Synthesis of highly functionalized phosphorus ylids containing heterocyclic rings and the related iminophosphoranes

Article abstract of DOI:10.1080/10426500701407482

Crystalline phosphorus ylides are obtained in excellent yields from the 1:1:1 addition reaction between triphenylphosphine, dimethyl acetylenedicarboxylate (DMAD) and NH and SH acids, such as 2-amino-4-phenyl thiazole, 2-amino-5-(3-chloro-benzyl) thiadiazole, 3-amino-2-methyl quinazolin-4-one and 3-amino-2-mercapto quinazolin-4-one. These stabilized phosphoranes undergo a smooth intramolecular reaction in boiling toluene to produce aryliminophosphoranes in excellent yields.

Full text of DOI:10.1080/10426500701407482

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Synthesis of Highly
Functionalized Phosphorus
Ylids Containing Heterocyclic
Rings and the Related
Iminophosphoranes
Hojatollah Khabazzadeh a , Kazem Saidi a , Hassan
Sheibani a & Mohammad Reza Islami a
a Department of Chemistry , Shahid Bahonar
University of Kerman , Kerman, Iran
Published online: 16 Jul 2007.
To cite this article: Hojatollah Khabazzadeh , Kazem Saidi , Hassan Sheibani
& Mohammad Reza Islami (2007) Synthesis of Highly Functionalized Phosphorus
Ylids Containing Heterocyclic Rings and the Related Iminophosphoranes,
Phosphorus, Sulfur, and Silicon and the Related Elements, 182:9, 2163-2170, DOI:
10.1080/10426500701407482
To link to this article: http://dx.doi.org/10.1080/10426500701407482
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Phosphorus, Sulfur, and Silicon, 182:2163–2170, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701407482
Synthesis of Highly Functionalized Phosphorus Ylids
Containing Heterocyclic Rings and the Related
Iminophosphoranes
Hojatollah Khabazzadeh
Kazem Saidi
Hassan Sheibani
Mohammad Reza Islami
Department of Chemistry, Shahid Bahonar University of Kerman,
Kerman, Iran
Crystalline phosphorus ylides are obtained in excellent yields from the 1:1:1
addition reaction between triphenylphosphine, dimethyl acetylenedicarboxylate
(DMAD) and NH and SH acids, such as 2-amino-4-phenyl thiazole, 2-amino-5-
(3-chloro-benzyl) thiadiazole, 3-amino-2-methyl quinazolin-4-one and 3-amino-2-
mercapto quinazolin-4-one. These stabilized phosphoranes undergo a smooth in-
tramolecular reaction in boiling toluene to produce aryliminophosphoranes in ex-
cellent yields.
Keywords Dimethyl acetylenedicarboxylate; phosphorus ylide; quinazolin-4-one;
thiazole
INTRODUCTION
In the realm of ylide compounds and their value for a variety of in-
dustrial, biological and chemical synthetic uses, phosphorus ylides are
playing increasingly pivotal roles.1,2 For a reaction to be synthetically
applicable, should have readily available starting materials, high yields
and furthermore the product must be free of contaminants so as to
avoid the need for extensive purification.3 The chemistry of ylide com-
pounds has provided chemists with exceptionally fertile ground for
the design and development of new bond formation.4 Since the pio-
neering work by Staudinger and Meyre in 1919,5 on the preparation
of iminophosphoranes, compounds of general structure R3P NR, the
Received November 18, 2006; accepted March 31, 2007.
The authors express appreciation to the Shahid Bahonar University of Kerman Fac-
ulty Research Committee for its support of this investigation.
Address correspondence to Kazem Saidi, Department of Chemistry, Shahid Bahonar
University of Kerman, 76169, Kerman, Iran. E-mail: saidik@mail.uk.ac.ir
2163

2164
H. Khabazzadeh et al.
synthetic application of phosphorus ylides to the preparation of vari-
ous organic products has increased enormously during the last three
decades.6 Several methods for the preparation of iminophophoranes
have been developed.7−9
RESULTS AND DISCUSSION
As part of our continuing interest in this area, we have recently reported
synthesis of highly functionalized phosphorus ylides.10
Now, in this investigation we wish to report synthesis of stable phos-
phorus ylides from thiazoles and quinazolinones 1a–d (Scheme 1).
The ylides 2a, b were converted to iminophosphoranes 3a, b, when
the reaction mixture was refluxed in toluene (Scheme 2).
It is reasonable to assume that phosphorus ylide 2 results from the
initial addition of triphenylphosphine to DMAD and subsequent proto-
nation of the (1:1) adduct. Then the positively charged ion is attacked
by conjugate base of 1 to form stable phosphorus ylide 2 (Scheme 3).
The proposed structures of compounds 2a–d were supported by their
elemental analyses and spectroscopic properties, such as 1H NMR, 13
NMR, IR and mass spectral data.
C
There are two absorptions at the IR spectra in the region of carbonyl
groups. One of the carbonyl groups reveals a strong band at 1640 cm−1
which is conjugated with ylide moiety and the nonconjugated carbonyl
group appears at about 1750 cm.−1
Since the rotation about the partial double bond in E and Z isomers
is slow on the NMR time scale at ambient temperature (Scheme 4);
therefore, the presence of a mixture of two geometrical isomers E and Z
for compounds 2a–d was proven by their 13C NMR & 1H NMR absorp-
1
tion. For example H NMR and 13C NMR spectra of these compounds
show four singlets for methyl hydrogens and four absorptions for car-
bonyl groups respectively, which are indicative of the presence of two
isomers. Presence of the 31P-nucleus helps in assignment of compounds
2a–d by long range spin-spin coupling constants of 31P with 1H and 13
C
nuclei.
The 1H NMR spectrum of 2a shows four different sharp lines at δ =
3.15, 3.61, 3.71, and 3.80 ppm, which are due to the methoxy protons,
along with signals for methine protons at δ = 4.45 and 4.70 ppm which
appear as two multiplets respectively for minor and major isomers. Two
fairly broad signals at δ = 6.25 and 6.87 ppm are related to protons
of N-H groups. The mass spectra of compounds 2a–d did not reveal
molecular ion peak. Peaks at m/z 262 and 183 which are correspond to
Ph3P+ and C12H8P+ were observed. The 13C NMR of compound 2a is in
good agreement with the proposed structure of this compound. The 1H

Highly Functionalized Phosphorus Ylides
2165
SCHEME 1
NMR and 13C NMR spectra of compounds 2a–d are similar to those of
2a except for the signals from the aromatic rings which appear in the
corresponding chemical shifts.
Compounds 2a and 2b undergo a smooth and clean reaction in boiling
toluene to produce iminophosphoranes 3a and 3b. All of the attempts to
convert 2c to its related iminophosophorane were mostly unsuccessful.

2166
H. Khabazzadeh et al.
SCHEME 2
SCHEME 3
SCHEME 4
This transformation was suggested to proceed by an initial N-H pro-
ton shift onto the ylide carbon of the 2a and forms the phosphorus
betaine 4 and was followed by intramoleculr ring closure to produce
azaphosphetane 5 which can be in equilibrium with betaine 4. The
only product formed under these conditions was iminophosphorane 3
(Scheme 5).
1
The H NMR of 3a displays proton of thiazole ring at 6.41 and aro-
matic protons at 7.25–7.89 ppm. The 13C NMR of this compound reveals

Highly Functionalized Phosphorus Ylides
2167
SCHEME 5
seven distinct resonances for carbons of phenyl and thiazol rings. Sig-
3
nals of triphenylphosphine group appear at 128.56 (d, Jpc = 12.3 Hz,
Cmeta), 128.62 (d, 1Jpc =101.8 Hz Cipso), 132.21 (d, 4Jpc = 2.1 Hz, Cpara),
133.22 (d, 2J = 10.1 Hz, Cortho).
EXPERIMENTAL
General Procedures
Triphenylphosphine, dimethyl acetylenedicarboxylate, toluene, hexane
and ethyl acetate were obtained from Merck Chemical Company and
were used without further purification. Compounds 1a–d were pre-
pared according to the reported procedure in the literature.11−14 Melt-
ing points were obtained on a Gallenkamp melting point apparatus
and are uncorrected. IR spectra were measured on a Mattson 1000 FT-
1
IR spectrometer. The H and 13C NMR spectra were recorded with a
BRUKER DRX-500 AVANCE spectrometer at 500.1 and 125.7 MHz,
respectively. Mass spectra were recorded on a MS-QP2000A Shimadzu
mass spectrometer operating at an ionization potential of 70 eV. El-
emental analyses were performed by Ferdousi University (Mashhad)
using a Heracus CHN-O-Rapid analyzer.
Dimethyl 2-[(4-phenyl-1, 3-thiazol-2-yl)
amino]-3-(triphenylphosphoranylidine)-butanedioate (2a)
The procedure for the preparation of the title compound is described
as an example. To a magnetically stirred solution of triphenylphosphine
(0.52 g, 2.00 mmol) and 2-amino-4-phenyl tiazole (0.35 g, 2.00 mmol)
in ethyl acetate (4 mL) was added dropwise a mixture of DMAD (0.28
g, 2.00 mmol) in ethyl acetate (2 mL) at 0oC over 10 min. The reaction
mixture was then allowed to warm up to room temperature and stirred
for 2 h. The resulted precipitate was filtered off and then recrystallized
from 1:1 hexane–ethyl acetate.

2168
H. Khabazzadeh et al.
White powder, m.p. = 140–143◦C, yield = 1.04 g (90%); IR (KBr)
(νmax, cm−1): 3404 (NH), 1741 (C O), 1641 (C O). MS, m/z(%): 436
(M+-C6H8O4, 79), 333 (40), 262 (PPh3, 88), 183 (95), 113 (100). Anal.
Calcd. for C33H29N2O4PS: C, 68.26; H, 5.03; N, 4.82%. Found: 68.01; H,
4.95, N, 4.51%.
Major isomer (Z) (63%), 1H NMR: δ 3.15 and 3.71 (6H, s, 2OCH3), 4.70
(1H, m, P C CH), 6.56 (1H, s, thiazole ring), 6.87 (1H, br s, NH), 7.21–
1
7.77 (40H, m, arom).* 13C NMR: δ 43.29 (d, JPC = 128.1 Hz, P C)∗,
49.03 and 52.24 (2OCH3), 57.58 (d, 2JPC = 15.6 Hz, P C CH)∗, 100.73
(CH)∗, 126.13 (2CH)∗, 126.73 (d, 1JPC = 97.9 Hz, Cipso)∗, 128.06 (2CH)∗,
128.43 (CH)∗, 128.62 (d, 3JPC = 12.4 Hz, Cmeta)∗, 131.98 (Cpara)∗, 133.78
2
2
(d, JPC = 9.6 Hz, Cortho)∗, 150.91 (C)∗, 167.94 (C)∗, 170.16 (d, JPC
=
14.6 Hz, C O)∗, 173.99 (C O)∗.
Minor isomer (E) (37%), H NMR: δ 3.61 and 3.80 (6H, s, 2OCH3),
4.52 (1H, m, P = C-CH), 6.25 (1H, s br, NH), 6.68 (1H, s, thiazole ring).
13C NMR: δ 50.18 and 52.24 (2OCH3).
1
Dimethyl 2-[5-(3-chloro-benzyl)-[1, 3, 4] thiadiazol-2-yl)
amino]-3-(triphenylphosphorany-lidine)-butanedioate (2b)
White powder, m.p. = 120–124◦C, yield = 1.05 g (88%); IR (KBr)
(νmax, cm−1): 3379 (NH), 1765 (C O), 1620 (C O). MS, m/z (%): 517
(M+-C6H8O4, 32), 288 (100), 262 (PPh3, 25), 183 (47).
Major isomer (E) (77%), 1H NMR: δ 3.13 and 3.67 (6H, s, 2OCH3), 4.21
(2H, m, CH2)∗, 4.48 (1H, m, P C CH)∗, 6.88 (1H, br s, NH)∗, 7.21–7.68
1
(38H, m, arom)∗. 13C NMR: δ 38.65 (CH2), 42.89 (d, JPC = 126.7 Hz,
P C)∗, 49.12 and 52.32 (2OCH3), 57.84 (d, 2JPC = 16.1 Hz, P C CH)∗,
1
126.26 (d, JPC = 92.6 Hz, Cipso)∗, 127.27 (CH), 127.77 (CH), 128.67
3
(d, JPC = 12.3 Hz, Cmeta)∗, 129.11 (CH), 129.81 (CH), 132.23 (Cpara)∗,
2
133.72 (C)∗, 133.75 (d, JPC = 9.9 Hz, Cortho)∗, 134.31 (C), 150.51 (C)∗,
165.45 (C)∗, 170.29(d, 2JPC = 12.5 Hz, C O)∗, 173.03 (C O)∗.
1
Minor isomer (Z) (23%), H NMR: δ 3.56 and 3.80 (6H, s, 2OCH3).
13C NMR: δ 38.34 (CH2), 50.20 and 52.28 (2OCH3), 128.43 (CH), 128.53
(CH), 132.02 (CH), 132.10 (CH), 132.80 (C), 133.20 (C).
Dimethyl 2-[(2-methyl-4-oxo-3(4H)-quinazolinyl)
amino]-3-(triphenylphosphoranylidine)-butanedioate (2c)
White powder, m.p. = 174–177◦C, yield = 0.985 g (85%); IR
(KBr) (νmax, cm−1): 3305 (NH), 1765 (C O), 1691 (C O), 1641(C=N).
MS,m/z(%): 405 (M+-C9H8N3O, 100), 262 (PPh3, 18), 183 (25). Anal.
Calcd. for C33H30N3O5P: C, 68.39; H, 5.22; N, 7.25 %. Found: 68.07; H,
5.18, N, 7.25%.
*For two geometrical isomers.

Highly Functionalized Phosphorus Ylides
2169
1
Major isomer (Z) (73%), H NMR: δ 2.59 (1H, br s, NH), 3.20 (3H,
3
s, CH3), 3.66 and 3.76 (6H, s, 2OCH3), 3.80 (1H, d, JPH = 13.42 Hz,
P C CH)∗, 7.28-8.05 (38H, m, arom)∗. 13C NMR: δ 22.01 (CH3)∗, 42.08
1
2
(d, JPC = 133.9 Hz, P=C), 49.09 and 50.26 (2OCH3), 60.62 (d, JPC
=
19.5 Hz, P C CH), 125.94 (d, 1JPC = 91.8 Hz, Cipso), 128.53 (d, 3JPC
=
11.9 Hz, Cmeta), 131.79 (Cpara)∗, 131.95 (CH)∗, 132.02 (CH)∗, 132.11 (C)∗,
132.94 (C)∗, 133.29 (CH)∗, 133.45 (d, 2JPC = 9.6 Hz, Cortho), 134.13 (CH)∗,
147.50 (C)∗, 165.25 (C O)∗, 169.60 (d, JPC = 14.46 Hz, C O), 173.03
2
(C O).
1
Minor isomer (E) (27%), H NMR: δ 2.47 (1H, br s, NH), 2.70 (3H,
s, CH3), 3.80 and 3.82 (6H, s, 2OCH3).13C NMR: δ 39.86 (d, JPC
=
1
2
141.0 Hz, P C), 50.09 and 52.25 (2OCH3), 61.62 (d, JPC = 18.6 Hz,
P C CH), 126.58 (d, 1JPC = 95.5 Hz, Cipso), 128.39 (d, 3JPC = 11.8 Hz,
Cmeta), 133.38 (d, 2JPC = 9.5 Hz, Cortho), 170.69 (d, 2JPC = 16.5 Hz, C O).
Dimethyl 2-[(3-amino-4-oxo-3, 4-dihydro-2-quinazolinyl)
sulfanyl]-3-(triphenylphosphora-nylidine)-butanedioate (2d)
White powder, m.p. = 157–160◦C, yield = 1.04 g (87%); IR (KBr) (νmax
,
cm−1): 3330 and 3203 (NH2), 1746 (C O), 1682 (C O), 1640 (C O).
MS,m/z(%): 320 (M+-Ph3P=O, 15), 301 (20), 288 (85), 277 (46), 262
(PPh3, 67), 183 (100), 108 (39), 77 (44), 51 (40).
Major isomer (Z) (60%), 1H NMR: δ 3.09 and 3.77 (6H, s, 2OCH3), 4.39
(2H, s, NH2), 4.59 (1H, d, 3JPH = 15.6 Hz, P C CH)∗, 7.05–8.07 (38H, m,
1
arom)∗. 13C NMR: δ 40.82 (d, JPC = 128.1 Hz, P C), 49.08 and 52.11
2
(2OCH3), 62.67 (d, JPC = 15.1 Hz, P C CH), 122.08 (CH)∗, 122.80
1
(CH)∗, 124.93 (CH)∗, 126.37 (d, JPC = 93.4Hz, Cipso), 126.48 (CH)∗,
3
4
128.48 (d, JPC = 11.6 Hz, Cmeta)∗, 131.90 (d, JPC = 2.0 Hz, Cpara)∗,
133.66 (d, 2JPC = 10.4 Hz, Cortho)∗, 134.02 (C)∗, 134.49 (C)∗, 150.25 (C),
161.88 (C O), 170.10 (d, 2JPC = 14.2 Hz, C O), 174.96 (d,3JPC = 7.0 Hz,
C O).
1
Minor isomer (E) (40%), H NMR: δ 3.5 and 3.74 (6H, s, 2OCH3),
4.57 (2H, s, NH2).13C NMR: δ 42.08 (d, JPC = 135.2 Hz, P=C), 50.22
1
2
and 52.00 (2OCH3), 62.44 (d, JPC = 14.1 Hz, P C CH), 150.048 (C),
162.019 (C O), 170.54 (d,2JPC = 16.3 Hz, C O), 175.14 (d, ,3JPC = 6.8
Hz, C O).
N-(4-Phenyl-1, 3-thiazol-2-yl) triphenyliminophosphorane (3a)
The process for the preparation of 3a is described as an example. A
mixture of 2a (0.52 g, 1.0 mmol) in toluene (10 mL) was refluxed for 8 h.
The solvent was removed under reduced pressure. Dimethyl fumarate
sublimated under reduced pressure and the residue recrystallised from
1:1 hexane– ethyl acetate as colorless crystals.

2170
H. Khabazzadeh et al.
White crystals, m.p. =162–166◦C, yield = 0.41 g (95%), IR (KBr) (νmax
,
cm−1): 1591, 1492, 1443, 1319, 1244. MS, m/z (%): 436 (M+, 100), 262
(PPh3, 40), 183 (82), 108 (53). Anal. Calcd. for C27H21N2PS: C, 74.29;
H, 4.85; N, 6.42 %. Found: 73.97; H, 4.58, N, 6.07%.
1H NMR: δ 6.41–7.89 (21H, m, arom). 13C NMR: δ 103.29 (C), 125.28
3
(CH), 125.75 (2CH), 126.77 (C), 128.17 (2CH), 128.56 (d, JPC = 12.3
1
4
Hz, Cmeta), 128.62 (d, JPC = 101.8 Hz, Cipso), 132.21 (d, JPC =2.1 Hz,
Cpara), 133.22 (d, 2JPC =10.1 Hz, Cortho), 137.85 (C), 149.68 (C).
N-(5-(3-Chloro-benzyl)-[1, 3, 4] thiadiazol-2-yl)
triphenyliminophosphorane (3b)
White crystals, m.p. = 138–140◦C, yield = 0.42 g (93%); IR (KBr)
(νmax, cm−1): 1594, 1581, 1481, 1426, 1320, 1230. MS,m/z(%): 519 (M+2,
12), 519 (M+, 30), 282 (100), 183(40). Anal. Calcd. for C27H21ClN3PS:
C, 66.73; H, 4.36; N, 8.65 %. Found: 66.42; H, 4.12, N, 8.46%.
1H NMR: δ 4.28 (2H, s, CH2), 7.20-7.81 (19H, m, arom). 13C NMR: δ
37.54 (CH2), 127.26 (d, 1JPC = 91.2Hz, Cipso), 127.32 (CH), 127.62 (CH),
3
128.82 (d, JPC = 12.6 Hz, Cmeta), 129.14 (CH), 129.74 (CH), 132.65
(Cpara), 133.12 (d, 2JPC = 10.2 Hz, Cortho), 133.37 (C), 134.21 (C), 138.89
(C), 152.14 (C).
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