Subsequent Acid Hydrolysis Research Articles

ChemInform Abstract: Pyrrolizidine Alkaloids. The Synthesis and Absolute Configuration of All Stereoisomers of 4-Carboxy-4-ethyl-3-hydroxy-2-isopropyl-4- butanolide, the Necic Acid Component of Axillaridine.

All stereoisomers (4a,b–7a,b) of 4-carboxy-4-ethyl-3-hydroxy-2-isopropyl-4-butanolide, the necic acid component of axillaridine, have been synthesized. Methyl(E)-(S)-(+)-2-ethyl-4-methoxycarbonyl-5-methyl-2- hexenoate (12a) was converted into γ-lactone acids, 4a (2S,3S,4S), 5a (2S,3R,4R), and 5b (2R,3S,4S), by a series of reactions: Epoxidation with m-chloroperbenzoic acid, treatment with acetone in the presence of tin(IV) chloride, acidic hydrolysis with formic acid, and alkaline hydrolysis with barium hydroxide. Similarly, (R)-(−)-enantiomer (12b) was also transformed into γ-lactone acids 4b (2R,3R,4R), 5b and 5a. Subsequently, (E)-(S)-(+)-4-carboxy-2-ethyl-5-methyl-2-hexenoic acid (13a) and its (R)-(−)-enantiomer (13b) were esterified with chloromethyl methyl ether in the presence of triethylamine to give the corresponding bis(methoxymethyl) esters (26a and 26b). Oxidation of 26a with potassium permanganate and subsequent acidic hydrolysis afforded γ-lactone acids, 6a (2S,3R,4S) and 7a (2S,3S,4R). Simi...

Nanogels of poly(acrylic acid): Uptake and release behavior with fluorescent oligothiophene‐labeled bovine serum albumin

AbstractNanometer‐sized poly(acrylic acid) (PAA) hydrogels were synthesized by emulsion polymerization of methyl acrylate and subsequent acidic hydrolysis. The nanohydrogel was characterized by spectroscopic methods (FTIR and 1H‐NMR) and scanning probe techniques, and their pH‐dependent swelling behavior was studied by dynamic light scattering. To determine the suitability of PAA nanogels as pH‐sensitive carriers for biomedical applications, uptake and release of an oligothiophene fluorophore and its albumin conjugated from PAA nanogels were investigated as a function of pH by absorption and photoluminescence measurements. It was observed that uptake and release processes of both the oligothiophene and its conjugate could be controlled by changing the pH of the external solution. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Efficient Synthesis of α-Ketoamides via 2-Acyl-5-aminooxazoles by Reacting Acyl Chlorides and α-Isocyanoacetamides

Acyl chlorides and alpha-isocyanoacetamides undergo an efficient reaction in dichloromethane in the presence of triethylamine to give 2-acyl-5-aminooxazoles. Subsequent acid hydrolysis of the 5-aminooxazole moiety leads to alpha-ketoamides in good overall yields.

Synthesis of Poly(acrylic acid) Nanogels and Application in Loading and Release of an Oligothiophene Fluorophore and Its Bovine Serum Albumin Conjugate

AbstractSummary: Nanometer‐sized poly(acrylic acid) (PAA) hydrogels were synthesized by emulsion polymerization of methyl acrylate and subsequent acid hydrolysis, and their pH‐dependent swelling behaviour was studied by dynamic light scattering. To determine the suitability of PAA nanogels as pH‐sensitive carriers for biomedical applications, loading and release of an oligothiophene fluorophore and its albumin conjugate onto the PAA nanogels were investigated as a function of pH by absorption and photoluminescence measurements. It was observed that loading and release processes of both the oligothiophene and its conjugate could be controlled by changing pH of their solutions.

Alkylation of acyl and sulfonyl derivatives of 3,5-diamino-1-phenyl-1,2,4-triazole

Alkylation of 3-acylamino-, 5-amino-1-phenyl-3-tosylamino-1,2,4-triazoles and 3,5-diacetylamino-1-phenyl-1,2,4-triazole in the presence of an equimolar amount of sodium methylate in DMSO occurs regioselectively at the amide (sulfamide) group nitrogen atom. The benzylation of 3-acetylamino-5-amino-1-phenyl-1,2,4-triazole with excess base and benzyl chloride also alkylates the amino group at position 5. Alkylamino-1-R-1,2,4-triazoles can be conveniently prepared by alkylation of the corresponding acetylamino-1,2,4-triazoles in the presence of base and subsequent acid hydrolysis of the N-acetyl-N-alkyl derivatives.

The influence of solid/liquid separation techniques on the sugar yield in two-step dilute acid hydrolysis of softwood followed by enzymatic hydrolysis

BackgroundTwo-step dilute acid hydrolysis of softwood, either as a stand-alone process or as pretreatment before enzymatic hydrolysis, is considered to result in higher sugar yields than one-step acid hydrolysis. However, this requires removal of the liquid between the two steps. In an industrial process, filtration and washing of the material between the two steps is difficult, as it should be performed at high pressure to reduce energy demand. Moreover, the application of pressure leads to more compact solids, which may affect subsequent processing steps. This study was carried out to investigate the influence of pressing the biomass, in combination with the effects of not washing the material, on the sugar yield obtained from two-step dilute acid hydrolysis, with and without subsequent enzymatic digestion of the solids.ResultsWashing the material between the two acid hydrolysis steps, followed by enzymatic digestion, resulted in recovery of 96% of the mannose and 81% of the glucose (% of the theoretical) in the liquid fraction, regardless of the choice of dewatering method (pressing or vacuum filtration). Not washing the solids between the two acid hydrolysis steps led to elevated acidity of the remaining solids during the second hydrolysis step, which resulted in lower yields of mannose, 85% and 74% of the theoretical, for the pressed and vacuum-filtered slurry, respectively, due to sugar degradation. However, this increase in acidity resulted in a higher glucose yield (94.2%) from pressed slurry than from filtered slurry (77.6%).ConclusionPressing the washed material between the two acid hydrolysis steps had no significant negative effect on the sugar yields of the second acid hydrolysis step or on enzymatic hydrolysis. Not washing the material resulted in a harsher second acid hydrolysis step, which caused greater degradation of the sugars during subsequent acid hydrolysis of the solids, particularly in case of the vacuum-filtered solids. However, pressing in combination with not washing the material between the two steps enhanced the sugar yield of the enzymatic digestion step. Hence, it is suggested that the unwashed slurry be pressed to as high a dry matter content as possible between the two acid hydrolysis stages in order to achieve high final sugar yields.

Synthesis and reactions of α-fluoro-α-amino amides

N-(( S)-1-Phenylethyl)halofluoroethanamides have been investigated as precursors to N-protected α-fluoro-α-amino amides by nucleophilic displacement of halide with nitrogen nucleophiles such as potassium phthalimide, sodium succinimide, sodium glutarimide, trimethylamine and sodium azide. With single diastereoisomers of the iodofluoroethanamide, clean inversion of configuration occurs at room temperature, but subsequent epimerisation may occur as a result of the liberated iodide. The α-fluoro-α-amino amides made underwent a wide variety of reactions depending on conditions, but in many cases the carbon–fluorine bond was compromised. However, reacting trimethylamine and N-(( S)-1-phenylethyl)iodofluoroethanamide gave the corresponding α-fluorobetaine amide, and subsequent acidic hydrolysis led to α-fluorobetaine as the first example of an ‘unprotected’ α-fluoroamino acid.

Role of the Countercation in Diastereoselective Alkylations of Pyramidalized Bicyclic Serine Enolates. An Easy Approach to α-Benzylserine

The use of a chiral serine equivalent as an excellent chiral building block has been demonstrated in the synthesis of alpha-benzylserine through a diastereoselective lithium enolate alkylation reaction and subsequent acid hydrolysis. The role of a coordinating countercation (lithium) in the alkylation reaction has been investigated. Theoretical studies have been performed in order to elucidate the stereochemical outcome of the alkylation process, which occurs with total retention of configuration.

Covalent Biofunctionalization of Silicon Nitride Surfaces

Covalently attached organic monolayers on etched silicon nitride (SixN4; x >/= 3) surfaces were prepared by reaction of SixN4-coated wafers with neat or solutions of 1-alkenes and 1-alkynes in refluxing mesitylene. The surface modification was monitored by measurement of the static water contact angle, XPS, IRRAS, AFM, and ToF-SIMS, and evidence for the formation of Si-C bonds is presented. The etching can be achieved by dilute HF solutions and yields both Si-H and N-H moieties. The resulting etched SixN4 surfaces are functionalized by terminal carboxylic acid groups in either of two ways: (a) via attachment of a 10-undecenoic acid 2,2,2-trifluoroethyl ester (trifluoro ethanol ester) and subsequent thermal acid hydrolysis; (b) through attachment of a photocleavable ester, and subsequent photochemical cleavage, as this would allow photopatterned functionalized SixN4. The carboxylic acids are successfully used for the attachment of oligopeptides (aspartame) and complete proteins using EDC/NHS chemistry. Finally, an amino-terminated organic monolayer can be formed by reaction of HF-treated SixN4 surfaces with a N-(omega-undecylenyl)phthalimide, which yields an amino-terminated surface upon deprotection with hydrazine.

Nucleophilic trifluoromethylation of some polycyclic ketones

Ruppert’s reagent (CF3-SiMe3) was used in the reaction with derivatives of pentacyclo[5.4.0.0.0.0]undecane-8,11-dione (‘cage’ dione) in the presence of dry CsF to yield trifluoromethyl O-silylated products. Subsequent acidic hydrolysis gave the corresponding hydroxy derivatives. In the case of the ‘cage’ dione the transannular cyclization leading to oxahexacyclic (O-bridged) product was observed.

A New Route for Installing the Isocyclic Ring on Chlorins Yielding 131-Oxophorbines

A new route to 13(1)-oxophorbines, the parent macrocycle of chlorophylls, begins with the synthesis of a 13-bromochlorin. Pd-mediated coupling of the latter with tributyl(1-ethoxyvinyl)tin and subsequent acidic hydrolysis afforded the 13-acetylchlorin (1). Treatment of 1 with NBS afforded the 15-bromo analogue in 70% yield. Pd-mediated alpha-arylation closed the isocyclic ring to give the 13(1)-oxophorbine (2) in 85% yield. Facile access to 13(1)-oxophorbines should enable a variety of spectroscopic studies and diverse applications.

Synthesis of Benzene‐1‐alanine‐3‐glycine as Carba Analogues of Cystine.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Benzene‐1‐Alanine‐3‐Glycine as Carba Analogues of Cystine

Methodology has been developed for the synthesis of C4‐carba‐bridged cystine analogues with a 1,3‐disubstituted phenyl group inserted into the chain. Stereoselective bromobenzylation of the Schöllkopf chiron and a subsequent bromine‐lithium exchange provided a lithiated species for conversion to a higher order cyanocuprate. The latter was cross‐coupled with an α‐bromoacylaminoacetate. Subsequent mild acid hydrolysis provided orthogonally protected amino acids.

Concise Two-Step Synthesis of γ-Pyrone from Acetone

γ-Pyrone (1) is readily accessible in 59% overall yield via 1,1,5,5-tetraethoxy-3-pentanone (10b) and subsequent acidic hydrolysis. The synthesis enables an easy scale up, as demonstrated for intermediate 10b.

A Practical and Stereoselective Synthesis of Cinnamyl Alcohols Bearing α‐Cyano or α‐Ester Functional Group from Baylis—Hillman Adducts.

Cinnamyl alcohols bearing ester, acid, or nitrile functional group at the 2-position are very useful synthons for the synthesis of various biologically important compounds. Synthesis of cinnamyl alcohol derivatives from the BaylisHillman adducts has been reported by us and other groups. The conversion can be carried out directly by using 20% aqueous sulfuric acid (for the Baylis-Hillman adducts derived from acrylonitrile) or trifluoroacetic acid (for the Baylis-Hillman adducts derived from acrylates). Recently, Basavaiah and coworkers have reported the two-step, onepot conversion method: TMSOTf-assisted conversion of Baylis-Hillman alcohol into the corresponding primary acetate with acetic anhydride and the following partial hydrolysis with K2CO3 in methanol. In the above chemical transformation, the conversion of secondary acetate into the primary one is the key step. Rearrangement of secondary acetate into the primary one was conducted by following reaction conditions such as DABCO/THF/reflux, montmorillonite K10 clay/microwave, and TMSOTf (cat.)/CH2Cl2. Direct conversion of BaylisHillman alcohol into the corresponding primary acetate can be carried out by the Basavaiahs method: acetic anhydride in the presence of TMSOTf. However, TMSOTf is a moisturesensitive and somewhat expensive reagent. During the preparation of Baylis-Hillman acetate, we found that the use of acetic anhydride in the presence of a catalytic amount of sulfuric acid in CH2Cl2 afforded directly the corresponding primary acetate in excellent yield. In these regards we envisioned that we could develop the more convenient and practical method to convert the BaylisHillman alcohol into the primary acetate or eventually to primary alcohol (Scheme 1 and Table 1). The reaction of Baylis-Hillman adducts with acetic anhydride (1.5 equiv.) in the presence of sulfuric acid (10 mol%) gave the corresponding rearranged cinnamyl acetates quantitatively in dichloromethane at room temperature within 30 min (Actually, the cinnamyl acetate derivatives could be isolated in 92-95% yields.). In order to obtain the corresponding cinnamyl alcohols in a one-pot we tried some reaction conditions for the next partial hydrolysis. Addition of water to the reaction mixture (two-phase system) afforded the hydrolyzed cinnamyl alcohols in trace amounts. The use of THF instead of CH2Cl2 showed better results in the hydrolysis step. However, neither the acetylation in THF nor the subsequent acidic hydrolysis in aq. THF was efficient. As a next choice, we used methanol as solvent after the formation of rearranged acetate in CH2Cl2 and added K2CO3. However, this process showed incomplete reaction and produced some side products. Thus, we finally adapted the two-step procedure involving the well-known hydrolysis protocol, K2CO3 in methanol, after simple workup process of the primary acetates (vide infra). The representative examples are shown in Table 1. As shown in Table 1, the method can be applicable to both of the Baylis-Hillman adducts derived from acrylates or acrylonitrile. The yields are higher than the reported in all cases. The formation of the cinnamyl alcohols is highly stereoselective (E for the ester and acetyl derivatives and Z for the nitrile analogs) as reported. The method has some advantages over the previous methods: (1) higher yields in

4‐(tert‐Butyldimethylsilyloxy)benzylidene Acetal: A Novel Benzylidene‐Type Protecting Group for 1,2‐Diols.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of a 2,3‐Di‐O‐Substituted Heptose Structure by Regioselective 3‐O‐Silylation of a 2‐O‐Substituted Heptose Derivative.

A 3,4-diol derivative of 2-O-benzyl (Bn) heptose (Hep), methyl 6,7-di-O-acetyl-2-O-benzyl-L-glycero-α-D-manno-heptopyranoside (3), was treated with both triethylsilyl (TES) and tert-butyldimethylsilyl (TBDMS) chlorides to regioselectively form the 3-O-silyl ethers 4 and 6, respectively. To examine whether silylation of the 3,4-diol of a 2-O-substituted disaccharide also gives the corresponding 3-O-silylated disaccharide, we synthesized α-GlcN3-(1⇄2)-Hep 11a by coupling a Hep 2-OH acceptor 9 with a GlcN3 trichloroacetimidate 10. As expected from the results obtained using the 2-O-Bn Hep 3, treatment of α-GlcN3-(1⇄2)-Hep-3,4-diol 14 with TESCl followed by acetylation gave only the 3-O-TES 15. Compound 14 was converted into the 3-OH acceptor 16 by silylation/acetylation — without isolating 15 — and subsequent acid hydrolysis. By coupling the disaccharide 3-OH acceptor 16 with per-O-benzylated β-lactosyl trichloroacetimidate 17, we obtained the desired 2,3-branched tetrasaccharide, α-Lac-(1⇄3)-[α-GlcN3-(1⇄2)]-Hep 18a. Hydrogenation of 18a, followed by N-acetylation, gave α-Lac-(1⇄3)-[α-GlcNAc-(1⇄2)]-Hep 22. Thus, we synthesized the 2,3-dibranched Hep by utilizing the 2-O-substituted Hep. This regioselective O-3-silylation of the 2-O-substituted Hep provides an intermediate that can be utilized for the synthesis of not only 2,3- and 3,4-dibranched Hep but also the 2,3,4-tribranched Hep structures present in lipooligo- and lipopolysaccharides produced by pathogenic Gram-negative bacteria. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Lipids and their modes of occurrence in two surface sediments from the Danube delta and northwestern Black Sea: implications for sources and early diagenetic alteration: I. Carboxylic acids

Two surface sediments from the Danube delta and an adjacent area of the northwestern Black Sea were subjected to sequential treatment in order to obtain comprehensive qualitative and quantitative information on carboxylic acid moieties. Four acid fractions, corresponding to distinct pools, were thus obtained from each sample: (1) an organic solvent-extractable fraction corresponding to the “unbound” acids, (2) an “OH −-labile” fraction (released by classical alkaline hydrolysis of the solvent-extracted material) corresponding to the ester-bound acids, (3) a “H +-labile” fraction (obtained via subsequent acid hydrolysis of extracted and base-hydrolysed material) corresponding to amide- and/or ether-bound acids, (4) the “tightly-bound” acids released by TMAH thermochemolysis of the insoluble, non-hydrolysable and HF/HCl-resistant material. The existence of these four pools of acids reflects differences in the mode of linkage of the acid moieties and/or in the protection provided by the (macro)molecular structures into which they are incorporated. Considerable qualitative and quantitative differences were observed, for a given sample, depending on the particular pool, and large differences were also noted, for a given pool, between the two samples. The biogeochemical investigation of the carboxylic acids according to their modes of occurrence in these two surface sediments with contrasting locations provides information on (i) the relative importance of microalgal, bacterial and terrestrial contributions in surface sediments, as well as the types of species implicated and (ii) the extent of early diagenetic alteration.

4-( tert-Butyldimethylsilyloxy)benzylidene acetal: a novel benzylidene-type protecting group for 1,2-diols

A novel 1,2-diol-protecting group, p-silyloxybenzylidene group, has been developed. In addition to the stepwise deprotection conditions including desilylation and the subsequent acidic hydrolysis of the p-hydroxybenzylidene group in AcOH–THF–H 2O, we have established the one-pot deprotection under basic conditions [K 2CO 3 (5 equiv), NH 2OH·HCl (5 equiv), and CsF (1 equiv) in MeOH–H 2O].

A Practical and Stereoselective Synthesis of Cinnamyl Alcohols Bearing α-Cyano or α-Ester Functional Group from Baylis-Hillman Adducts

Cinnamyl alcohols bearing ester, acid, or nitrile functional group at the 2-position are very useful synthons for the synthesis of various biologically important compounds. Synthesis of cinnamyl alcohol derivatives from the BaylisHillman adducts has been reported by us and other groups. The conversion can be carried out directly by using 20% aqueous sulfuric acid (for the Baylis-Hillman adducts derived from acrylonitrile) or trifluoroacetic acid (for the Baylis-Hillman adducts derived from acrylates). Recently, Basavaiah and coworkers have reported the two-step, onepot conversion method: TMSOTf-assisted conversion of Baylis-Hillman alcohol into the corresponding primary acetate with acetic anhydride and the following partial hydrolysis with K2CO3 in methanol. In the above chemical transformation, the conversion of secondary acetate into the primary one is the key step. Rearrangement of secondary acetate into the primary one was conducted by following reaction conditions such as DABCO/THF/reflux, montmorillonite K10 clay/microwave, and TMSOTf (cat.)/CH2Cl2. Direct conversion of BaylisHillman alcohol into the corresponding primary acetate can be carried out by the Basavaiahs method: acetic anhydride in the presence of TMSOTf. However, TMSOTf is a moisturesensitive and somewhat expensive reagent. During the preparation of Baylis-Hillman acetate, we found that the use of acetic anhydride in the presence of a catalytic amount of sulfuric acid in CH2Cl2 afforded directly the corresponding primary acetate in excellent yield. In these regards we envisioned that we could develop the more convenient and practical method to convert the BaylisHillman alcohol into the primary acetate or eventually to primary alcohol (Scheme 1 and Table 1). The reaction of Baylis-Hillman adducts with acetic anhydride (1.5 equiv.) in the presence of sulfuric acid (10 mol%) gave the corresponding rearranged cinnamyl acetates quantitatively in dichloromethane at room temperature within 30 min (Actually, the cinnamyl acetate derivatives could be isolated in 92-95% yields.). In order to obtain the corresponding cinnamyl alcohols in a one-pot we tried some reaction conditions for the next partial hydrolysis. Addition of water to the reaction mixture (two-phase system) afforded the hydrolyzed cinnamyl alcohols in trace amounts. The use of THF instead of CH2Cl2 showed better results in the hydrolysis step. However, neither the acetylation in THF nor the subsequent acidic hydrolysis in aq. THF was efficient. As a next choice, we used methanol as solvent after the formation of rearranged acetate in CH2Cl2 and added K2CO3. However, this process showed incomplete reaction and produced some side products. Thus, we finally adapted the two-step procedure involving the well-known hydrolysis protocol, K2CO3 in methanol, after simple workup process of the primary acetates (vide infra). The representative examples are shown in Table 1. As shown in Table 1, the method can be applicable to both of the Baylis-Hillman adducts derived from acrylates or acrylonitrile. The yields are higher than the reported in all cases. The formation of the cinnamyl alcohols is highly stereoselective (E for the ester and acetyl derivatives and Z for the nitrile analogs) as reported. The method has some advantages over the previous methods: (1) higher yields in