Some Aspects of the Reaction of Methyl 4,6-O-benzylidene-α-D-glucopyranoside 2,3-Carbonate with 1-Dodecanol: Novel Non-Ionic Surfactants

Abstract

The reaction of methyl 4, 6-0-benzylidene-α-D-glucopyranoside 2, 3-cyclic carbonate (2) with 1-dodecanol in the presence of a catalytic amount of triethylamine to yield the 2-O-and the 3-O-alkoxycarbonyl esters 5 and 6 is described. Catalytic hydrogenation of 5 and 6 gave the deprotected mono-esters 3 and 4 which are of interest as potential non-ionic surfactants. The corresponding ethoxycarbonyl esters 7 and 8 were also prepared and their possible role as intermediates in the formation of 2 is discussed.     

Phosphonic-Acid Analogues of the N-Acetyl-2-deoxyneiiraniinic Acids: Synthesis and Inhibition of Vibrio cholerae Sialidase

The phosphonic acids 3 and 4 were prepared to compare their inhibitory activity on Vibrio cholerae sialidase with the one of the corresponding N-acetyl-2-deoxyneuraminic acids 5 and 6 . Thus, hydrogenation and benzylation of methyl N-acetyl-2,3-didehydro-2-deoxyneuraminate (1MeNeu2en5Ac; 7) gave a mixture of the fully O-benzylated benzyl and methyl esters 9 and 10 , the partially O-benzylated benzyl and methyl esters 11 and 12 , and the fully O-and N-benzylated benzyl and methyl esters 13 and 14 (Scheme 1). Transesterification of 9 to 10 and hydrolysis of 10 gave the acid 15 . Oxidative decarboxylation of 15 with Pb(OAc)₄ gave a 1:9 mixture of the α-and β-D-glycero-D-galacto-acetates 16 and 17 . Phosphonoylation of 17 with P(OMe)₃ and Me₃SiOTf gave a 1.3:1 mixture of the phosphonates 18 and 19 , which were deprotected to give the (4-acetamido-2,4-dideoxy-D-glycero-α-and β-D-galacto-octopyranosyl)phosphonic acids 3 and 4 , respectively. The acid 6 was obtained by epimerization of the tert-butyl ester 23 with lithium N-cyclohexylisoproylamide and deprotection. The phosphonic acids 3 (K_i 5.5 10_-5 M) and 4 (K_i 2.3.10^?4 M ) are stronger inhibitors of Vibrio cholerae sialidase than the anomeric N-acetyl-2-deoxyneuraminic acids 5 (K_i 2.3 10^?3 M ) and 6 . Both 3 and 4 inhibit the Vibrio cholerae sialidase, while only the carboxylic acid 5 , possessing an equatorial COOH group is an inhibitor.     

Microwave‐Assisted Synthesis of Quinoline Derivatives from Isatin

Microwave irradiation has been used for a rapid and efficient synthesis of quinoline‐4‐carboxylic acids 5a–g and 1,2,3,4‐tetrahydroacridine‐9‐carboxylic acid (6) from the reaction of isatins 1–3 with acyclic and cyclic ketones in basic medium. 2‐Hydroxyquinoline‐4‐carboxylic acid (11) was also obtained by irradiating a mixture of isatin 1 and malonic acid in AcOH. The esters of 5f and 11 and their respective hydrazides 8 and 13 were also prepared under MWI.     

Synthesis of 2-thiobenzimidazole derivatives as potential antifilarial agents

Several 5-benzoyl-2-thiobenzimidazole and 2-thiobenzimidazole aliphatic acids, esters, and N,N-dialkyl-carboxamides and thiocarboxamides were prepared by reacting bromo aliphatic acids, bromo aliphatic esters, and N,N-dialkylcarbamoyl or thiocarbamoyl chlorides with 5-benzoyl-2-thiobenzimidazole or 2-thiobenzimidazole in the presence of base. 2-Thiocarbomethoxy- and 2-thiocarboethoxybenzimidazole were prepared by the reaction of 2-thiobenzimidazole with methyl or ethyl chloroformate in the presence of base. However, the reaction of 5-benzoyl-2-thiobenzimidazole with ethyl chloroformate, afforded 5-benzoyl-2-ethylthiobenz-imidazole.     

Preparation of Amides of Carboxylic Acid Herbicides for Gas Chromatographic Analysis

Abstract

Amides of 14 carboxylic acid herbicides were prepared by reacting the free acid with the amine in toluene for 1 hr at 80[ddot]C in the presence of PCl₃ or P₂I₄. The acids include phenoxyacetic acids, arylacetic acids, and benzoic acids. Aniline, o-toluidine, 3,5-bis(trifluoromethyl)aniline, piperidine, and tetrahydroquinoline were the amine components. Excess of reagents and by-products of the reaction were removed by partitioning into aqueous acid and base. Retention times relative to 2,4-D anilide on 1% OV-22 and FSOT RSL-150 columns are listed for the anilides and should be useful for confirmation purposes. The anilides of 2,4-D, silvex and 2,4,5-T were obtained in better than 90% yield.     

Furan derivatives. Part 8 On substituent effects in the synthesis of 4,5-dihydro-3H-naphtho[1,8-bc]furans

4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 6 which have various substituents (R¹ and R²) have been synthesized from 8-oxo-5,6,7,8-tetrahydro-1-naphthyloxyacetic acids 1 and 3 or their ethyl esters 2 . The reaction of acids 1 and 3 with sodium acetate in acetic anhydride gave a mixture of furans 4 and 6 and lactones 5 and 7 . The ratios of the products were varied according to the types of substituents (R¹ and R²) in acids 1 and 3 . As the substituent R¹ (R² = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, production of furans 4 became more difficult. However, when a phenyl group was used as the substituent, furan 4 was obtained in good yield. Similarly, as the substituent R² (R¹ = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, furan formation was more difficult. In contrast, acids 3 which had electron-withdrawing substituents such as chlorine, bromine or a nitro group at the 4-position afforded furans 6 in good yield. 4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 4,5-dihydro-3H-naphtho[1,8-bc]furan-2-carbocylic acids 8 were synthesized from the reaction of esters 2 and potassium hydroxide in dioxane. When the substituents R¹ or R² in esters 2 were varied from hydrogen to a methyl, ethyl or isopropyl group the total yields of furans 4 and furancarboxylic acids 8 were reduced.     

5-氟尿嘧啶N1-甲酰基氨基酸、短肽的合成及抗肿瘤活性

5-氟尿嘧啶N¹-甲酰氯分别与Gly、Val、Leu、Ile、Phe、Asp和Glu的苄酯反应,制备了7种5-氟尿嘧啶-N¹-甲酰基氨基酸苄酯。氢解后得到了相应的5-氟尿嘧啶N¹-甲酰氨基酸。将其进一步与氨基酸甲酯或二肽甲酯缩合,制备了5-氟尿嘧啶N¹-甲酰基二肽甲酯和三肽甲酯。5-氟尿嘧啶-N¹-甲酰基二肽甲酯也可采用5-氟尿嘧啶-N¹-甲酰氯与二肽甲酯直接反应制备。     

A Facile Synthesis of 2-Imino-1-pyrrolidinealkanoic Acids

Sulfuryl chloride isocyanate was used in a mild, one pot conversion of methyl 2-oxo-1-pyrrolidinealkanoic acid esters 5–7 to their corresponding 2-imino-1-pyrrolidinealkanoic acids 2–4.     

Separation and Determination of Monoalkanolamides of Soybean Oil Fatty Acids by RP-HPLC of the Crude Reaction Product

Abstract

A reverse-phase HPLC technique, previously developed by us, was used to achieve satisfactory separation and determination of monoalkanolamides of the soybean oil fatty acids. Four reaction products, each containing a mixture of similar monoalkanolamides of the soybean fatty acids, were analyzed without pretreatment. Structurally, the four monoalkanolamides series differ in their alkanol moiety, having two or three carbon atoms in the alkanol chain which is substituted or unsubstituted. A series of N-methyl monoethanolamides was also prepared and HPLC analyzed. In each case, the separated components were isocratically eluted with a ternary solvent system of tetrahydrofuran-acetonitrile-water at pH 2.6 (37.5:37.5:25 v/v/v), followed by detection with a differential refractometer. In all cases, the elution order was in accordance with the length as well as with the degree of unsaturation of the hydrophobic chain of the monoalkanolamides. The sequence of the eluted components was elucidated by chromatographing, under the same conditions, of the corresponding commercially purchased pure fatty acid methyl esters. As control compounds, the corresponding stearoyl monoalkanolamides, prepared in our laboratory, were individually chromatographed. The HPLC results showed that, in addition to the expected monoalkanolamides, unreacted methyl esters and sometimes amine-esters were separated and detected. For each alkanolamine used, the amidation reaction was discussed.     

Synthesis of 2-alkyl-2-(3-cyanopyridin-2-ylthio)propionic acids

Derivatives of 2-alkyl-2-mercaptopropionic acid were synthesized based on the substituted 3-cyanopyridin-2(1H)-thiones. The synthesis was carried out by the heating of a mixture of thione, alkyl methyl ketone, and chloroform in the presence of a base. The reaction proceeds readily for acetone, whereas alkyl methyl ketones require a prolonged heating in the presence of a phase-transfer catalyst. Methyl esters were prepared from the acids obtained. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1967–1970, October, 2007.     

Synthesis of some new benzimidazole-5(6)-carboxylic acids

The title compounds, 1,2-dialkyl-benzimidazole-5(6)-carboxylic acids 34–45 were prepared at four steps; 1) preparation of mono amide derivatives 1–11 by the reaction of methyl 3,4-diaminobenzoate and substituted phenyl or phenoxyacetic acid chlorides; 2) preparation of the methyl benzimidazolecarboxyl-ates 12–22 , with zinc chloride and dry hydrogen chloride gas; 3) alkaline hydrolysis of the esters 23–33 ; and 4) substitution of the imidazole ring with benzyl or p-fluorobenzyl bromide, in alkali medium. 2-Aryl-benzimidazole-5(6)-carboxylic acids 50–53 were prepared via the oxidative condensation of 3,4-diaminobenzoic acid and aromatic aldehydes with cupric ion.     

Synthesis and Characterization of Diastereoisomerically Pure Tetracyclo[6.2.1.13,6.02,7]dodec‐9‐ene‐4‐carboxylic Acid Derivatives

The synthesis and detailed NMR analysis of diastereoisomerically pure samples of 4‐methyltetracyclo[6.2.1.1^3,6.0^2,7]dodec‐9‐ene‐4‐carboxylic acid ( 2 ), tetracyclo[6.2.1.1^3,6.0^2,7]dodec‐9‐ene‐4‐carboxylic acid ( 6 ) and their tert‐butyl esters are reported. Mixtures containing two isomers of the methyl esters of these compounds were obtained by a twofold, sequential Diels‐Alder reaction between cyclopentadiene, and methyl methacrylate or methyl acrylate, respectively. Pure diastereoisomers of the acids were prepared by selective hydrolysis of their methyl esters.     

Use of Some Silver Salts of Aromatic Sulfonic Acids in Thin-Layer Chromatography

Abstract

Some silver salts of aromatic sulfonic acids were used for thin-layer impregnation. The chromatographic properties of these salts were examined by separation of fatty acid methyl esters with different degrees of saturation as well as of their cis- and trans-isomers. Benzene sulfonic acid silver salt was more thoroughly investigated. An attempt was made to prove the effect of the anion of the different silver salts on the R_f values of a model mixture of fatty acid methyl esters.     

Determination of Phenoxy Acid Pesticides in Frog and Fish Tissues by Gas Chromatography-Mass Spectrometry

A gas chromatography-mass spectrometric GC-MS method has been developed for the determination of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in frog and fish tissues. After homogenization and sonication of 5 g samples, purification was achieved by a liquid phase extraction procedure using methyl-tert-butyl ether. The extract was reacted for 30 min at 80 °C with 10 % H₂SO₄ in methanol to form the corresponding methyl esters, which were simultaneously extracted with petroleum ether, and analysed by GC-MS in selected ion monitoring mode. Detection limits were 1.0 and 0.5 μg. kg^?1 for 2,4-D and 2,4,5-T respectively in tissue samples and the calibration curves showed good linearity (r ≥ 0.999). Twenty-five frog samples and forty-six fish samples from various regions in Korea were analyzed. 2,4,5-T was detected up to a maximum concentration of 16.2 μg kg^?1 in frogs and fish. The developed method may be valuable for the national monitoring project of endocrine disruptors (EDs) in biota.     

Solvent-modulated chemoselective deprotections of trialkylsilyl esters and chemoselective esterifications

A series of trialkylsilyl esters were deprotected or transesterificated into their corresponding carboxylic acids or methyl esters under a catalytic amount of CBr₄ in alcohol reaction system. This method enables to desilylate secondary sp³-carbon, sp²-carbon, sp-carbon and aryl tethered trialkylsilyl esters to carboxylic acids, whereas primary sp³-carbon tethered trialkylsilyl esters were further converted into their methyl esters under CBr₄/MeOH reaction conditions. The highly chemoselective deprotections can be modulated and achieved by the introduced protecting trialkylsilyl groups and the used alcohols such as MeOH and EtOH under this photochemically-induced reaction conditions.     

Synthesis of trifluoromethyl derivatives of alkyl 2-nitromethylphosphonopropionates and -phosphonobutyrates

By adding diethyl hydrogen phosphite to 5-trifluoromethyl-2-furaldehyde (5-trifluoromethylfur-2-yl)(diethoxyphosphoryl)methanol was synthesized. It was oxidized with DMSO-acetic anhydride mixture to diethyl 5-trifluoromethyl-2-furoyl phosphonate. The reaction of the latter with ethoxymethylenetriphenylphosphorane gives ethyl (2E)-3-(diethoxyphosphoryl)-3-(5-trifluoromethylfur-2-yl)propenoate. Analogous reaction of (diethoxyphosphoryl)(5-trifluoromethylfur-2-yl)acetic aldehyde yields ethyl (4E)-4-(diethoxyphosphoryl)-4-(5-trifluoromethylfur-2-yl)-but-3-enoate. The addition of nitromethane to these esters of unsaturated acids in the presence of potassium fluoride gives a mixture of diastereomers of phosphorylated esters of 2-nitromethyl-3-(5-trifluoromethylfur-2-yl)propanoic and 3-nitromethyl-4-(5-trifluoromethylfur-2-yl)butanoic acids respectively. By the reduction of ethyl nitropropanoate with zinc and formic acid in dioxane ethyl 2-aminomethyl-3-(diethoxyphosphoryl)-3-(5-trifluoromethylfur-2-yl)propanoate was prepared in a low yield. It may be considered as the derivative of β-alanine containing additional pharmacophore fragments.     

糖基修饰的氨基酸类化合物的合成

通过对5种氨基酸酯化和氨基保护得到苄氧羰基氨基酸甲酯, 经肼解制备苄氧羰基氨基酸酰肼, 然后分别与3种不同的糖基异硫氰酸酯反应, 制备了相应的目标化合物15个, 且产率均在60%以上. 所有新化合物均经元素分析, IR, MS和¹H NMR确证. 同时探索了苄氧羰基氨基酸甲酯肼解的最佳反应条件.     

SYNTHESIS OF N-PHOSPHOPEPTIDES COUPLED BY DICHLOROTRIPHENYLPHOSPHORANE

Coupling of N-phosphoamino acids 2 and amino acid methyl esters by dichlorotriphenylphosphorane 3 produced N-phosphopeptide methyl esters 5, which were sequentially hydrolyzed in triethylamine or dilute NaOH aqueous solution. The target products N-phosphodipeptides 6 were obtained in reasonable yields and high purity after isolation using extraction method. The convenient and efficient approach could be generally used for synthesis of polypeptides.     

Unusual Formation of 1,2,4-Oxadiazine Core in Reaction of Amidoximes with Maleic or Fumaric Esters

We have developed a simple and convenient method for the synthesis of 3-aryl- and 3-hetaryl-1,2,4-oxadiazin-5-ones bearing an easily functionalizable (methoxycarbonyl)methyl group at position 6 via the reaction of aryl or hetaryl amidoximes with maleates or fumarates. The conditions for this reaction were optimized. Different products can be synthesized selectively in good yields depending on the base used and the ratio of reactants: substituted (1,2,4-oxadiazin-6-yl)acetic acids, corresponding methyl esters, or hybrid 3-(aryl)-6-((3-(aryl)-1,2,4-oxadiazol-5-yl)methyl)-4H-1,2,4-oxadiazin-5(6H)-ones. The reaction is tolerant to substituents’ electronic and steric effects in amidoximes. As a result, a series of 2-(5-oxo-3-(p-tolyl)-5,6-dihydro-4H-1,2,4-oxadiazin-6-yl)acetic acids, their methyl esters, and 1,2,4-oxadiazoles based on them were prepared and characterized by HRMS, ¹H, and ¹³C NMR spectroscopy. The structures of three of them were elucidated with X-ray diffraction.     

GC—MS analysis of carboxylic acids in petroleum after esterification with fluoroalcohols

The GC–MS characteristics of carboxylic acid esters prepared from fluorine-containing alcohols were compared to those of methyl esters. The GC retention of 2,2,2-trifluoroethyl (TFE) esters was less than, and 2,2,3,3,4,4,4-heptafluoro-1-butyl (HFB) esters was approximately equivalent to that of methyl esters. Mass spectra of TFE and HFB aliphatic esters show significantly more intense molecular and key fragment ions than those of methyl esters. Also, owing to their significantly higher molecular weights, TFE or HFB ester molecular ions and most fragment ions of interest occur at significantly higher m/z values than most potential interfering ions. Data for about 70 individual TFE and HFB esters are reported. Application of the methodology to a petroleum-derived carboxylic acid concentrate resulted in identification of straight chain, isoprenoid, methyl-substituted straight chain (2-, 3-, 5-,10-, 12-positions along chain), and dimethyl-substituted straight chain acids containing from 11 to 22 carbons. Benzoic acid and homologs with up to 3-carbons in alkyl substitutents were minor components in the sample. The procedure provided for forming TFE and HFB esters from free acids requires less time and effort than a previously reported method, while retaining its capability for achieving essentially quantitative conversion. Free hydroxyl groups in alcohols and phenols are converted to trifluoroacetate esters concurrently with formation of TFE/HFB carboxylic acid esters. The reaction products, including compounds with two functional groups (diacids, salicylic acid, etc.), chromatograph well on conventional nonpolar GC stationary phases.