Novel communication: Some novel organosulfur amino acid derivatives as potential antiparasitic agents

Article abstract of DOI:10.1080/10426500601142221

The chalones 1, 14, and 26 reacted with chlorosulfonic acid to give corresponding sulfonyl chlorides 2, 15, and 27, which condensed with nucleophiles to give amino acid derivatives 3-6, 16-18, and 28-31. Some of the corresponding methyl esters 7, 8, 19-20

Full text of DOI:10.1080/10426500601142221

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Phosphorus, Sulfur, and Silicon
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Novel Communication: Some
Novel Organosulfur Amino
Acid Derivatives as Potential
Antiparasitic Agents
Ragab A. El-Sayed a
a Chemistry Department , Al-Azhar University , Nasr
City, Cairo, Egypt
Published online: 20 Apr 2007.
To cite this article: Ragab A. El-Sayed (2007) Novel Communication: Some
Novel Organosulfur Amino Acid Derivatives as Potential Antiparasitic Agents,
Phosphorus, Sulfur, and Silicon and the Related Elements, 182:5, 1143-1151, DOI:
10.1080/10426500601142221
To link to this article: http://dx.doi.org/10.1080/10426500601142221
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Phosphorus, Sulfur, and Silicon, 182:1143–1151, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500601142221
Novel Communication: Some Novel Organosulfur Amino
Acid Derivatives as Potential Antiparasitic Agents
Ragab A. El-Sayed
Chemistry Department, Al-Azhar University, Nasr City, Cairo, Egypt
The chalones 1, 14, and 26 reacted with chlorosulfonic acid to give correspond-
ing sulfonyl chlorides 2, 15, and 27, which condensed with nucleophiles to give
amino acid derivatives 3–6, 16–18, and 28–31. Some of the corresponding methyl
esters 7, 8, 19–20, and 32–34 were prepared. Hydrazinolysis of these methyl esters
yielded hydrazides 9, 10, 21, 22, and 35–36. Coupling reaction of some amino acid
derivatives with amino acid methyl ester hydrochloride in THF-Et3N using dicy-
clohexylcarbodiimide method furnished the desired dipeptide methyl ester’s 11–13,
23–25, and 37–38. Some spectroscopic evidence including NMR spectra analysis
are briefly discussed.
Keywords Chalones amino acid derivatives; chlorosulfonation; sulfonyl chloride; reac-
tions with nucleophiles as an essential amino acid
INTRODUCTION
The work described in this article forms part of our general pro-
gram concerned with the chemistry and biological evaluation of ary-
sulfonyl derivatives.1−12 Chalcone derivatives are of interest as po-
tential biocides, since some naturally occurring antibiotics,13 and
aminochalcones14,15 owe their activity to the presence of the α, β-
unsaturated carbonyl group. Chlorosulfonation provides a useful route
to a variety of sulfonyl derivatives by nucleophilic displacement of the
chlorine atom in the resulting sulfonyl chloride. These compounds are
of interest for potential biocidal activity.16−19
Early workers20 examined the sulfonation of chalcone and 4-
methoxychalcone and concluded that the latter gave sulfonic acid.
Later, several chalcone-4-sulfonamides were prepared by a conden-
sation of N-substituted P-sulfonyl benzaldiacetates with substituted
acetophenones.21 In chalcones (1 and 26) the 4- or 5-position should be
active due to the activating influence of the olefinic double bond.
Received May 23, 2006; accepted October 17, 2006.
Address correspondence to Ragab A. El-Sayed, Chemistry Department, Faculty of
Science, Al-Azhar University, Nasr City, Cairo, Egypt. E-mail:dr ragabaly@yahoo.com
1143

1144
R. A. El-Sayed
We have demonstrated that the optimum conditions for the chloro-
sulfonation of chalcone (75% yield) were by a reaction with a reagent
(6 mol. equivalent); for 3 weeks at r.t., the more reactive P-methoxy chal-
cone reacted faster under similar conditions (63% yield in one week or
75% yield in 24 h, respectively).
DISCUSSION
The present work involves the chlorosulfonation of chalcones 1, 14, and
16 (Chart 1).
The chalcones were prepared by the standard procedure22,23 involv-
ing base-catalyzed condensation of the appropriate aromatic aldehyde
and accetophenone or the p-methoxy derivatives.
The different chalcones were reacted with chlorosulfonic acid, gener-
ally, 6 mol. equivalents or 3 mol. equivalents in excess thionyl chloride
at r.t., to give the corresponding sulfonyl chlorides, which were con-
densed with a range of amino acid to give the sulfonamide listed in
Table I.
Chalcones are active due to the powerful combined electron-donating
methoxy group and the alkenic double bond in enhancing reactivity of
the benzene ring with respect to electrophilic attack. The NMR spectra
of chlacone which demonstrated that the alkenic H-proton (δ 7.79, 7.72)
the most sensitive to substitutent effects.
The NMR spectra of 2-thienylidene sulfonylamino acid showed
the resonance of thiophene protons as a doublet (δ 7.7). In chalcone
PhCO.CH CH moiety was estimated from the literature-data for
PhCO and CH CH group.24
The electron impact mass spectra of the majarity of the chalcone
sulfonylamino acid derivatives showed the molecular ions M+.
EXPERIMENTAL
Melting points were taken on a Griffin melting point apparatus and
are uncorrected. Infrared analysis of solid samples were run as a KBr
1
disc on a Schimadzu model 440 spectrophotometer. H NMR spectra
were measured in DMSO-d6 as a solvent unless otherwise stated us-
1
ing Fx 90 Q Fourier Transform H NMR. Mass spectra were obtained
using a Schimadzu (Japan). GC. M.S. QP 1000 Ex spectrometer using
the direct inlet system. TLC analyses were carried out on Merek silica
gel plates and developed with n-butanol-acetic acid-water (4:1:1) using
iodine, ninhydrin, and benzidine as spraying agents.
Compounds 2, 15, and 27 were prepared according to the procedure
described earlier.25,26

Organosulfur Amino Acid Derivatives
1145
CHART 1
Coupling Reaction 3–5, 16–18, and 28–31: General Procedure
To an amino acid (0.11 mol) in a water (25 mL) THF (15 mL) mixture
was added triethylamine (5 mL), followed by a protionwise addition

1146

1147

1148

Organosulfur Amino Acid Derivatives
1149
of sulfonyl chlorides (0.1 mol) during 30 min. The temperature of the
reaction mixture during the process of the addition was kept at 10◦C.
Stirring continued for 4 h at 20◦C. Tetrahydrofuran was removed by
concentration of the reaction mixture under reduced pressure. Wa-
ter (50 mL) was then added and acidified with 2M HC1 to pH5. The
crude products were filtered and recrystallized (ethanol-water). All
of products 3–5, 16–18, and 28–31 were chromatographicallv homo-
geneous by iodine and benzidine development in TLC, Table I and
Chart 1.
IR of 4:
ν3400 cm−1 (NH), ν1690 cm−1 (CO), ν1420, 1360
cm−1 (SO2-NH), ν1600 cm−1 (Ar-C=C), ν1320,
1160 cm−1 (SO2)
IR of 17:
IR of 30:
ν1680 cm−1 (CO), ν1600 cm−1 (Ar-C=C), ν1320,
1180 cm−1 (SO2)
ν3200 cm−1 (NH), ν1680 cm−1 (CO), ν1610 cm−1
(Ar-C=C), ν1350, 1160 cm−1 (SO2)
1H NMR of 4: (DMSO-d6): δ1.1–1.2 (s, 3H, CH3), δ4.2–4.6 (s, αH,
CH), δ4.7–5.2 (s, H, NH), δ7.8–7.7 (9H, ArH), δ8.1,
7.4 (alkenic Ha, Hb), δ10.9 (s, H, COOH). MS of 4:
m/z 359 (M+)
1H NMR of 17: (DMSO-d6): δ0.9[s, 6H, (CH3)2], δ1.97 (s, H, β CH),
δ4.26 (s, H, αCH), δ3.97 (s, 3H, O CH3), δ4.8–5.2
(s, H, NH), δ8.30–7.03 (10H, ArH and alkenic Ha,
Hb), (Ha) 7.79, 7.72, (Hb) 7.53, 7.49, δ10.9 (s, H,
COOH). MS of 17: m/z 417 (M+)
1H NMR of 30: (DMSO-d6): δ0.9[s, 6H, (CH3)2], δ4.5(s, 2H, CH2),
δ8.4–7.5 (9H, ArH), and alkenic Ha, Hb, δ9.8 (s, H,
COOH), δ10.49 (s, H, SO2NH). MS of 30: m/z 407
(M+)
1H NMR of 31: (DMSO-d6): δ 0.9[s, 6H, (CH3)2], δ8.5–7.5(9H, ArH
and CH CH), δHa, 7.72, δHb 7.53, δ7.7 (s, 2H, thio-
phene 3,4-H), δ3.4–3.2 (4H, N · CH2 · CH3), δ1.3–
1.15(6H, N-CH2-CH3). MS of 31: 349 (M+), 277
(M-NEt2), signals removed by D2O tratment 213
(M-SO2-NEt2).
Synthesis of Chalcone Sulfonylamino Acid Methyl Esters 7–8,
19–20, and 33–34: General Procedure
A suspension of coupling reaction products 5–6, 17, 18 28, and 30 (0.2
mole) in absolute methanol (100 mL) was cooled to −10◦C, and pure

1150
R. A. El-Sayed
thionyl chloride (2.2 mL) was added dropwise during 1 h. The reac-
tion mixture was stirred for an additonal 3–4 h at r.t. after standing
overnight, and the solvent was removed by vacuum distillation. The
residual solid material was recrystallized (methanol-water). (cf., Table
I, Chart 1).
IR of 8:
ν3300, 3180 cm−1 (NH), ν1600, 1610 cm−1 (CO),
ν1370, 1170 cm−1 (SO2-NH), ν1610 cm−1 (ArC C),
ν1350, 1150 cm−1 (SO2), ν1360 cm−1 (COOCH3)
1H NMR of 19: (DMSO-d6): δ8.2–7.0(Ar-H and alkenic Ha, Hb),
δ3.51–3.41(s, 3H, COOCH3)
1H NMR of 32: (DMSO-d6): δ8.04(s, H, NH), δ3.75(s, 3H, COOCH3),
δ4.4(H, αCH), δ1.2(3H, βCH3) absence of OH proton,
and other peak in support of their structure
Synthesis of Chalcone Sulfonylamino Acid Hydrazides 9, 10,
19, 20, and 35, 36: General Procedure
The methyl esters 7, 8, 19, 20, 33, and 34 (0.2 mol) were dissolved in
ethanol (100 mL), and hydrazine hydrate 85% (0.2 mol) was added. The
reaction mixture was stirred for 3 h at 20◦C and left for 24 h at r. t. The
crystalline products 19, 10, 19, 20, 35, and 36 were filtered off, washed
with water, and recrystallized (ethanol–water).
IR of 35:
ν3340, 3125 cm−1 (NH), ν1640 cm−1 (CO), ν1600,
1550 cm−1 Ar C C, ν1340, 1180 cm−1 (SO2)
1H NMR of 36: (DMSO-d6): δ9(H, SO2NH), δ8.2–7.5(Ar-H), δ5.50 (H,
NH), δ5.61 (2H, NH2)
Synthesis of Chalcone Sulfonylamino Dipeptide Methyl Esters
11–13, 23–25, and 37–38: General Procedure
To a solution of amino acid methyl ester hydrochloride (0.11 mol) in
THF (100 mL) was added trethylamine (5 mL). The solution was stirred
at 20◦C for 30 min and cooled to 0◦C, where the sulfonyl amino acid
(0.001 mol) and dicyclohexylcarbodiimide DCC (1.62 g) were added to
the mixture. The reaction mixture was stirred for 2 h at 0◦C and for
another 2 h at r.t. The precipitated dicyclohexylurea was filtered off, and
acetic acid (2 mL) was added to the solution, which was left standing
overnight. A precipitate was filtered off and the remaining solution
was distilled under vacuum. The remaining solid was recrystallized
(ethanol-water). The products were chromatographically homogeneous.

Organosulfur Amino Acid Derivatives
1151
IR of 12:
ν3300, 3100 cm−1 (NH, CONH), ν1750 cm−1 (CO),
ν1320 cm−1 (COOCH3)
1H NMR of 12: (DMSO-d6): δ7.82 (s, 2H, SO2NH), δ8.04(s, H, CONH),
δ3.8(s, 3H, COOCH3), δ3.65(s, 2H, CH2), δ4.32(s, H,
α-CH-alalyl) δ1.21(s, 3H, CH3 alalyl) and other bands
supporting the structure of dipeptide
1H NMR of 37: (DMSO-d6): δ3.84(s, 3H, COOCH3), δ4.26(s, H, αCH
νalyl), δ 1.79(s, H, βCH-valyl), δ0.95[s, 6H, (CH3)2],
δ3.65(s, 2H, CH2) and other bands supporting the
structure of dipeptide
REFERENCES
[1] R. A. El-Sayed, J. Serb. Chem. Soc., 56, 311 (1991).
[2] R. A. El-Sayed, N. S. Khalaf, F. A. Kora, and Y. A. Abbas, Pak. J. Sci. Industrial
Research, 34, 369 (1991).
[3] R. A. El-Sayed, N. S. Khalaf, F. A. Kora, and M. F. Badie, J. Chem. Soc. Pak., 14 49,
(1992).
[4] R. A. El-Sayed, N. S. Khalaf, F. A. Kora, and M. H. El-Haki, Proc. Ind. Nat. Sci.
Acad., 58, 389 (1992).
[5] R. A. El-Sayed, J. Ind. Chem. Soc., 69, 618 (1992).
[6] R. A. El-Sayed, N. S. Khalaf, F. A. Kora, and M. A. El-Gazzar, J. Serb. Chem. Soc.,
59, 727 (1994).
[7] R. A. El-Sayed, Ind. Chem. Soc., 75, 53 (1998)
[8] R. A. El-Sayed, Phosphorus, Sulfur, and Silicon, 131, 207 (1997).
[9] R. A. El-Sayed, Chemistry of Heterocyclic Compounds, 7, 821 (1998).
[10] R. A. El-Sayed, Chemistry of Heterocyclic Compounds, 1, 95 (2001).
[11] R. A. El-Sayed, Phosphorus, Sulfur, and Silicon, 179, 237 (2004).
[12] R. A. El-Sayed, Phosphorus, Sulfur, and Silicon, 181, (2006).
[13] W. B. Geiger and J. E. Conn, J. Amer. Chem. Soc., 67, 112 (1945).
[14] D. H. Marrian, P. B. Russell, and A. R. Todd, J. Chem. Soc., 1419 (1947).
[15] D. N. Dhar, Chemistry of Chalcenes, (Wiley, New York, 1981).
[16] L. Weinstein, Sulfonamides in the Pharmacological Basic of Therapeutics L. S. Good-
man and A. Goodman, Eds. (Macmillan, London, and New York, pp. 1177–1203,
1970).
[17] R. J. Cremyln, J. Chem. Soc., 1132 (1965).
[18] R. J. Cremyln, J. Chem. Soc., 77 (1967).
[19] R. J. Cremyln, J. Chem. Soc. (C), 1341 (1969).
[20] P. Pfeiffer and P. A. Negreanu, Ber., 50, 1465 (1917).
[21] K. K. Hsu, M. S. Lo, and F. C. Chen, J. Chinese Chem. Soc., 16, 91 (1969); Chem.
Abs., 72, 31393V (1970).
[22] Vogels, Practical Organic Chemistry, 5th, ed., pp. 1034 (Longnnan, Harlow, 1989).
[23] N. R. El-Rayyes, G. H. Havakeemian, and H. S. Hmoud, J. Chem. Eng. Data., 29,
225 (1984).
[24] E. Pretch, T. Clero, J. Seibe, and W. Simon, Spectral Data for Structure Determina-
tion of Organic Compounds, (Springer–Verleg, Berlin, 1989).
[25] F. J. Swinbourne and O. O. Shode, J. Chinese Chem. Soc., 31, 383 (1984).
[26] F. J. Swinbourne, P. Bassin, D. Dane, and Mitchell, Phosphorus, Sulfur, and Silicon,
63, 385 (1991).