Study of reaction between activated acetylenes and N,N'-diethyl-2- thiobarbituric acid in the presence of isocyanides or triphenylphosphine

Article abstract of DOI:10.1002/hc.20601

In a series of separate experiments reaction between N, N'-diethyl-2-thiobarbituric acid and acetylenic diesters in the presence of isocyanides or triphenylphosphine led to highly functionalized 4H-pyrano[2,3-d]thiopyrimidine or 1,4-di-ionic organophospho

Full text of DOI:10.1002/hc.20601

Heteroatom Chemistry
Volume 21, Number 4, 2010
Study of Reaction between Activated
ꢀ
Acetylenes and N,N -Diethyl-2-thiobarbituric
Acid in the Presence of Isocyanides or
Triphenylphosphine
Ghasem Marandi,1 Malek Taher Maghsoodlou,2 Nourallah Hazeri,2
Reza Heydari,2 Sayyed Mostafa Habibi Khorassani,2 Ali Ebrahimi,2
Sakineh Mollaee Poor,2 Hassan Hosseini Mahdiabad,2
Mahmoud Nassiri,2 and Roya Kabiri3
1Department of Chemistry, Faculty of Science, Payame Noor University of Khoy, Khoy, Iran
2Department of Chemistry, The University of Sistan & Baluchestan, P. O. Box 98135-674,
Zahedan, Iran
3Faculty of Chemistry, The University of Tabriz, Tabriz, Iran
Received 14 November 2009; revised 13 March 2010
Wiley InterScience (www.interscience.wiley.com). DOI
ABSTRACT: In a series of separate experiments
10.1002/hc.20601
reaction between N,Nꢀ-diethyl-2-thiobarbituric acid
and acetylenic diesters in the presence of isocyanides
or triphenylphosphine led to highly functionalized
4H-pyrano[2,3-d]thiopyrimidine
or
1,4-di-ionic
INTRODUCTION
1
organophosphorus derivatives. The H NMR spectra
of diethyl-7-(2,6-dimethylphenylamino)-4-oxo-2-thio-
1,3-diethyl-4H-pyrano[2,3-d]pyrimidine-5,6-dicarbo-
xylate showed dynamic NMR effect that was at-
tributed to restricted rotation around the aryl-nitrogen
single bond. Activation free energy (ꢀG=) for this
In recent years, the synthetic application of mul-
tifunctional heterocycles has been widely investi-
gated [1,2]. In spite of extensive developments in
the chemistry of modified isocyanates [3], little at-
tention has been paid to the synthesis of pyrimidine
[4–7]. In general, barbiturates and thiobarbiturates
are drugs from pyrimidine derivatives. Today these
compounds are infrequently used as anticonvulsants
and also induction of anesthesia [8]. Barbiturate
drugs are used as sedative-hypnotic agents [9]. In
addition, recently, there has been increasing interest
in the synthesis of organophosphorus compounds,
that is those bearing a carbon atom bond directly
to a phosphorus atom [10–31]. This interest arises
from the greater stability of these compounds com-
pared to the phosphate analogues [32] and recogni-
tion of the value of such compounds in a wide range
process is about 54.85
2 kJ mol−1. Betaines as
1,4-diionic organophosphorus compounds in this
reaction are possessed of two vicinal stereogenic
centers and exist in the solution as a mixture of
ꢂ
C
two diastereoisomers.
2010 Wiley Periodicals, Inc.
Heteroatom Chem 21:228–235, 2010; Published online in
Correspondence to: Malek Taher Maghsoodlou; e-mail:
mt maghsoodlou@yahoo.com.
Contract grant sponsor: Research Council of the University of
Sistan & Baluchestan.
c
ꢀ
2010 Wiley Periodicals, Inc.
228

Study of Reaction Between Activated Acetylenes and N,Nꢀ-Diethyl-2-thiobarbituric Acid 229
SCHEME 1
of industrial, biological, and chemical synthetic as-
pects [33,34].
by their IR spectra. Of special interest are the strong
carbonyl absorption bands at 1683–1717 cm−1 and
fairly broad NH peak at about 3165–3335 cm−1 for
all compounds. (See the Experimental section). Al-
though we have not yet established the mechanism
of the reaction between alkyl or aryl isocyanides
and dimethyl acetylenedicarboxylate (DMAD) in the
presence of N,Nꢀ-diethyl-2-thiobarbituric acid in
an experimental manner, a possible explanation is
proposed in Scheme 2. On the basis of the well-
established chemistry of isocyanides [10–13,41,42],
it is reasonable to assume that compound 4 results
from initial addition of the alkyl isocyanide 1 to
the acetylenic ester 2 and subsequent protonation
of the 1:1 adduct by N,Nꢀ-diethyl-2-thiobarbituric
acid 3 (Scheme 2). Then the positively charged ion
is probably attacked by the enolate anion of the
CH acid in accord with two ways. The first step
(Scheme 2) involves a Michael addition that leads
to the keteneimine 5. Compound 5 apparently iso-
merizes under the reaction condition, to produce the
fused heterocyclic system 4. Enaminocarbonyl com-
pound 6 is unfavored according to the second way
(Scheme 2) because spectral data were not compat-
ible with the structure of compound 6.
In the set of investigations made on the develop-
ment of heterocyclic and organophosphorus com-
pound synthesis [35–40], we now describe a one-
pot, synthesis of N,Nꢀ-diethyl-2-thiobarbituric acid
containing heterocyclic 4 and organophosphorus
derivatives 9 using isocyanides 1 or triphenylphos-
phine 7 and acetylenic diesters 2 in the presence of
N,Nꢀ-diethyl-2-thiobarbituric acid 3 (see Schemes 1
and 4).
RESULTS AND DISCUSSION
The reaction between alkyl or aryl isocyanides 1 and
electron-deficient acetylenic esters 2 in the presence
of strong CH-acid 3 proceeded at ambient tempera-
ture in CH2Cl2 and was completed within 5 days. The
structure of 4 was assigned on the basis of elemen-
1
tal analyses, infrared (IR), H, 13C NMR, and mass
spectral data. The mass spectra of 4H-pyrano[2,3-
d]thiopyrimidines 4a–d are similar and displayed
molecular ion peaks at appropriate m/z values. Ini-
tial fragmentations involve loss of the side chains
and scission of the enaminoester system. The 1H
NMR spectrum of compound 4a exhibited nine sin-
gle sharp lines, readily recognizable arising from
C-methyl (δ = 1.26 and 1.40), tert-butyl (δ = 1.44),
methoxy (δ = 3.68 and 3.71), methylene (δ = 4.50 and
4.57), methine (δ = 4.58), and a broad band for the
NH group at δ = 8.99 ppm, indicating intramolecular
hydrogen bond formation with the vicinal carbonyl
group.
The presence of two separate signals for the
1
Ar-Me2 groups in both H and 13C NMR spectra of
4d can be explained on the basis of restricted ro-
tation around the N-aryl bond (see Scheme 3). The
1H NMR spectrum of 4d in 1,2-dichlorobenzene at
70◦C showed resonances arising from C-Me pro-
tons, which are appreciably broadened in compar-
ison with corresponding signals in the spectrum
measured at room temperature, whereas the N-Et
and O-Et resonances remain unchanged. The Ar-Me2
protons coalesce near 90◦C and appear as a fairly
sharp symmetrical resonance at 110◦C. No further
The 13C NMR spectrum showed 17 distinct res-
onances consistent with the enaminoester struc-
ture. The structural assignments of compounds 4a–d
made on the basis of NMR spectra were supported
Heteroatom Chemistry DOI 10.1002/hc

230 Marandi et al.
SCHEME 2
(see Table 1). An application of the absolute rate the-
ory with a transmission coefficient of 1 gave free en-
ergy of activation (ꢀG=) of 54.85 kJ mol−1, in which
all known sources of errors were estimated and in-
cluded [44]. The experimental data available were
not suitable for obtaining meaningful values of ꢀH=
and ꢀS=, even though the errors in ꢀG= were not
large [45].
In a series of other experiment from reactions
between triphenylphosphine and acetylenic diesters
in the presence of N,Nꢀ-diethyl-2-thiobarbituric acid,
the hitherto unknown butanedioates 9a–c generated
in 90–97% yield (Scheme 4). All the compounds are
stable crystalline solids whose structure is fully sup-
SCHEME 3
dynamic NMR effect was observed up to 120◦C, as
the highest temperature investigated.
ported by elemental analyses and IR, 1H, 13C, and 31
P
NMR spectroscopy and mass spectroscopy data. The
mass spectra of these 1:1:1 adducts displayed fairly
weak molecular ion peaks. Any initial fragmentation
involved the loss of ester moieties and scission of
the ring. A cyclic six-membered ring structure for
compound 9 (compound 10) is unfavored because
spectral data were not compatible with the structure
of compound 10.
Although no extensive line-shape analysis was
undertaken for 4d, nevertheless the variable tem-
perature spectra allowed calculating the free energy
barrier for the restricted N-aryl bond rotation [43]
in 4d. From the coalescence of the N-Me proton res-
√
onances and using the expression k = πꢀν/ 2, the
first-order rate constant (k) was calculated for the
N-aryl bond rotation in 4d about 66.81 s−1 at 90◦C
TABLE 1 First-Order Rate Constants, Standard Gibbs Energies, and Selected Activation Parameters for 4d in 1,2-
Dichlorobenzene
Compound
T(◦C)
Ar-Me (δ, ppm)
ꢀν (Hz)
K(s−1
)
Tc(◦K)
263
ꢀG=(kJ mol−1
54.85
)
4a
27
110
2.27
2.37
2.35
30
66.81
2
Heteroatom Chemistry DOI 10.1002/hc

Study of Reaction Between Activated Acetylenes and N,Nꢀ-Diethyl-2-thiobarbituric Acid 231
SCHEME 4
31P NMR spectroscopic data (δ = 23–25), which is in
agreement with the presence of a Ph3P+-C grouping
[24,25]. On the basis of the chemistry of trivalent
phosphorus nucleophiles [1–5], it is reasonable to
assume that compound 9 results from the initial ad-
dition of triphenylphosine to the acetylenic ester and
subsequent protonation of the 1:1 adduct by CH-acid
5. Then, the positively charged ion is attacked by the
enolate anion the CH-acid to generate ylide 8. Com-
pound 8 apparently isomerizes, under the reaction
conditions, to produce the 1,4-diionic compound 9.
If the compound 10 was obtained instead of
compound 9, then we were to expect a doublet at
about δ = 160 for the C O P moiety in the 13C NMR
spectra. Structure 9 was further confirmed by the
1
The H NMR (500 MHz) spectra of compounds
9a–c displayed signals for vicinal methine protons
at δ 4.81–5.91, which appear as two sets of dou-
ble doublets for the major and minor diastereoiso-
mers. The vicinal proton–proton coupling constant
SCHEME 5
Heteroatom Chemistry DOI 10.1002/hc

232 Marandi et al.
(3 JHH) as a function of a torsion angle can be ob-
tained from the Karplus equation [25]. Typically,
Jgauche and Janti vary between 1.5–5 and 10–14 Hz,
The process for the preparation of dimethyl-7-
tert-butylamino-4-oxo-2-thio-1,3-diethyl-4H-pyrano-
[2,3-d]pyrimidine-5,6-dicarboxylate (4a) is described
as an example. To a magnetically stirred solution of
N, Nꢀ-diethyl-2-thiobarbituric acid (0.20 g, 1 mmol)
and DMAD (0.14 g, 1 mmol) in CH2Cl2 (6 mL),
dropwise a mixture of tert-butyl isocyanide (0.83 g,
1 mmol) in CH2Cl2 (2 mL) was added at −10◦C over
10 min. The reaction mixture was then allowed to
warm up to room temperature and to stand for
5 days. The solvent was removed under reduced
pressure, the solid residue was washed by (2×3)
cm3 cold diethyl ether, and the product 4a was
obtained as white powder. Yield: 0.36 g (85%), mp =
148–149◦C, IR (KBr) (νmax, cm−1): 3190 (N H); 1685,
3
respectively. Observation of JHH 10.2–12.1 Hz for
the vicinal protons in major and minor diastereoiso-
mers of compounds 9a–c indicates an antiarrange-
ment for these protons. The assignments of the
(2S,3S)-9 and (2R,3S)-9 configurations of 9a–c are
based on the three-bond carbon–phosphorus cou-
pling, 3 JPC. Vicinal carbon–phosphorus coupling de-
pends on configuration, as expected, trans couplings
being larger than cis ones. The Karplus relation
can be derived from the data for organophosphorus
compounds with tetra- and penta-valent phospho-
rus [41]. The observation of 3 JPC of 11–15 Hz for the
C(CO)2 group is in agreement with the (2R∗,3R∗)-9
for the major diastereoisomer (see the Experimen-
tal section). On the other hand, the measurement of
3 JPC of 18–20 Hz for the ester C O group is in ac-
cord with the (2R∗,3S∗)-9 for the minor diastereoiso-
mer (see Scheme 5). In conclusion, we have found
that the reaction of 1,3-diethyl-2-thiobarbituric acid,
with dialkyl acetylenedicarboxylates in the presence
of triphenylphosphine, leads to a facile synthesis of
highly functionalized 1,4-diionic organophosphorus
compounds 9a–c with excellent yields.
1
1738 (C O). H NMR (500.1 MHz, CDCl3): δH 1.26
(3H, t, J = 7.0 Hz, NCH2CH ), 1.40 (3H, t, J =
3
7.0 Hz, NCH2CH ), 1.44 (9H, s, CMe3), 3.68 and 3.71
3
(6H, s, 2 OCH3), 4.50 and 4.57 (4H, m, 2NCH CH3),
2
4.58 (1H, s, CH), 8.99 (1H, br s, NH· · ·O C). 13C
NMR (125.8 MHz, CDCl3): δC 11.31 and 12.90
(2OCH2CH3), 30.40 (NCMe3), 35.60 (CH), 43.84 and
44.67 (2NCH2CH3), 52.83 (CMe3), 51.44 and 52.57
(2OCH3), 74.21 and 92.99 (2C C O), 151.41 (C S),
158.94 and 159.07 (2C C O), 169.27 (NCO), 173.56
and 174.98 (2C O). MS (m/z, %): 425 (M+, 1), 336
(66), 310 (59), 223 (63), 195 (20), 178 (20), 163
(26), 57 (100), 41 (65). Anal Calcd for C19H27N3O6S
(425.50): C, 53.63; H, 6.40; N, 9.88; Found: C, 53.85;
H, 6.41; N, 9.75.
In fact, the reaction of isocyanides or triph-
enylphosphine with electron-deficient acetylenic
diesters in the presence of N, Nꢀ-diethyl-2-
thiobarbituric acid provides
a simple one-pot
entry into the synthesis of polyfunctional 4H-
pyrano[2,3-d]thiopyrimidine or highly functional-
ized 1,4-diionic organophosphorus compounds of
potential synthetic interest. The 1H NMR spectra
of the product 4d displayed the dynamic NMR
effect that is attributed to restricted rotation
around the aryl-nitrogen single bond and polarized
carbon–carbon double bond.
Dimethyl-7-cyclohexylamino-4-oxo-2-thio-1,3-
diethyl-4H-pyrano[2,3-d]pyrimidine-5,6-
dicarboxylate (4b)
White Powder. Yield: 0.40 g (83%), mp = 152–
153◦C, IR (KBr) (νmax, cm−1): 3314 (N H); 1691, 1730
1
(C O). H NMR (500.1 MHz, CDCl3): δH 1.18–2.10
EXPERIMENTAL
(10H, m, 5 CH2), 1.27 (3H, t, J = 6.8 Hz, NCH2CH ),
3
Melting points were measured on an Electrother-
mal 9100 apparatus and are uncorrected. Elemental
analyses for C, H, and N were performed using
a Heraeus (Banau, Germany) CHN-O-Rapid an-
alyzer. IR, 1H, 13C, and 31P NMR spectra were
measured on a Shimadzu (Tokyo, Japan) IR-460
and Bruker (Rheinstetten, Germany) DRX-500
Avance spectrometer at 500.1, 125.8, and 202.4 MHz,
respectively. Mass spectra were recorded on a
Shimadzu GC/MS QP 1100 EX mass spectrometer,
operating at an ionization potential of 70 eV.
Isocyanides, alkyl acetylenedicarboxylates, and
N,Nꢀ-diethyl-2-thiobarbituric acid were obtained
from Fluka and used without further purification.
1.41 (3H, t, J = 6.8 Hz, NCH2CH ), 3.58–3.80 (1H,
3
m, NCH), 3.70 and 3.72 (6H, 2s, 2 O CH3), 4.32–4.60
(4H, m, 2NCH CH3), 4.58 (1H, s, CH), 8.62 and 8.64
2
(1H, d, NH· · ·O C). 13C NMR (125.8 MHz, CDCl3):
δC 11.36 and 12.75 (2NCH2CH3), 24.47, 25.18, 33.69,
33.95, and 35.67 (5CH2 of cyclohexyl), 35.70 (CH),
43.81 and 44.94 (2NCH2CH3), 51.12 (N CH), 51.33
and 52.63 (2OCH3), 72.77 and 92.92 (2C C O),
151.43 (C S), 157.59 and 159.08 (2C C O), 169.05
(NCO), 173.60, 175.08 (2C O). MS (m/z, %): 451
(M+, 2), 392 (100), 305 (23), 223 (38), 163 (29), 59
(36), 55 (95), 41 (61). Anal Calcd for C21H29N3O6S
(451.53): C, 55.86; H, 6.47; N, 9.31; Found: C, 56.07;
H, 6.38; N, 9.25.
Heteroatom Chemistry DOI 10.1002/hc

Study of Reaction Between Activated Acetylenes and N,Nꢀ-Diethyl-2-thiobarbituric Acid 233
1,3-diethyl-2-thiobarbituric acid (0.2 g, 1 mmol) in
ethyl acetate (5 mL), dropwise a mixture of dimethyl
acetylene-dicarboxylate (0.14 g or 1 mmol) in ethyl
acetate (2 mL) over 4 min was added. After 40 min
stirring at room temperature, the product was fil-
tered and washed with cold diethyl ether (3 × 5 mL)
to give a cream powder. Yield 0.57 g, 94%. m.p
160–162◦C; IR (KBr) (νmax, cm−1): 1734, 1741, and
1749 (C O). MS (m/z, %): 604 (M+, 3), 546 (M-2Et,
42), 486 (M-2CO2Me, 37), 406 (M C8H10N2O2S, 27),
262 (Ph3P, 81), 183 (Ph2P, 100), 108 (PhP, 42), 77
(Ph, 29). Anal. Calcd. for C32H33O6N2SP (604.65): C,
63.56; H, 5.50; N, 4.63. Found: C, 63.61; H, 5.57; N,
4.60.
Di-tert-Butyl-7-cyclohexylamino-4-oxo2-thio-
1,3-diethyl-4H-pyrano[2,3-d]pyrimidine-5,6-
dicarboxylate (4c)
Pale-Yellow Powder. Yield: 0.39 g (78%), mp =
124–127◦C, IR (KBr) (νmax, cm−1): 3300 (N H); 1686,
1
1717 (C O). H NMR (500.1 MHz, CDCl3): δH 1.26
–1.85 (10H, m, 5CH2), 1.28 (3H, t, J = 6.8 Hz,
NCH2CH ), 1.37 (3H, t, J = 6.8 Hz, NCH2CH ), 1.46
3
3
and 1.51 (18H, 2s, 2CMe3), 3.54 (1H, m, N CH), 4.45
(1H, s, CH), 4.56 and 4.60 (4H, m, 2NCH CH3), 8.58
2
(1H, s, NH· · ·O C). 13C NMR (125.8 MHz, CDCl3):
δC 11.41 and 12.73 (2NCH2CH3), 24.75 and 25.26
(2CH2 of cyclohexyl), 28.00 and 28.48 (6 Me of
2CMe3), 27.80, 33.90, and 34.15 (3 CH2 of cyclo-
hexyl), 37.25 (CH), 43.72 and 44.90 (2NCH2CH3),
51.21 (N CH), 80.27 and 81.25 (2CMe3), 74.45
and 93.71 (2 C C O), 151.55 (C S), 157.33 and
159.05 (2C C O), 168.35 (NCO), 172.90 and 175.06
(2C O). MS (m/z, %): 535 (M+, 5), 434 (28), 378
(100), 379 (33), 252 (28), 57 (33). Anal Calcd for
C27H41N3O6S (535.70): C, 60.54; H, 7.71; N, 7.84;
Found: C, 60.65; H, 7.60; N, 7.81.
Major isomer. 1H NMR (500.1 MHz, CDCl3):
3
δ 1.29 (6H, t, JHH = 6.9 Hz, 2 NCH2CH3) , 3.18,
3.30 (6H, 2s, 2OCH3), 4.56 (4H, m, 2ABX3 system
2NCH2CH3), 5.02 (1H, dd, 3 JHH = 10.5 Hz and 3 JPH
=
3
6.6 Hz, P CH CH), 5.80 (1H, dd, JHH = 10.5 Hz
2
and JPH = 14.5 Hz, P CH CH), 7.53–7.87 (15H,
m, 3C6H5); 13C NMR (125.8 MHz, CDCl3): δ 12.78
(2NCH2CH3), 41.55 and 41.60 (2NCH2), 42.54 (d,
2 JPC = 4.7 Hz, P CH CH), 43.33 (d, 1 JPC = 41.6 Hz,
3
P CH), 52.71 and 52.93 (2OCH3), 87.71 (d, JPC
=
11.2 Hz, P C C C), 120.76 (d, 1 JPC = 88.0 Hz, Cipso),
Diethyl-7-(2,6-dimethylphenylamino)-4-oxo-2-
thio-1,3-diethyl-4H-pyrano[2,3-d]pyrimidine-
5,6-dicarboxylate (4d)
129.54 (d, 3 JPC = 12.9 Hz, Cmeta), 134.12 (Cpara), 134.28
2
(d, JPC = 9.5 Hz, Cortho), 161.14 (O C C C O),
166.88 and 173.74 (2C O, ester), 176.09 (C S). 31P
NMR (202.4 MHz, CDCl3): δ 24.28 ((Ph)3P+ C).
Minor isomer. 1H NMR (500.1 MHz, CDCl3):
Pale-Yellow Powder. Yield: 0.43 g (87%), mp =
182–185◦C, IR (KBr) (νmax, cm−1): 3245 (N H);
1693, 1734 (C O). 1H NMR (500.1 MHz, CDCl3):
3
δ 1.17 (6H, t, JHH = 6.9 Hz, 2NCH2CH3), 3.31,
δH 0.73 (3H, t, J = 6.5 Hz, N CH2CH ), 1.25
3
3.59 (6H, 2s, 2OCH3), 4.20 (4H, m, 2ABX3 sys-
(3H, t, J = 6.5 Hz, N CH2CH ), 1.23–1.42 (6H,
3
3
tem 2NCH2CH3), 5.09 (1H, dd, JHH = 11.3 Hz and
m, 2OCH2CH ), 2.24 and 2.35 (6H, 2s, ArMe2),
3
3
3 JPH = 7.0 Hz, P CH CH), 5.84 (1H, dd, JHH
=
3.90–4.24 (4H, m, 2OCH CH3), 4.25–4.52 (4H, m,
2
2
11.3 Hz and JPH = 15.2 Hz, P CH CH), 7.53–7.87
(15Haro, m, 3C6H5);13C NMR (125.8 MHz, CDCl3): δ
12.78 (2NCH2CH3), 42.01 and 42.18 (2NCH2), 42.46
N-CH CH3), 4.68 (1H, s, CH), 7.10–7.21 (3H, m,
2
ArH), 7.28 (1H, s, NH· · ·O C). 13C NMR (125.8 MHz,
CDCl3): δC 11.34 and 11.95 (2NCH2CH3), 14.16 and
14.35 (2OCH2CH3), 18.25 and 18.36 (ArMe2), 36.06
(CH), 43.70 and 44.87 (2NCH2CH3), 60.38 and 61.41
(2OCH2CH3), 74.81 and 92.78 (2C C O), 128.03,
128.19, 128.37, 133.78, 136.04, and 137.04 (6Carom),
151.48 (C S), 157.19 and 159.04 (2 C C O), 168.67
(NCO), 172.95 and 174.95 (2C O). MS (m/z, %): 501
(M+, 10), 428 (100), 241 (26), 156 (20), 144 (21), 105
(17), 77 (12). Anal Calcd for C25H31N3O6S (501.60):
C, 59.86; H, 6.23; N, 8.38; Found: C, 59.91; H, 6.20;
N, 8.42.
1
(P CH CH), 43.18 (d, JPC = 50.8 Hz, P CH),
3
52.55 and 52.71 (2OCH3), 87.99 (d, JPC = 2.5 Hz,
1
P C C C), 120.78 (d, JPC = 86.3 Hz, Cipso), 129.51
3
(d, JPC = 12.9 Hz, Cmeta), 134.08 (Cpara), 134.28 (d,
2 JPC = 9.5 Hz, Cortho), 161.03 (O C C C O), 167.33
(d, 2 JPC = 1.7 Hz, C O, ester), 173.17 (d, 3 JPC = 18.0
Hz, C O, ester), 175.69 (C S). 31P NMR (202.4 MHz,
CDCl3): δ 23.97 ((Ph)3P+ C).
(2R∗,3R∗)-1,3-Diethyl-4,6-dioxo-2-thioxo-5-[2-
(triphenylphosphonio)-1,2-bis(ethoxycarbonyl)-
ethyl]tetrahydropyrimidin-5-ide (9b)
Preparation of (2R∗,3R∗)-1,3-Diethyl-4,6-dioxo-
2-thioxo-5-[2-(triphenylphosphonio)-1,2-
bis(methoxycarbonyl)ethyl]tetrahydropyrimidin-
5-ide (9a)
White Powder. Yield: 0.57 g, 90%. mp = 162–
164◦C; IR (KBr) (νmax, cm−1): 1728, 1735, and 1746
(C O). MS (m/z, %): 632 (M+, 5), 574 (M-2Et, 23),
486 (M-2CO2Et, 36), 449 (M-PPh2, 49), 262 (PPh3,
100), 262 (PPh2, 96), 183 (PPh, 52), 77 (Ph, 28). Anal.
General Procedure. To a magnetically stirred so-
lution of triphenylphosphine (0.26 g, 1 mmol) and
Heteroatom Chemistry DOI 10.1002/hc

234 Marandi et al.
Calcd. for C34H37O6N2SP (632.71): C, 64.54; H, 5.89;
N, 4.43. Found: C, 64.69; H, 6.04; N, 4.51.
δ 12.70 (2NCH2CH3), 27.05 and 27.36 (2s, 2CMe3),
2
41.31 and 42.17 (2NCH2), 42.42 (d, JPC = 4.7 Hz,
Major isomer. 1H NMR (500.1 MHz, CDCl3):
δ 0.87–1.32 (12H, m, 2OCH2CH3 and 2NCH2CH3),
3.61 and 3.78 (4H, 2m, 2ABX3 system, 2OCH2CH3),
4.61 (4H, m, ABX3 system 2NCH2CH3), 5.29 (1H,
br, P CH CH), 5.66 (1H, br, P CH CH), 7.48–7.90
(15H, m, 3C6H5); 13C NMR (125.8 MHz, CDCl3): δ
12.72 (2NCH2CH3), 13.56 and 13.79 (2OCH2CH3),
P CH CH), 43.45 (d, 1 JPC = 42.9 Hz, P CH), 81.63
3
and 84.01 (2C, 2OCMe3), 88.36 (d, JPC = 11.9 Hz,
1
P C C C), 122.23 (d, JPC = 88.9 Hz, Cipso), 129.26
3
(d, JPC = 12.8 Hz, Cmeta), 133.43 (Cpara), 134.41 (d,
2 JPC = 9.6 Hz, Cortho), 160.99 (O C C C O), 165.52
and 172.76 (2 C O, ester), 175.75 (C S). 31P NMR
(202.4 MHz, CDCl3): δ 25.17 ((Ph)3P+ C).
2
1
41.60 and 41.66 (2NCH2), 42.58 (d, JPC = 4.5
Minor isomer. H NMR (500.1 MHz, CDCl3): δ
1
Hz, P CH CH), 43.38 (d, JPC = 43.3 Hz, P CH),
1.02 and 1.27 (18H, 2s, 2CMe3), 1.07–1.23 (6H, br,
2NCH2CH3), 4.18 (4H, br, 2NCH2CH3), 5.15 (1H, dd,
3
61.81 and 62.62 (2OCH2CH3), 88.52 (d, JPC = 12.0
1
3
Hz, P C C C), 121.32 (d, JPC = 88.3 Hz, Cipso),
3 JHH = 10.7 Hz, and JPH = 6.5 Hz, P CH CH),
3
4
3
2
129.50 (d, JPC = 12.9 Hz, Cmeta), 133.87 (d, JPC
=
5.76 (1H, dd, JHH = 10.7 Hz, and JPH = 15.7 Hz,
P CH CH), 7.43–7.85 (15H, m, 3C6H5);13C NMR
(125.8 MHz, CDCl3): δ 12.70 (2NCH2CH3), 27.14 and
27.74 (2s, 2CMe3), 41.63 and 41.71 (2NCH2), 42.47
(P CH CH), 42.84 (d, 1 JPC = 49.8 Hz, P CH), 80.63
2.6 Hz, Cpara), 134.35 (d, 2 JPC = 9.7 Hz, Cortho), 161.00
(O C C C O), 166.88 and 173.74 (2C O, ester),
176.05 (C S). 31P NMR (202.4 MHz, CDCl3): δ 24.28
((Ph)3P+ C).
Minor isomer. 1H NMR (500.1 MHz, CDCl3):
δ 0.87–1.32 (12H, m, 2OCH2CH3 and 2NCH2CH3),
3.61 and 3.78 (4H, 2m, 2ABX3 system, 2OCH2CH3),
4.21 (4H, m, ABX3 system, 2NCH2CH3), 5.07 (1H,
and 83.62 (2C, 2OCMe3), 88.57 (d, JPC = 2.1 Hz,
3
1
P C C C), 118.49 (d, JPC = 85.2 Hz, Cipso), 129.33
3
(d, JPC = 12.9 Hz, Cmeta), 133.43 (Cpara), 134.48 (d,
2 JPC = 9.6 Hz, Cortho), 160.79 (O C C C O), 165.09
(d, 2 JPC = 1.7 Hz, C O, ester), 171.82 (d, 3 JPC = 18.1
Hz, C O, ester), 175.45 (C S). 31P NMR (202.4 MHz,
CDCl3): δ 25.31 ((Ph)3P+ C).
3
3
dd, JHH = 11.0 Hz and JPH = 6.0 Hz, P CH CH),
3
3
5.90 (1H, dd, JHH = 11.0 Hz and JPH = 13.2 Hz,
P CH CH), 7.48–7.90 (15H, m, 3C6H5); 13C NMR
(125.8 MHz, CDCl3): δ 13.31 (2NCH2CH3), 14.05
and 14.19 (2OCH2CH3), 41.91 and 41.98 (2NCH2),
REFERENCES
42.49 (d, 2 JPC = 4.6 Hz, P CH CH), 42.66 (d, 1 JPC
=
50.3 Hz, P CH), 61.33 and 62.23 (2OCH2CH3), 88.67
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(d, JPC = 2.3 Hz, P C C C), 118.02 (d, JPC
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3
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(2R∗,3R∗)-1,3-Diethyl-4,6-dioxo-2-thioxo-5-[2-
(triphenylphosphonio)-1,2-bis(tert-butoxy-
carbonyl)ethyl]tetrahydropyrimidin-5-ide (9c)
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N, 3.95.
Major isomer. 1H NMR (500.1 MHz, CDCl3):
δ 0.94 and 0.99 (18H, 2s, 2CMe3), 1.07–1.23 (6H, br,
2NCH2CH3), 4.56 (4H, br, 2NCH2CH3), 4.85 (1H, dd,
3 JHH = 10.4 Hz,3 JPH = 6.2 HZ, P CH CH), 5.64 (1H,
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