], and H-Bond [Š] for I
N(1) C(2)
C(2) C(3)
C(2) N(6)
C(3) C(4)
C(3) N(7)
C(4) N(5)
N(5) N(13)
1.293
1.485
1.378
1.343
1.438
1.213
1.019
N(1) C(2) C(3)
C(2) C(3) C(4)
C(2) C(3) N(7)
C(3) C(4) N(5)
C(4) N(5) N(13)
114.5
118.5
126.4
170.9
124.2
N(1) C(2) C(3) C(4)
C(2) C(3) N(5) H(13)
N(6)H ´´´ O
17.0
86.0
2.007
For a detailed investigation of the bond relations in the molecule, a series of ketene
imines and comparable structures were calculated ab initio (6-31G*/MP2) yielding
bond lengths, bond orders, and torsion angles which are given in Tables 4 and 5. The

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observed changes of the charge distribution in the molecules upon modification of the
substitution pattern are presented in Table 6.
Table 4. Calculated Bond Lengths [Š] (bond orders) and Torsion Angles [8] for Substituted Ketene Imines
Bond lengths [Š] (bond orders)
N(1) C(2)
C(2) C(3)
C(2) N(6)
C(3) C(4)
C(3) N(7)
C(4) N(5)
N(5) H(13)
1.293(1.75)
1.485(0.93)
1.378(1.03)
1.343(1.43)
1.438(0.82)
1.213(1.94)
1.019(0.75)
1.292(1.76)
1.480(0.98)
1.387(1.01)
1.333(1.55)
1.437(0.94)
1.237(1.85)
1.025(0.77)
1.290(1.77)
1.472(0.96)
1.399(0.97)
1.327(1.65)
1.085(0.87)
1.231(1.89)
1.023(0.76)
±
±
1.495(0.94) 1.507(0.91)
±
±
1.332(1.53) 1.319(1.75)
1.446(0.83) 1.087(0.88)
1.227(1.88) 1.243(1.85)
1.023(0.75) 1.025(0.78)
Bond angles [8]
N(1) C(2) C(3)
C(2) C(3) C(4)
C(2) C(3) N(7)
C(3) C(4) N(5)
C(4) N(5) H(13)
114.5
118.5
126.4
170.9
124.2
118.8
119.0
118.5
168.3
115.8
119.9
119.8
120.8
172.4
117.1
Torsion angles [8]
N(1) C(2) C(3) C(4)
C(2) C(3) C(5) H(13)
17.0
86.0
7.8
88.0
18.9
87.6
a) The same numbering of the atoms is used for all the structures (cf. also I; Sect. 3).
Table 5. Calculated Bond Lengths [Š] (bond orders) for the Molecules Used as Reference
C(1) C(2)
C(2) C(3)
C(2) N(5)
C(3) N(4)
1.495(0.94)
1.332(1.53)
1.446(0.83)
1.227(1.88)
1.494(0.96)
1.403(1.05)
1.373(1.08)
1.192(2.64)
1.422(1.12)
1.408(1.04)
1.500(0.77)
1.185(2.36)
1.082(0.89)
1.330(0.96)
1.462(0.81)
±
±
±
±
±
1.336(1.87)
±
±
1.282(1.85)
N(1) C(2)
C(2) C(3)
C(2) N(6)
C(3) C(4)
C(3) N(7)
C(4) N(5)
N(5) C(13)
1.267(1.86)
1.486(0.96)
1.364(1.08)
1.364(1.32)
1.407(0.92)
1.145(2.21)
1.392(0.78)
a) The same numbering of the atoms is used for all the structures.

Helvetica Chimica Acta ± Vol. 81 (1998)
2399
Table 6. Calculated Charge Distributions [e] for Various Substitution Patterns of the Molecules (cf. Tables 4
and 5)
R
Charges
NO2
NH2
0.023
0.155
0.131
2.7
H
Ha)
0.027
0.221
0.195
1.8
X
Y
R
m [D]
0.031
0.360
0.392
2.8
0.016
0.196
0.212
2.1
a) X ˆ CH3.
Depending on the nature of R in III (Table 6), charge displacements up to 0.6 e
between the fragment Y and the substituent R are induced. Surprisingly, the total
charge of the fragment X is extraordinarily stable (max. fluctuation 0.06 e). The nature
of R influences the bond lengths and bond orders in X ˆ CNH(NH2) very little. The
X
Y bond is a single bond, and, although both fragments possess an almost coplanar
p-system, no increase in the bond order is detected. The bond Y R is also a single
bond with little bond-order variation upon changing R. The bond order of Y R is
lower than that of X Y, reaching its lowest value for R ˆ NO2. The C,N bond in Y is a
double bond for R ˆ H, NH2 increasing its bond order by ca. 5% for R ˆ NO2. These
results did not support a large contribution from a mesomeric structure of type II.
In contrast to the CˆN bond, the CˆC bond in Y is highly dependent on the
substituent R (Table 4). The bond order of the CˆC bond in methylketene imine (X ˆ
Me, R ˆ H; cf. Table 4) is ca. 5% lower than in ethylene (cf. Table 4). In the
amidinoketene imine (X ˆ CNH(NH2), R ˆ H; cf. Table 4), it decreases by a further
6% reaching the value 1.65, which represent 94% of the methylketene-imine value and
88% of that of ethylene. In the series of amidinoketene imines with R ˆ H, NH2, NO2,
the bond order of the CˆC bond in Y remarkably drops from 1.65 (94%) to 1.55 (89%)
and 1.43 (82%).
Based on the atomic net charges, the charge displacement Y! R as a function of R
reveals that the charge is mainly taken from C(3), while only a little flows from the
CˆNH group to the R substituent (Table 6). Thus, replacing R ˆ H by R ˆ NO2 causes
a charge displacement from C(3) to R of ca. 0.46 e, which corresponds to 77% of the
total charge displacement to the NO2 group; 8% are coming from X ˆ CNH(NH2) and
15% from the CˆNH bond. This is in accordance with the differences found between
ethylene and nitroethylene though the CˆC bond order decreases there by only 4%
(Table 5).
4. Discussion. ± Ketene imines of type 1 were reported to react with aliphatic and
aromatic amines affording amidines in good yields [37][38]. Likewise, Goerdeler et al.

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isolated from the reaction of aniline with unstable alkene-diimines, formed by S-
extrusion from isothiazolimines, amidine derivatives which allowed the indirect
determination of the yields of formed ketene imines [5][28]. In accordance with these
results, the presence of amines in the reaction mixture, as well as addition of amine after
the completed desulfurization of 4-nitroisothiazol-5(2H)-imine 3, led to amidine
derivatives 5 in good yields (Scheme 2 and Table 1). Therefore, also in this case, the
presence of an unstable intermediate A as the main product of the reaction can be
postulated. Surprisingly, neither aniline nor substituted anilines yielded the expected
amidines, and the reaction proceeded as in the absence of amines yielding
decomposition compounds and the N-oxide 4 as a minor product [32].
Following the discussion of the reactivity of amines in the reaction with ketene
imines by Stevens et al. [37], we tried to correlate the reaction capability with the pKa
values of the used amines (Table 7). Thus, only relatively basic amines (pKa > 8)
reacted with the intermediate A to yield the expected amidine derivatives; 4-
methoxyaniline (pKa ˆ 5.29) and aniline (pKa ˆ 4.62) failed to react, in analogy with
the results for some other ketene imines [5][37]. Steric hindrance as the inhibiting
factor in these reactions was ruled out, as the expected derivatives from the reactions of
A with PhCH2NH2 and PhSH could be isolated (cf. Table 1 and Scheme 2).
Table 7. pKa Values of the Compounds Used as Trapping Reagents
a
Compound
pKa
)
Compound
pKa
Pyrrolidine
Et2NH
EtNH2
PhCH2NH2
Morpholine
4-Methoxyaniline
PhNH2
11.27
10.98
10.63
9.34
8.36
5.29
i-PrSH
PrSH
BuSH
PhSH
10.86
10.82
10.78
6.50
16.60
7.14
MeOH
4-Nitrophenol
PhCOSH
PhCOOH
4.62
5.66
4.20
a) pKa Values of the ammonium salt.
In contrast to the results with the amines, the reactions with thiols yielded the
predicted adduct 6 only in the case of PhSH (pKa ˆ 6.50). The less acidic (pKa > 10)
i-PrSH, PrSH, and BuSH did not lead to any product, and again the reaction behavior
was similar to that in the absence of nucleophiles. Whereas identical results were
achieved when MeOH (pKa ˆ 16.60) was used as reagent or as solvent, the addition of
the more acidic 4-nitrophenol (pKa ˆ 7.14) affected the reaction course as amines did.
It should be noted, however, that the presumably formed primary adduct 9
decomposed during workup, and only the observed reaction behavior and the analysis
of the crude product by mass spectrometry gave evidence of its formation.
Furthermore, the addition of PhCOOH (pKa ˆ 4.20) as well as PhCOSH (pKa ˆ
5.66), after desulfurization of 3, yielded products which would involve, as precursors,
the expected adducts of the acids with intermediate A (Schemes 3 and 4).
Accordingly, ketene imines are known to add carboxylic acids giving enol esters,
which are used as acylating agents. Their formation was explained via an intermediate
acid/ketene imine adduct, which undergoes spontaneous intramolecular acyl migration

Helvetica Chimica Acta ± Vol. 81 (1998)
2401
[39 ± 41]. Mechanistic studies have shown that the driving force of this reaction is the
affinity of the acid proton to the ketene imine; the stronger the acid, the faster the
reaction [42]. Taking these results into account, one could propose a mechanism for the
reaction of A with acidic reagents which involves the formation of a transition state B
leading to the unstable adduct C (Scheme 6).
Scheme 6
In the case of PhCOOH, we assume that C (cf. 7a, Scheme 3) possesses a favorable
geometry for an easy O,N-acyl migration, similar to that observed for the addition
products of amines and ketene imines [38]. In contrast, in the adduct C of PhCOSH
and A (cf. 8a, Scheme 4), the large S-atom might induce a different geometry, which
apparently hinders the intramolecular acylation facilitating the hydrolysis of the
unstable C. A diverging feature of the O,N- and S,N-acyl migrations is also the large
energy difference of the products (2 CˆO vs. CˆO and CˆS). Therefore, an early TS=
is to be expected in the first case and a late TS= in the second case.
In summary, it seems that not only the nucleophilicity but also the acidity of the
reagent is dominant in the reaction of nucleophiles with A. By examination of the
results, one could ascertain the pKa influences of different nucleophiles on this reaction.
Whereas the increase in the basicity is proportional to the nucleophilicity and,
therefore, to the reaction ability within the series of the amines, the effect for acidic
compounds is the opposite. This becomes understandable considering the proposed
mechanism, where the release of the acidic H-atom would favor the nucleophilic
addition. Thus, in contrast to the other thiols, the acidity of PhSH, in addition to the
stabilizing effect of the Ph ring on the formed anion, probably promotes the attack of
the S-atom at the electrophilic C-atom of the ketene imine; analogously, 4-nitrophenol
led to reaction while MeOH failed.
Interestingly, the two IR bands at 2337 and 2261 cm 1 of the reaction mixture of the
desulfurization of 3 disappeared instantaneously when the solutions were treated with
the nucleophiles. The isolated products could arise only from the addition of the
reagents to the proposed ketene imine A and, therefore, the amidine derivatives 5, the
thioimidate 6, the amide 7, and the thioamide 8 undoubtedly establish that A is the
unstable intermediate of the reaction. The shift of the IR bands compared with those of
1
typical ketene imines (ca. 2000 cm ) could be explained by the influence of the NO2
group which might give rise, due to its strong electron-withdrawing effect, to changes of
the electronic characteristic of the cumulene. In fact, the ab initio calculations indicate

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Helvetica Chimica Acta ± Vol. 81 (1998)
that 3-imino-2-nitroprop-2-enamidines are conveniently described by the single
structure I (cf. Sect. 3); on the other hand, two further resonance structures, one of
those analogous to the polar resonance form II, contribute significantly to the ground
state of simple ketene imines of type 1 [43]. Theoretical studies and crystal structure
analyses of those ketene imines [44][45] further support the contribution of the
structure II, showing an increase of the CˆN bond order depending on the substituents.
Taking into account the extent of the contribution of the resonance structures to
their ground state, the reactivity differences between other 3-imino-2-nitro-prop-2-
enamidines of type A and ketene imines could be explained. Thus, ketene imines are
reported to react not only as electrophiles at the central C-atom but also as
nucleophiles at the terminal C-atom [12]. In contrast, the results of the calculations for
I display a decrease of the nucleophilicity of the terminal C-atom, as the charge
displacement to the NO2 group is mainly taken from this C-atom (cf. C(3) in I, Sect. 3).
The formation of the 1,2,4-oxadiazole derivative7) 10 confirmed, on one hand, the
electrophilic character of the ketene-imine C(3)-atom and showed, on the other hand,
the participation of the NO2 group in the reaction, as also achieved in the absence of
nucleophiles as trapping reagents [32]. The proposed reaction mechanism could
explain the different behavior of A and similar ketene imines, which typically undergo
cycloadditions with phenyl isothiocyanate and phenyl isocyanate, while A failed to
react. Probably, in A, where the electronic effects cause a high reactivity in the
molecule, the O-atoms of the NO2 group can easily reach the electrophilic C(2)-atom of
the cumulene. This, together with several reactive sites of A, could induce many parallel
reactions, thus leading to numerous decomposition compounds (cf. [32]). Nevertheless,
the addition of strong nucleophiles as trapping reagents to the reaction mixture allows a
ready blocking of the electrophilic C(2)-atom yielding stable adducts as proof for the
appearance of the transient 3-imino-2-nitroprop-2-enamidine A.
We thank the analytical units of our institute for spectra and analyses. Financial support of this work by the
Swiss National Science Foundation and F. Hoffmann-La Roche AG, Basel, is gratefully acknowledged. D.M.A.
thanks the Eidgenössische Stipendienkommission für ausländische Studierende for a scholarship.
Experimental Part
1. General. TLC: silica-gel 60-F254 plates (0.25 mm; Merck); CH2Cl2/hexane 6 :1, CH2Cl2/MeOH 20 :1, and
100 :1 as eluents. Column chromatography (CC): silica gel 60 (0.040 ± 0.063 mesh; Merck). Medium-pressure
liquid chromatography (MPLC): pump LABOMATIC MD-80/100, UV detector LABOCORD-200 (254 nm);
LiChroprep Si 60 (Merck), 15 ± 25 mm; column Kronlab HPP-VPC, 540 Â 40 mm. Solvent: CH2Cl2 (puriss.,
abs., over molecular sieve; H2O < 0.005%; Fluka). M.p.: Mettler-FP-5 apparatus, uncorrected. IR Spectra:
1
Perkin-Elmer-1600 FT-IR spectrophotometer; in KBr, absorption bands in cm
.
1H- (300 or 600 MHz) and
13C-NMR (75.5 or 150.9 MHz) Spectra: Bruker ARX-300 and Bruker AMX-600 instrument, in CDCl3 unless
otherwise stated; d in ppm; coupling constants J in Hz. Signal multiplicity was indirectly interpreted from the
DEPT spectra and signal assignment was achieved using 2D-NMR correlation spectra. CI-MS (NH3 as
ionization gas): Finnigan SSQ-700 or MAT-90 instrument; ESI mode on a Finnigan TSQ-700 triple quadrupole
spectrometer.
2. Starting Material. 4-Nitro-N,2-diphenyl-3-(phenylamino)isothiazol-5(2H)-imine (3) was synthesized
according to the general procedure described in [30][47].
7
)
The synthesis of similar 1,2,4-oxadiazole derivatives starting from 4-nitroimidazoles have been described
by Suwinski et al. [46], though via a different reaction mechanism involving reduction of the NO2 to a NO
group.

Helvetica Chimica Acta ± Vol. 81 (1998)
2403
3. 2-Nitro-N-phenyl-3,3-bis(phenylamino)prop-2-enamidines 5. General Procedure. Method A: To a soln. of
3 (0.5 mmol) in abs. CH2Cl2 (4 ml), containing the correponding amine (5 mmol), a soln. of Ph3P (136 mg,
0.5 mmol) in abs. CH2Cl2 (1.5 ml) was added at 08 under N2. The mixture was stirred for 1 h raising the temp. to
r.t., then, the solvent was evaporated, and the residue separated by CC (CH2Cl2/MeOH). The compounds were
purified by repeated CC.
Method B: To a soln. of 3 (0.5 mmol) in abs. CH2Cl2 (4 ml), a soln. of Ph3P (136 mg, 0.5 mmol) in abs.
CH2Cl2 (1.5 ml) was added at 08 under N2. After 2 min, the desulfurization was completed (monitoring by TLC
and IR), and the corresponding amine (5 mmol) was added. Workup and purification as in Method A.
3.1. 1-Morpholino-2-nitro-N-phenyl-3,3-bis(phenylamino)prop-2-enimine (5a). CC with CH2Cl2/MeOH.
Yield of 5a: 226 mg (99%, Method A), 205 mg (90%, Method B). Yellow crystals. M.p. 113 ± 1158. IR: 3364w,
3239m, 3056m, 2962m, 2920m, 2856m, 1584s, 1525s, 1496s, 1439s, 1353s, 1278s, 1243s, 1204s, 1112s, 1061s, 1021m,
1002m, 944w, 912w, 855w, 810w, 751s, 722w, 692s. 1H-NMR: 11.82 (br. s, 2 NH); 7.19 (t, J ˆ 7.8, 2 arom. H); 7.0 ±
6.7 (m, 9 arom. H); 6.48 (br. s, 4 arom. H); 3.69 (br. s, 2 CH2O); 3.55 (br. s, 2 CH2N). 13C-NMR: 150.9 (s, C(3));
150.6 (s, C(1)); 148.9 (s, 1 arom. C); 134.8 (br. s, 2 arom. C); 128.0, 127.8, 125.2, 122.5, 121.9, 120.5 (6d,
‡
15 arom. CH); 107.9 (s, C(2)); 65.6 (br. t, 2 CH2O); 45.0 (br. t, 2 CH2N). ESI-MS: 466 ([M ‡ Na] ), 444 ([M ‡
‡
H] ). Anal. calc. for C25H25N5O3 (443.51): C 67.70, H 5.68, N 15.79; found: C 67.89, H 5.69, N 15.53.
3.2. 2-Nitro-N-phenyl-3,3-bis(phenylamino)-1-(pyrrolidin-1-yl)prop-2-enimine (5b). CC with CH2Cl2/
MeOH. Yield of 5b: 205 mg (93%, Method A); 158 mg (72%, Method B). Yellow crystals. M.p. 117 ± 1198.
IR: 3422w (br.), 3157m, 3053m, 2974m, 2867m, 1622s, 1586s, 1535s, 1496s, 1442s, 1350s, 1261s, 1227s, 1204s,
1
1143m, 1120m, 1098m, 1072m, 998w, 942m, 917m, 844w, 754s, 693s. H-NMR ((D6)DMSO, 363 K): 9.38 (br. s,
2 NH); 7.29 (t, J ˆ 7.5, 2 arom. H); 7.2 ± 7.0 (m, 7 arom. H); 6.9 ± 6.7 (m, 6 arom. H); 3.34 (m, 2 CH2N); 1.83
(m, 2 CH2). 13C-NMR ((D6)DMSO, 363 K): 154.3 (s, C(3)); 148.2 (br. s, C(1)); 142.6, 140.5 (2 br. s, 3 arom. C);
127.9, 127.4, 124.2, 122.3, 121.5, 120.6 (6d, 15 arom. CH); 109.1 (s, C(2)); 48.0 (t, 2 CH2N); 23.6 (t, 2 CH2). ESI-
‡
MS: 428 ([M ‡ H] ). Anal. calc. for C25H25N5O2 (427.51): C 70.24, H 5.89, N 16.38; found: C 69.99, H 6.06,
N 16.16.
3.3. N1,N1-Diethyl-2-nitro-N2-phenyl-3,3-bis(phenylamino)prop-2-enamidine (5c). CC with CH2Cl2/MeOH.
Yield of 5c: 201 mg (91%, Method A). Yellow crystals. M.p. 170 ± 1738. IR: 3356w, 3156m, 3056m, 2973m,
2931m, 1625s, 1582s, 1517s, 1497s, 1446s, 1356s, 1297m, 1262s, 1230s, 1208s, 1178m, 1091s, 1058s, 998w, 917m,
896m, 876w, 844w, 803w, 752s, 693s. 1H-NMR: 11.92 (br. s, 2 NH); 7.20 (t, J ˆ 7.8, 2 arom. H); 7.0 ± 6.7
(m, 9 arom. H); 6.6 ± 6.2 (br. m, 4 arom. H); 3.31 (br. s, 2 CH2); 1.18 (br. s, 2 Me). 13C-NMR: 150.6 (s, C(3));
150.0 (s, C(1)); 149.0 (s, 1 arom. C); 135.2 (br. s, 2 arom. C); 128.0, 127.6, 124.7, 122.7 (br.), 121.6, 120.7, (6d,
‡
15 arom. CH); 109.3 (s, C(2)); 42.4, 40.7 (2br. t, 2 CH2); 14.3, 11.0, (2br. q, 2 Me). ESI-MS: 430 ([M ‡ H] ).
Anal. calc. for C25H27N5O2 (429.52): C 69.91, H 6.34, N 16.31; found: C 69.80, H 6.04, N 16.51.
3.4. N1-Benzyl-2-nitro-N2-phenyl-3,3-bis(phenylamino)prop-2-enamidine (5d). CC with CH2Cl2/MeOH.
8
Yield of 5d: 172 mg (76% ), Method A). Yellow crystals. M.p. 91 ± 938. IR: 3366m, 3288m, 3057m, 1611s, 1587s,
1
1539s, 1496s, 1441s, 1356s, 1217s, 1123m, 1073s, 1028m, 999w, 913w, 752s, 693s. H-NMR ((D6)DMSO): 10.08
(br. s, 1 NH); 9.14 (br. s, 2 NH); 7.8 ± 6.6 (m, 15 arom. H); 4.14 (br. s, CH2). 13C-NMR ((D6)DMSO): 154.7 (br.,
C(3)); 150.8 (br. s, C(1)); 147.1, 138.0 (2br. s, 2 arom. C); 137.0 (s, 2 arom. C); 128.4, 128.1, 127.3, 127.0, 124.7,
‡
123.1, 121.6 (br.), 119.2 (br.) (8d, 20 arom. CH); 111.0 (s, C(2)); 46.8 (t, CH2). ESI-MS: 927 ([2M ‡ H] ), 486
‡
‡
([M ‡ Na] ), 464 ([M ‡ H] ). Anal. calc. for C28H25N5O2 (463.54): C 72.55, H 5.44, N 15.11; found: C 72.52,
H 5.27, N 15.15.
4. Phenyl 2-Nitro-N-phenyl-3,3-bis(phenylamino)prop-2-enethioimidate (6). According to the General
Procedure, Method B (cf. 3), PhSH (0.5 ml, 5.2 mmol) was added after desulfurization of 3. CC with CH2Cl2/
MeOH. Yield of 6: 149 mg (62%). Yellow crystals. M.p. 140 ± 1418 (dec.). IR: 3278w (br.), 3054m, 2956w,
2922w, 2867w, 1611s, 1594s, 1583s, 1521s, 1497s, 1480s, 1460s, 1440s, 1400s, 1351s, 1286s, 1239m, 1222s, 1207s,
1172m, 1156m, 1067s, 1025m, 1000w, 948m, 922m, 905m, 879m, 847w, 770m, 752s, 743s, 700s, 691s. 1H-NMR:
10.40 (br. s, 2 NH); 7.5 ± 6.8 (m, 20 arom. H). 13C-NMR: 163.7 (s, C(1)); 150.4 (s, C(3)); 148.3, 136.4 (2s,
3 arom. C); 135.3 (d, 2 arom. CH); 130.0 (s, 1 arom. C); 129.4, 129.2, 128.9, 128.8, 128.7, 125.5, 122.1, 120.3, (8d,
‡
18 arom. CH); 115.2 (s, C(2)). ESI-MS: 467 ([M ‡ H] ). Anal. calc. for C27H22N4O2S (466.56): C 69.51, H 4.75,
N 12.01; found: C 69.29, H 4.85, N 12.00.
5. N-[2-Nitro-1-(phenylamino)-2-(N-phenylcarbamoyl)ethenyl]-N-phenylbenzamide (7). According to the
General Procedure, Method B (cf. 3), PhCOOH (635 mg, 5.2 mmol) was added after desulfurization of 3. CC
with CH2Cl2/MeOH. Yield of 7: 165 mg (67%). Yellow crystals. M.p. 104 ± 1068 (dec.). IR: 3303m, 3061m,
8
)
The yield of the reaction may be higher, but the isolation of the compound was particularly difficult.

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Helvetica Chimica Acta ± Vol. 81 (1998)
2924w, 1672s, 1581s, 1538s, 1483s, 1445s, 1403m, 1334s, 1285s, 1179m, 1140m, 1101m, 1075m, 1049m, 1027w,
1002w, 889m, 864w, 786m, 756s, 722m, 691s. 1H-NMR (CD3CN, 220 K): 11.29, 9.11 (2s, 2 NH); 7.7 ± 6.5
(m, 20 arom. H). 13C-NMR (CD3CN, 220 K): 172.0 (s, CˆO); 159.2 (s, (PhNH)2C); 154.2 (s, CˆO); 139.7,
138.7, 135.8, 133.5 (4s, 4 arom. C); 132.4, 129.8, 129.7, 129.3, 129.2, 128.9, 128.7, 128.4, 127.2, 125.5, 124.7 (11d,
‡
‡
18 arom. CH); 123.2 (s, NO2C); 119.1 (d, 2 arom. CH). ESI-MS: 501 ([M ‡ Na] ), 479 ([M ‡ H] ).
9
6. 2-Nitro-N-phenyl-3,3-bis(phenylamino)prop-2-enethioamide (8) ). According to the General Procedure,
Method B (cf. 3), PhCOSH (635 mg, 5.2 mmol) was added after desulfurization of 3. CC with CH2Cl2/MeOH.
‡
‡
10
Yield of 8 (cf. [34]): 150 mg (75%). ESI-MS: 391 ([M ‡ H] ), 389 ([M H] ) ).
7. 4-Nitrophenyl 2-Nitro-N-phenyl-3,3-bis(phenylamino)prop-2-enimidate (9). According to the General
Procedure, Method B (cf. 3), 4-nitrophenol (723 mg, 5.2 mmol) was added after desulfurization of 3. CC with
11
‡
CH2Cl2/MeOH ). ESI-MS: 496 ([M ‡ H] ).
8. 4,5-Dihydro-4-methyl-N1,N2,5-triphenyl-1,2,4-oxadiazole-3-carbamidine (10). According to the General
Procedure, Method A (cf. 3), in presence of 0.6 ml (5.2 mmol) of (benzylidene)(methyl)amine. CC with
CH2Cl2/MeOH and MPLC with CH2Cl2/hexane. Yield of 10: 42.7 mg (36%). White crystals. M.p. 169 ± 1708. IR:
3295m, 3136m, 3060m, 2923m, 2854w, 2804w, 1641s, 1590s, 1549s, 1483s, 1477s, 1446s, 1409m, 1372m, 1328s,
1290m, 1218s, 1176w, 1156w, 1118m, 1072m, 1016m, 901w, 830m, 758s, 697s. 1H-NMR (CD2Cl2, 208 K): 7.76
(d, J ˆ 7.9, 2 arom. H); 7.46 (br. s, 1 NH); 7.4 ± 7.3 (m, 5 arom. H); 7.28 (t, J ˆ 7.5, 2 arom. H); 7.16 (t, J ˆ 7.4,
1 arom. H); 7.09 (t, J ˆ 7.4, 1 arom. H); 7.01 (d, J ˆ 7.5, 2 arom. H); 6.89 (d, J ˆ 7.3, 2 arom. H); 5.94 (s, CH);
2.30 (s, Me). 13C-NMR (CD2Cl2, 208 K): 153.3 (s, C(3)); 148.2 (s, 1 arom. C); 140.4 (s, (NH)CˆN); 138.8, 135.4
(2s, 2 arom. C); 130.0, 128.9, 128.8, 128.5, 127.6, 123.5, 123.2, 121.0, 119.3 (9d, 15 arom. CH); 99.0 (d, C(5)); 31.5
‡
‡
‡
(q, Me). ESI-MS: 735 ([2M ‡ Na] ), 379 ([M ‡ Na] ), 357 ([M ‡ H] ). Anal. calc. for C22H20N4O (356.43):
C 74.14, H 5.66, N 15.72; found: C 74.08, H 5.47, N 15.36.
12
9. Crystal-Structure Determination of 8 and 10 (see Table 8, and Figs. 1 and 2) ). All measurements were
made on a Rigaku-AFC5R diffractometer using graphite-monochromated MoKa radiation (l ˆ 0.71069 Š) and
a 12-kW rotating anode generator. The w/2q scan mode was employed for data collection. The intensities were
corrected for Lorentz and polarization effects, but not for absorption. Data collection and refinement
parameters are given in Table 8, views of the molecules are shown in Figs. 1 and 2. The structures were solved by
direct methods using SHELXS86 [48], which revealed the positions of all non-H-atoms. The asymmetric unit of
8 contains two symmetry-independent molecules plus a partially occupied site for a H2O molecule. The mol-%
of H2O is ca. 10%. In the asymmetric unit of 10, there are also two symmetry-independent molecules. The
atomic coordinates of the two molecules were tested carefully for a relationship from a higher symmetry space
group using the MISSYM routine [49] of the program PLATON [50], but none could be found. The non-H-
atoms of 8 and 10 were refined anisotropically. All of the H-atoms bonded to N-atoms were placed in the
positions indicated by a difference electron-density map and their positions were allowed to refine together with
individual isotropic displacement parameters. The H-atoms of H2O in 8 were similarly located, but not refined.
All remaining H-atoms were fixed in geometrically calculated positions (d(C H) ˆ 0.95 Š), and they were
assigned fixed isotropic displacement parameters with a value equal to 1.2 Ueq of the parent C-atom. Refinement
of the structures was carried out on F using full-matrix least-squares procedures, which minimized the function
P
w( j Fo j j Fc j )2. Neutral atom scattering factors for non-H-atoms were taken from [51a] and the scattering
factors for H-atoms from [52]. Anomalous dispersion effects were included in Fcalc. [53]; the values for f ' and f ''
were those of [51b]. All calculations were performed using the TEXSAN crystallographic software package
[54].
9
)
)
)
The expected adduct could not be isolated, only the product of its hydrolysis.
Usually observed peak in the MS spectra of thioacrylamides of this series.
According to TLC, only one main product has been formed in the reaction, but it decomposed to
undefined compounds during flash chromatography. However, the MS of an isolated impure fraction
indicated the desired adduct.
Crystallographic data (excluding structure factors) for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as deposition No. CCDC-104936 and 104937
for 8 and 10, resp. Copies of the data can be obtained, free of charge, on application to the CCDC,
12 Union Road, Cambridge CB2 1EZ, U.K. (fax: ‡ 44-(0)1223-336033 or e-mail: deposit@ccdc.cam.
ac.uk).
10
11
12
)

Helvetica Chimica Acta ± Vol. 81 (1998)
2405
Table 8. Crystallographic Data for Compounds 8 and 10
8
10
Crystallized from
Empirical formula
Formula weight
Crystal color, habit
Crystal dimensions [mm]
Temperature [K]
Crystal system
Space group
MeOH
C21H18N4O2S ´ 0.1 H2O
392.26
yellow, tablet
0.12 Â 0.23 Â 0.45
173(1)
monoclinic
P21/n
MeOH
C22H20N4O
356.43
colorless, prism
0.10 Â 0.25 Â 0.33
173(1)
monoclinic
P21
Z
8
4
Reflections for cell determination
25
25
2q Range for cell determination [8]
Unit cell parameters a [Š]
24 ± 39
13.272(3)
15.687(4)
19.045(2)
93.93(1)
3956(1)
1.317
26 ± 39
7.336(5)
20.981(3)
12.706(5)
90.96(4)
1955(2)
1.211
b [Š]
c [Š]
b [8]
V [Š3]
3
Dcalc [g cm
]
1
m(MoKa) [mm
2q(max) [8]
]
0.188
50
0.0769
55
Total reflections measured
Symmetry independent reflections
Reflections used [I > 2s(I)]
Parameters refined
7584
6971
4114
538
4962
4605
2602
495
Final
R
0.0521
0.0422
1.585
0.0516
0.0370
1.377
1
wR (w ˆ [s2(Fo) ‡ (0.005Fo)2]
)
Goodness of fit
7
Secondary extinction coefficient
±
4.7(8) Â 10
Final Dmax/s
D1 (max; min) [e Š
0.0003
0.26; 0.26
0.0002
3
]
0.21; 0.20
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Received October 26, 1998