Synthesis of 2,3-dihydro-1,3-thiazin-4(1 H)-ones and their remarkably facile recyclization to 2,3-dihydropyrimidin-4(1 H)-ones

Article abstract of DOI:10.1002/hc.20129

Functionalized 2,3-dihydro-1,3-thiazin-4(1 H)-one derivatives have been synthesized by cyclocondensation of 3-alkyl(aryl)amino-2-cyano-3- mercaptoacrylamides with aldehydes and ketones under acidic catalysis. 6-Alkyl(aryl)amino-5-cyano-2,3-dihydro-1,3-thiazin-4(1 H)-ones, when treated with a dilute solution of potassium hydroxide, are converted into the potassium salts of isomeric compounds, 1-alkyl-(aryl)-5-cyano-6-mercapto-2,3- dihydropyrimidin-4(1 H)-ones. Alkylation of the latter with dimethyl sulfate in situ furnishes 1-alkyl(aryl)-6-alkylthio-5-cyano-2,3-dihydropyrimidin-4(1 H)-ones, whereas boiling them in ethanol with an excess of hydrochloric acid leads to starting 2,3-dihydro-1,3-thiazin-4(1 H)-ones.

Full text of DOI:10.1002/hc.20129

Heteroatom Chemistry
Volume 16, Number 5, 2005
Synthesis of 2,3-Dihydro-1,3-Thiazin-4(1H )-
ones and Their Remarkably Facile Recyclization
to 2,3-Dihydropyrimidin-4(1H )-ones
Mykhaylo V. Vovk, Volodymyr A. Sukach, Alexander N. Chernega,
Volodymyr V. Pyrozhenko, Andriy V. Bol’but,
and Alexander M. Pinchuk
Institute of Organic Chemistry, National Academy of Science of Ukraine, Kyiv, Ukraine
Received 14 October 2004; revised 16 February 2005
pyrazoles [5,6], thiazoles [7], isothiazoles [8,9], and
ABSTRACT: Functionalized 2,3-dihydro-1,3-thiazin-
thiophenes [10,11]. Based on the condensation of
4(1H)-one derivatives have been synthesized by cyclo-
3-alkylthio-2-cyano-3-mercaptoacrylamide with car-
condensation of 3-alkyl(aryl)amino-2-cyano-3-mer-
bonyl compounds (aldehydes and ketones) under
captoacrylamides with aldehydes and ketones under
acidic conditions, Yokoyama found a convenient
acidic catalysis. 6-Alkyl(aryl)amino-5-cyano-2,3-dihy-
synthetic route to 2,5,6-substituted 2,3-dihydro-1,3-
dro-1,3-thiazin-4(1H)-ones, when treated with a dilute
thiazin-4(1H)-ones [12]. However, the reaction
solution of potassium hydroxide, are converted into
of the related compound, 2-cyano-3-mercapto-3-
the potassium salts of isomeric compounds, 1-alkyl-
phenylaminoacrylamide, with acetaldehyde, ben-
(aryl)-5-cyano-6-mercapto-2,3-dihydropyrimidin-
zaldehyde, and acetone provided a product for
4(1H)-ones. Alkylation of the latter with dimethyl
which unequivocal structural determination failed
sulfate in situ furnishes 1-alkyl(aryl)-6-alkylthio-5-
(Goerdeler and Keuser [13]). Though the compounds
cyano-2,3-dihydropyrimidin-4(1H)-ones, whereas
obtained were presumably 2,3-dihydropyrimidin-
boiling them in ethanol with an excess of hydrochloric
4(1H)-ones, the alternative 2,3-dihydro-1,3-thia-
acid leads to starting 2,3-dihydro-1,3-thiazin-4(1H)-
zin-4(1H)-one structure could not be ruled out
ꢀ
C
ones.
2005 Wiley Periodicals, Inc. Heteroatom Chem
completely.
In the course of our research on new efficient
16:426–436, 2005; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20129
accesses to 2,3-dihydro-1,3-azin-4(1H)-ones [14,15],
we have reproduced and substantially extended
Goerdeler’s experiments aiming at accurate struc-
tural determination of the cyclocondensation prod-
ucts and study of their chemical behavior.
INTRODUCTION
3-Mercaptoacrylamide derivatives noted for several
reaction centers in their structure are used in syn-
theses of functionalized heterocyclic systems includ-
ing pyrimidines [1,2], 1,3-thiazines [3], pyridines [4],
RESULTS AND DISCUSSION
We have established that 3-alkyl(aryl)amino-2-
cyano-3-mercaptoacrylamides 1a–d react with a
variety of carbonyl compounds 2a–l on boiling
in ethanol for 2 h in the presence of catalytic
amounts of p-toluenesulfonic acid (p-TSA) to give
Dedicated to Professor Dr. Alfred Schmidpeter on the occasion
of his 75th birthday.
Correspondence to: M. V. Vovk; e-mail: mvovk@i.com.ua.
c
ꢀ
2005 Wiley Periodicals, Inc.
426

Synthesis of 2,3-Dihydro-1,3-Thiazin-4(1H )-ones and Their Remarkably Facile Recyclization to 2,3-Dihydropyrimidin-4(1H )-ones 427
1: R1 = Me (a), Et (b), Bn (c), Ph (d)
2: R2 = H, R3 = Me (a), 6ꢁ,6ꢁ-dimethylbicyclo[3.1.1]hept-2ꢁ-en-2ꢁ-yl (b), Ph
(c), 4-MeOC6H4 (d), 4-NO2C6H4 (e), (R)-2ꢁ,3ꢁ-dihydro-1,4-benzodioxin-6ꢁ-yl
(f); R2 = R3 = Me (g); R2 = Me, R3 = i-Pr (h); R2,R3 = cyclopentyliden (k);
R2,R3 = adamantyliden (l)
SCHEME 1
6-alkyl(aryl)amino-5-cyano-2,3-dihydro-1,3-thiazin-
under more severe conditions (on boiling the
reagents in i-PrOH or heating them without a
solvent in the presence of p-TSA). Nor were the
desired products furnished by an attempted reaction
with carbonyl compounds activated by electron-
acceptor substituents (ethylpyruvate, isatine, and
phenylglyoxal).
4(1H)-ones 3a–o in excellent yields (Scheme 1,
Table 1). High yields of products 3 also result from
boiling the reagents not long in glacial acetic acid.
These conditions, however, are not appropriate for
the reaction of sterically hindered aliphatic ketones
such as pinacolone and menthone. Acetophenone,
cycloheptanone, and 2,5-dimethylheptan-4-one
proved not to enter the cyclocondensation even
The structure of compounds 3 is reliably sup-
1
ported by elemental analysis, IR, H NMR, and 13C
TABLE 1 Elemental Analytical Data of Compounds 3
Calcd (Found)
Compound
Number
R1
Me
Et
R 2
H
R3
Formula
C
H
N
S
3a
Ph
Ph
C12H11N3OS
245.30
13H13N3OS
259.33
C9H13N3OS
211.29
C19H17N3OS
351.43
12H11N3OS
245.30
C20H21N3OS
351.47
C17H13N3OS
307.38
C17H12N4O3S
352.37
C19H15N3O3S
365.41
13H13N3OS
259.33
15H17N3OS
287.39
C15H15N3OS
285.37
58.76
(58.99)
60.21
(60.48)
51.16
(50.89)
64.94
(64.70)
58.76
(58.50)
68.35
(68.41)
66.43
(66.20)
57.95
(58.27)
62.45
(62.59)
60.21
(60.07)
62.69
(62.94)
63.13
(62.83)
68.35
4.52
(4.62)
5.05
(4.88)
6.20
17.13
(16.91)
16.20
(16.03)
19.89
13.07
(13.20)
12.36
(12.14)
15.18
(15.40)
9.12
(9.37)
13.07
(12.81)
6.12
(5.94)
10.43
(10.70)
9.10
(9.33)
8.77
(9.00)
12.36
(12.11)
11.16
(11.38)
11.24
(11.51)
9.12
3b
H
C
3c
Et
Me
H
Me
(6.27)
4.88
(5.04)
4.52
(20.08)
11.96
(12.23)
17.13
3d
Bn
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-MeOC6H4
Me
3e
H
C
(4.40)
6.02
(6.18)
4.26
(12.27)
11.96
(12.27)
13.67
3f
H
6ꢁ,6ꢁ-Dimethylbicyclo-
[3.1.1]hept-2-enꢁ-2ꢁ-yl
Ph
3g
H
(4.22)
3.43
(3.57)
4.14
(13.38)
15.90
(16.18)
11.50
3h
H
4-NO2C6H4
3k
H
2ꢁ,3ꢁ-Dihydro-1,4-
benzodioxin-6ꢁ-yl
Me
(3.96)
5.05
(4.89)
5.96
(11.22)
16.20
(16.33)
14.62
3l
Me
Me
C
3m
3n
i -Pr
(CH2)4
C
(6.10)
5.30
(5.42)
6.02
(14.41)
14.72
(14.95)
11.96
3o
Adamantyliden
C
20H21N3OS
351.47
(68.62)
(5.81)
(12.04)
(9.46)

428 Vovk et al.
NMR spectroscopy as well as by X-ray diffraction.
The IR spectra display the absorption bands at 3230
(NH), 2220 (CN), and 1660 cm−1 (C O). The 1H NMR
spectra are characterized by the signals from the ex-
ocyclic NH protons at 9.94–10.15 (R1 = Ph) or 8.18–
8.85 ppm (R1 = Alk). A resonance of the endocyclic
NH proton is found in the region 7.89–8.45 ppm and
easily identified at R2 = H by the spin–spin coupling
with the proton at position 2 of the thiazine ring (the
spin–spin coupling constant J amounts to 1–4 Hz).
The thiazine moiety gives rise to a characteristic dou-
blet at 4.95–6.06 ppm with the same value of J or to
a doublet of quartets (R3 = Me).
method. The perspective view of molecule 3m and se-
lected geometrical parameters are given in Fig. 1. The
S(1)N(1)C(1–4) six-membered heterocycle is essen-
tially nonplanar (deviations from the least-squares
˚
plane exceed 0.38 A) and has a half-chair conforma-
tion. The C(10–15) benzene ring is twisted out of this
plane by 66.4◦. In the solid state, the molecules of 3m
are joined in the chains by the N(2) H· · ·O(3) hydro-
˚
˚
gen bonds (N· · ·2.860(4) A, O· · ·H 2.09(4) A, NHO
148(3)◦) (see Fig. 2).
Methylation of 2,3-dihydro-1,3-thiazin-4(1H)-
ones 3 with dimethyl sulfate under basic conditions
led to an unexpected result. The reaction proved
to involve the sulfur atom thus affording 1-alkyl-
(aryl)-6-methylthio-5-cyano-2,3-dihydropyrimidin-
4(1H)-ones 4a–c,e–k,n in high yields. Alkylation
with benzyl chloride in ethanol in the presence
of triethylamine provides the analogous products,
viz. 1-alkyl(aryl)-6-benzylthio-5-cyano-2,3-dihydro-
pyrimidin-4(1H)-ones 4d,l,m (Scheme 2, Table 2).
Treating compounds 3b and 3h with a dilute KOH
solution, we isolated, in the individual state, the salts
of the corresponding thiols 6a and 6b forming as
intermediates in the alkylation of thiazines 3. They
If R2 and R3 are different substituents, a chiral
center appears in the 2,3-dihydro-1,3-thiazin-4(1H)-
one structure of compounds 3 and therefore the sig-
nal from the CH2 group in the substituent R1 is split
into the ABM (R1 = Bn) or ABMX3 system (R1 = Et).
Compounds 3 are also characterized by the 13C NMR
signals from the carbon atoms of the thioaminal frag-
ment, with their chemical shifts ranging from 51.90
to 71.82 ppm.
Peculiarities of molecular and crystal struc-
ture of 3m have been studied by X-ray diffraction
◦
˚
FIGURE 1 Perspective view and labeling scheme for the molecule 3m. Selected bond lengths (A) and angles ( ): S(1) C(1)
1.863(5), S(1) C(4) 1.753(4), N(1) C(1) 1.446(6), N(1) C(2) 1.339(6), N(2) C(4) 1.336(5), C(2) C(3) 1.453(6), C(3) C(4)
1.383(5), C(1)S(1)C(4) 97.5(2), C(1)N(1)C(2) 125.4(4), S(1)C(1)N(1) 107.5(3), N(1)C(2)C(3) 117.2(4), C(2)C(3)C(4) 125.9(4),
C(4)C(3)C(9) 119.2(4).

Synthesis of 2,3-Dihydro-1,3-Thiazin-4(1H )-ones and Their Remarkably Facile Recyclization to 2,3-Dihydropyrimidin-4(1H )-ones 429
FIGURE 2 Crystal packing of the compound 3m.
crystallize from water and are stable to aqueous
acetic acid; at the same time, they are quantitatively
converted into starting thiazines 3, if heated in
ethanol with an excess of hydrochloric acid.
4(1H)-ones 4f so that the product ratio was 65:35,
according to the 1H NMR data.
The interconversions described can be ac-
counted for by the following mechanism (Scheme 4).
A base causes proton abstraction from the nitrogen
atom in position 3 and the thiazine ring opening.
Then the resulting intermediate A cyclizes to the sta-
ble thiolate B and alkylation of the latter in situ yields
products 4. In the case of derivative 3o, the pyrimi-
dine ring closure cannot occur in the intermediate A
(presumably due to steric hindrances) and the sub-
sequent methylation leads to the hydrolysis product
5b. The mechanism suggested is consistent with the
fact that compounds 5 provide no cyclic products
in the reaction with carbonyl compounds 2 both in
acidic and basic media. The reverse recyclization of
unstable 2,3-dihydropyrimidin-4(1H)-ones C to the
corresponding 2,3-dihydro-1,3-thiazin-4(1H)-ones
3 proceeds via N-alkylidene derivatives D which are
also likely to be intermediately form in the reaction
Formation of the pyrimidine structure was
corroborated by chemical conversions. Compound
4l was hydrolyzed in the mixture of dioxane and
concentrated hydrochloric acid to produce mainly
3-benzylthio-2-cyano-3-phenylaminoacrylamide
5a readily obtainable via reverse synthesis, i.e.,
benzylation of 2-cyano-3-mercapto-3-phenylamino-
acrylamide 1d (Scheme 3). The two samples of
compound 5a thus prepared were proved to be
identical by elemental analysis as well as by IR and
1H NMR spectroscopy. Methylation of the derivative
3o under similar conditions resulted in the mixture
of 2-cyano-3-methylthio-3-phenylaminoacrylamide
5b and adamantanone. As expected, methylation of
the obtained mixture of diastereomers 3f provided
the mixture of diastereomeric 2,3-dihydropyrimidin-
SCHEME 2

430 Vovk et al.
TABLE 2 Elemental Analytical Data of Compounds 4 and 6
Calcd (Found)
Compound
Number
R1
Me
Et
R 2
H
R3
R 4
Formula
C
H
N
S
4a
Ph
Ph
Me
C13H13N3OS
259.33
14H15N3OS
273.36
10H15N3OS
225.31
C26H23N3O2S
441.56
C13H13N3OS
259.33
C21H23N3OS
365.50
18H15N3OS
321.40
C18H14N4O3S
366.40
C20H17N3O3S
379.44
20H19N3OS
349.46
22H23N3OS
377.51
C16H17N3OS
299.40
60.21
5.05
16.20
12.36
(60.48) (4.93) (15.87) (12.51)
61.51 5.53 15.37 11.73
(61.79) (5.44) (15.21) (12.03)
53.31 6.71 18.65 14.23
(53.60) (6.79) (18.65) (14.00)
4b
H
Me
C
4c
Et
Me
H
Me
Me
C
4d
Bn
Ph
Ph
Ph
Ph
Ph
4-MeOC6H4
Me
Bn
70.72
(70.46) (5.37)
60.21 5.05
5.25
9.52
(9.27)
16.20
7.26
(7.39)
12.36
4e
H
Me
(60.44) (5.21) (16.04) (12.62)
4f
H
6ꢁ,6ꢁ-Dimethylbicyclo-
[3.1.1]hept-2-en-2-yl
Ph
Me
69.01
(68.67) (6.42) (11.77)
67.27 4.70 13.07
6.34
11.50
8.77
(8.48)
9.98
4g
H
Me
C
(67.48) (4.80) (12.84) (10.36)
4h
H
4-NO2C6H4
Me
59.01
(59.21) (3.82) (15.54)
63.31 4.52 11.07
(63.05) (4.39) (11.41)
68.74 5.48 12.02
(69.05) (5.57) (12.31)
70.00 6.14 11.13
(70.08) (6.26) (11.31)
64.19 5.72 14.03
3.85
15.29
8.75
(8.43)
8.45
(8.18)
9.18
(9.47)
8.49
(8.14)
10.71
4k
H
2ꢁ,3ꢁ-Dihydro-1,4-
benzodioxin-6ꢁ-yl
Me
Me
4l
Ph Me
Ph Me
Ph
Bn
C
4m
4n
i -Pr
(CH2)4
Ph
Bn
Me
C
(64.47) (5.65) (14.20) (10.96)
52.50 4.07 14.13 10.78
(52.77) (3.90) (14.30) (11.05)
6a
Et
H
H
Potassium salt
C
13H12KN3OS
297.43
6b
Ph
4-NO2C6H4
Potassium salt C17H11KN4O3S
390.47
52.29
2.84
14.35
8.21
(8.04)
(52.01) (2.97) (14.15)
SCHEME 3

Synthesis of 2,3-Dihydro-1,3-Thiazin-4(1H )-ones and Their Remarkably Facile Recyclization to 2,3-Dihydropyrimidin-4(1H )-ones 431
SCHEME 4
between compounds 1 and 2 leading to thiazines 3.
The possibility of interconversions between partially
hydrogenated 1,3-thiazines and pyrimidines was
previously demonstrated with the examples of 2-
arylimino-2,3,5,6-tetrahydro-1,3-thiazin-4(1H)-ones
[16], 4,4,6-trimethyl-1,4-dihydropyrimidin-2(3H)-
ones [17], and 2-thioxo-2,3,5,6-tetrahydro-1,3-
thiazin-4(1H)-ones [18].
registered in the mixture (CD3)2SO:CCl4 (2:1) on a
Varian-Gemini spectrometer (300 MHz) using TMS
as internal standard. 13C NMR spectra were regis-
tered in (CD3)2SO on a Varian-Gemini spectrometer
(75.5 MHz) using TMS as internal standard.
X-ray Structure Determination of 3m
Compounds 4 and 6 were characterized spectro-
1
scopically by the IR, H NMR, and 13C NMR meth-
Crystal data: C15H17N3OS, M = 287.4, orthorom-
˚
ods. A distinction between the thiazine and pyrim-
idine structural types is clearly manifested in the
13C NMR spectra: the resonances of the aminal car-
bon atoms in compounds 4 (δ 68.99–82.84 ppm) are
shifted downfield from those of the thioaminal car-
bon atoms in compounds 3. Importantly, the differ-
ence in chemical shift between two diastereotopic
protons in the methylene group of the substituent
R1is much larger for S-methylated pyrimidine 4b
and the corresponding salt 6a (0.27 and 1.54 ppm,
respectively) than for thiazine 3b (0.05 ppm, multi-
plet). This effect points to the spatial approach of
the methylene group and the chiral center of the
molecule in going from the thiazine to pyrimidine
structure.
bic, a = 8.075(5), b= 15.190(8), c= 11.971(8) A,
3
−1
˚
V = 1468(2) A , Z = 4, d = 1.30 g cm , space group
Pna21 (N 33), µ = 2.20 cm−1, F(000) = 608.0, crys-
tal size ca. 0.19 × 0.28 × 0.49 mm. All crystallo-
graphic measurements were performed at 20◦C on
a CAD-4-Enraf-Nonius diffractometer operating in
the ω-2θ scan mode (the ratio of the scanning rates
ω/2θ = 1.2). The intensity data were collected within
the range 2 < θ < 25◦ (0 < h< 9, 0 < k< 18, 0 <l < 14
plus Friedel equivalents) using graphite monochro-
˚
mated Mo Kꢀ radiation (λ = 0.71069 A). Intensities of
3028 reflections (1351 unique reflection, Rint 0.020)
were measured. Data were corrected for Lorentz and
polarization effects, and an empirical absorption cor-
rection based on azimuthal scan data [19] was ap-
plied. The structure was solved by direct methods
and refined by full-matrix least-squares technique in
the anisotropic approximation using the CRYSTALS
program package [20]. In the refinement 972 reflec-
tions with I > 3σ(I) were used. All hydrogen atoms
were located in the different Fourier maps and in-
cluded in the final refinement with fixed positional
and thermal parameters (only the H(1) and H(2)
atoms were refined isotropically). Convergence was
obtained at R= 0.033 and Rw = 0.034, GOF = 1.205
Thus, we have developed an efficient method to
synthesize 6-alkyl(aryl)amino-5-cyano-2,3-dihydro-
1,3-thiazin-4(1H)-ones and studied their conversion
into the derivatives of isomeric 1-alkyl(aryl)-5-cyano-
6-mercapto-2,3-dihydropyrimidin-4(1H)-ones.
EXPERIMENTAL
IR spectra were recorded on a UR-20 spectropho-
tometer in KBr tablets. 1H NMR spectra were

432 Vovk et al.
(189 refined parameters; obs./variabl. 5.1; the largest
and minimal peaks in the final difference map, 0.22
117.24 (CN), 127.31, 128.66, 129.12, 136.74 (Carom),
165.64 (C O), 168.20 (C6).
3
˚
and −0.17 e/A ). Chebushev weighting scheme [21]
with parameters 0.77, 0.25, 0.81, 0.08, and 0.25 was
used. The Flack test [22] was applied for the ab-
solute configuration determination (the enantiopole
parameter was refined to 0.1(1) using 1878 reflec-
tions with the nonavereged Friedel equivalents).
Full crystallographic details have been deposited
at Cambridge Crystallographic Data Centre (CCDC).
Any request to the CCDC for this materials should
quote the full literature citation and reference num-
ber CCDC252077.
5-Cyano-6-ethylamino-2-phenyl-2,3-dihydro-1,3-
thiazin-4(1H)-one 3b. Yield 75% (method A); mp
236–238◦C; IR (ꢁ/cm−1): 3280 (NH), 2230 (CN), 1660
(C O); 1H NMR δ 1.12 t (3H, CH3, J = 7.2 Hz),
3.28 m (2H, CH2), 6.06 d (1H, CH, J = 2.5 Hz),
7.35–7.51 m (5H, Harom), 8.20 d (1H, NH, J = 2.5
Hz), 8.25 t (1H, NH, J = 5.4 Hz); 13C NMR δ 15.28
(CH3), 40.16 (CH2), 57.97 (CH), 73.29 (C5), 117.28
(CN), 127.32, 128.65, 129.11, 136.65 (Carom), 165.74
(C O), 166.78 (C6).
5-Cyano-2,2-dimethyl-6-ethylamino-2,3-dihydro-
1,3-thiazin-4(1H)-one 3c. Yield 76% (method A);
mp 238–240◦C; IR (ꢁ/cm−1): 3310 (NH), 2220 (CN),
1660 (C O); 1H NMR δ 1.14 t (3H, CH3, J = 6.9 Hz),
1.64 s (6H, 2 CH3), 3.31 dqua (2H, CH2, J1 = 6.9 Hz,
J2 = 5.4 Hz),7.89 s (1H, NH), 8.18 t (1H, NH, J = 5.4
Hz); 13C NMR δ 15.19 (CH3), 29.50 (2CH3), 61.12
(C2), 72.00 (C5), 117.18 (CN), 164.59 (C O), 166.26
(C6).
3-Alkyl(aryl)amino-2-cyano-3-
mercaptoacrylamides 1a–d
To a stirred and ice-water cooled mixture of
cyanoacetamide (0.1 mol) and the corresponding
alkyl(aryl)isothiocyanate (0.1 mol) in DMF (150 mL),
40% aqueous KOH (15 mL) was added dropwise.
Then the reaction mixture was held on a water bath
for 1 h. On cooling down, the solution was diluted
with water (150 mL) and filtered; the filtrate was
acidified with concentrated HCl to pH 2–3. A result-
ing precipitate was filtered off, washed with water,
dried, and used in further reactions without addi-
tional purification.
6-Benzylamino-5-cyano-2-(4-methoxyphenyl)-
2,3-dihydro-1,3-thiazin-4(1H)-one 3d. Yield 88%
(method A); mp 209–211◦C; IR (ꢁ/cm−1): 3320, 3180
(NH), 2220 (CN), 1670 (C O); 1H NMR δ 3.77 s (3H,
OCH3), 4.45 dd (1H, CHAHB, J1 = 15.9 Hz, J2 = 6.0
Hz), 4.55 dd (1H, CHAHB, J1 = 15.9 Hz, J2 = 6.0
General Procedure for Preparation of 6-Alkyl
(aryl)amino-5-cyano-2,3-dihydro-1,3-thiazin-
4(1H)-ones 3a–o
Hz), 6.00 d (1H, CH, J = 1.8 Hz), 6.92 d (2H, Harom
,
J = 8.1 Hz), 7.18–7.45 m (7H, Harom), 8.17 d (1H, NH,
J = 1.8 Hz), 8.85 t (1H, NH, J = 6.0 Hz); 13C NMR δ
48.04 (CH2), 55.22 (OCH3), 58.10 (CH), 73.99 (C5),
116.06 (CN), 113.96, 127.04, 127.35, 127.95,128.53,
128.77, 137.92, 159.77 (Carom), 165.51 (C O), 167.38
(C6).
Method A. A mixture of compound 1 (0.01 mol),
the corresponding carbonyl compound 2 (0.01 mol),
and p-TSA (0.002 mol) in ethanol (20 mL) was boiled
for 2 h. On cooling the solution, a resulting precipi-
tate was filtered off, washed with ethanol, dried, and
recrystallized from ethanol.
5-Cyano-2-methyl-6-phenylamino-2,3-dihydro-
1,3-thiazin-4(1H)-one 3e. Yield 90% (method A);
mp 268–270◦C (lit. 275◦C [13]); IR (ꢁ/cm−1): 3340
(NH), 2230 (CN), 1660 (C O); 1H NMR δ 1.46 d (3H,
CH3, J = 6.6 Hz), 4.95 dqua (1H, CH, J1 = 6.6 Hz,
J2 = 2.2 Hz), 7.18–7.40 m (5H, Harom), 8.08 d (1H,
NH, J = 2.2 Hz), 10.07 s (1H, NH); 13C NMR δ 18.93
(CH3), 51.90 (CH), 77.11 (C5), 116.51 (CN), 125.74,
126.88, 128.96, 138.13 (Carom), 165.26 (C O), 166.77
(C6).
Method B. A mixture of compound 1 (0.01 mol)
and the corresponding carbonyl compound
(0.01 mol) in glacial acetic acid (20 mL) was boiled
for 0.5 h. On cooling the solution, a resulting precipi-
tate was filtered off, washed with ethanol, dried, and
recrystallized from ethanol.
2
5-Cyano-6-methylamino-2-phenyl-2,3-dihydro-
1,3-thiazin-4(1H)-one 3a. Yield 71% (method A);
mp 245–247◦C; IR (ꢁ/cm−1): 3300 (NH), 2220 (CN),
1660 (C O); 1H NMR δ 2.90 d (3H, CH3, J = 3.0
Hz), 6.06 d (1H, CH, J = 2.0 Hz), 7.25–7.41 m (3H,
Harom), 7.47–7.53 m (2H, Harom), 8.20–8.22 m (2H, 2
NH); 13C NMR δ 31.59 (CH3), 58.05 (CH), 73.04 (C5),
(RR,RS)-5-Cyano-2-(6ꢁ,6ꢁ-dimethylbicyclo[3.1.1]-
hept-2ꢁ-en-2ꢁ-yl)-6-phenylamino-2,3-dihydro-1,3-
thiazin-4(1H)-one 3f. Yield 80% (method A); mp
230–232◦C; IR (ꢁ/cm−1): 3310 (NH), 2230 (CN), 1660
(C O); H NMR δ 0.73 s (3H, CH3), 1.05–1.33 m
(4H, Haliph), 1.98–2.41 m (5H, Haliph), 5.19 s (0.5H,
1

Synthesis of 2,3-Dihydro-1,3-Thiazin-4(1H )-ones and Their Remarkably Facile Recyclization to 2,3-Dihydropyrimidin-4(1H )-ones 433
(method A); mp 211–213◦C; IR (ꢁ/cm−1): 3320 (NH),
2230 (CN), 1660 (C O); 1H NMR δ 0.93 d (3H, CH3,
J = 6.4 Hz), 0.96 d (3H, CH3, J = 6.4 Hz), 1.48 s (3H,
CH3), 2.29 sept (1H, CH, J = 6.4 Hz), 7.17–7.40 m
(5H, Harom), 8.11 s (1H, NH), 9.96 s (1H, NH); 13C
NMR δ 16.82, 18.30 (2CH3), 23.01 (CH3), 36.50 (CH),
68.75 (C2), 76.58 (C5), 116.32 (CN), 125.58, 126.72,
128.95, 138.01 (Carom), 164.10 (C O), 164.70 (C6).
CH), 5.30 s (0.5H, CH), 5.54 s (0.5H, CH), 5.68 s
(0.5H, CH), 7.16–7.45 m (5H, Harom), 8.07 s (0.5H,
NH), 8.16 s (0.5H, NH), 9.94 s (0.5H, NH), 10.00 s
(0.5H, NH); 13C NMR δ 20.50, 20.93 (CH3), 25.74
(CH3), 30.62 (CH2), 31.01, 31.12 (CH2), 37.51 (Cquat),
39.82 (CH), 42.51, 42.85 (CH), 57.35, 58.61 (CH),
77.20, 77.48 (C5), 116.41 (CN), 120.16, 121.98 (CH),
125.29, 125.35, 126.60, 128.76, 128.84, 137.74,
138.01 (Carom), 142.35, 143.37 (Cquat), 164.25, 164.82,
165.03, 165.32 (C O, C6).
5-Cyano-6-phenylamino-2,2-cyclopentyliden-2,3-
dihydro-1,3-thiazin-4(1H)-one 3n. Yield 75%
(method A); mp 232–324◦C; IR (ꢁ/cm−1): 3200 (NH),
2230 (CN), 1660 (C O); 1H NMR δ 1.57–1.81 m (4H,
2CH2), 1.95–2.06 m (4H, 2CH2), 7.17–7.46 m (5H,
5-Cyano-2-phenyl-6-phenylamino-2,3-dihydro-
1,3-thiazin-4(1H)-one 3g. Yield 85% (method A),
80% (method B); mp 264–266◦C (lit 267–268◦C
[13]); IR (ꢁ/cm−1): 3350, 3260 (NH), 2230 (CN),
1660 (C O); 1H NMR δ 6.06 d (1H, CH, J = 2.5 Hz),
7.18–7.55 m (10H, Harom), 8.45 d (1H, NH, J = 2.5
Hz), 10.15 s (1H, NH); 13C NMR δ 58.18 (CH), 77.50
(C5), 116.43 (CN), 125.62, 127.34, 128.97, 136.38,
137.87 (Carom), 165.51 (C O), 165.60 (C6).
H
arom), 8.26 s (1H. NH), 10.03 s (1H, NH); 13C NMR
δ 22.52 (2CH2), 39.91 (2CH2), 69.93 (C2), 77.10 (C5),
116.34 (CN), 125.51, 126.65, 128.91, 138.06 (Carom),
164.77 (C O), 165.68 (C6).
5-Cyano-6-phenylamino-2,2-adamantyliden-
2,3-dihydro-1,3-thiazin-4(1H)-one 3o. Yield 66%
(method A); mp 260–262◦C; IR (ꢁ/cm−1): 3300 (NH),
2230 (CN), 1650 (C O); 1H NMR δ 1.47–181 m (8H,
5-Cyano-2-(4-nitrophenyl)-6-phenylamino-2,3-
dihydro-1,3-thiazin-4(1H)-one 3h. Yield 84%
(method A), 77% (method B); mp 255–257◦C; IR
(ꢁ/cm−1): 3330, 3250 (NH), 2230 (CN), 1660 (C O);
1H NMR δ 6.22 d (1H, CH, J = 2.0 Hz), 7.15–7.41 m
(5H, Harom), 7.70 d (2H, Harom, J = 9 Hz), 8.23 d (2H,
H
H
aliph), 1.90–1.94 m (2H, Haliph), 2.21–2.32 m (4H,
aliph), 7.17–7.41 m (5H, Harom), 7.93 s (1H, NH),
10.01 (1H, NH); 13C NMR δ 25.83, 26.05, 31.91,
33.62, 35.87, 37.29 (Caliph), 71.82 (C2), 76.88 (C5),
116.45 (CN), 125.27, 126.62, 128.97, 138.27 (Carom),
161.14 (C6), 164.25 (C O).
H
arom, J = 9 Hz), 8.62 d (1H, NH, J = 2.0 Hz), 10.15 s
(1H, NH); 13C NMR δ 56.40 (CH), 77.47 (C5), 116.07
(CN), 123.76, 125.66, 127.06, 128.28, 129.04, 137.72,
145.23, 147.53 (Carom), 164.63 (C O), 164.96 (C6).
General Procedure for Preparation of 1-Alkyl-
(aryl)-5-cyano-6-methylthio-2,3-
dihydropyrimidin-4(1H)-ones 4a–c,e–k,n
5-Cyano-(2ꢁ,3ꢁ-dihydro-1,4-benzodioxin-6ꢁ-yl)-6-
phenylamino-2,3-dihydro-1,3-thiazin-4(1H)-one 3k.
Yield 79% (method A), 69% (method B); mp 240–
242◦C; IR (ꢁ/cm−1): 3360, 3250 (NH), 2230 (CN),
1660 (C O); 1H NMR δ 4.22 s (4H, 2CH2), 5.93
d (1H, CH, J = 2.2 Hz), 6.75–7.01 m (3H, Harom),
7.17–7.43 m (5H, Harom), 8.34 d (1H, NH, J = 2.2 Hz),
10.12 (1H, NH); 13C NMR δ 57.86 (CH), 64.05, 64.10
(2CH2), 77.35 (C5), 116.40 (CN), 116.18, 117.19,
120.33, 125.56, 126.86, 128.92, 137.87, 143.16,
143.16, 144.06 (Carom), 165.44 (C O), 165.69 (C6).
To a stirred 0.75 N aqueous KOH solution (20 mL),
compound 3a–c,e–k,n (0.01 mol) and dimethyl sul-
fate (1.9 mL, 0.02 mol) were added successively. A re-
sulting precipitate was filtered off, washed with wa-
ter, dried, and recrystallized from ethanol.
5-Cyano-1-methyl-6-methylthio-2-phenyl-2,3-
dihydropyrimidin-4(1H)-one 4a. Yield 60%; mp; IR
(ꢁ/cm−1): 3210 (NH), 2230 (CN), 1650 (C O); 1H
NMR δ 2.56 s (3H, SCH3), 3.47 s (3H, CH3), 5.87 d
(1H, CH, J = 3.9 Hz), 7.30–7.45 m (5H, Harom), 8.49
d (1H, NH, J = 3.9 Hz); 13C NMR δ 16.78 (SCH3),
40.50 (CH3), 71.43 (CH), 82.06 (C5), 117.33 (CN),
125.59, 128.57, 128.65, 138.72 (Carom), 161.76 (C O),
165.63 (C6).
5-Cyano-2,2-dimethyl-6-phenylamino-2,3-dihydro-
1,3-thiazin-4(1H)-one 3l. Yield 85% (method A);
mp 249–251◦C (lit. 254–255◦C [13]); IR (ꢁ/cm−1):
1
3230 (NH), 2230 (CN), 1670 (C O); H NMR δ 1.62
s (6H, 2CH3), 7.17–7.42 m (5H, Harom), 8.11 s (1H,
NH), 10.02 s (1H, NH); 13C NMR δ 29.38 (2CH3),
61.24 (C2), 76.32 (C5), 116.38 (CN), 125.79, 126.84,
128.95, 137.86 (Carom), 164.36 (C6), 165.21 (C O).
5-Cyano-1-ethyl-6-methylthio-2-phenyl-2,3-dihy-
dropyrimidin-4(1H)-one 4b. Yield 73%; mp 179–
181◦C; IR (ꢁ/cm−1): 3300 (NH), 2230 (CN), 1670
(C O); 1H NMR δ 1.7 t (3H, CH3, J = 7.2 Hz), 2.59 s
(3H, SCH3), 3.75 sex (1H, CHAHB, J = 7.2 Hz), 4.02
5-Cyano-2-isopropyl-2-methyl-6-phenylamino-
2,3-dihydro-1,3-thiazin-4(1H)-one 3m. Yield 70%

434 Vovk et al.
sex (1H, CHAHB, J = 7.2 Hz), 5.93 d (1H, CH, J = 3.6
Hz), 7.28–7.47 m (5H, Harom), 8.58 d (1H, NH, J = 3.6
Hz); 13C NMR δ 14.89, 16.92 (2CH3), 48.29 (CH2),
68.99 (CH), 84.45 (C5), 117.02 (CN), 125.40, 125.52,
128.48, 139.30 (Carom), 161.79 (C O), 165.48 (C6).
253–255◦C; IR (ꢁ/cm−1): 3290 (NH), 2230 (CN), 1680
(C O); H NMR δ 2.18 s (3H, SCH3), 6.20 d (1H,
1
CH, J = 6.9 Hz), 7.38–7.54 m (5H, Harom), 7.73 d
(2H, Harom, J = 9.0 Hz), 8.30 d (2H, Harom, J = 9.0
Hz), 9.02 d (1H, NH, J = 6.9 Hz); 13C NMR δ 15.30
(SCH3), 73.31 (CH), 90.12 (C5), 115.48 (CN), 123.91,
125.46, 127.54, 127.70, 129.83, 142.82, 146.30,
147.66 (Carom), 160.23 (C O), 165.43 (C6).
5-Cyano-1-ethyl-6-methylthio-2-phenyl-2,3-dihy-
dropyrimidin-4(1H)-one 4c. Yield 67%; mp 170–
172◦C; IR (ꢁ/cm−1): 3300 (NH), 2230 (CN), 1670
1
(C O); H NMR δ 1.20 t (3H, CH3, J = 7.0 Hz), 1.50
5-Cyano-2-(2 ꢁ,3 ꢁ-dihydro-1,4-benzodioxin-6 ꢁ-yl)-
6-methylthio-1-phenyl-2,3-dihydropyrimidin-4(1H)-
one 4k. Yield 72%; mp 178–180◦C; IR (ꢁ/cm−1):
s (6H, 2CH3), 2.65 s (3H, SCH3), 3.75 qua (2H, CH2,
J = 7.0 Hz), 7.81 s (1H, NH); 13C NMR δ 16.30 (CH3),
18.01 (SCH3), 25.61 (2CH3), 42.28 (CH2), 72.94 (C2),
81.65 (C5), 117.58 (CN), 161.67 (C O), 165.21 (C6).
1
3300 (NH), 2230 (CN), 1670 (C O); H NMR δ 2.14
s (3H, SCH3), 4.25 s (4H, 2CH2), 5.89 d (1H, CH,
J = 3.9 Hz), 6.81–6.92 m (3H, Harom), 7.26–7.60 m
(5H, Harom), 8.76 d (1H, NH, J = 3.9 Hz); 13C NMR δ
15.38 (SCH3), 64.11 (2CH2), 73.53 (CH), 89.54 (C5),
115.92 (CN), 114.92, 117.28, 118.80, 125.41, 127.47,
129.75, 131.75, 142.93, 143.32, 143.65 (Carom), 160.50
(C O), 164.75 (C6).
5-Cyano-2-methyl-6-methylthio-1-phenyl-2,3-di-
hydropyrimidin-4(1H)-one 4e. Yield 69%; mp 224–
226◦C; IR (ꢁ/cm−1): 3310, 3200 (NH), 2230 (CN),
1680 (C O); 1H NMR δ 1.46 d (3H, CH3, J = 6.6 Hz),
2.13 s (3H, SCH3), 5.01 m (1H, CH), 7.27–7.61 m
(5H, Harom), 8.10 d (1H, NH, J = 1.8 Hz); 13C NMR δ
15.88, 19.94 (2CH3), 69.15 (CH), 86.61 (C5), 116.48
(CN), 126.50, 127.87, 129.50, 141.81 (Carom), 160.67
(C O), 164.74 (C6).
5-Cyano-6-methylthio-1-phenyl-2,2-cyclopentyl-
iden-2,3-dihydro-1,3-thiazin-4(1H)-one 4n. Yield
67%; mp 198–200◦C; IR (ꢁ/cm−1): 3290, 3200 (NH),
2230 (CN), 1670 (C O); 1H NMR δ 1.59–1.85 m (8H,
4CH2), 2.32 s (3H, SCH3), 7.28–7.33 m (2H, Harom),
7.44–7.50 m (3H, Harom), 8.37 s (1H, NH); 13C NMR
δ 16.93 (SCH3), 21.48 (2CH2), 36.49 (2CH2), 82.84
(C2), 86.30 (C5), 116.65 (CN), 128.96, 129.30, 129.33,
139.87 (Carom), 161.77 (C O), 167.34 (C6).
(RR,RS)-5-Cyano-2-(6ꢁ,6ꢁ-dimethylbicyclo[3.1.1]-
hept-2ꢁ-en-2ꢁ-yl)-6-methylthio-1-phenyl-2,3-dihydro-
1,3-thiazin-4(1H)-one 4f. Yield 65%; mp 210–215◦C;
IR (ꢁ/cm−1): 3360 (NH), 2230 (CN), 1680 (C O);
1H NMR δ 0.80 s (1.5H, CH3), 0.82 s (1.5H, CH3),
1.13 m (1H, CH), 1.32 s (3H, CH3), 2.04–2.49 m
(9H, Haliph), 5.16 s (0.35H, CH), 5.23 s (0.65H, CH),
5.55 d (0.35H, CH, J = 4.8 Hz), 5.60 d (0.65H, CH,
J = 4.8 Hz), 7.27–7.52 m (5H, Harom), 8.39 d (0.65H,
NH, J = 4.8 Hz), 8.45 d (0.35H, NH, J = 4.8 Hz);
13C NMR δ 15.18, 15.30 (SCH3), 20.73 (CH3), 25.87,
26.07 (CH3), 30.71 (CH2), 31.50, 31.62 (CH2), 37.52,
37.77 (Cquat), 39.50 (CH), 42.00, 42.11 (CH), 73.89,
74.16 (CH), 89.45, 89.85 (C5), 115.83, 116.02 (CN),
119.42, 121.19 (CH), 124.78, 125.07, 127.22, 129.69,
144.39 (Carom), 143.39, 143.48 (Cquat), 160.04, 160.30
(C O), 163.65, 164.00 (C6).
1-Alkyl(aryl)-6-benzylthio-5-cyano-2,3-
dihydropyrimidin-4(1H)-ones 4d,l,m
A mixture of compound 3d,l,m (0.01 mol), benzyl
chloride (1.39 g, 0.011 mol), and triethylamine (2.1
mL, 0.015 mol) in ethanol (20 mL) was boiled for
2 h. On cooling the solution, resulting crystals were
filtered off, dried, and recrystallized from ethanol.
5-Cyano-1-benzyl-6-benzylthio-2-(4 ꢁ-methoxy-
phenyl)-2,3-dihydropyrimidin-4(1H)-one 4d. Yield
69%; mp 169–171◦C; IR (ꢁ/cm−1): 3300, 3180 (NH),
2220 (CN), 1660 (C O); 1H NMR δ 3.75 s (3H,
OCH3), 4.19 d (1H, CHAHB, J = 13 Hz), 4.36 d (1H,
CHAHB, J = 13 Hz), 4.65 d (1H, CHAHB, J = 16 Hz),
5.34 d (1H, CHAHB, J = 16 Hz), 5.68 d (1H, CH,
J = 3.6 Hz), 6.90 d (2H, Harom, J = 10 Hz), 7.10–7.41
m (12H, Harom), 8.36 d (1H, NH, J = 3.6 Hz); 13C
NMR δ 38.22 (SCH2), 55.10 (NCH2), 55.17 (OCH3),
69.21 (CH), 85.93 (C5), 117.30 (CN), 113.94, 127.27,
127.84, 128.88, 130.31, 135.95, 136.41, 159.46
(Carom), 161.36 (C O), 162.29 (C6).
5-Cyano-1,2-diphenyl-6-methylthio-2,3-dihydro-
pyrimidin-4(1H)-one 4g. Yield 78%; mp 217–219◦C;
IR (ꢁ/cm−1): 3310, 3200 (NH), 2230 (CN), 1680
1
(C O); H NMR δ 2.16 s (3H, SCH3), 6.03 d (1H,
CH, J = 4.8 Hz), 7.36–7.55 m (10H, Harom), 8.81 d
(1H, NH, J = 4.8 Hz); 13C NMR δ 15.39 (SCH3),
73.98 (CH), 89.74 (C5), 115.87 (CN), 125.47, 126.08,
127.54, 128.68, 128.75, 129.80, 138.80, 143.03
(Carom), 160.59 (C O), 164.95 (C6).
5-Cyano-6-methylthio-2-(4ꢁ-nitrophenyl)-1-phenyl-
2,3-dihydropyrimidin-4(1H)-one 4h. Yield 70%; mp

Synthesis of 2,3-Dihydro-1,3-Thiazin-4(1H )-ones and Their Remarkably Facile Recyclization to 2,3-Dihydropyrimidin-4(1H )-ones 435
5-Cyano-6-benzylthio-2,2-dimethyl-1-phenyl-2,3-
dihydropyrimidin-4(1H)-one 4l. Yield 69%; mp
233–235◦C; IR (ꢁ/cm−1): 3300, 3190 (NH), 2230
General Procedure for Preparation of
1-Alkyl(aryl)-5-cyano-6-mercapto-2,2-dimethyl-
1-phenyl-2,3-dihydropyrimidin-4(1H)-one
Potassium Salts 6a,b
1
(CN), 1670 (C O); H NMR δ 1.26 s (6H, 2CH3),
4.05 s (2H, CH2), 6.98–7.03 m (2H, Harom), 7.14–7.18
m (2H, Harom), 7.24–7.42 m (6H, Harom), 8.11 s (1H,
NH); 13C NMR δ 26.68 (2CH3), 37.77 (SCH2), 73.43
(C2), 86.08 (C5), 117.09 (CN), 127.67, 128.50, 129.39,
135.85, 138.97 (Carom), 161.11 (C O), 161.62 (C6).
Compound 3b,h (0.01 mol) was dissolved in 0.75 N
aqueous KOH (20 mL) at heating. On cooling the so-
lution, a resulting precipitate was filtered off, washed
with water, and dried.
5-Cyano-1-ethyl-6-mercapto-2-phenyl-2,3-dihy-
dropyrimidin-4(1H)-one 6a. Yield 82%; mp 240–
242◦C; IR (ꢁ/cm−1): 3350 (NH), 2210 (CN), 1610
5-Cyano-6-benzylthio-2-isopropyl-2-methyl-1-
phenyl-2,3-dihydropyrimidin-4(1H)-one 4m. Yield
63%; mp 234–236◦C; IR (ꢁ/cm−1): 3300, 3200 (NH),
2230 (CN), 1670 (C O); 1H NMR δ 0.89–0.95 m
(9H, 3CH3), 2.49 m (1H, CH), 3.94 d (1H, CHAHB,
J = 12.9 Hz), 4.12 d (1H, CHAHB, J = 12.9 Hz), 6.82
d (1H, Harom, J = 7.5 Hz), 7.00–7.10 m (2H, Harom),
7.25–7.53 m (7H, Harom), 8.31 s (1H, NH); 13C NMR δ
17.01, 17.57 (2CH3), 20.58 (CH3), 33.89 (CH), 37.38
(CH2), 78.88 (C2), 88.91 (C5), 116.62 (CN), 127.71,
128.56, 128.75, 128.82, 129.32, 130.21, 135.36,
140.16 (Carom), 160.29 (C O), 162.92 (C6).
1
(C O); H NMR δ 1.04 t (3H, CH3, J = 6.9 Hz), 3.03
sex (1H, CHAHB, J = 6.9 Hz), 4.57 sex (1H, CHAHB,
J = 6.9 Hz), 5.59 (1H, CH, J = 3.9 Hz), 7.19–7.46
m (6H, Harom, NH); 13C NMR δ 13.61 (CH3), 44.37
(CH2), 69.03 (CH), 78.60 (C5), 123.68 (CN), 126.11,
127.61, 128.15, 141.94 (Carom), 164.10 (C O), 184.37
(C6).
5-Cyano-6-mercapto-1-phenyl-2-(4ꢁ-nitrophenyl)-
2,3-dihydropyrimidin-4(1H)-one 6b. Yield 75%;
mp 270–274◦C; IR (ꢁ/cm−1): 3380 (NH), 2210 (CN),
1620 (C O); 1H NMR δ 5.90 d (1H, CH, J = 4.0 Hz),
7.15–7.31 m (5H, Harom), 7.62 d (2H, Harom, J = 8.0
3-Benzylthio-2-cyano-3-phenylaminoacrylamide
5a
Hz), 7.86 d (1H, NH, J = 4.0 Hz), 8.27 d (2H, Harom
,
J = 8.0 Hz); 13C NMR δ 71.52 (CH), 83.37 (C5),
122.37 (CN), 123.42, 125.21, 126.99, 127.63, 128.07,
145.50, 147.04, 149.52 (Carom), 163.35 (C O), 184.90
(C6).
Method A. A mixture of compound 1d (2.19 g,
0.01 mol), benzyl chloride (1.39 g, 0.011 mol), and tri-
ethylamine (2.1 mL, 0.015 mol) in ethanol (20 mL)
was boiled for 2 h. On cooling the solution, a re-
sulting precipitate was filtered off, dried, and recrys-
tallized from ethanol. Yield 77%; mp 138–140◦C; IR
(ꢁ/cm−1): 3410, 3210 (NH), 2220 (CN), 1670 (C O);
1H NMR δ 3.83 s (2H, CH2), 6.95 br s (1H, NH2),
7.10–7.49 m (11H, Harom, NH2), 12.54 s (1H, NH).
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