Mild Acid Catalysis Research Articles

Sulfinamide Crossover Reaction.

This study unveils a new catalytic crossover reaction of sulfinamides. Leveraging mild acid catalysis, the reaction demonstrates a high tolerance to structural variations, yielding equimolar products across diverse sulfinamide substrates. Notably, small sulfinamide libraries can be selectively oxidized to sulfonamides, providing a new platform for ligand optimization and discovery in medicinal chemistry. This crossover chemotype provides a new tool for high-throughput experimentation in discovery chemistry.

Shifted Selectivity in Protonation Enables the Mild Deuteration of Arenes Through Catalytic Amounts of Bronsted Acids in Deuterated Methanol.

Taking advantage of the "differentiating effect" of the solvent methanol, deuterations of electron-rich aromatic systems can be carried out under mild acid catalysis and thus under far milder conditions than known so far. The exceptional functional group tolerance observed under the optimized conditions, which even includes highly acid-labile groups, results from a hitherto unexploited shifted selectivity in protonation, and enabled simple and straightforward access to complex deuterium-labeled compounds.

Acid Assisted Organosolv Delignification of Beechwood and Pulp Conversion towards High Concentrated Cellulosic Ethanol via High Gravity Enzymatic Hydrolysis and Fermentation.

Background: Future biorefineries will focus on converting low value waste streams to chemical products that are derived from petroleum or refined sugars. Feedstock pretreatment in a simple, cost effective, agnostic manner is a major challenge. Methods: In this work, beechwood sawdust was delignified via an organosolv process, assisted by homogeneous inorganic acid catalysis. Mixtures of water and several organic solvents were evaluated for their performance. Specifically, ethanol (EtOH), acetone (AC), and methyl- isobutyl- ketone (MIBK) were tested with or without the use of homogeneous acid catalysis employing sulfuric, phosphoric, and oxalic acids under relatively mild temperature of 175 °C for one hour. Results: Delignification degrees (DD) higher than 90% were achieved, where both AC and EtOH proved to be suitable solvents for this process. Both oxalic and especially phosphoric acid proved to be good alternative catalysts for replacing sulfuric acid. High gravity simultaneous saccharification and fermentation with an enzyme loading of 8.4 mg/gsolids at 20 wt.% initial solids content reached an ethanol yield of 8.0 w/v%. Conclusions: Efficient delignification combining common volatile solvents and mild acid catalysis allowed for the production of ethanol at high concentration in an efficient manner.

The fast and effective isolation of nanocellulose from selected cellulosic feedstocks

A new process for the production of nanocellulose from selected cellulose-containing natural materials has been developed. The liquefaction reaction, using glycols and mild acid catalysis (methane sulphonic acid), was applied to four model materials, namely cotton linters, spruce wood, eucalyptus wood and Chinese silver grass. The process contains only four steps, the milling, the glycolysis reaction, centrifugation and final rinsing with an organic solvent. The nanocrystalline cellulose recovery was between 56% and 75%. The crystallinity index was greater than that of the starting materials due to the liquefaction of lignin, hemicelluloses and amorphous cellulose. The final product was a stable, highly concentrated nanocrystalline cellulose suspension in the organic medium. The liquid residue, after the liquefaction of the cotton linters contained significant quantities of levulinic acid. Different sugars were identified in the liquid residues that were derived from cellulose and hemicelluloses during the liquefaction reaction.

Condensation of hydroxy naphthazarins with aromatic aldehydes

Hydroxy naphthazarins (2,5,8-trihydroxy-1,4-naphthoquinones) react with aromatic aldehydes containing no hydroxy groups at position 2 under mild acid catalysis to form 3,3′-(arylmethylene)bisnaphthazarins. On the example of o-vanillin, it was shown that the reaction of 2-hydroxybenzaldehydes with hydroxy naphthazarins under the same conditions leads to 7,10-dihydroxy-12H-benzo[b]xanthene-6,11-dione derivatives.

Heterogeneous Reactions of Glyoxal on Particulate Matter: Identification of Acetals and Sulfate Esters

Reactive uptake of glyoxal onto particulate matter has been studied in laboratory experiments in a 2 m3 Teflon reaction chamber. Inorganic seed particles of different composition were utilized, including (NH4)2SO4, (NH4)2SO4/ H2SO4, NaNO3, and simulated sea salt, while the relative humidity and acid concentration were varied. The organic composition of the growing particles was measured in situ with an aerosol mass spectrometer, providing particle mass spectra as a means of product identification. Aerosol physical characteristics were also measured with a differential mobility analyzer and condensation nucleus counter. Regardless of seed composition, particle growth was rapid and continuous over the course of several hours. Identification of several mass fragments greater than the glyoxal monomer suggested that heterogeneous reactionsto form glyoxal adducts of lowvolatility had occurred. Temporal analysis of the mass fragments was consistent with a proposed acid-catalyzed mechanism whereby glyoxal is first hydrated, followed by self-reaction to form cyclic acetal structures. Increased relative humidity slowed the formation of higher order oligomers, also consistent with the proposed mechanism. The relative contribution of various oligomers to the overall organic composition was strongly dependent on the relative humidity and hence the particulate water concentration. A mild acid catalysis was also observed upon increasing the acidity of the seed particles. Specific mass fragments were found that could only arise from sulfate esters and were not present on the non-sulfur-containing seed particles. This first evidence of the formation of organic sulfates in particles is presented together with a proposed mechanism and molecular structure. These results suggest that the formation of these products of glyoxal uptake can contribute significantly to secondary organic aerosol.

Synthesis of Novel 6‐Enaminopurines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of novel 6-enaminopurines.

Two different approaches have been used for the synthesis of 6-enaminopurines 6 from 5-amino-4-cyanoformimidoyl imidazoles. In the first approach imidazoles 1 were reacted with ethoxymethylenemalononitrile or ethoxymethylenecyanoacetate under mild experimental conditions and this led to 9-substituted-6-(1-amino-2,2-dicyanovinyl) purines 6a-f or 9-substituted-6-(1-amino-2-cyano-2-methoxycarbonylvinyl) purines 6g-k. These reactions are postulated to occur through an imidazo-pyrrolidine intermediate 7, which rapidly rearranges to the 6-enaminopurine 6. In the second approach 6-methoxyformimidoyl purines 3, prepared in two efficient steps from 5-amino-4-cyanoformimidoyl imidazoles 1, were reacted with malononitrile and methylcyanoacetate with a mild acid catalysis (ammonium acetate or piperidinium acetate) to give 6-enaminopurines 6a, 6d, 6f, 6g and 6k in very good yields. Only low yields were obtained for the 6-enaminopurine 6j, as competing nucleophilic attack on C-8 of either 3d or 6jcauses ring opening with formation of pyrimido-pyrimidines 11 and 10a respectively.

Reactions of Resorcinols with Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reactions of resorcinols with ketones

New products of the condensation of resorcinols with ketones under conditions of mild acid catalysis were studied.

New syntheses of 7-substituted-2-aminothieno- and furo[3,2-d]pyrimidines

In a recent publication, we have the described the synthesis of 7-substituted-2-amino-1,5-dihydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones which are potent inhibitors of the enzyme Purine Nucleoside Phosphorylase from the corresponding 3-aminopyrroIe-2-carboxylate esters. A key step in the synthesis is condensation of the amino group with the highly reactive guanylating reagents 3 or 4 followed by annulation. The furo[3,2-d]pyrimidin-4-one and thieno[3,2-d]pyridin-4-one are closely related rings systems. However, these rings have not been reported in the literature with a 2-amino, substituent which would arise from such guanylation reactions. In this report, the syntheses of the novel furans 5 are described based on our improved pyrrole synthesis (Scheme 1). The syntheses of the novel thiophenes 6 are described. The guanylation of 5 and 6 were studied and compared to 2. The 3-amino group of 5 and 6 failed to react with 3 or 4 under mild acid catalysis; conditions under which 2 easily condensed. Guanylation was finally achieved by generating the carbodiimide intermediate of 3 under mercury catalysis affording the guanylated adducts which were converted to the novel 2-aminothieno- and furo[3,2-d]pyrimidin-4-ones 16.

Flavan derivatives. XVI. Acid-catalysed reactions of secondary benzyl alcohols and 1-tetralols in methanol

Under solvolytic conditions I-phenylpropan-1-01 and its p-methyl and p-methoxy derivatives gave 1 -arylprop- 1 -enes. 1 -(3,4-Dimethoxypheny1)propan- 1-01 behaved similarly, but in addition gave the known propene dimer di-isohomogenol (di-isoeugenol dimethyl ether). Ring-proton coupling constants (J 7.3 and 9.2 CIS) appear consistent with a staggered trans-trans-configuration for this dimer,$ in agreement with earlier interpretations of chemical evidence. 1-(2,4,6-Trimethoxy- pheny1)propan-1-01 proved very reactive and gave the symmetrical dibenzyl ether under very mild acid catalysis, but with higher acid concentration it gave the prop-1-ene accompanied by a 1,l-diarylpropane formed by electrophilic displace- ment of the propan-1-01 side-chain. Tetralin-1-01 and cis- and trans-tetralin-1,2-diols, which lack activating aromatic substituents, were stable towards methanolic acetic acid (3%) or hydrogen chloride (3%). 6-Methoxytetralin-1-01, however, gave 1,6-dimethoxytetralin with methanolic 0.001% acetic acid, but with higher tetra101 concentration it gave the symmetrical bis-tetralyl ether. 6-Methoxytetralin-1-01 gave 3,4-dihydro-6-methoxynaphthalene and its known dimer when heated with methanolic hydrogen chloride (1%). Nuclear magnetic resonance showed that the tetralins are conformationally mobile, and the spectra were consistent with rapid interconversion of two half-chair conformations. 3-Phenyltetralin-1-01 (tetralin analogue of flavan-3-01) was obtained in the l,3-cis-form and existed in the confor- mationally stable half-chair form with both substituents equatorial. Spin-spin coupling constants of cis- and trans-carbonates of tetralin-1,2-diols are close to values recorded for their flavandiol analogues.

The SN mechanism in aromatic compounds. XXXVI. Reactivity of monochlorodiazabenzenes

An investigation has been made of the reactions of p-nitrophenoxide ion in methanol with equimolar quantities (0.01-0.02M) of the six monochlorodiaza-benzenes, viz. 3- and 4-chloropyridazine (1,2- diazabenzene); 2-, 4-, and 5-chloro-pyrimidines (1,3-diazabenzene); and 2-chloropyrazine (1,4-diazabenzene) in the presence of a tenfold excess (0.1-0.2M) of p-nitrophenol. Results have been compared with earlier results from the pyridine series, and reactivity shown to be in reasonable agreement with that predicted from kinetic data for the pyridine series assuming independent activation by each nitrogen. There is evidence for mild acid catalysis by the p-nitrophenol added to prevent concurrent methanolysis. It is estimated that this leads to an increase in Hammett substituent constant (σ-) values of only 0.2 units or less. The reactivity order is 2- > 4-chloro-N-methylpyridinium > 2- > 4- chloro-pyrimidine > 4-chloropyridazine≈3-chloropyridazine≈2- chloropyrazine>3-chloro-N-methylpyridinium≈5-chloropyrimidine, and this corresponds with the theoretical order as modified by mild acid catalysis, more effective in the order ortho-> meta- > para- to the point of substitution, and including the inverted order, 2- > 4- chloropyrimidine, whereas the usual reactivity order with anionic reagents is 4- > 2-chloropyrimidine.

Synthese von Zwischenprodukten für den Aufbau corticotrop wirksamer Polypeptide III. Das Decapeptid H·Ser‐Tyr‐Ser‐Met‐Glu‐His‐Phe‐Arg‐Try‐Gly·OH und einige seiner Derivate

The synthesis of the decapeptide H·Ser‐Tyr‐Ser‐Met‐Glu‐His‐Phe‐Arg‐Try‐Gly·OHt) which constitutes an essential portion of the corticotropin (ACTH) and α‐melanotropin (α‐MSH) molecules, as well as 4 derivatives thereof (I, II, III, V) is described in detail. The derivative BOC‐Ser‐Tyr‐Ser‐Met‐Glu(OBu1)‐His‐Phe‐Arg‐Try‐Gly·OH is, on account of its excellent crystallinity, the easy removability of the protecting groups by mild acid catalysis (BOC‐, ‐OBut), and the fact that the C‐terminal amino‐acid residue cannot racemize on condensation with other peptides, an especially useful intermediate for syntheses in the field of the hormones of the pituitary9,12). The introduction of the γ‐t‐butyl ester of glutamic acid is a new feature which proves especially valuable in connection with N‐t‐butoxycarbonyl‐lysine3)4)9). These protecting groups can be removed even from very complicated peptides by mild acid catalysis in excellent yield which is a definite improvement over current methods.