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Journal of Oleo ScienceCopyright ©2018 by Japan Oil Chemists’ Societydoi : 10.5650/jos.ess17214J. Oleo Sci. 67, (5) 551-569 (2018)

Synthesis, Surface Parameters, and Biodegradability of Water-soluble Surfactants for Various ApplicationsRefat El-Sayed1, 2＊ , Hawazin H Alotaibi1 and Heba A Elhady1, 3

1 Chemistry Department, College of Applied Sciences, Umm Al-Qura University, 21955Makkah, SAUDI ARABIA2 Chemistry Department, Faculty of Science, Benha University, EGYPT3 Chemistry Department, Faculty of Science (Girl’s), Al-Azhar, University, Cairo, EGYPT

1 INTRODUCTIONSurface-active molecules have attracted wide interest for

applications due to unique functional properties such as low toxicity and relative ease of preparation used as emul-sifiers, wetting, foams, spreading agents and in several in-dustries including organic chemicals, petroleum, petro-chemicals, detergents, cosmetics, pharmaceuticals and biotechnological applications1－3）. The presence of hydro-philic and hydrophobic regions in surfactants, which makes them accumulate at the interfaces between hydrocarbons and water, hence reducing surface tension between the surfaces. Thus promoting the transfer of nutrients through the membranes and affecting the various host interactions of the microbial4, 5）. The surfactants can be used for envi-ronmental clean-up through biodegradation, industrial waste disposal and biological treatment of contaminated soils6）. Also, the biological activities help them to control diseases as therapeutic agents7, 8）. A resistant adhesive against many pathogens suggests that its usefulness as suitable ingredients to combat the coating of adhesives for medical insertion materials results in a reduction in a large number of hospital infections without the use of synthetic drugs9）. On the other hand, the heterocyclic compounds

＊Correspondence to: Refat El-Sayed, Chemistry Department, College of Applied Sciences, Umm Al-Qura University, 21955Makkah, SAUDI ARABIAE-mail: refat_elsayed@yahoo.comAccepted December 26, 2017 (received for review September 30, 2017)Journal of Oleo Science ISSN 1345-8957 print / ISSN 1347-3352 onlinehttp://www.jstage.jst.go.jp/browse/jos/　　http://mc.manusriptcentral.com/jjocs

have a great deal of attention given their interesting thera-peutic, biological and pharmaceutical activities10－13）. Het-erocyclic derivatives are distributed and necessary for life, which possesses widespread pharmacological properties such as antipyretic and analgesic activities14）. Also, many of these compounds are widely used in nature and in the regular clinical15, 16）. The use of these compounds to syn-thesize surface active agents has become very important in various fields because of their dual functions as a better surface and biological properties than traditional surface surfaces17）. Because of low toxicity and rapid biological degradation, they are considered one of the pharmaceuti-cal and cosmetic applications18）.

These notes and our interest in the chemistry of hetero-cycles19－23）prompted us to synthesize various nonionic sur-factants factors that carry pyrazole, thiazole, imidazole, pyridine, thiazine, and pyrimidine nucleus using fatty acids and then followed by addition of number of moles of pro-pylene oxide to the list of active hydrogen atoms to form a new class of surface compounds that have declared surface characteristics. Surface parameters, biodegradability and biological activity of the new surfactants were studied.

Abstract: The synthesis of water-soluble heterocyclic compounds was verified on the basis of nonionic surfactants for use as surface-active agents. Surface characteristics such as surface and interfacial tensions, cloud point, wetting time, emulsion stability, foaming height and foaming stability were measured for these surface factors in aqueous solutions. In addition, the critical micelle concentration (CMC), the surface pressure at CMC (πcmc), the effectiveness of surface tension reduction (pC20), the maximum surface concentration (Γma.) and the minimum area/molecule at the aqueous solution/air interface (Amin) were calculated. Moreover, the biodegradability for these nonionic surfactants has been investigated. Furthermore, the antimicrobial evaluation has been evaluated with some surfactants that have demonstrated a potent cytotoxicity as antibacterial, antifungal and anticancer. These surfactants have a good water solubility, low toxicity, environmentally friendly environment, high foam, good emulsifier and easy production that will be used them in various fields such as medical drugs, insecticides, detergents, emulsifiers, cosmetics, inks clothing, leather industry and oil recovery.

Key words: design, surface properties, antimicrobial activities

R. E.-Sayed, H. H Alotaibi and H. A. Elhady

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2 ExperimentalAll melting points were obtained on a Gallenkamp

melting point device using the open capillary method. In-frared spectra were recorded on Thermo scientific spectra（Nicolet iS50 FTIR）. The NMR spectra on a Brocker spec-trometer operating at 850 MHz were used to record spectra of 1H and 13C NMR using deuterochloroform（CDCl3）as a solvent. Mass spectra have been run on LCMSMS equip-ment. All spectral analyses were performed at the Magnetic Resonance Center, Faculty of Science, King Abdulaziz Uni-versity, Saudi Arabia. CHNS elemental analyzer model EA3000 EURO VECTOR used to perform the elemental analysis. Du Nouy tensiometer（Kruss Type 8451）used for measurements the surface properties at 25℃. The biologi-cal activity was surveyed at the Regional Center for Mycol-ogy and Biotechnology, Al-Azhar University, Cairo, Egypt.

2.1. Synthesis2.1.1. Synthesis of（Z）-2-（amino（substituted）methylene）

-3-oxo-icosanenitrile（4a,b）A mixture of 2-stearoyl malononitrile 3（2.32g, 7 mmol）

and piperidine or morpholine（0.6 mL, 7 mmol）was heated in ethanol（20 mL）for 3hrs and then cooled. The product has been filtered hard and re-crystallized to give the adducts 4a,b, respectively.（Z）-2-（Amino（piperidin-1-yl）methylene）-3-oxoicosaneni-trile（4a）

As green yellow crystals（ethanol）, yield（1.83 g, 79％）, m.p.: 145-147℃. IR（γ/cm－1）: 3321-3201（NH2）, 2914, 2847（aliphatic CH）, 2228（CN）, 1698（CO）; 1HNMR（δ, ppm）: 0.87（t, 3H, terminal CH3）, 1.25-1.44（m, 32H, 16CH2 of alkyl chain）, 1.61（m, 6H, 3CH2）, 2.43（m, 4H, 2CH2）, 6.46（s, 2H, NH2）; 13CNMR（δ, ppm）:14.1, 22.7, 24.9, 29.0, 29.25, 29.38, 29.5, 29.6, 29.7, 29.7, 29.7, 31.9, 34.0, 56.9, 65.2, 104.2, 168. 7, 179.6. Anal. Calcd. （％）for C26H47N3O（417.67）: C, 74.77; H, 11.34; N, 10.06. Found: C, 74.59; H, 11.15; N, 10.24.（Z）-2-（Amino（morpholino）methylene）-3-oxoicosaneni-trile（4b）

As pale yellow crystals（ethanol）, yield（1.71 g, 74％）, m.p.: 151-153℃. IR（γ/cm－1）: 3311-3227（NH2）, 2917, 2850（aliphatic CH）, 2225（CN）, 1687（CO）; 1HNMR（δ, ppm）: 0.88（t, 3H, terminal CH3）, 1.25-1.62（m, 32H, 16CH2 of alkyl chain）, 2.90（m, 6H, 2CH2）, 3.23（m, 4H, CH2OCH2）, 6.22（s, 2H, NH2）. Anal. Calcd. （％）for C25H45N3O2（419.64）: C, 71.55; H, 10.81; N, 10.01. Found: C, 71.32; H, 10.66; N, 10.17.2.1.2 Synthesis of 1-（3-amino-5-（substituted）-1H-pyrazol-

4-yl）octadecan-1-one（5a,b）The equivalent amounts of hydroxylamine hydrochloride

（0.48 g, 7 mmol）and enamino-nitrile 4a,b（7 mmol）, in each case with anhydrous sodium acetate（0.57 g, 7 mmol）were refluxed in glacial acetic acid（20 mL）for 6 hrs. After cooling, the mixture was poured on cold water and then fil-

tered and re-crystallized to give the products 5a,b, respec-tively.1-（3-Amino-5-（piperidin-1-yl）-1H-pyrazol-4-yl）octadecan-1-one（5a）

As pale yellow crystals（1,4-dioxane）, yield（2.39 g, 82％）, m.p.: 119-121℃. IR（γ/cm－1）: 3321-3284（NH and NH2）, 2915, 2847（aliphatic CH）, 1698（CO）, 1591（C＝N）,; 1HNMR（δ, ppm）: 0.86（t, 3H, terminal CH3）, 1.30-1.34（m, 32H, 16CH2 of alkyl chain）, 1.61（t, 6H, 3CH2）, 2.89（m, 4H, 2CH2）, 8.03（s, 2H, NH2）, 11.11（s, 1H, NH）; 13C NMR（δ, ppm）: 14.1, 22.7, 24.7, 29.0, 29.3, 29.4, 29. 5, 29.6, 29.7, 29.7, 29.7, 31.9, 34.0, 93.3, 154.3, 154.6, 179.6; MS: m/z（％）（M＋＝432（18）. Anal. Calcd. （％）for C26H48N4O（432.69）: C, 72.17; H, 11.18; N, 12.95. Found: C, 72.38; H, 11.37; N, 12.76.1-（3-Amino-5-（morpholino）-1H-pyrazol-4-yl）octadecan-1-one（5b）

As deep yellow crystals（1,4-dioxane）, yield（2.26 g, 77％）, m.p.: 126-128℃. IR（γ/cm－1）: 3332-3227（NH and NH2）, 2917, 2848（aliphatic CH）, 1689（CO）, 1580（CN）; 1HNMR（δ, ppm）: 0.88（t, 3H, terminal CH3）, 1.25-1.41（m, 32H, 16CH2 of alkyl chain）, 2.99（m, 4H, 2CH2）, 3.42（m, 4H, CH2OCH2）, 8.19（s, 2H, NH2）, 10.88（s, 1H, NH）. Anal. Calcd. （％）for C25H46N4O2（434.66）: C, 69.08; H, 10.67; N, 12.89. Found: C, 69.25; H, 10.49; N, 12.66.2.1.3 Synthesis of 4-amino-6-（substituted）-5-stearoyl-

pyrimidin-2（1H）-one（6a,b）and 1-（4-amino-6-（sub-stituted）-2-thioxo-1,2-dihydropyrimidin-5-yl）octa-decan-1-one（7a,b）

A mixture of enaminonitrile 4a,b（7 mmol）, sodium ethoxide（0.16 g sodium in 10 mL ethanol, 7 mmol）and urea（0.42 g, 7 mmol）or thiourea（0.53 g, 7 mmol）was stirred in boiling ethanol（15 mL）for 5 hrs, in each case, then cooled. The solution was neutralized by ice/hydro-chloric acid. The solid obtained has been filtered and re-crystallized to give the pyrimidine derivatives（6a,b）and（7a,b）, respectively.4-Amino-6-（piperidin-1-yl）-5-stearoylpyrimidin-2（1H）-one（6a）

As light green crystals（1,4-dioxane）, yield（2.16 g, 74％）, m.p.: 160-162℃. IR（γ/cm－1）: 3355-3291（NH and NH2）, 2914, 2847（aliphatic CH）, 1699, 1681（CO）, 1605（C＝C）, 1599（C＝N）; 13CNMR（δ, ppm）: 14.10, 22.7, 24.7, 29.1, 29.3, 29.4, 29.5, 29.6, 29.7, 29.7, 29.7, 31.9, 33.9, 58.5, 76.9, 152.0, 158.7, 167.6, 182.6. Anal. Calcd. （％）for C27H48N4O2

（460.70）: C, 70.39; H, 10.50; N, 12.16. Found: C, 70.57; H, 10.67; N, 12.38.4-Amino-6-（morpholino）-5-stearoylpyrimidin-2（1H）-one（6b）

As deep yellow crystals（1,4-dioxane）, yield（1.94 g, 66％）, m.p.: 167-169℃. IR（γ/cm－1）: 3338-3256（NH and NH2）, 2917, 2848（aliphatic CH）, 1696, 1680（CO）, 1595（CN）; 1HNMR（δ, ppm）: 0.89（t, 3H, terminal CH3）, 1.31-1.65（m, 32H, 16CH2 of alkyl chain）, 3.49（m, 4H, 2CH2）,

Synthesis of Functional Surfactants

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3.71（m, 4H, CH2OCH2）, 8.11（s, 2H, NH2）, 11.03（s, 1H, NH）. Anal. Calcd. （％）for C26H46N4O3（462.67）: C, 67.50; H, 10.02; N, 12.11. Found: C, 67.71; H, 10.20; N, 12.30.1-（4-Amino-6-（piperidin-1-yl）-2-thioxo-1,2-dihydropyrimi-din-5-yl）octadecan-1-one（7a）

As deep green crystals（1,4-dioxane）, yield（1.95 g, 67％）, m.p.: 158-160℃. IR（γ/cm－1）: 3388-3187（NH2）, 2917, 2850（aliphatic CH）, 1689（CO）, 1587（CN）; 13CNMR（δ, ppm）: 14.2, 22.7, 24.70, 29.1, 29.3, 29.4, 29.4, 29.6, 29.6, 29.7, 31.9, 33.9, 55.4, 76.8, 167.1, 175.3, 179.1, 187.0. Anal. Calcd. （％）for C27H48N4OS（476.76）: C, 68.02; H, 10.15; N, 11.75; S, 6.73. Found: C, 68.19; H, 10.37; N, 11.60; S, 6.55.1-（4-Amino-6-（morpholino）-2-thioxo-1,2-dihydropyrimi-din-5-yl）octadecan-1-one（7b）

As light brown crystals（1,4-dioxane）, yield（1.91 g, 65％）, m.p.: 167-169℃. IR（γ/cm－1）: 3406-3183（NH and NH2）, 2915, 2848（aliphatic CH）, 1680（CO）, 1550（C＝N）; 1HNMR（δ, ppm）: 0.86（t, 3H, terminal CH3）, 1.21-1.74（m, 32H, 16CH2 of alkyl chain）, 2.88（m, 4H, 2CH2）, 3.38（m, 4H, CH2OCH2）, 8.02（s, 2H, NH2）, 10.94（s, 1H, NH）; Anal. Calcd. （％）for C26H46N4O2S（478.73）: C, 65.23; H, 9.68; N, 11.70; S, 6.70. Found: C, 65.40; H, 9.82; N, 11.86; S, 6.52.2.1.4 Synthesis of 2,4-diamino-6-（substituted）-5-stearoyl-

nicotinonitrile（8a,b）A solution of enaminonitrile 4a,b（7 mmol）in DMF（20

mL）, in each case and malononitrile（0.46 g, 7 mmol）with a few drops of triethylamine was heated under reflux for 6 hrs, and the mixture was cooled and poured on cold water. The resulting solid was filtered and re-crystallized to give the derivatives（8a,b）. respectively.2,4-Diamino-6-（piperidin-1-yl）-5-stearoylnicotinonitrile（8a）

As light brown crystals（1,4-dioxane）, yield（2.51 g, 86％）, m.p.: 116-118℃. IR（γ/cm－1）: 3421-3201（2NH2）, 2915, 2848（aliphatic CH）, 2224（CN）, 1688（CO）, 1539（C＝N）; 1HNMR（δ, ppm）: 0.89（t, 3H, terminal CH3）, 1.19-1.52（m, 32H, 16CH2 of alkyl chain）, 1.62（m, 6H, 3CH2）, 3.39（m, 4H, 2CH2）, 6.72（s, 2H, NH2）, 7.82（s, 2H, NH2）; MS: m/z（％）（M＋-1＝482（19）. Anal. Calcd. （％）for C29H49N5O（483.73）: C, 72.00; H, 10.21; N, 14.48. Found: C, 72.21; H, 10.38; N, 14.29.2,4-Diamino-6-（morpholino）-5-stearoylnicotinonitrile（8b）

As brown crystals（1,4-dioxane）, yield（2.41 g, 82％）, m.p.: 127-129℃. IR（γ/cm－1）: 3385-3227（2NH2）, 2918, 2850（aliphatic CH）, 2220（CN）, 1687（CO）; 1HNMR（δ, ppm）: 0.91（t, 3H, terminal CH3）, 1.22-1.50（m, 32H, 16CH2 of alkyl chain）, 3.22（m, 4H, 2CH2）, 3.46（m, 4H, CH2OCH2）, 6.85（s, 2H, NH2）, 7.88（s, 2H, NH2）. Anal. Calcd. （％）for C28H47N5O2（485.71）: C, 69.24; H, 9.75; N, 14.42. Found: C, 69.03; H, 9.58; N, 14.27.2.1.5 Synthesis of（E）-2-（amino（substituted）methylene）

-3-oxoicosanoic acid（9a,b）A mount of enaminonitrile 4a,b（7 mmol）, in each case

was stirred in sulfuric acid（10 mL）for overnight at room temperature and then poured on ice. The precipitate formed was filtered, dried and re-crystallized to produce the products（9a,b）. respectively.（E）-2-（amino（piperidin-1-yl）methylene）-3-oxoicosanoic acid（9a）

As light brown crystals（ethanol）, yield（1.83 g, 79％）, m.p.: 113-115℃. IR（γ/cm－1）: 3406-3183（OH of COOH and NH2）, 2916, 2848（aliphatic CH）, 1738, 1679（CO）; 1HNMR（δ, ppm）: 0.86（t, 3H, terminal CH3）, 1.28-1.39（m, 32H, 16CH2 of alkyl chain）, 1.59（m, 6H, 3CH2）, 3.66（m, 4H, 2CH2）, 8.28（s, 2H, NH2）, 11.36（s, 1H, OH）. Anal. Calcd. （％）for C26H48N2O3（436.67）: C, 71.51; H, 11.08; N, 6.42. Found: C, 71.73; H, 11.26; N, 6.61.（E）-2-（amino（morpholino）methylene）-3-oxoicosanoic acid（9b）

As orange crystals（ethanol）, yield（2.11 g, 72％）, m.p.: 122-124. IR（γ/cm－1）: 3422-3197（OH of COOH and NH2）, 2917, 2850（aliphatic CH）, 1707, 1683（CO）; 1HNMR（δ, ppm）: 0.90（t, 3H, terminal CH3）, 1.22-1.49（m, 32H, 16CH2 of alkyl chain）, 1.60（m, 4H, 2CH2）, 3.26（m, 4H, CH2OCH2）, 8.15（s, 2H, NH2）and 10.98（s, 1H, OH）. Anal. Calcd. （％）for C25H46N2O4（438.64）: C, 68.45; H, 10.57; N, 6.39. Found: C, 68.27; H, 10.68; N, 6.53.2.1.6 Synthesis of（Z）-1-amino-2-（4,5-dihydro-1H-imidaz-

ol-2-yl）-1-（substituted）icos-1-en-3-one（10a,b）Ethylenediamine（2 mL）was added drop-drop to enami-

nonitrile 4a,b（7 mmol）in ethanol（20 mL）with few drops of carbon disulfide, in each case. The mixture was heated for 8 hrs on a water bath. The mixture was treated with cold water. The obtained solid has been filtered and re-crystal-lized to give products（10a,b）, respectively.（Z）-1-amino-2-（4,5-dihydro-1H-imidazol-2-yl）-1-（piperi-din-1-yl）icos-1-en-3-one（10a）

As deep yellow crystals（ethanol）, yield（2.00 g, 69％）, m.p.: 126-128℃. IR（γ/cm－1）: 3379-3201（NH and NH2）, 2914, 2847（aliphatic CH）, 1698（CO）; 1HNMR（δ, ppm）: 0.88（t, 3H, terminal CH3）, 1.34-1.61（m, 32H, 16CH2 of alkyl chain）, 1.64（m, 6H, 3CH2）, 3.40（m, 4H, 2CH2）, 7.55（s, 1H, NH）, 9.05（s, 2H, NH2）. 13CNMR（δ, ppm）: 14.1, 22.7, 24.7, 29.0, 29.2, 29.3, 29.4, 29.6, 29.6, 29.7, 31.9, 33.9, 55.1, 62.6, 72.2, 157.1, 167.2, 179.6. Anal. Calcd. （％）for C28H52N4O（460.74）: C, 72.99; H, 11.38; N, 12.16. Found: C, 72.83; H, 11.47; N, 12.27.（Z）-1-amino-2-（4,5-dihydro-1H-imidazol-2-yl）-1-（morpho-lino）icos-1-en-3-one（10b）

As brown crystals（ethanol）, yield（1.91 g, 65％）, m.p.: 131-132℃. IR（γ/cm－1）: 3364-3187（NH and NH2）, 2916, 2848（aliphatic CH）, 1684（CO）; 1HNMR（δ, ppm）: 0.89（t, 3H, terminal CH3）, 1.25-1.52（m, 32H, 16CH2 of alkyl chain）, 3.17（m, 4H, 2CH2）, 3.33（m, 4H, CH2OCH2）, 7.48（s, 1H, NH）, 8.74（s, 2H, NH2）. Anal. Calcd. （％）for C27H50N4O2

（462.71）: C, 70.08; H, 10.89; N, 12.11. Found: C, 70.26; H, 10.77; N, 12.24.

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2.1.7 Synthesis of（Z）-1-amino-2-（benzo［d］oxazol-2-yl）-1-（substituted）icos-1-en-3-one（11a,b）and/or（Z）-1-amino-2-（1H-benzo［d］imidazol-2-yl）-1-（substi-tuted）icos-1-en-3-one（12a,b）

Equal amounts of enaminonitrile 4a,b（7 mmol）and o-aminophenol or o-phenylenediamine（7 mmol）were heated in ethanol（20 mL）with a few drops of piperidine for 24hrs. After cooling, the resulting precipitate was filtered and re-crystallized to give products（11,12）a,b, respectively.（Z）-1-amino-2-（benzo［d］oxazol-2-yl）-1-（piperidin-1-yl）icos-1-en-3-one（11a）

As pale yellow crystals（ethanol）, yield（2.25 g, 77％）, m.p.: 126-128. IR（γ/cm－1）: 3354, 3197（NH2）, 2916, 2849（aliphatic CH）, 1689（CO）; 1HNMR（δ, ppm）: 0.88（t, 3H, terminal CH3）, 1.32-1.33（m, 32H, 16CH2 of alkyl chain）, 1.61（m, 6H, 3CH2）, 2.33（m, 4H, 2CH2）, 6.86（s, 2H, NH2）and 7.26-7.29（m, 4H, ArH）. Anal. Calcd. （％）for C28H52N4O（460.74）: C, 72.99; H, 11.38; N, 12.16. Found: C, 72.86; H, 11.55; N, 12.31.（Z）-1-amino-2-（benzo［d］oxazol-2-yl）-1-（morpholino）icos-1-en-3-one（11b）

As deep yellow crystals（ethanol）, yield（2.11 g, 72％）, m.p.: 132-134. IR（γ/cm－1）: 3368, 3204（NH2）, 2914, 2847（aliphatic CH）, 1698（CO）; 1HNMR（δ, ppm）: 0.86（t, 3H, terminal CH3）, 1.32-1.39（m, 32H, 16CH2 of alkyl chain）, 3.12（m, 4H, 2CH2）, 3.38（m, 4H, CH2OCH2）, 6.64（s, 2H, NH2）. Anal. Calcd. （％）for C27H50N4O2（462.71）: C, 70.08; H, 10.89; N, 12.11. Found: C, 70.26; H, 10.77; N, 12.24.（Z）-1-amino-2-（1H-benzo［d］imidazol-2-yl）-1-（piperidin-1-yl）icos-1-en-3-one（12a）

As reddish yellow crystals（1,4-dioxane）, yield（2.27 g, 78％）, m.p.: 111-113℃. IR（γ/cm－1）: 3361-3231（NH2）, 2915, 2847（aliphatic CH）, 1700（CO）; 1HNMR（δ, ppm）: 0.90（t, 3H, terminal CH3）, 1.22-1.42（m, 32H, 16CH2 of alkyl chain）, 1.60（m, 6H, 3CH2）, 2.30（m, 4H, 2CH2）, 6.96（s, 2H, NH2）, 7.26-7.51（m, 4H, ArH）, 10.80（s, 1H, NH）. Anal. Calcd. （％）for C32H52N4O（508.78）: C, 75.54; H, 10.30; N, 11.01. Found: C, 75.71; H, 10.39; N, 11.18.（Z）-1-amino-2-（1H-benzo［d］imidazol-2-yl）-1-（morpholi-no）icos-1-en-3-one（12b）

As brown crystals（ethanol）, yield（2.15 g, 73％）, m.p.: 123-125℃. IR（γ/cm－1）: 3367-3188（NH and NH2）, 2917, 2849（aliphatic CH）, 1693（CO）; 1HNMR（δ, ppm）: 0.87（t, 3H, terminal CH3）, 1.21-1.34（m, 32H, 16CH2 of alkyl chain）, 2.29（m, 4H, 2CH2）, 3.49（m, 4H, CH2OCH2）, 6.83（s, 2H, NH2）, 7.11-7.42（m, 4H, ArH）, 10.14（s, 1H, NH）. Anal. Calcd. （％）for C31H50N4O2（510.75）: C, 72.90; H, 9.87; N, 10.97. Found: C, 72.77; H, 9.74; N, 10.85.2.1.8 Synthesis of（Z）-N'-（（E）-2-cyano-3-oxo-1-（substitut-

ed）icos-1-en-1-yl）-N-phenylcarbamimido-thioic acid（13a,b）

An equimolar amount of enaminonitrile 4a,b（7 mmol）, in each case in DMF（20 mL）containing sodium hydroxide（0.28 g, 7 mmol）and phenyl isothiocyanate（0.94 g, 7

mmol）was stirred for 24 hrs. Then poured on ice/hydro-chloric acid. The resulting solid was filtered and re-crystal-lized to produce compounds（13a,b）, respectively（Z）-N'-（（E）-2-cyano-3-oxo-1-（piperidin-1-yl）icos-1-en-1-yl）-N-phenylcarbamimidothioic acid（13a）

As yellow crystals（ethanol）yield（2.00 g, 70％）, m.p.: 129-131℃. IR（γ/cm－1）: 3201（NH）, 2914, 2847（aliphatic CH）, 2223（CN）, 1698（CO）; 1HNMR（δ, ppm）: 0.87（t, 3H, terminal CH3）, 1.25-1.63（m, 32H, 16CH2 of alkyl chain）, 1.63（m, 6H, 3CH2）, 1.93（s, 1H, SH）, 2.33（m, 4H, 2CH2）, 7.08-7.43（m, 5H, ArH）, 7.89（s, 1H, NH）. Anal. Calcd. （％）for C33H52N4OS（552.86）: C, 71.69; H, 9.48; N, 10.13; S, 5.80. Found: C, 71.56; H, 9.60; N, 10.26; S, 5.67.（Z）-N'-（（E）-2-cyano-3-oxo-1-（morpholino）icos-1-en-1-yl）-N-phenylcarbamimidothioic acid（13b）

As orange crystals（ethanol）yield（1.94 g, 66％）, m.p.: 135-137℃. IR（γ/cm－1）: 3311（NH）, 2918, 2850（aliphatic CH）, 1706（CO）; 1HNMR（δ, ppm）: 0.89（t, 3H, terminal CH3）, 1.23-1.60（m, 32H, 16CH2 of alkyl chain）, 1.73（s, 1H, SH）, 3.27（m, 4H, 2CH2）, 3.42（m, 4H, CH2OCH2）, 7.23-7.48（m, 5H, ArH）, 8.11（s, 1H, NH）. Anal. Calcd. （％）for C32H50N4O2S（554.83）: C, 69.27; H, 9.08; N, 10.10; S, 5.78. Found: C, 69.35; H, 9.22; N, 10.25; S, 5.90.2.1.9 Synthesis of（E）-2-（（（Z）-（4-amino-3-phenylthiazol-2

（3H）-ylidene）amino）（substituted）methylene）-3-oxoicosane-nitrile（14a,b）

A mixture of derivatives 13a,b（5 mmol）in DMF（15mL）, in each case and chloroacetonitrile（0.38 g, 5 mmol）was heated for 7 hrs. The solid obtained was filtered and re-crystallized to give derivatives（14a,b）, respectively.（E）-2-（（（Z）-（4-amino-3-phenylthiazol-2（3H）-ylidene）amino）（piperidin-1-yl）methylene）-3-oxoicosane-nitrile（14a）

As pale yellow crystals（1,4-dioxine）, yield（1.85 g, 67％）; m.p.: 110-112℃. IR（γ/cm－1）: 3333, 3201（NH2）, 3079（CH aromatic）, 2915, 2848（CH aliphatic）, 2224（CN）, 1698（CO）, 1628（CH oliphenic）; 1H NMR（δ, ppm）: 0.87（t, 3H, terminal CH3）, 1.25-1.34（m, 32H, 16 CH2 of alkyl chain）, 1.62（m, 6H, 3CH2）, 2.32（m, 4H, 2CH2）, 6.91（s, 2H, NH2）, 6.11-7.53（m, 5H, ArH）; MS: m/z（％）（M＋-1＝590（33）. Anal. Calcd. （％）for C35H53N5OS（591.89）: C, 71.02; H, 9.03; N, 11.83; S, 5.42. Found: C, 71.13; H, 9.16; N, 11.67; S, 5.61（E）-2-（（（Z）-（4-amino-3-phenylthiazol-2（3H）-ylidene）amino）（morpholino）methylene）-3-oxoicosane-nitrile（14b）

As pale yellow crystals（1,4-dioxine）, yield（1.75 g, 63％）; m.p.: 118-120℃. IR（γ/cm－1）: 3378, 3332（NH2）, 2915, 2848（CH aliphatic）, 2221（CN）, 1696（CO）; 1H NMR（δ, ppm）: 0.88（t, 3H, terminal CH3）, 1.27-1.63（m, 32H, 16 CH2 of alkyl chain）, 3.19（m, 4H, 2CH2）, 3.37（m, 4H, CH2OCH2）, 4.99（s, 1H, CH）, 6.68（s, 2H, NH2）, 7.21-7.56（m, 5H, ArH）. Anal. Calcd. （％）for C34H51N5O2S（593.87）: C, 68.76; H, 8.66; N, 11.79; S, 5.40. Found: C, 68.58; H, 8.58; N, 11.62; S, 5.21

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2.1.10 Synthesis of 1-（4-imino-3-phenyl-6-（substituted）-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl）octadec-an-1-one（15a,b）

Phenyl isothiocyanate（0.94g, 7 mmol）was added to en-aminonitrile 4a,b（7 mmol）in DMF（20 mL）containing tri-ethylamine（0.5 mL）, in each case and then heated for 8hrs. The mixture was poured into ice/water mixture with a few drops of acetic acid. The product has been filtered and re-crystallized to give pyrimidine derivatives（15a,b）. respectively.1-（4-Imino-3-phenyl-6-（piperidin-1-yl）-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl）octadecan-1-one（15a）

As reddish yellow crystals（1,4-dioxane/DMF）, m.p. 120-122℃, yield:（2.27 g, 78％）. IR（γ/cm－1）: 3314, 3224（2NH）, 3058（CH aromatic）, 2917, 2850（CH aliphatic）, 1691（CO）. 1HNMR（δ, ppm）: 0.83（t, 3H, terminal CH3）, 1.34-1.55（m, 32H, 16CH2 of alkyl chain）, 1.63（m, 6H, 3CH2）, 2.34（m, 4H, 2CH2）, 7.25-7.77（m, 6H, ArH and NH）, 10.90（s, 1H, NH）; MS: m/z（％）（M＋＝552（25）. Anal. Calcd. （％）for C33H52N4OS（552.86）: C, 71.69; H, 9.48; N, 10.13; S, 5.80. Found: C, 71.55; H, 9.40; N, 10.22; S, 5.67.1-（4-Imino-3-phenyl-6-（morpholino）-2-thioxo-1,2,3,4-tet-rahydropyrimidin-5-yl）octadecan-1-one（15b）

As light brown crystals（1,4-dioxane/DMF）, m.p. 129-131℃, yield:（2.17 g, 74％）. IR（γ/cm－1）: 3306, 3195（2NH）, 3066（CH aromatic）, 2914, 2849（CH aliphatic）, 1684（CO）. 1HNMR（δ, ppm）: 0.63（t, 3H, terminal CH3）, 1.26-1.58（m, 32H, 16CH2 of alkyl chain）, 3.04（m, 4H, 2CH2）, 3.21（m, 4H, CH2OCH2）,7.23-7.61（m, 6H, ArH and NH）, 11.04（s, 1H, NH）. Anal. Calcd. （％）for C32H50N4O2S（554.83）: C, 69.27; H, 9.08; N, 10.10; S, 5.78. Found: C, 69.34; H, 9.20; N, 10.25; S, 5.70.2.1.11 Synthesis of 1-（4-amino-6-（substituted）pyrimidin-

5-yl）octadecan-1-one（16a,b）Formamide（0.3 g, 7 mmol）was added to enaminonitrile

4a,b（7 mmol）in dimethyl formamide（20 mL）with a few drops of piperidine, in each case, and then heated for 7 hrs. The mixture was poured upon ice/hydrochloric acid for complete precipitation. The solid obtained was filtered and re-crystallized to give compounds（16a,b）, respectively.1-（4-Amino-6-（piperidin-1-yl）pyrimidin-5-yl）octadecan-1-one（16a）

As pale yellow crystals（1,4-dioxane）, m.p.; 107-109℃, yield（2.07 g, 71％）. IR（γ/cm－1）: 3331, 3216（NH2）, 2916, 2849（CH aliphatic）, 1689（CO）; 1HNMR（δ, ppm）: 0.87（t, 3H, terminal CH3）, 1.31-1.34（m, 32H, 16CH2 of alkyl chain）, 1.61（m, 6H, 3CH2）, 2.34（m, 4H, 2CH2）, 7.82（s, 2H, NH2）, 8.83（s, 1H, CH＝N）. Anal. Calcd. （％）for C27H48N4O（444.70）: C, 72.92; H, 10.88; N, 12.60. Found: C, 72.83; H, 10.76; N, 12.43.1-（4-Amino-6-（morpholino）pyrimidin-5-yl）octadecan-1-one（16b）

As deep yellow crystals（1,4-dioxane）, m.p.; 115-117℃, yield（1.94 g, 66％）. IR（γ/cm－1）: 3407, 3201（NH2）, 2914,

2847（CH aliphatic）, 1696（CO）; 1HNMR（δ, ppm）: 0.63（t, 3H, terminal CH3）, 1.26-1.58（m, 32H, 16CH2 of alkyl chain）, 3.04（m, 4H, 2CH2）, 3.21（m, 4H, CH2OCH2）, 7.74（s, 2H, NH2）, 9.25（s, 1H, CH＝N）; 13CNMR（δ, ppm）: 14.1, 22.7, 24.9, 29.1, 29.2, 29.3, 29.4, 29.6, 29.6, 29.6, 29.6, 29.7, 29,9, 31.9, 34.1, 34.4, 51.4, 60.1, 108.0, 158.5, 161.8, 174.4, 182.2. Anal. Calcd. （％）for C26H46N4O2（446.67）: C, 69.91; H, 10.38; N, 12.54. Found: C, 69.77; H, 17.38; N, 12.63.2.1.12 Synthesis of 6-（substituted）-5-stearoylpyrimidin-4

（3H）-one（17a,b）To a solution of enaminonitrile 4a,b（7 mmol）in ethanol

（25 mL）, in each case and formic acid（0.32g, 7 mmol）was added. The solution was heated for 3 hrs. Hydrogen peroxide（5 mL）and potassium carbonate（10％, 10 mL）were added with reflux for 1hr other. After cooling, the re-sulting solid was filtered and re-crystallized to yield pyrimi-dine derivatives（17a,b）, respectively.6-（Piperidin-1-yl）-5-stearoylpyrimidin-4（3H）-one（17a）

As light brown crystals（ethanol）, m.p. 103-105℃, yield:（1.72 g, 59％）. IR（γ/cm－1）: 3289（NH）, 2915, 2850（CH ali-phatic）, 1711, 1699（CO）; 1HNMR（δ, ppm）: 0.87（t, 3H, ter-minal CH3）, 1.25-1.34（m, 32H, 16CH2 of alkyl chain）, 1.62（m, 6H, 3CH2）, 2.34（m 4H, 2CH2）, 7.66（s, 1H, CH＝N）, 10.95（s, 1H, NH）. Anal. Calcd. （％）for C27H47N3O2（445.68）: C, 72.76; H, 10.63; N, 9.43. Found: C, 72.61; H, 10.75; N, 9.59.6-（Morpholino）-5-stearoylpyrimidin-4（3H）-one（17b）

As brown crystals（ethanol）, m.p. 112-114℃, yield:（1.56 g, 53％）. IR（γ/cm－1）: 3248（NH）, 2914, 2847（CH aliphat-ic）, 1708, 1694（CO）, 1541（C＝N）; 1HNMR（δ, ppm）: 0.89（t, 3H, terminal CH3）, 1.23-1.38（m, 32H, 16CH2 of alkyl chain）, 3.11（m, 4H, 2CH2）, 3.35（m, 4H, CH2OCH2）, 7.74（s, 1H, CH＝N）, 10.55（s, 1H, NH）. Anal. Calcd. （％）for C26H45N3O3（447.65）: C, 69.76; H, 10.13; N, 9.39. Found: C, 69.89; H, 10.22; N, 9.55.2.1.13 Synthesis of 1-（6-imino-4-（substituted）-2-thioxo-

3,6-dihydro-2H-1,3-thiazin-5-yl）octadecan-1-one（18a,b）

The excess of carbon disulfide（1 mL）was added to en-aminonitrile 4a,b（7 mmol）in dry pyridine（20 mL）, in each case and followed by stirring for overnight at room temper-ature. The reaction mixture was neutralized by cold water/hydrochloric acid. The separated solid was filtered and re-crystallized to yield thiazine derivatives（18a,b）, respec-tively.1-（6-Imino-4-（piperidin-1-yl）-2-thioxo-3,6-dihydro-2H-1,3-thiazin-5-yl）octadecan-1-one（18a）

As light yellow powder（ethanol）, yield（1.69 g, 58％）, m.p. 107-109℃. IR（γ/cm－1）: 3463, 3201（2NH）, 2915, 2848（aliphatic CH）, 1699（CO）; 1HNMR（δ, ppm）: 0.88（t, 3H, terminal CH3）, 1.25-1.34（m, 32H, 16CH2 of alkyl chain）, 1.62（m, 6H, 3CH2）, 2.27（m, 4H, 2CH2）, 3.55（s, 1H, NH）, 10.35（s, 1H, NH）. Anal. Calcd. （％）for C27H47N3OS2

（493.81）: C, 65.67; H, 9.59; N, 8.51; S, 12.99. Found C,

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65.79; H, 9.77; N, 8.60; S, 12.83.1-（6-Imino-4-（morpholino）-2-thioxo-3,6-dihydro-2H-1,3-thiazin-5-yl）octadecan-1-one（18b）

As orange powder（ethanol）, yield（1.65 g, 56％）, m.p. 123-125℃. IR（γ/cm－1）: 3365, 3194（2 NH）, 2917, 2848（ali-phatic CH）, 2205（CN）, 1674（CO）; 1HNMR（δ, ppm）: 0.89（t, 3H, terminal CH3）, 1.21-1.44（m, 32H, 16CH2 of alkyl chain）, 3.13（m, 4H, 2CH2）, 3.15（m, 4H, 2CH2）, 3.70（s, 1H, NH）, 10.87（s, 1H, NH）. Anal. Calcd. （％）for C26H45N3O2S2

（495.78）: C, 62.99; H, 9.15; N, 8.48; S, 12.94. Found C, 62.83; H, 9.27; N, 8.37; S, 12.77.2.1.14 Synthesis of 1-（6-（substituted）-2,4-dithioxo-

1,2,3,4-tetrahydro pyrimidin-5-yl）octadecan-1-one（19a,b）

An equal amount of carbon disulfide（0.53 g, 7 mmol）and enaminonitrile 4a,b（7 mmol）in dry pyridine（25 mL）, in each case was heated under reflux for 2 hrs. The reaction mixture was cooled, then poured onto ice/water with neu-tralized with dilute HCl. The solid product has been filtered and re-crystallized to give pyrimidine derivatives（19a,b）, respectively. 1-（6-（Piperidin-1-yl）-2,4-dithioxo-1,2,3,4-tetrahydropy-rimidin-5-yl）octadecan-1-one（19a）

As pale yellow crystals（ethanol）, yield（2.36 g, 81％）; m.p.: 147-149℃. IR（γ/cm－1）: 3204（NH）, 2914, 2847（ali-phatic CH）, 1698（CO）. 1H NMR（δ, ppm）: 0.87（t, 3H, ter-minal CH3）, 1.33-1.36（m, 32H, 16 CH2 of alkyl chain）, 1.61（m, 6H, 3CH2）, 2.33（m, 4H, 2CH2）, 8.03（s, 1H, NH）, 11.33（s, 1H, NH）. Anal. Calcd. （％）for C27H47N3OS2（493.81）: C, 65.67; H, 9.59; N, 8.51; S, 12.99. Found: C, 65.49; H, 9.34; N, 8.70; S, 12.811-（6-（Morpholino）-2,4-dithioxo-1,2,3,4-tetrahydropyrimi-din-5-yl）octadecan-1-one（19b）

As deep yellow crystals（ethanol）, yield（2.47 g, 84％）; m.p.: 156-158℃. IR（γ/cm－1）: 3229（NH）, 2917, 2847（ali-phatic CH）, 1696（CO）. 1H NMR（δ, ppm）: 0.85（t, 3H, ter-minal CH3）, 1.20-1.32（m, 32H, 16 CH2 of alkyl chain）, 3.10（m, 4H, 2CH2）, 3.32（m, 4H, 2CH2）, 8.44（s, 1H, NH）, 11.87（s, 1H, NH）. Anal. Calcd. （％）for C26H45N3O2S2（495.78）: C, 62.99; H, 9.15; N, 8.48; S, 12.94. Found: C, 62.86; H, 9.27; N, 8.33; S, 12.77.2.1.15 Synthesis of 4-amino-2-phenyl-6-（substituted）

-5-stearoyl nicotinonitrile（20a,b）A solution of enaminonitrile 4a,b（7 mmol）in DMF（20

mL）with piperidine（4 drops）and benzylidine malononitrile（1.08 g, 7 mmol）was heated for 7 hrs, and then left to cool. The reaction mixture was neutralized by ice/water, filtered and re-crystallized to yield pyridine derivatives（20a,b）, re-spectively.4-Amino-2-phenyl-6-（piperidin-1-yl）-5-stearoylnicotinoni-trile（20a）

As reddish yellow crystals（ethanol）, yield（1.93 g, 66％）; m.p.: 107-109℃. IR（γ/cm－1）: 3337, 3194（NH2）, 2916, 2848（aliphatic CH）, 2216（CN）, 1700（CO）. 1H NMR（δ, ppm）:

0.87（t, 3H, terminal CH3）, 1.24-1.59（m, 32H, 16 CH2 of alkyl chain）, 1.60（m, 6H, 3CH2）, 2.28（m, 4H, 2CH2）, 3.66（s, 2H, NH2）, 7.26-7.48（m, 5H, ArH）; MS: m/z（％）（M＋＝544（35）. Anal. Calcd. （％）for C35H52N4O（544.81）: C, 77.16; H, 9.62; N, 10.28. Found: C, 77.33; H, 9.81; N, 10.52.4-amino-6-morpholino-2-phenyl-5-stearoylnicotinonitrile（20b）

As orange crystals（ethanol）, yield（1.82 g, 62％）; m.p.: 114-116 ℃. IR（γ/cm－1）: 3346（NH）, 2917, 2848（aliphatic CH）, 2221（CN）, 1698（CO）. Anal . Calcd. （％）for C34H50N4O2（546.79）: C, 74.68; H, 9.22; N, 10.25. Found: C, 74.87; H, 9.40; N, 10.41

2.2 Preparation of nonionic surfactants from the synthe-sized compounds

An equimolar amount of synthesized compounds（4-20）a,b（0.01 mol）, in each case, and 0.5％ KOH was heated to above its melting points, then the propylene oxide was subtracted wisely with the continuous stirring to produce the nonionic surfactants（21-37）a,b, respectively. The amount of propylene oxide, which was reactivated, and the mean degree of propoxylate was calculated by weighted the increase in mass of the mixture after the addition of propylene oxide24）. The structure of the latter products was based on the IR and 1HNMR spectra.

Compound（21a）: IR（ν/cm－1）: Broad band at 3405 for（OH）, 2928, 2851（CH aliphatic）, 2243（CN）, 1707（CO）, 1104, 914（C-O-C）ether of poly propoxy chain; 1H NMR（δ, ppm）: Multiple signals in region（3.01–3.90 ppm）for the propoxy protons besides the other signals of the com-pound.

Compound（22b）: IR（ν/cm－1）: Broad band at 3393 for（OH）, 2926, 2849（CH aliphatic）, 1675（CO）, 1103, 911（C-O-C）ether of poly propoxy chain; 1H NMR（δ, ppm）: Multiple signals in region（3.22–3.801 ppm）for the propoxy protons beside the other signals of the compound.

Compound（25b）: IR（ν/cm－1）: Broad band at 3385 for（OH）, 2925, 2850（CH aliphatic）, 2213（CN）, 1677（CO）, 1103, 911（C-O-C）ether of poly propoxy chain; 1H NMR（δ, ppm）: Multiple signals in region（3.02–3.691 ppm）for the propoxy protons besides the other signals of the com-pound.

Compound（26a）: IR（ν/cm－1）: Broad band at 3389 for（OH）, 2926, 2854（CH aliphatic）, 1717, 1656（2CO）, 1107, 919（C-O-C）ether of poly propoxy chain; 1H NMR（δ, ppm）: Multiple signals in region（3.12–3.82 ppm）for the propoxy protons besides the other signals of the compound.

Compound（27a）: IR（ν/cm－1）: Broad band at 3392 for（OH）, 2925, 2849（CH aliphatic）, 2243（CN）, 1687（CO）, 1104, 913（C-O-C）ether of poly propoxy chain.

Compound（30a）: IR（ν/cm－1）: Broad band at 3391 for（OH）, 2927, 2854（CH aliphatic）, 1661（CO）, 1107, 909（C-O-C）ether of poly propoxy chain; 1H NMR（δ, ppm）: Multiple signals in region（3.06–3.75 ppm）for the propoxy

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protons besides the other signals of the compound.Compound（31a）: IR（ν/cm－1）: Broad band at 3408 for

（OH）, 2925, 2851（CH aliphatic）, 1695（CO）, 1107, 912（C-O-C）ether of poly propoxy chain; 1H NMR（δ, ppm）: Multiple signals in region（3.10–3.79 ppm）for the propoxy protons besides the other signals of the compound.

Compound（33a）: IR（ν/cm－1）: Broad band at 3399 for（OH）, 2917, 2849（CH aliphatic）, 1666（CO）, 1106, 909（C-O-C）ether of poly propoxy chain.

Compound（35a）: IR（ν/cm－1）: Broad band at 3420 for（OH）, 2929, 2854（CH aliphatic）, 1712（CO）, 1129, 905（C-O-C）ether of poly propoxy chain.Evaluation of the surface properties2.2.1 Surface and interfacial tension

Surface and interfacial tension characteristics for a solu-tion of the surfactant（10 mmol）were measured using a Kruss du Nouy tensiometer, Type K6（Kruss GmbH, Hamburg, Germany）at 25℃ and the light paraffin oil was used for interfacial tension25）.2.2.2 Cloud point（C.P.）

A cloud point was recorded by heating of the surfactant solution（10 mmol）in deionized water until it became tur-bidity26）.2.2.3 Wetting time

Wetting time was measured in seconds using a solution of the surfactant（10 mmol）and cotton skein（1 g）at 25℃27）.2.2.4 Foaming properties28, 29）

Place a certain amount of surfactant（10 mmol）in a glass cylinder（100 mL）and circulate for 10 seconds at 25℃, then foam height was measured. Also, the stability of foam was calculated using this equation:

Foam stability（％）＝ （Foam volume after 5 min/Foam volume after 0 min）×100 （1）

2.2.5 Emulsion stabilityThe emulsion stability was determined by calculating the

time taken to separate the aqueous layer of a mixture of the surfactant（10 mL, 20 mol）and light paraffin oil（6 mL）30）.Surface parameters for some of the prepared compounds:Critical Micelle Concentration（CMC）

CMC of the surfactant was detected using surface tension method of fresh surfactants solutions at different concentrations（0.1 to 0.000005 mol/L）. The surface tension values were plotted against the corresponding con-centrations31）.Efficiency（pC20）

The efficiency（pC20）at 25℃ has been determined as a negative logarithm of surfactant concentration in the bulk phase required to produce a 20 dyne/cm reduction in the surface tension of the solvent（water）32）.Effectiveness（πcmc）

The surface pressure value（effectiveness）of the tested compounds was calculated from the following expression:

πcmc＝γo－γcmc （2）

Where γcmc is the surface tension at CMC and γo is the surface tension measured by the pure water at the appro-priate temperature32）. Maximum surface excess concentration（Γma.）

The maximum surface excess Γma was obtained from the relationship:

Γma＝（δγ/δlog C）/ 2.303RT （3）

Where（δ γ/δ log C）is the slope of the c vs. - Log C plot, T is absolute temperature, R＝8.314 Jmol－1 K－1 33）.Minimum surface area per molecule（Amin）

The average area occupied by each adsorbent molecule is given on the interface according to this relationship33）:

Amin＝1016/Γmax. N （4）

Where N is Avogadro’s number（6.023×1023）and Γma is the maximum surface excess.

2.3 BiodegradabilityThe biodegradability was carried out by the Die-away

test in the River Nile water of the surfactant using a surface tension method34）. From the surface tension mea-surements, the percentage of biodegradation（D％）was cal-culated as follows:

D＝（γt－γo）/（γbt－γo）×100 （5）

Where γo＝surface tension at zero time, γt＝surface tension at time t, γbt＝surface tension of blank experiment at time t（without samples）

2.4 Antimicrobial activity2.4.1 Antibacterial and antifungal

The new compounds were tested in the laboratory against certain Gram-positive bacteria such as Staphylo-coccus aureus（RCMB010010）, Bacillus subtilis（NRRL B-543）and Gram-negative bacteria such as Salmonella ty-phimurium（ATCC 14028）, Escherichia coli（ATCC 25955）and fungi such as Candida albicans（ATCC® CRM 10231TM）, Aspergillus flavus（RCMB 002002）using a well diffusion method35）.2.4.2 Anticancer activity

Some of the synthesized compounds were evaluated at different concentrations（3.9, 7.8, 15.6, 31.25, 62.5, 125, 250 and 500 μg mL－1）of their inhibitory activity for the growth of human cancer cells against two cell lines: Hepa-tocellular carcinoma（HePG2）and colon carcinoma（HCT-116）. Cell growth measurements were identified as useful as described in method36, 37）and doxorubicin drug was used as a standard reference.

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3 RESULTS AND DISCUSSION3.1 Chemistry

Heterocyclic derivatives combinations with active surface properties and potential pharmaceutical activity were synthesized using fatty acid（1）. Where, the heating of 1 with thionyl chloride gave stearoyl chloride 2, which was coupled smoothly with the malononitrile by electro-philic substitution reaction to afford 2-stearoylmalononi-trile（3）38）. Treatment of 3 with piperidine or morpholine produced enaminonitrile derivatives 4a,b as a key starting point（Scheme 1）. The presence of cyano and amino groups in the enaminonitrile derivatives that make them highly reactive and widely used as reactants or reaction in-termediates, which are conveniently located to enable in-teractions with active reagents to form a variety of hetero-cyclic moieties39）. Thus, compounds 4a,b were heated with hydroxylamine hydrochloride in glacial acetic acid, in each case and gave the pyrazole derivatives 5a,b.

Aminonitrile derivatives and their useful role as synthetic intermediates are suitable for building new compounds in one or two easy reaction steps due to possessions a multi-functional unit property. Thus, heating of urea or thiourea with 4a,b in ethanol containing sodium ethoxide produced pyrimidine derivatives 6a,b or 7a,b, respectively. The pres-ence of CN group adjacent to the NH2 group in precursor 4a,b increases the effectiveness of different nucleophiles. Thus, the reaction of 4a,b with malononitrile in dimethyl-formamide with triethylamine was given 2,4-diamino-6-（substituted）-5-stearoyl-nicotinonitrile（8a,b）（Scheme 2）. Also, hydrolysis of 4a,b by stirring on the cold with sulfuric acid gave（E）-2-（amino（substituted）methylene）-3-oxoico-sanoic acid（9a,b）. Moreover, the reaction of ethylenedi-amine with enaminonitrile 4a,b in ethanol with a few drops of carbon disulfide is furnished the imidazole derivatives 10a,b. Similarly, heating of 4a,b with o-phenylenediamine and/or o-aminophenol in ethanol with a few drops of piperi-dine afforded products 11a,b and/or 12a,b, respectively. In this reaction, an initial addition of hydrogen to cyano group was added, followed by intramolecular cyclization with the loss of the NH3 molecule to produce adducts 11a,b and/or 12a,b, respectively.

Heterocyclic derivatives are playing an important role in the manufacture of drugs due to their polyfunctionalized.

Therefore, we investigated the reaction of phenyl isothio-cyanate with enaminonitrile derivatives in alkaline medium at a different condition. Thus, phenyl isothiocyanate is stirred with enaminonitrile 4a,b in dimethylformamide containing sodium hydroxide at room temperature produc-ing a nonisolable intermediate（A）, which acidified with dil.HCl and given products 13a,b. Furthermore, heating of the compound 13a,b with chloroacetonitrile in boiling dimeth-ylformamide with a few drops of triethylamine was afforded thiazole derivative 14a,b through the corresponding acyclic intermediate（B）（Scheme 3）.

A large variety of reactants carrying（N＝C＝S）unit is subject to cyclization to interact with different compounds to provide different heterocyclic compounds. Therefore, we have extended our synthetic program to synthesize heterocyclic ring systems using phenyl isothiocyanate. The reaction of enaminonitrile 4a,b with phenyl isothiocyanate in boiling DMF with triethylamine, gave pyrimidine the de-rivatives 15a,b, respectively, through the intermediate（C）. Also, the heating of the enaminonitrile 4a,b with for-mamide in dimethylformamide with a few drops of piperi-dine resulted in the formation of pyrimidine derivatives 16a,b. The efficiency of o-aminonitriles toward formic acid is great interest because it is converted by acid or base to the corresponding pyrimidine derivatives. Thus, treatment of enaminonitrile 4a,b with formic acid in ethanol gave the nonisolable intermediate D, which was oxidized by treat-ment with alkaline hydrogen peroxide to afford pyrimidine derivatives 17a,b. In this reaction, the initial hydration of the nitrile group to the carboxamide was carried out, and then cyclization is carried in alkaline medium.

Scheme 1　Synthesis of the key start compounds（4a,b）.i）SOCl2, i i）CH2（CN）2, i i i）Piperidine or morpholine.

Scheme 2　Reactions of the key start compounds（4a,b）.i）NH2OH/HCl, ii）NH2CONH2 or NH2CSNH2, iii）CH2（CN）2, iv）H2SO4, v）NH2（CH2）2NH2, vi）NH2C6H4OH（o）or NH2C6H4NH2（o）.

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The behavior of enaminonitrile towards carbon disulfide has been studied under different reaction conditions to es-tablish synthetic approaches to more nitrogen heterocyclic derivatives. Thus, stirring of enaminonitrile 4a,b with carbon disulfide in pyridine at room temperature gave the thiazine derivatives 18a,b, respectively, by the intermedi-ate（E）（Scheme 4）. Furthermore, the heating of 4a,b with the carbon disulfide in pyridine gave the pyrimidine deriva-tives 19a,b. Finally, compounds 20a,b can be obtained by another reaction via the reaction of 4a,b with benzylidene malononitrile in dimethylformamide containing a catalytic amount of piperidine. Newly synthesized compounds were established on their basic analyzes and spectral data（see experimental part）.

3.2 Preparation of surface-active agentsNonionic surfactants are amphiphilic chemicals that

enhance desorption and bioavailability by increasing the solubility due to their properties, efficiency, economy, ease of handling and formulating, which are used in different applications40, 41）. Thus, our aim was to synthesize of sur-face-active agents containing heterocyclic moiety. There-fore, adding 7 moles of propylene oxide to the prepared compounds（4-20）a,b in presence of KOH gave nonionic products（21-37）a,b（Schemes 5 and 6）. The compounds that were prepared were based on IR and 1HNMR spectra（Experimental part）. The reaction conditions are sum-marized in Table 1.

3.3 Evaluation of the surface activityIn order to verify the industrial viability of this com-

pounds-based on nonionic surfactants as an alternative to oil or other commercial surfactants. Surface properties and other parameters were assessed and presented in Tables 2 and 3.3.3.1 Surface and Interfacial tension

Surfactant molecules containing hydrophilic and hydro-phobic parts. The hydrophilic part is directed to the water phase and the hydrophobic part is located at the air–water interface. It was found that adsorption of surfactant mole-cules in the air–water interface decreases the surface tension of the solution. This means that these products have the ability to reduce the surface tension. In compar-ing, structural surfactants indicated that morpholine deriv-atives are more effective in reducing the surface tension than piperidine derivatives. Where the surfactants 35a,b showed maximum ability than other the related structure, while compounds 33a, 36a have a low aptitude to reduce the surface tension of aqueous system in the series of am-phiphile. Also, pyrimidine derivatives 32a,b revealed

Scheme 3　Reactions of the key start compounds（4a,b）.i）PhNCS/NaOH/rt, ii）dil.HCl, iii）ClCH2CN, iv）DMF/TEA, v）PhNCS/DMF/reflux, vi）HCONH2.

Scheme 4　Reactions of the key start compounds（4a,b）.i）HCOOH/EtOH, ii）K2CO3/H2O2, iii）CS2/Pyr/rt, iv）CS2/Pyr/ref, v）PhCH=C（CN）2 / DMF/Piperidine.

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higher effective than other pyrimidine derivatives. In addi-tion, pyridine derivatives 37a,b revealed higher effective than pyridine derivatives 25a,b. Moreover, the surfactants 27a,b and 29a,b showed the same reduction in surface tensions as results in Table 2. On the other hand, the results showed that these compounds have lower interfa-cial tension values. 3.3.2 Cloud point

Cloud point is an important property for the perfor-mance of surfactants and a characteristic observation of the surfactant molecules is that they exhibit a reverse solu-bility versus temperature behavior in water; therefore, their solutions tend to become evidently muddy at a well-defined temperature, where the surfactant solution phase separates into two phases. The values of the cloud points in Table 2, revealed that the surfactant molecules 22b, 25b, 30b, 36b showed high cloud points, which mean good performance of these compounds in hot water, and reflect the fact that it can use over a wide range of temperatures, which is useful in judging the storage stability of products. 3.3.3 Wetting ability

The ability of wetting property is the most standard for selecting surfactant molecules for use in industrial applica-tions such as the use of textile processing, where the

ability of wetting for surfactant molecules may accelerate the diffusion or penetration of alkali chemicals and dyes into the fibers and improve detergency or dyeing effects. The results in Table 2 showed that these molecules have the ability to wet fabric substrates and are more efficient as a wetting agent. Among the studied groups, the surfac-tant molecules 22b, 24b, 31b, 37b showed the most effi-cient wetting agents and exhibited shorter drowning time.3.3.4 Emulsion stability

One of the most important properties of surfactant mol-ecules is emulsion stability for use in a large number of ap-plications such as paints, foam agents, cosmetics and phar-maceutical industries. In fabric processing operations as dyeing and textile scouring, the surfactant's ability to emulsify oil impurities is critical. Therefore, the surfactants should be added to the dye bath to remove oil impurities from the fibers. The emulsion strength of the surfactant molecule has been detected by dispersion the surfactant from the bulk solution to the interface between oil and water and the physical properties of the adsorbed layers formed from surfactant molecules around the inner phase drop. The results in Table 2 showed that the tested com-pounds had a low emulsification tendency and therefore their safe applicability in various applications. Among our

Scheme 5　Preparation of surfactants（21-28）a,b.

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products compounds 21b, 24b, 27b, 30b, 32b, 36b showed the shorting time to form emulsion layer.3.3.5 Foaming Properties

Surfactant molecules are very useful in various applica-tions, requiring a small or large amount of foam as in the dying process; however, foams can be undesirable; they are created by passing gas in liquid during the movement of machines. In addition, in washing the hair, the foam of the shampoo not only surrounds the grease but also imparts to the company’s sense and fulfillment; it will feel unpleasant if the foam to disappear immediately. In our study, the foam performance of the surfactant molecules of the initial foam（after 0 min observation）was performed and the foam stability（after 5 minutes）. The results in Table 2 showed that the foam heights of our products ranged from 35 and 46 mm, which mean that these products showed foam properties.3.3.6 Evaluation of some surface parameters

The critical micelle concentration（CMC）, effectiveness（πcmc）, efficiency（pC20）, maximum surface excess（Γma.）, and minimum surface area（Amin）were investigated of some of the synthesized compounds（21,22,24-29,32,34,36,37）a,b and summarized in Table 3.3.3.6.1 Critical micelle concentration（CMC）

The efficiency of surfactant molecules can be deter-

mined by the CMC property, which reveals the required amount of surfactant molecule to reach the maximum re-duction of surface tension. Where the surfactant molecule has a low value of CMC that enjoys excellent emulsion, sol-ubility and detergency properties. When surfactant con-centration is increased, surface tension decreases steadily and at critical concentrations, there is no significant reduc-tion in surface tension. This demonstrates the realization of saturation in the surface adsorbed layer and starting the forming of micelle in the bulk. Of the results in Table 3. It is obvious for testing surfactants that a sharp reduction in surface tension was observed with increased concentra-tion. The increase in the value of CMC obtained can be at-tributed to an increase in the solubility of the surfactant molecules i.e., the presence of an oxygen or nitrogen atom in a chain of hydrophobic as polar atoms lead to an in-crease in the CMC.3.3.6.2 Effectiveness（πcmc）

An important factor in determining the surface proper-ties is the effectiveness of adsorption. In addition, the dif-ference between the surface tension of distilled water and the CMC values were used to determine the effectiveness（πcmc）of the amphiphilic molecules. The maximum reduc-tion in surface tension due to the dissociation of surfactant molecule has been indicated by the effectiveness πcmc,

Scheme 6　Preparation of surfactants（29-37）a,b.

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which becomes a measure of the effectiveness of the am-phiphile to reduce the surface tension of water. In general, the results in Table 3 show that the tested compounds have the potential to reduce the surface tension in the aqueous system. Moreover, the effectiveness values ranged from 29.2 to 43.4 dyne/cm.

3.3.6.3 Efficiency（pC20）The concentration of surfactant molecule required to

give 20 mN/m reduction in surface tension is known as the efficiency of surfactant adsorption（pC20）. In comparing the adsorption efficiency of air/water interface of the surfac-tant molecule, the adsorption efficiency values are very im-

Table 1　Reaction conditions of propoxylated compounds.

Sample Temperature ℃

Propoxylated products Yield % Solvent of

crystallization Color Shape

4a 140-150 21a 79 Benzene Deep brown Solid4b 150-160 21b 77 Benzene Light brown Solid5a 115-125 22a 82 Ethanol Pale yellow Semi-solid5b 120-130 22b 79 Ethanol Brown Semi-solid6a 150-160 23a 84 Methanol Pale yellow Solid6b 150-160 23b 82 Methanol Orange Solid7a 155-165 24a 80 Ethanol Deep yellow Solid7b 160-170 24b 78 Ethanol yellow Solid8a 115-125 25a 83 Ethanol Deep orange Semi-solid8b 120-130 25b 80 Ethanol Light brown Semi-solid9a 110-120 26a 76 Ethanol White yellow Oil9b 120-130 26b 76 Ethanol Orange Oil10a 120-130 27a 77 Benzene Yellow Semi-solid10b 125-135 27b 75 Benzene Pale yellow Semi-solid

11a 120-130 28a 80 Ethanol Reddish brown Semi-solid

11b 130-140 28b 79 Ethanol Brown Semi-solid12a 110-120 29a 78 Ethanol Brown Oil12b 120-130 29b 77 Ethanol Brown Oil13a 125-135 30a 81 Ethanol Light brown Oil13b 130-140 30b 79 Ethanol Brown Oil14a 105-115 31a 82 Methanol Pale yellow Oil14b 115-125 31b 80 Methanol Deep yellow Oil15a 115-125 32a 78 Ethanol Brown Semi-solid15b 125-130 32b 77 Ethanol Brown Semi-solid16a 105-115 33a 82 Ethanol Light brown Oil16b 110-120 33b 80 Ethanol Deep brown Oil17a 100-110 34a 83 Ethanol Deep yellow Oil17b 110-120 34b 80 Ethanol Brown Oil18a 105-115 35a 77 Benzene Yellow Semi-solid18b 120-130 35b 75 Benzene Pale yellow Semi-solid19a 140-150 36a 80 Ethanol Deep yellow Solid 19b 150-160 36b 79 Ethanol Brown Solid 20a 100-110 37a 80 Ethanol Deep brown Oil20b 110-120 37b 79 Ethanol Deep brown Oil

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portant. Because of this absorption between water mole-cules, the surfactant molecule reduces the surface tension. The greater Pc20 value, the more efficient surfactant mole-cule to reduce the surface tension and the more efficient

the adsorbent in the interface. The results in Table 3 show that the tested molecules have a good tendency to their surface activity.

Table 2　Surface properties of the synthesized compounds（21-37）a,b.

Sample S. T (dyne/cm)

I. T(dyne/cm)

C.P℃

Wetting(sec)

Emulsion Stability

(min)

Foam height(mm)

Foaming stability

(%)0 min 5 min21a 35 9.1 68 86 26 47 36 76.5921b 35 8.7 76 79 18 50 41 82.0022a 39 11.3 73 92 52 48 37 77.0822b 38 10.6 81 74 46 70 55 78.5723a 38 13.8 66 99 33 55 41 74.5423b 37 11.3 76 93 27 73 54 73.9724a 39 12.8 71 84 29 31 22 70.9624b 37 12.0 79 75 18 46 35 76.0825a 40 14.6 76 98 35 42 34 80.9525b 38 10.8 81 86 26 50 43 86.0026a 37 11.3 66 93 31 28 19 67.8526b 34 10.7 71 85 20 48 37 77.0827a 39 13.2 68 98 28 37 21 56.7527b 36 9.8 75 92 18 49 36 73.4628a 37 14.2 70 95 35 28 22 78.5728b 34 13.0 76 89 28 27 19 70.3729a 39 11.7 68 97 37 37 25 67.5629b 36 9.8 75 93 25 52 38 73.0730a 38 13.6 74 88 25 49 38 77.5530b 37 13.2 80 81 17 78 66 84.6131a 37 11.6 62 78 35 36 25 69.4431b 35 10.5 70 74 29 56 41 73.2132a 37 10.4 65 89 28 39 26 66.6632b 34 8.5 74 84 18 51 39 76.4733a 41 14.4 72 91 41 25 17 68.0033b 39 14.0 77 85 32 38 31 81.5734a 39 11.7 69 99 25 10 8 80.0034b 36 9.5 74 89 22 37 24 64.8635a 31 12.4 65 90 41 43 33 76.7435b 30 11.8 70 83 38 55 40 72.7236a 42 11.2 76 87 22 51 43 84.3136b 38 9.7 80 85 17 62 51 82.2537a 39 14.7 69 78 44 32 21 65.6237b 37 13.6 78 72 34 51 38 74.51

Error of measurements was: Surface Tension (S.T) and Interfacial Tension (IFT) = ±0.1 dynes/cm. Cloud point (C.P) = ±1℃. Wetting time = ±1 sec. Emulsion = ±1 min. Foam height = ±2 mm.

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3.3.6.4 Maximum surface excess（Γma.）The value of maximum surface excess Γma. is very useful

to measure the effectiveness of compound adsorption. So the material will reduce surface tension and thus exist excess when or near the surface. Pumping of surfactant molecules into the boundary surfaces between the phases of the formation of the adsorbed layer is one of the most objective applications of surfactants as a vital branch of chemistry in many applications. In addition, when the surface tension is reduced give a clear activity of the com-pound. Values of Γma. were calculated and listed in Table 3.3.3.6.5 Minimum surface area（Amin）

Based on the minimum surface area of the surfactant molecules in the air/water interface in the surface satura-tion, it gives some information about the degree of packing and orientation of the surface tension adsorbent molecule. The results in Table 3 showed that all the testing surfac-tants had lower Amin values, which indicated highly packed molecules in the interface. The values of area per molecule showed that these molecules were located in the tail posi-

tion on the surface.3.3.7 Biodegradability

The biodegradability of the tested compounds was re-corded in Table 4, which showed that these surfactants factors are determined as biodegradable compounds and pass international level（98％ after 8 days）, which means that the biodegradation of these surfactants significantly reduces the toxicity and safety of human as well as the en-vironment. Where the compounds 22a,b, 33a,b, 34a,b and 36a,b showed above 90％ degradation after 7 days than the remaining compounds.3.3.8 Biological assessment3.3.8.1 Antibacterial activity

Some testing compounds showed varying inhibitory effects on the growth of bacterial strains. The results in Table 5 indicated that the pyrimidine derivative 36a showed the best biological activity against Bacillus subtil-is. While the pyrimidine derivative 24b showed better bio-logical activity against Staphylococcus aureus. On the other hand, the piperidine derivative 30a revealed better

Table 3　Surface parameters of some the synthesized surfactants.

Sample CMC×10－3

(mmol/L)γcmc

(dyne/cm) pC20×10－5 πcmc

(dyne/cm)Γma×10－3

(mol/m2)Amin×10－5

nm2

21a 2.1 37.2 4.2 35.6 1.72 0.96 21b 2.4 36.7 1.2 36.1 1.34 1.23 22a 7 40.7 13 32.1 1.25 1.3322b 3.8 38.8 4.0 34.0 1.29 1.2824a 3.2 43.0 15 29.2 1.22 1.3624b 2.8 39.1 3.1 33.7 1.65 1.0125a 3.2 41.2 13 31.6 1.45 1.1425b 2.5 42.5 4.0 30.3 1.09 1.5226a 3.2 39.2 5.4 33.6 1.4 1.1826b 2.5 36.3 1.0 36.5 1.2 1.3827a 3.2 42.3 16 30.5 1.32 1.2627b 3.1 37.7 3.2 35.1 1.39 1.1928a 3.2 38.2 9.0 34.3 1.6 1.0328b 1.9 36.12 2.0 36.7 1.5 1.129a 1.9 41.2 5.0 31.6 1.19 1.3929b 1.5 37.7 2.0 35.1 1.39 1.1932a 4.2 38.2 2.5 34.6 1.57 1.0532b 3.9 36.6 1.2 36.2 1.42 1.1634a 3.1 40.8 4.0 32.0 1.16 1.4334b 1.6 37.8 0.5 35.0 1.05 1.5836a 2.7 43.4 9.0 43.4 1.17 1.4136b 2.45 41.7 2.2 41.7 0.84 1.9737a 3.2 41.6 15.0 31.2 1.4 1.1837b 3.2 39.7 11.0 33.1 1.5 1.1

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biological activity against Escherichia coli compared with the reference. Moreover, the thiazole derivative 31a showed good activity toward Salmonella typhimurium.3.3.8.2 Antifungal activity

The results depicted in Table 5, revealed that some tested compounds exhibit a varying degree of microbial in-hibition as antifungal agents. Where, the pyrimidine 23a, pyridine 24b, thiazine 35a, and pyrimidine 36a derivatives

exhibited better antifungal potentials than other com-pounds against Aspergillus flavus. In addition, we ob-served that the pyrimidine derivatives 32b and 36a exhib-ited broad-spectrum antifungal profile against Candida albicans. In conclusion, the nature of substituents and heterocyclic skeleton of molecules have a strong impact on the extent of antibacterial and antifungal activities.

Table 4　Biodegradability of the synthesized surfactants.

Sample 1st day 2nd day 3rd day 4th day 5th day 6th day 7th day 8th day21a 40 47 55 63 74 80 88 9221b 39 45 52 60 69 77 86 9222a 44 51 60 68 77 85 93 －22b 43 49 58 65 74 80 90 －23a 42 49 57 65 74 81 88 9223b 42 48 56 63 71 80 87 9024a 44 51 60 67 75 81 88 9324b 42 50 57 65 72 80 86 9125a 43 50 58 66 76 83 90 －25b 41 48 55 64 73 80 87 9126a 40 46 53 60 70 78 86 9226b 39 45 53 58 69 76 82 9027a 44 50 57 65 77 84 90 －27b 40 46 52 61 73 80 88 9128a 41 49 57 66 75 82 88 9328b 38 45 54 62 71 80 87 9229a 39 47 55 63 70 79 86 9229b 37 44 52 60 68 75 84 9030a 42 47 56 65 76 83 90 －30b 42 46 56 64 74 80 88 9531a 43 50 59 68 77 84 90 －31b 40 48 56 66 74 80 87 9332a 41 48 55 63 70 78 83 9032b 39 45 51 60 68 75 82 9033a 45 53 60 69 78 85 92 －33b 42 49 57 66 76 82 90 －34a 44 51 60 70 79 88 94 －34b 40 48 57 66 77 85 90 －35a 36 45 54 63 71 80 87 9235b 34 42 50 60 68 77 85 9136a 45 53 60 69 78 86 91 －36b 42 52 59 67 75 84 90 －37a 43 50 58 68 77 83 90 －37b 41 49 55 64 72 80 88 93

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3.3.8.3 Anticancer activitySome of the tested compounds were evaluated for their

in vitro cytotoxicity against two cell lines of human cancer:（HePG2）and（HCT-116）at different concentrations with use the doxorubicin as a reference drug. The viability cells（％）were determined by the colorimetric method. The calculat-

ed response parameter was the value of IC50, which corre-sponds to the concentration required for 50％ inhibition of cell viability. The inhibitory concentration fifty（IC50）for the tested compounds of（HePG2）and（HCT-116）was calculated from Tables 6 and 7, respectively. The results of inhibitory concentration fifty（IC50）data were summarized in Table 8

Table 5　Antimicrobial activity of some synthesized compounds.

Sample

Gram-positive bacteria Gram-negative bacteria Fungi

Bacillus Subtilis NRRL B-543

Staphylococcus Aureus RCMB

010010

Escherichia Coli ATCC 25955

Salmonella typhimurium ATCC

14028

Aspergillus flavus RCMB

002002

Candida Albicans ATCC

1023121a － － － 10 11 －23a 10 12 11 － 15 －24b 8 13 8 － 13 1226b － － 13 － 11 －27b － － － － 11 1629a － － 16 11 － 930a － － 18 10 12 1431a － － 12 12 9 832b － 7 － － 10 1834b － 8 － － 9 －35a － － 12 － 13 －36a 12 8 15 － 15 20

Gentamycin 24 26 17 30Ketoconazole 16 20

The sample was tested at 5 mg/mL concentration. The sensitivity of microorganisms to the tested compounds is identified in the following manner: Highly sensitive = Inhibition zone 15–20 mm; moderately sensitive = Inhibition zone 10–15 mm; slightly sensitive = Inhibition zone 5–10 mm; Not sensitive = Inhibition zone 0–5 mm. Each result represents the average of triplicate readings.

Table 6　Anticancer activity of some of the synthesized compounds against the HepG2 cell line.

SampleViability（%）

Concentration.（μg/ml）0 3.9 7.8 15.6 31.25 62.5 125 250 500

21a 100 100 98.73 95.16 90.64 79.82 70.69 39.85 27.4623a 100 100 98.04 95.26 90.79 78.54 62.93 46.37 38.2624b 100 100 100 99.62 95.49 89.42 72.18 46.91 26.8026b 100 100 100 100 98.14 90.32 76.08 57.86 31.5227b 100 99.87 97.31 92.06 84.60 66.95 45.81 29.64 16.2329a 100 100 100 96.83 91.56 78.12 70.35 51.74 34.0830a 100 94.58 91.26 87.43 69.02 48.67 32.14 18.60 10.9131a 100 94.36 87.21 81.48 73.08 67.83 38.56 28.27 15.6932b 100 100 100 100 99.16 93.94 80.73 41.52 24.3834b 100 100 98.79 96.41 85.22 78.70 66.19 37.94 26.7135a 100 100 100 100 99.17 94.56 79.41 49.63 27.3836a 100 100 99.51 96.42 90.39 81.27 63.18 42.56 30.84

Doxorubicin 100 37.54 30.69 23.87 16.45 9.68 6.43 3.97 3.6

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and showed that some of the tested compounds revealed significant activity as reference drug. In particular, piperi-dine derivative 30a, which has shown the best significant against two cell lines of antitumor cancer. Where the com-pound 30a has less IC50 values than other tested com-pounds against（HePG2）and（HCT-116）. These preliminary results of the biological examination of the tested com-pounds give an idea of the potential importance of these compounds acting against bacteria, fungi, and cancer, which give an encouraging framework in the field that may lead to the discovery of a potent microbial agent.

4 CONCLUSIONNew classes of environmentally safe surface active

agents bearing heterocyclic nucleus such as piperidine, morpholine, pyrazole, thiazole, imidazole, pyridine and py-rimidine derivatives in different molecular weights have been designed and synthesized from renewable and easily available resources. Propoxylation of these heterocycles was produced nonionic surfactants（21-37）with surface-ac-tive properties, which showed good degradation suscepti-bility within 7-8 days. The newly compounds（21-37）exhibit varying degrees of microbial inhibition such as anti-bacterial, antifungal and anticancer. Some of these com-pounds revealed that the most effective cells against human hepatocellular cancer cells（HePG2）and human colon carcinoma（HCT-116）. Therefore, these surfactants have low toxicity to human and environment because of their solubility and good biodegradability. Moreover, they can be used in different fields as cosmetics, dyes, emulsifi-ers, drugs, pesticides and many other industries.

5 ACKNOWLEDGEMENTAuthors would like to thank the King Abdulaziz city for

science and technology for the helping and providing facili-ties for carrying out the research work.

REFERENCES1） Vijayakumar, S.; Saravanan, V. Biosurfactants-types,

sources and applications. Res. J. Microbiol. 10, 181-

Table 7　Anticancer activity of some of the synthesized compounds against the HCT-116 cell line.

SampleViability（%）

Concentration.（μg/ml）0 3.9 7.8 15.6 31.25 62.5 125 250 500

21a 100 95.12 90.67 81.24 63.71 57.14 45.43 34.28 23.9623a 100 100 99.42 96.35 89.56 68.71 59.23 45.67 30.4824b 100 100 98.19 95.48 89.62 76.84 58.91 45.28 23.4126b 100 100 97.94 92.36 84.92 65.33 52.81 36.15 24.5627b 100 96.38 94.06 89.84 75.31 62.05 45.98 32.36 21.5229a 100 100 100 99.85 87.24 68.19 47.28 39.62 30.4630a 100 89.17 85.03 78.26 59.65 32.27 21.08 14.86 8.4231a 100 94.48 80.36 74.51 66.70 52.46 38.14 27.52 18.2432b 100 99.56 92.34 85.29 78.96 60.14 48.02 32.91 18.6934b 100 94.86 91.75 84.03 67.18 58.04 46.86 35.14 17.4835a 100 98.76 96.12 90.37 81.24 55.91 40.86 31.72 20.6236a 100 100 97.64 89.61 74.53 56.38 43.15 36.69 28.91

Doxorubicin 100 42.98 35.21 26.47 18.85 9.14 6.71 4.98 3.07

Table 8　 IC50（μg）values of tumor cell lines after 72 h continuous exposure to test.

Sample HepG2 HCT-11621a 209 10123a 223 21024b 235 20726a 325 14627b 113 10929a 275 11730a 60.5 42.331a 101 73.232b 223 11534a 197 10735a 248 8736a 205 92.6

Doxorubicin 0.85 1.73

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