C-aminoimidoylation and C-thiocarbamoylation of esters, sulfones, and ketones

Article abstract of DOI:10.1021/jo070545c

(Chemical Equation Presented) Esters, sulfones, and ketones were C-aminoimidoylated and C-thiocarbamoylated by benzotriazole-1-carboxamidines 8a-g and 1-(alkyl-or-arylthiocarbamoyl)benzotriazoles 9a-i, respectively. The present work represents the first s

Full text of DOI:10.1021/jo070545c

C-Aminoimidoylation and C-Thiocarbamoylation of Esters, Sulfones,
and Ketones
Alan R. Katritzky,*,† Niveen M. Khashab,# Danniebelle N. Haase,# Megumi Yoshioka,#
Ion Ghiviriga,‡ and Peter J. Steel§
UniVersity of Florida, Department of Chemistry, GainesVille, Florida 32611-7200,
UniVersity of Canterbury, Christchurch, New Zealand,
Center for Heterocyclic Compounds and Nuclear Magnetic Resonance Facility
Katritzky@chem.ufl.edu
ReceiVed March 15, 2007
Esters, sulfones, and ketones were C-aminoimidoylated and C-thiocarbamoylated by benzotriazole-1-
carboxamidines 8a-g and 1-(alkyl-or-arylthiocarbamoyl)benzotriazoles 9a-i, respectively. The present
work represents the first systematic approach to these compound classes, the few previously known
examples of which were obtained by diverse approaches.
Introduction
known products 2 were prepared by nucleophilic attack of
amines on isoxazolones 1 leading to ring opening and loss of
CO2.4
C-Aminoimidoylation and C-thiocarbamoylation are both
relatively unexplored synthetically in contrast to the wide atten-
tion given to C-acylation1a-c and C-imidoylation.2a-c This
reflects the wide availability of both acylating and imidoylating
reagents and the lack of reagents for C-aminoimidoylation and
C-thiocarbamoylation. Literature examples of compounds that
could conceptually have been made by C-aminoimidoylation
and C-thiocarbamoylation have generally been accessed by
multistep synthesis.3a-d
Substructure searches disclosed no literature examples of
the C-aminoimidoylation of esters; known examples of such
Likewise, no example of C-aminoimidoylation by C-C bond
formation at a sulfone was identified; one possible product of
such a reaction 5 was prepared by the reaction of an alkyl â,â-
dichlorovinyl sulfone 3 with 4-methoxyaniline 4.5
* Author to whom correspondence should be addressed. Phone: 352-392-
0554. Fax: 352-392-9199.
† University of Florida.
# Center for Heterocyclic Compounds.
‡ Nuclear Magnetic Resonance Facility.
§ University of Canterbury.
(1) (a) Shivers, J. C.; Dillon, M. L.; Hauser, C. R. J. Am. Chem. Soc.
1947, 69, 119. (b) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. J.
Org. Chem. 2003, 68, 1443. (c) Bachman, G. B.; Hokama, T. J. Am. Chem.
Soc. 1959, 81, 4882.
(2) (a) Fustero, S.; Pina, B.; Simo´n-Fuentes, A. Tetrahedron Lett. 1997,
38, 6771. (b) Fustero, S.; Pina, B.; Garcia de la Torre, M.; Navarro, A.;
Ram´ırez de Arellano, C.; Simo´n, A. Org. Lett. 1999, 1, 977. (c) Fustero,
S.; Pina, B.; Salavert, E.; Navarro, A.; Ram´ırez de Arellano, M. C.; Simo´n
Fuentes, A. J. Org. Chem. 2002, 67, 4667.
(3) (a) Shi, Y.; Zhang, J.; Grazier, N.; Stein, P. D.; Atwal, K. S.; Traeger,
S. C.; Callahan, S. P.; Malley, M. F.; Galella, M. A.; Gougoutas, J. Z. J.
Org. Chem. 2004, 69, 188. (b) Barun, O.; Ila, H.; Junjappa, H. J. Org.
Chem. 2000, 65, 1583. (c) Kantlehner, W.; Mergen, W. W. Synthesis 1979,
5, 343. (d) Kantlehner, W.; Mergen, W. W.; Haug, E. Liebigs Ann. Chem.
1983, 2, 290.
N,N′-Disubstituted ketene aminals 6 are used in many
syntheses, especially in the construction of heterocyclic
compounds.3a Structurally, ketene aminals are C-aminoimid-
(4) Wicks, Z. W., Jr.; Patel, P. P. J. Org. Chem. 1981, 46, 4068.
10.1021/jo070545c CCC: $37.00 © 2007 American Chemical Society
Published on Web 08/04/2007
6742
J. Org. Chem. 2007, 72, 6742-6748

C-Aminoimidoylation and C-Thiocarbamoylation
SCHEME 1. Literature Methods for the Preparation of
Ketene Aminals 6
SCHEME 2. Preparation of C-Thiocarbamoylation Product
7
FIGURE 1. X-ray structure of methyl 3-(isopropylamino)-2-phenyl-
3-thioxopropanoate (12a).
SCHEME 5. Preparation of Reagents 8 and 9
SCHEME 3. N-Aminoimidoylation with Benzotriazole-
1-carboxamidines 8
3), and (ii) di- and trisubstituted thioureas,8 N-hydroxythioureas,
and thiosemicarbazides9 using novel 1-(alkyl/arylthiocarbam-
oyl)benzotriazole thiocarbamoylating reagents (Scheme 4). In
the present paper, we demonstrate that esters, sulfones, and
ketones can be C-aminoimidoylated by benzotriazole-1-car-
boxamidines 8a-g and C-thiocarbamoylated by 1-(alkyl/arylth-
iocarbamoyl)benzotriazoles 9a-i. Our simple procedure com-
prises deprotonation of esters, sulfones, and ketones in the
presence of a strong base, followed by nucleophilic substitution
of the benzotriazolyl group in benzotriazole-1-carboxamidines
8a-g or 1-(alkyl/arylthiocarbamoyl)benzotriazoles 9a-i.
SCHEME 4. Reactions of 1-(Alkyl/arylthiocarbamoyl)-
benzotriazoles 9
Results and Discussion
oylated ketones that have been prepared (Scheme 1) starting
from (i) activated methylene compounds and isothiocyanates,3a
(ii) oxoketene N,S-acetals and lithiated secondary amines or
aniline,3b or (iii) tris(dimethylamino)ethoxymethane and simple
ketones.3c,d Methods i-iii (Scheme 1) each consist of multisteps
with average overall yields of ca. 30%. Methods (i) and (ii) are
related to C-aminoimidoylation but no such reaction of a ketone
was located in a search of the literature.
Again, no direct C-thiocarbamoylation of an ester could be
found. Potential ester C-thiocabamoylation products 7 were
prepared from an isothiocyanate, a carboxylic acid and an
alcohol in the presence of n-BuLi (Scheme 2).3b-d
Preparation of Benzotriazole-1-carboxamidines 8a-g and
1-(Alkyl/aryl-thiocarbamoyl) Benzotriazoles 9a-i. Bis(ben-
zotriazolyl)methanethione10 and amines afforded 1-(alkyl-or-
arylthiocarbamoyl)benzotriazoles 9a-i8, converted in turn by
triphenylphosphine ylides into the benzotriazole-1-carboxam-
idines 8a-g (Scheme 5).6
C-Aminoimidoylation and C-Thiocarbamoylation of Es-
ters. Reactions of 2.0 equiv of ester enolates (from ester 11
with 2.5 equiv potassium tert-butoxide) with 1.0 equiv of
benzotriazole-1-carboxamidines 8a-g or 1-(alkyl-or-arylthio-
carbamoyl)benzotriazoles 9a-i afforded 10a-d and 12a-c,
respectively; after limited optimization, yields of 20-63% were
obtained (Scheme 6, Table 1). Elemental analysis, X-ray data,
and NMR spectral data support the structural assignments.
Different tautomeric structures are possible for the ester
Recently, we synthesized (i) 1,2,3-trisubstituted guanidines,6
N-hydroxy-, and N-amino-guanidines7 using novel benzotri-
azole-1-carboxamidine N-aminoimidoylating reagents (Scheme
(5) Martynov, A. V.; Mirskova, A. N.; Kalikhman, I. D.; Makerov, P.
V.; Vitkovskii, V. Y.; Voronkov, M. G. Zh. Org. Khim. 1979, 15, 2349.
(6) Katritzky, A. R.; Khashab, N. M.; Bobrov, S. HelV. Chim. Acta 2005,
88, 1664.
(7) Katritzky, A. R.; Khashab, N. M.; Bobrov, S.; Yoshioka, M. J. Org.
Chem. 2006, 71, 6753.
(8) Katritzky, A. R.; Ledouux, S.; Witek, R. M.; Nair, S. K. J. Org.
Chem. 2004, 69, 2976.
(9) Katritzky, A. R.; Khashab, N. M.; Gromova, A. V. ARKIVOC 2006,
iii, 226.
(10) Larsen, C.; Steliou, K.; Harpp, D. N. J. Org. Chem. 1978, 43, 337.
J. Org. Chem, Vol. 72, No. 18, 2007 6743

Katritzky et al.
SCHEME 6. Preparation from Esters 11a-e of the C-Aminoimidoylation Products 10a-d and the C-Thiocarbamoylation
Products 12a-c
SCHEME 7. Preparation from Sulfone 14 of C-Aminoimidoylation Product 13 and C-Thiocarbamoylation Product 15
TABLE 1. C-Aminoimidoylation and C-Thiocarbamoylation of Esters 11a-e To Give 10a-d and 12a-c
ester
R1
R2
reagent
R3
R
product
yield, %
11a
11b
11c
11d
11e
11c
11b
H
Me
Et
Me
Et
Me
Me
Et
8a
8d
8e
8f
9b
9f
Bn
p-Tol
m-CNC6H4
p-Tol
m-CNC6H4
-
-
-
10a
10b
10c
10d
12a
12b
12c
63
24
51
20
50
27
49
CO2Et
CO2Me
CN
Ph
CO2Me
CO2Et
CH(CH3)Ph
CH2CH(CH3)CH2CH3
Allyl
i-Pr
CH(CH3)Ph
(CH2)2Ph
9h
TABLE 2. C-Aminoimidoylation and C-Thiocarbamoylation of Ketones 17a-d To Give 16a-d and 18a-d
ketone
R1
R2
reagent
R3
R
product
yield, %
17a
17b
17c
17a
17a
17d
17b
17c
H
H
Me
H
H
Bn
H
Me
Ph
2-Thienyl
Me
Ph
Ph
Ph
2-Thienyl
Me
8g
8b
8g
8c
9d
9h
9d
9i
(CH2)2Ph
n-Bu
(CH2)2Ph
n-Bu
n-Bu
(CH2)2Ph
n-Bu
Ph
p-Tol
Ph
p-ClC6H4
-
-
-
-
16a
16b
16c
16d
18a
18b
18c
18d
32
27
27
31
50
65
51
40
t-Bu
products; however, the X-ray data for compound 12a shows
that it exists as the CH rather than OH tautomer in the solid
state (Figure 1). More experiments including 2D-NMR were
utilized to verify the tautomeric forms of the compounds (as
described later in this paper).
C-Aminoimidoylation and C-Thiocarbamoylation of Sul-
fones. The procedures just described for esters effected the
C-aminoimidoylation and C-thiocarbamoylation of sulfone 14
in yields of only around 10%. However, stirring 2.0 equiv of
sulfone 14 with 2.5 equiv of potassium tert-butoxide in THF at
room temperature for 1 h followed by the addition of the
corresponding benzotriazole reagent (8b or 9c) afforded com-
pounds 13 and 15 in yields of 30-40% (Scheme 7).
C-Aminoimidoylation and C-Thiocarbamoylation of Ke-
tones. Reaction of enolates from ketones 17a-d with 8 or 9
gave the C-aminoimidoylation and C-thiocarbamoylation prod-
ucts 16a-d and 18a-d (27-65% yields, after limited optimiza-
tion, Table 2) during 0.5-4.0 h (Scheme 8) as monitored by
TLC. For compounds 16a and 18a-d, 2D NMR correlation
experiments were used to assign the 1H and 13C chemical shifts
(described later in the paper).
FIGURE 2. X-ray structure of 5-methyl-4-phenyl-5-(2-thienyl)-1,3-
oxazolidine-2-thione (19a).
of 19a was corroborated by X-ray crystallography (Figure 2).
Literature reports the preparation of 2-thioxo-oxazolidines by
cycloaddition of R-metalated alkyl isothiocyanates to carbonyl
compounds.11
Compound Characterization and Tautomeric Structures.
The tautomeric structure of a heterocyclic [or indeed any]
Reactions of ketones with 9a (R3) Bn) afforded the isomeric
oxazolinethiones 19 instead of the expected product (Scheme
9). Structures 19a-c were verified by NMR and the structure
(11) Hoppe, D.; Follmann, R. Chem. Ber. 1976, 109, 3047.
6744 J. Org. Chem., Vol. 72, No. 18, 2007

C-Aminoimidoylation and C-Thiocarbamoylation
1
FIGURE 3. Relevant H and 13C chemical shifts in compounds 10b-d.
1
FIGURE 4. Relevant H and 13C chemical shifts in compounds 12a-c.
SCHEME 8. Preparation from Ketones 17a-d of the
C-Aminoimidoylation Products 16a-d and
C-Thiocarbamoylation Products 18a-d
SCHEME 9. Formation of Thioxo-oxazolidines 19
compound can profoundly influence its physical properties [e.g.,
boiling point, solubility] and chemical properties [e.g., acid/
base, electron distribution, reactivity]. It was therefore of interest
to investigate the tautomeric structures of the parent compounds,
and in particular, to know whether they exist in the enol or
keto forms. On examination in chloroform-d at 25 °C, no keto
tautomers were detected by NMR for any of the compounds
10b-d. Coupling of one of the NH protons with the alpha
protons on R3 allowed assignment of the NH protons, and
supported our conclusion that 10b-d all are present in solution
as the keto-enamine tautomers, as depicted in Figure 3.
in both compounds. Thus, the tautomeric structure of 13 differs
from the compounds of structure 10: although sulfone and ester
groups are both electron-withdrawing, the electron-withdrawing
ability of sulfones is mainly exerted via induction, whereas esters
have considerable conjugative ability, which may explain the
difference in tautomeric character.
Compound 16a was present in chloroform-d solution as a
mixture of two compounds in a 7:1 ratio both with the same
hydrocarbon skeleton, as revealed by the gHMBC spectra.
Exchange peaks in the NOESY spectrum between protons such
as 5.43 with 5.35, 7.88 with 7.67, 7.03 with 6.97, 7.13 with
7.26, 2.89 with 3.00, and 3.49 with 3.60 indicated that these
species were interconverting. The chemical shift of the carbonyl
carbon in 16a is closer to that expected for an aromatic ketone
than for an enol. Furthermore, the chemical shift for the
imidamide carbon is closer to that in compounds 10 than that
seen in compound 13. These chemical shifts suggest that both
isomers of 16a are keto-enamine forms. Of the exchange cross-
peaks of 11.77, the largest is 4.76, indicating that the two
isomers differ in the amine hydrogen facing the carbonyl group
In the chloroform-d solutions of 12a-c at 25 °C, the only
tautomers detected were the thiocarbonyl forms shown (Figure
4). The alpha protons in R3 couple with the NH proton in all
of these compounds. The difference in tautomerism between
compounds 10 and compounds 12b,c can be explained by the
delocalization of the electrons from the electron-donor R4N into
the electron withdrawing ester groups.
Compounds 13 and 15 exist in chloroform-d solutions at
25 °C solely as the imino and thiocarbonyl forms, respectively
(Figure 5). The alpha protons in R3 couple with the NH proton
J. Org. Chem, Vol. 72, No. 18, 2007 6745

Katritzky et al.
1
FIGURE 5. Relevant H and 13C chemical shifts in compounds 13
and 15.
FIGURE 8. 1H and 13C chemical shifts and the tautomers/rotamers
for compound 18a.
FIGURE 6. 1H and 13C chemical shifts for the Major (M) and minor
(m) isomers of compound 16a.
FIGURE 9. 1H and 13C chemical shifts for the tautomers of compound
18c in acetone-d6.
hindrance in the enol of 16c, where the two methyls, R1 and R2
have to be syn-periplanar.
1
FIGURE 7. Relevant H and 13C chemical shifts in compound 16c.
Compound 18a in chloroform-d solution at 25 °C displays
an equilibrium between three species, in a ratio 44:5:1. The
interconversion of these species was demonstrated by exchange
peaks in the NOESY spectrum. The major compound is the
keto tautomer, whereas the other two are enol tautomers, as
demonstrated by the chemical shift of the carbon bearing the
oxygen atom. The significant deshielding of the NH proton in
the keto form as compared to the enol forms suggests a hydrogen
bond in the keto form, as in Figure 8. The spectra were repeated
in acetone-d6, a hydrogen bond acceptor that would compete
with the carbonyl group of 18a for hydrogen bonding. The
chemical shift of the NH proton in the enol moved downfield
by 2 ppm, while for the keto form the change was only 0.07
ppm, demonstrating intramolecular hydrogen bonding in the
ketone. The two enol species have to be the Z and E isomers
resulting from rotation about the C-N bond in the thioamide.
Thioamides are known to prefer the Z configuration and this is
the configuration in the intramolecular hydrogen-bonded keto
species. The similarity of the proton chemical shifts at the NCH2
in the ketone (3.71 ppm) and in the major enol form (3.67 ppm)
indicates that the latter is also in the Z configuration. The E
configuration is present in the enol tautomer and not in the
ketone because it strengthens the resonance-assisted hydrogen
bonding (RAHB) in the enol. This is demonstrated by the higher
chemical shift value of the proton involved in the RAHB in the
minor E enol form (14.86 ppm) as compared to the Z enol (14.54
ppm).
and involved in the hydrogen bond. In the major isomer of 16a,
NOE’s between 5.43 and 3.49, 2.89, and between 4.76 and 7.03
demonstrate that in this isomer the aniline NH is involved in
the hydrogen bond and that the alkyl group on the other nitrogen
is anti to the aniline nitrogen, as depicted in Figure 6. The
chemical shifts of the protons involved in the hydrogen bond
agree with this assignment: in compounds 10c and 10d, the
aniline hydrogen is more deshielded than the alkylamino one.
For the minor isomer, the NOE’s offered no information on
the syn/anti geometry of the aniline group, because they were
mainly transferred NOE’s. It is reasonable however to assume
the same geometry as in the major isomer. Exchange peaks
between 5.43, 5.35, and all the four NH protons indicate that
the keto tautomer is present in the equilibrium, although it was
not detected in the proton spectra. Another transient species
displays a signal at 13.26, in exchange with all of the
exchangeable protons in both isomers.
Compounds 16b and 16d displayed equilibria similar to that
for 16a. The species with the aniline NH involved in hydrogen
bonding is ca. 7 times more abundant than the other isomer.
Compound 16c is solely in the imidamide form in chloroform-d
solution at 25 °C, as indicated by the coupling between the
protons at 3.70 and 1.13 (Figure 7). The difference in tautom-
erism between 16c and 16a,b,d, may be explained by the steric
6746 J. Org. Chem., Vol. 72, No. 18, 2007

C-Aminoimidoylation and C-Thiocarbamoylation
20.8, 20.4, 13.9. Anal. Calcd for C25H28N2O2S: C, 71.40; H, 6.71;
N, 6.66. Found: C, 71.55; H, 6.96; N, 6.52.
Compound 18c in chloroform-d solution at 25 °C occurs
solely as the keto tautomer. The chemical shift of the NH proton
is 9.22 ppm, indicating an intramolecular hydrogen bond. In
acetone-d6 solution, both tautomers are present, and the keto:
enol ratio is 1:0.44 (Figure 9). For compound 18a also, the
proportion of the enol was larger in acetone (keto:enol ) 45:
55) than in chloroform (keto:enol ) 88:12). As with the case
of 18a, no E rotamer of the enol form was detected in acetone
solution.
Compounds 18b and 18d in chloroform-d solution at 25 °C
display the keto tautomer only. The enol tautomer is higher in
energy when R1 is not H, due to steric repulsion between R1
and R2, which have to be syn-periplanar in the enol.
N-Cyclohexyl-2-phenyl-2-(phenylsulfonyl)ethanethioamide (15).
Recrystallized from EtOAc-hexanes to give white microcrystals
1
(40%); mp 148.9-149.7 °C; H NMR (CDCl3) δ 9.08 (br s, 1H),
7.76-7.73 (m, 2H), 7.67-7.62 (m, 1H), 7.52-7.47 (m, 2H), 7.41-
7.30 (m, 5H), 5.57 (s, 1H), 4.38-4.35 (m, 1H), 2.06 (br s, 2H),
1.78-1.65 (m, 2H), 1.58 (br s, 3H), 1.50-1.34 (m, 3H); 13C NMR
(CDCl3) δ 190.0, 137.2, 134.5, 129.7, 129.3, 129.2, 129.0, 128.7,
81.7, 54.8, 31.1, 30.8, 25.4, 24.4. Anal. Calcd for C20H23NO2S2:
C, 64.31; H, 6.21; N, 3.75. Found: C, 63.96; H, 6.25; N, 3.62.
General Procedure for the Preparation of Compounds 16a-d
and 18a-d. To a solution of the desired ketone (2.0 mmol) in
THF (20 mL) was added 2.5 mmol of potassium t-butoxide,
followed by 1.0 mmol of the appropriate reagent 8 or 9 (Scheme
8). The mixture was stirred at room temperature until full conversion
of starting materials (0.5-4.0 h). The crude was then evaporated
under reduced pressure, washed with water (3 × 30 mL), and finally
extracted with diethyl ether (3 × 30 mL). Evaporation of the organic
fraction followed by flash column chromatography on silica gel
afforded 16a-d or 18a-d in moderate yields.
Conclusion
Successful C-aminoimidoylation and C-thiocarbamoylation
of esters, sulfones, and ketones were achieved in 40% average
yield under mild reaction conditions. This method provides easy
access to interesting classes of compounds for further transfor-
mations.
3-Oxo-N-phenethyl-N′,3-diphenylpropanimidamide (Mixture
of Tautomers) (16a). Recrystallized from EtOAc-hexanes to give
white microcrystals (32%); mp 156.2-157.7 °C. In CDCl3 solution
16a exists as 16a (M), 87% and 16a (m), 13%. 1H NMR (CDCl3)
δ 13.06 (s, 0.87H, M) 11.77 (s, 0.13H, m), 7.88 (d, J ) 7.1 Hz,
1.74H, M), 7.67 (d, J ) 7.1 Hz, 0.26H, m), 7.40-7.41 (m, 2.61H,
M), 7.34-7.24 (m, 6.00H, M + m), 7.25 (t, J ) 7.6 Hz, 0.87H,
M), 7.13 (d, J ) 7.6 Hz, 1.74H, M), 7.03 (d, J ) 6.6 Hz, 1.74H,
M), 6.97 (d, J ) 6.6 Hz, 0.26H, m), 5.78 (s, 0.13H, m), 5.43 (s,
0.87H, M), 5.35 (s, 0.13H, m), 4.76 (br s, 0.87H, M), 3.60 (q, J )
5.6 Hz, 0.26H, m), 3.49 (q, J ) 5.6 Hz, 1.74H, M), 3.00 (t, J )
6.9 Hz, 0.26H, m), 2.89 (t, J ) 6.9 Hz, 1.74H, M); 13C NMR
(CDCl3) δ 185.6, 185.3, 161.1, 159.6, 141.8, 139.4, 138.1, 136.5,
136.5, 130.2, 130.0, 129.3, 129.1, 129.0, 127.2, 126.9, 126.8, 126.3,
125.7, 125.4, 124.4, 76.0, 43.7, 43.6, 37.0, 35.3. Anal. Calcd for
C23H24N2O2: C, 76.64; H, 6.71; N, 7.77. Found: C, 76.61; H, 6.32;
N, 7.64.
Experimental Section
General Procedure for the Preparation of Compounds 10a-
d, 12a-c, 13, and 15. To a solution of the desired ester or sulfone
(2.0 mmol) in THF (15 mL), was added potassium t-butoxide (2.5
mmol). After stirring the mixture for 30 min, 1.0 mmol of the
desired reagent 8 or 9 as added to the reaction mixture. The progress
of the reaction was monitored by TLC. Upon completion, water
(20 mL) was added to quench the reaction followed by extraction
with dichloromethane (3 × 30 mL). The combined extracts were
dried over magnesium sulfate and the solvent removed under
vacuum. The crude mixture was purified by gradient column
chromatography over silica gel (EtOAc-hexanes) to give the desired
products in moderate yields.
Methyl (Z)-3-(Benzylamino)-3-(4-toluidino)-2-propenoate (10a).
Colorless oil (63%); 1H NMR (CDCl3) δ 7.33-7.18 (m, 5H), 7.07
(d, J ) 8.2 Hz, 2H), 6.79 (d, J ) 8.2 Hz, 2H), 4.28 (br s, 2H), 3.85
(s, 3H), 2.27 (s, 3H); 13C NMR (CDCl3) δ 158.6, 153.4, 145.7,
139.4, 131.7, 130.1, 128.5, 127.1, 126.9, 122.6, 67.6, 53.6, 45.4,
20.7. Anal. Calcd for C18H20N2O2: C, 72.95; H, 6.80; N, 9.45.
Found: C, 73.18; H, 6.46; N, 9.84.
N-Butyl-3-oxo-3-phenylpropanethioamide (Mixture of Tau-
tomers) (18a). Brown oil (50%). In CDCl3 solution 18a exists as
a major isomer, 18a (M), 88% and two minor isomers, 18a (m),
1
10% and 18a (m′), 2%. H NMR (CDCl3) δ 14.86 (br s, 0.02H,
m′), 14.54 (br s, 0.10H, m), 9.28 (br s, 0.88H, M), 8.04 (d, J ) 7.3
Hz, 1.76H, M), 7.94 (d, J ) 7.3 Hz, 0.04H, m), 7.76 (d, J ) 7.3
Hz, 0.20H, m), 7.63 (d, J ) 7.5 Hz, 0.88H, M), 7.51 (t, J ) 7.5
Hz, 1.76H, M), 7.46-7.38 (m, 0.35H, m + m′), 6.07 (s, 0.02H,
m′), 5.94 (s, 0.10H, m), 4.50 (s, 1.76H, M), 3.73-3.65 (m, 1.96H,
M + m), 1.73-1.63 (m, 1.96H, M + m), 1.48-1.40 (m, 1.96H, M
+ m), 0.97 (t, J ) 7.3 Hz, 2.94H, M + m); 13C NMR (CDCl3) δ
197.2, 194.2, 191.7, 167.0, 136.1, 135.1, 134.5, 130.8, 129.2, 128.9,
128.7, 125.8, 98.0, 52.7, 46.5, 44.3, 30.4, 30.1, 20.5, 20.4, 14.0.
Anal. Calcd for C13H17NOS: C, 66.35; H, 7.28; N, 5.95. Found:
C, 66.62; H, 7.41; N, 5.52.
Methyl 3-(Isopropylamino)-2-phenyl-3-thioxopropanoate (12a).
Recrystallized from EtOAc-hexanes to give white microcrystals
1
(20%); mp 105.6-107.4 °C; H NMR (CDCl3) δ 8.98 (br s, 1H),
7.38-7.40 (m, 5H), 5.09 (s, 1H), 4.62-4.55 (m, 1H), 3.71 (s, 3H),
1.27 (d, J ) 6.6 Hz, 3H), 1.21 (d, J ) 6.6 Hz, 3H); 13C NMR δ
(CDCl3) 194.8, 172.3, 135.2, 129.2, 128.5, 127.4, 64.7, 52.9, 47.6,
21.0. Anal. Calcd for C13H17NO2S: C, 62.12; H, 6.82; N, 5.57.
Found: C, 61.89; H, 6.65; N, 5.48.
General Procedure for the Preparation of Compounds 19a-
c. To a solution of the desired ketone (2.0 mmol) in THF (20 mL)
was added potassium t-butoxide (2.5 mmol). After stirring the
mixture for 30 min, 1.0 mmol of N-benzyl-1H-benzo[d][1,2,3]-
triazole-1-carbothioamide 9 was added to the reaction mixture. The
mixture was stirred at room temperature for 4.0 h. The reaction
was then stopped and the solvent evaporated under vacuum. The
crude product was washed with water and then extracted with
diethyl ether. Evaporation of the organic fraction followed by flash
column chromatography on basic alumina afforded 19a-c in
moderate yields.
Crystal data for 12a: C13H17NO2S, MW 251.34, orthorhombic,
space group P212121, a ) 8.1386(3), b ) 10.7325(4), c ) 15.5997-
(6) Å, V ) 1362.60(9) Å3, F(000) ) 536, Z ) 4, T ) -180 °C, µ
(Mo KR) ) 0.228 mm-1, Dcalcd ) 1.225 g.cm-3, 2θmax 61° (CCD
area detector, Mo KR radiation), GOF ) 1.08, wR(F2) ) 0.067
(all 4167 data), R ) 0.024 (4105 data with I > 2σI).
N-Butyl-N′-(4-methylphenyl)-2-phenyl-2-(phenylsulfonyl)-
ethanimidamide (13). Recrystallized from EtOAc-hexanes to give
white microcrystals (30%); mp 117.6-119.2 °C; 1H NMR δ
(CDCl3) 7.66 (t, J ) 8.4 Hz, 3H), 7.51 (t, J ) 7.1 Hz, 2H), 7.53-
7.35 (m, 1H), 7.31-7.30 (m, 7H), 6.92 (d, J ) 7.8 Hz, 2H), 6.11
(s, 1H), 6.11 (d, J ) 8.1 Hz, 2H), 5.20 (s, 1H), 3.39-3.36 (m,
2H), 1.73-1.67 (m, 2H), 1.52-1.45 (m, 2H), 1.00 (t, J ) 7.4 Hz,
3H); 13C NMR (CDCl3) δ 148.5, 146.5, 137.4, 134.2, 131.8, 130.8,
130.1, 129.4, 129.1, 128.9, 128.8, 128.7, 121.8, 68.4, 41.4, 31.0,
5-Methyl-4-phenyl-5-(2-thienyl)-1,3-oxazolidine-2-thione (19a).
Recrystallized from EtOAc-hexanes to give white microcrystals
1
(51%); mp 157.3-158.8 °C; H NMR (CDCl3) δ 7.39-7.37 (m,
1H), 7.27-7.26 (m, 2H), 7.15-7.14 (m, 1H), 7.06-7.03 (m, 2H),
5.23 (s, 1H), 1.43 (s, 3H); 13C NMR (CDCl3) δ 188.7, 145.9, 134.3,
J. Org. Chem, Vol. 72, No. 18, 2007 6747

Katritzky et al.
129.4, 129.1, 127.2, 126.8, 126.1, 124.7, 91.7, 70.8, 23.8. Anal.
Calcd. for C14H13NOS2: C, 61.06; H, 4.76; N, 5.09. Found: C,
61.40; H, 4.78; N, 5.09.
Acknowledgment. We thank Dr. Dennis Hall for his help
and useful suggestions.
Crystal Data for 19a. C14H13NOS2, MW 275.37, monoclinic,
space group P2/n, a ) 14.3023(4), b ) 5.7750(2), c ) 17.5354(5)
Å, â ) 112.690(1)°, V ) 1336.26(7) Å3, F(000) ) 576, Z ) 4, T
Supporting Information Available: Characterization data for
compounds (10b-d), (12b-c), (16b-d), (18b-d), and (19b-c)
and full details of the X-ray structure determinations as CIF
files. This material is available free of charge via the Internet at
http://pubs.acs.org.
) -180 °C, µ (Mo KR) ) 0.385 mm-1, Dcalcd ) 1.369 g.cm-3
,
2θmax 55° (CCD area detector, Mo KR radiation), GOF ) 1.05,
wR(F2) ) 0.076 (all 3065 data), R ) 0.028 (2981 data with I >
2σI).
JO070545C
6748 J. Org. Chem., Vol. 72, No. 18, 2007