Synthesis of oxo-phosphoranylidene aminobenzoic acid derivatives by a multicomponent reaction

Article abstract of DOI:10.1080/10426500903258790

2-Aminobenzoic acids or 4-aminobenzoic acid react with dimethyl acetylenedicarboxylate/triphenylphosphine in less than 20 min at 15-25C to produce new organic phosphorus compounds in good to excellent yields. The conversion occurs with selective N- over O-alkylation of the amino group and isolation of the products is accomplished simply by filtration. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903258790

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Phosphorus, Sulfur, and Silicon and the
Related Elements
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Synthesis of oxo-Phosphoranylidene
Aminobenzoic Acid Derivatives by a
Multicomponent Reaction
Abdolreza Iraj Mansouri a , Zahra Hassani a & Mohammad Reza Islami
a b
a Department of Material Science, International Center for Science ,
High Technology and Environmental Sciences , Kerman, Iran
b Department of Chemistry , Shahid Bahonar University , Kerman,
Iran
Published online: 02 Aug 2010.
To cite this article: Abdolreza Iraj Mansouri , Zahra Hassani & Mohammad Reza Islami (2010) Synthesis
of oxo-Phosphoranylidene Aminobenzoic Acid Derivatives by a Multicomponent Reaction, Phosphorus,
Sulfur, and Silicon and the Related Elements, 185:8, 1753-1758, DOI: 10.1080/10426500903258790
To link to this article: http://dx.doi.org/10.1080/10426500903258790
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Phosphorus, Sulfur, and Silicon, 185:1753–1758, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903258790
SYNTHESIS OF OXO-PHOSPHORANYLIDENE
AMINOBENZOIC ACID DERIVATIVES
BY A MULTICOMPONENT REACTION
Abdolreza Iraj Mansouri,1 Zahra Hassani,1
and Mohammad Reza Islami1,2
1Department of Material Science, International Center for Science, High
Technology and Environmental Sciences, Kerman, Iran
2Department of Chemistry, Shahid Bahonar University, Kerman, Iran
2-Aminobenzoic acids or 4-aminobenzoic acid react with dimethyl acetylenedicarboxy-
late/triphenylphosphine in less than 20 min at 15–25◦C to produce new organic phosphorus
compounds in good to excellent yields. The conversion occurs with selective N- over O-
alkylation of the amino group and isolation of the products is accomplished simply by
filtration.
Keywords Aminobenzoic acids; dimethyl acetylenedicarboxylate; phosphonium ylide
INTRODUCTION
We have recently described the use of Meldrum’s acid 1 and N,N’-dimethyl barbituric
acid 2 as CH-acids for the synthesis of 1,4-diionic compounds (Figure 1).1 H. J. Bestmann
and co-workers reported such compounds as an intermediate in the reaction of vinyl ke-
tone and an ylide.2–4 We have shown that 1,4-diionic compounds 3 possess two vicinal
stereogenic centers and are formed as a mixture of two diastereoisomers.1 Interconversion
between the two isomers via C-H proton exchange reactions of the Ph3P+-CH moieties
precludes their separation. We were interested to examine aminobenzoic acids as precursors
for the synthesis of these betaines, although, as far as we are aware, no example of this
family has been reported. We report in this article the behavior of aminobenzoic acids on
applying this methodology. However, in this case 1,4-diionic compounds were not formed,
and the final isolated products were identified as phosphonium ylides.
RESULTS AND DISCUSSION
It is known that the reaction of acetylenic esters and Ph3P produced the intermediate
4, which is sufficiently stabilized by resonance.5,6 Thus, compounds 5a,b were apparently
Received 13 April 2009; accepted 12 August 2009.
The authors thank the International Center for Science, High Technology and Environmental Sciences for
the support of this investigation.
Address correspondence to Zahra Hassani, Department of Material Science, International Center for Science,
High Technology and Environmental Sciences, Kerman, Iran. E-mail: hassanizahra@yahoo.com
1753

1754
A. I. MANSOURI ET AL.
O
O
O
COOR
H3C
CH3
O
X
X
O
O
N
N
PPh3
Z
H
H
COOR
O
O
O
1
2
3
Figure 1 Structures of CH-acids and 1,4-diionic compound.
obtained from initial addition of triphenylphosphine to the acetylenic ester as a Michael
acceptor7 and concomitant protonation of the intermediate 4 by the COOH group. Then the
positively charged ion is attacked by the nitrogen of amino group to form compounds 5a–b
(Scheme 1).
COOH
COOCH3
x
NH2
H3COOC
Ph3P
O
H3COOC
Ph3P
C
C C
Ph3P
+
COOCH3
OCH3
COOCH3
4
COO
x
H
PPh3
COOCH3
PPh3
H
N
HOOC
H
COO
NH2
N
COOCH3
H3COOC
Ph3P
H
,
CHCOOCH3
COOCH3
COOCH3
x
x
Not formed
X = H , Cl
5a-b
6
Scheme 1
We have in fact found that under the present reaction conditions, the compounds
5a–b cannot be converted to compound 6. Instead the very mild reaction conditions proved
to be ideal for the formation of N-substituted aminobenzoic acid derivatives containing
ylide moiety in good to excellent yields with high chemoselectivity of N-over O-alkylation.
The reason for such difference between products from Meldrum’s acid or N,N’-dimethyl
barbituric acid and products from the aminobenzoic acids is not clear to us, but the stability
of such betaines as dipolar systems depends on the balance between the energy required to
separate unlike charges and the energy of ylide formation, which could play an important
role. Also the transition state for proton exchange between ylide moiety and CH-acid or
COOH group might play a role in these reactions. As shown in Scheme 2, in Meldrum’s acid
or N,N’-dimethyl barbituric acid, the proton is transferred via a six-membered ring, and this
represents a favorable transition state geometry, whereas in amino acids the eight-membered
cyclic transition state is not favorable for transfer of the proton.
Compounds 5a–c were characterized on the basis of their spectroscopic data (1H
NMR, 13C NMR, IR) and elemental analysis data. These data are consistent with the

OXO-PHOSPHORANYLIDENE AMINOBENZOIC ACID DERIVATIVES
1755
CO2CH3
+
CO2CH3
CO2CH3
O
H
H
N
X
X
PPh3
+
Z
PPh3
H
COOCH3
O
O
O
X = O , NCH3
Z = C(CH3)2, C=O
Favorable geometry
Unfavorable geometry
Scheme 2
presence of two rotational isomers.8–12 The ylide moiety in these compounds is strongly
conjugated with the adjacent carbonyl group, and rotation about the partial C.C double
bond in 5-(E) and 5-(Z) geometrical isomers is slow at room temperature (Figure 2).
1
Thus the H NMR spectrum of compound 5a showed four sharp lines due to the
methoxy protons at δ = 2.99, 3.44, 3.53, and 3.55 ppm along with signals for the methine
protons at δ = 4.05 and 4.34 ppm, which appear as two doublets (3JPH = 18.2 Hz) for the Z
and E geometrical isomers. The aromatic protons appear at δ = 6.42–8.51 ppm. Protons of
COOH and two NH groups are observed as three broad signals at δ = 12.41, 5.65, and 5.98
ppm, respectively. These signals disappear when D2O is added. The 13C NMR spectrum of
5a displayed 30 distinct resonances in agreement with the mixture of two rotational isomers.
1
Although the presence of the 31P nucleus complicates both the H and 13C NMR spectra
of 5a, it helps in assignment of signals by long-range spin–spin couplings with 1H and 13
C
nuclei. The H and 13C NMR spectra of compound 5b are similar to those of 5a, except
for the signals resulting from the aromatic ring. With these results in hand, we next tried
to study the behavior of 4-aminobenzoic acid in the preparation of 1,4-diionic compounds.
It was assumed that the transfer of the proton would be intermolecular and betain 8 could
be formed. However, the expected compound 8 was not formed when 4-aminobenzoic acid
was used and the phosphorus compound 7 was obtained instead, although the COOH group
in the para position can act as an acid and the ylide moiety is very active for attracting such
protons (Scheme 3).
1
Again, the spectroscopic data (1H NMR, 13C NMR, IR) and elemental analysis data
1
were used for determination of the structure of the product. Thus the H NMR spectrum
of compound 7 showed four sharp lines due to the methoxy protons at δ = 2.97, 3.43,
3.56, and 3.58 ppm along with signals for the methine protons at δ = 4.02 and 4.31 ppm,
which appear as two doublets (3JPH = 18.2 Hz) for the Z and E geometrical isomers. The
aromatic protons appear as a multiplet at δ = 6.40–7.77 ppm. Protons of COOH and NH
COOH
CO2CH3
COOH
CO2CH3
O
OCH3
O
N
H
N
H
Ph3P
OCH3
Ph3P
5a-( )
5a-( )
Figure 2 Structure of Z and E geometrical isomers.

1756
A. I. MANSOURI ET AL.
OOC
COOCH3
COOCH3
H
N
PPh3
C
PPh3
COOCH3
NH
H2N
COOH
+
C
H3COOC
HOOC
COOCH3
H
COOCH3
Ph3P
H
7
8
Scheme 3
groups are observed as two broad signals at δ = 11.98 and 6.12 ppm, respectively. The 13
C
NMR spectrum of 7 displayed 28 distinct resonances in agreement with the mixture of two
rotational isomers.
In conclusion, we have reported an efficient multiple component condensation re-
action for the synthesis of phosphorus compounds using aromatic amino acids in good to
excellent yields.
EXPERIMENTAL
Dimethyl acetylenedicarboxylates, 2-aminobenzoic acid, 5-chloro-2-aminobenzoic
acid, 4-aminobenzoic acid, and triphenylphosphine were obtained from Merck Chemical
Co. and were used without further purification. Melting points were obtained on a Gal-
lenkamp melting point apparatus and were uncorrected. Elemental analyses for C, H, and
N were performed by the Tarbiat Moallem University using a Heracus CHN-O-Rapid ana-
lyzer. IR spectra were measured on a Mattson 1000 FT-IR spectrometer. 1H and 13C NMR
spectra were recorded on a Bruker DRX-500 AVANCE spectrometer at 500 and 125.77
MHz, respectively. Throughout this section, an asterisk (∗) denotes two rotamers.
Synthesis of Ylides 5: General Procedure
At 15–25◦C, dimethyl acetylenedicarboxylate (0.24 mL, 2 mmol) was added dropwise
to a stirred solution of triphenylphosphine (0.53 g, 2 mmol) and 2-aminobenzoic acid
(0.28 g, 2 mmol) in acetone (10 mL). After the addition was complete (approximately
5 min), the mixture was stirred for an additional 10 min and was subsequently filtered. The
solid collected in the filter was washed thoroughly with cold acetone to give a pale yellow
powder.
2-{3-Methoxy-1-(methoxycarbonyl)-3-oxo-2-(1,1,1-triphenyl-λ5-phosphany
lidene)propyl]amino} benzoic acid (5a). Yellow powder (0.84 g, mp 149–152◦C,
yield 77.8%); IR (KBr) (υmax,cm−1): 3365 (NH), 3055–2554 (OH), 1757, 1740 and 1670
(C O), Anal. Calcd. for C31H28NO6P (541.53): C, 68.76; H, 5.21; N, 2.59%. Found:
1
C, 68.68, H, 5.17; N, 2.43%. Major conformational isomer 5a-(Z) (52.4%): H NMR
3
(DMSO): δ = 2.99 (s 3H, OCH3), 3.53 (s, 3H, OCH3), 4.05 (d, JPH = 18.2 Hz, 1H,
P C CH), 5.69 (broad, 1H, NH), 6.42–8.51 (m, 38H, arom-H)∗, 12.41 (broad, 1H, OH)∗.
13C NMR (DMSO): δ = 42.0 (d, 1JPC = 128.6 Hz, P C), 48.5 (OCH3), 51.7 (OCH3), 55.1
(d, 2JPC = 13.2 Hz, P C CH), 110.5 (C), 113.9 (CH), 116.2 (CH), 126.2 (d, 1JPC = 91.2
Hz, C-i), 128.7 (d, 3JPC = 12.0 Hz, C-m)∗, 131.4 (CH), 132.2 (d, 4JPC = 2.0 Hz, C-p), 133.2
2
(C-o)∗, 133.5 (CH), 149.3 (C), 168.3 (C O)∗, 169.6 (d, JPC = 24.8 Hz, C O), 173.0
1
(C O)∗. Minor conformational isomer 5a-(E) (47.6%): H NMR (DMSO): δ = 3.44 (s,

OXO-PHOSPHORANYLIDENE AMINOBENZOIC ACID DERIVATIVES
1757
3H, OCH3), 3.55 (s, 3H, OCH3), 4.34 (d,3JPH = 18.2 Hz, 1H, P C CH), 5.98 (broad, 1H,
NH). 13C NMR (DMSO): δ = 43.2 (d, 1JPC = 128.6 Hz, P C), 49.4 (OCH3), 51.7 (OCH3),
54.2 (d, 2JPC = 10.3 Hz, P C CH), 110.9 (C), 114.7 (CH), 115.8 (CH), 126.2 (d, 1JPC
=
93.2 Hz, C-i), 131.1 (CH), 131.9 (C-p), 132.9 (CH), 149.6 (C), 169.2 (d, 2JPC = 21.9 Hz,
C O).
5-Chloro-2-{3-methoxy-1-(methoxycarbonyl)-3-oxo-2-(1,1,1-triphenyl-λ5-
phosphanylidene)propyl]amino} benzoic acid (5b). Yellow powder (1.1 g, mp
148–151◦C, yield 80.5%); IR (KBr) (υmax, cm−1): 3367 (NH), 3080–2519 (OH), 1753,
1741 and 1672 (C O), Anal. Calcd. for C31H27ClNO6P (575.98): C, 64.64; H, 4.72; N,
2.43%. Found: C, 64.47; H, 4.60; N, 2.30%. Major conformational isomer 5b-(Z) (54.7%):
3
1H NMR (DMSO): δ = 2.97 (s, 3H, OCH3), 3.54 (s, 3H, OCH3), 4.33 (d, JPH = 17.1
Hz, 1H, P C CH), 5.73 (broad, 1H, NH), 6.21–8.51 (m, 36H, arom-H)∗, 12.69 (broad,
1H, OH)∗. 13C NMR (DMSO): δ = 49.0 (d, 1JPC = 104.7 Hz, P C)∗, 51.8 (OCH3), 51.7
(OCH3), 55.4 (d, 2JPC = 17.0 Hz, P C CH), 111.7 (C), 113.3 (CH), 117.2 (CH), 125.9
1
3
(d, JPC = 96.6 Hz, C-i), 128.8 (d, JPC = 12.1 Hz, C-m)∗, 132.1 (C-p), 131.4 (CH)∗,
133.1 (d, JPC = 15.0 Hz, C-o), 133.8 (CH)∗, 147.9 (C), 150.1 (C), 167.7 (C O), 168.7
2
(d, 2JPC = 17.1 Hz, C O)∗, 172.7 (C O). Minor conformational isomer 5b-(E) (45.3%):
1H NMR (DMSO): δ = 3.43 (s, 3H, OCH3), 3.56 (s, 3H, OCH3), 4.02 (d, JPH = 17.1
3
Hz, 1H, P C CH), 6.04 (broad, 1H, NH). 13C NMR (DMSO): δ = 52.0 (OCH3), 52.2
(OCH3), 54.4 (d, 2JPC = 17.0 Hz, P C CH), 111.2 (C), 112.9 (CH), 118.1 (CH), 125.6
2
2
(d, JPC = 97.9 Hz, C-i), 130.3 (C-p), 133.0 (d, JPC = 15.6 Hz, C-o), 148.1 (C), 148.2
(C), 167.5 (C O), 172.5 (C O).
4-{3-Methoxy-1-(methoxycarbonyl)-3-oxo-2-(1,1,1-triphenyl-λ5-phosphany
lidene)propyl]amino} benzoic acid (7). Yellow powder (0.87 g, mp 118–120◦C,
yield 80.5%); IR (KBr) (υmax, cm−1): 3361 (NH), 3055–2544 (OH), 1753, 1741 and 1676
(C O), Anal. Calcd. for C31H28NO6P (541.53): C, 68.76; H, 5.21; N, 2.59%. Found: C,
68.55; H, 5.21; N, 2.42%. Major conformational isomer 7-(Z) (55.0%), 1H NMR (DMSO):
δ = 2.97 (s, 3H, OCH3), 3.56 (s, 3H, OCH3), 4.02 (d,3JPH = 18.2 Hz, 1H, P C CH),
6.12 (broad, 1H, NH)∗, 6.40–7.77 (m, 38H, arom-H)∗, 11.97 (broad, 1H, OH)∗. 13C NMR
(DMSO): δ = 41.5 (d, 1JPC = 122.8 Hz, P C), 48.5 (OCH3), 51.7 (OCH3), 55.0 (d, 2JPC
=
1
19.5 Hz, P C CH), 111.0 (C), 122.1 (CH)∗, 126.2 (d, JPC = 90.6 Hz, C-i), 129.0 (d,
2
3JPC = 12.0 Hz, C-m), 130.4 (CH), 132.2 (C-p), 133.2 (d, JPC = 10.1 Hz, C-o)∗, 151.2
2
3
(C), 167.5 (C O), 168.3 (d, JPC = 14.6 Hz, C O), 172.8 (d, JPC = 8.7 Hz, C O).
1
Minor conformational isomer 7-(E) (45.0%): H NMR (DMSO): δ = 3.43 (OCH3), 3.58
(s, 3H, OCH3), 4.31 (d, 3JPH = 18.2 Hz, 1H, P C CH). 13C NMR (DMSO): δ = 42.8 (d,
1JPC = 140.4 Hz, P C), 49.5 (OCH3), 52.3 (OCH3), 54.4 (d, 2JPC = 19.5 Hz, P C CH),
1
3
110.9 (C), 125.8 (d, JPC = 86.9 Hz, C-i), 128.8 (d, JPC = 12.2 Hz, C-m), 130.7 (CH),
132.7 (C-p), 156.5 (C); 167.4 (C O), 169.2 (d, 2JPC = 19.0 Hz, C O), 173.1 (d, 3JPC
=
9.0 Hz, C O).
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