1124-11-4Relevant academic research and scientific papers
Mechanistic Studies of 2-(1-Hydroxyethyl)-2,4,5-trimethyl-3-oxazoline Formation under Low Temperature in 3-Hydroxy-2-butanone/Ammonium Acetate Model Systems
Fu, Hui-Yin,Ho, Chi-Tang
, p. 1878 - 1882 (1997)
Volatile compounds formed from the reaction of 3-hydroxy-2-butanone/ammonium acetate at 25, 55 and 85 °C were investigated. Six compounds were characterized by gas chromatography - mass spectrometry (EI and CI). Among the volatile compounds identified, an interesting intermediate compound, 2-(1-hydroxyethyl)-2,4,5-trimethyl-3-oxazoline, was found. 15N-Labeled ammonium acetate was used to confirm the structure of 2-(1-hydroxyethyl)-2,4,5-trimethyl-3-oxazoline. The formation pathway of these volatile compounds was proposed. In these model systems, 2-(1-hydroxyethyl)-2,4,5-trimethyl-3-oxazoline was formed at the reaction temperature below 25 °C. On the other hand, tetramethylpyrazine was the major component when the reaction temperature was higher than 85 °C. The amounts of 2-(1-hydroxyethyl)-2,4,5-trimethyl-3-oxazoline and tetramethylpyrazine increased linearly with the increasing heating time at 55 °C. Protic solvents did not promote 2-(1-hydroxyethyl)-2,4,5-trimethyl-3-oxazoline formation but did favor the formation of tetramethylpyrazine. A kinetic study of 2-(1-hydroxyethyl)-2,4,5-trimethyl-3-oxazoline formation was also performed, and the activation energy was found to be 16.5 kcal/mol.
Combined effects of a buffer and solvent on tetramethylpyrazine formation in a 3-hydroxy-2-butanone/ammonium hydroxide system
Huang
, p. 1013 - 1015 (1997)
A phosphate buffer was found to significantly promote tetramethylpyrazine (TMP) formation in an acetoin (3-hydroxy-2-butanone)/ammonium hydroxide system. The effect of the phosphate ion on TMP formation was additive in the range of 0.05-0.2 M. The change in pH value of the system reveals that a proton-coupled redox type of reaction occurred during TMP formation. Phosphate serves both as proton donor and acceptor to facilitate proton transfer during the Schiff base formation between ammonia and 3-hydroxy-2-butanone. Protic solvents, methanol, and ethanol, were found to attract the water released from the system. The combination of a phosphate buffer and protic solvent led to the completion of TMP formation. The TMP formation mechanism in a phosphate buffer (pH 7.2) is proposed.
Formation of 2-(1-Hydroxyalkyl)-3-oxazolines from the Reaction of Acyloins and Ammonia Precursors under Mild Conditions
Shu, Chi-Kuen,Lawrence, Brian M.
, p. 2922 - 2924 (1995)
Studies on the reaction between acetoin and an ammonia precursor under mild conditions revealed that two major products were formed, one of which was tetramethylpyrazine (TMP) and the other an unknown compound.By spectral elucidation (MS, IR, NMR), this unknown compound has been identified as 2,4,5-trimethyl-2-(1-hydroxyethyl)-3-oxazoline (OXZ).Two homologs of OXZ were also prepared.A 3-week storage study demonstrated that OXZ was readily formed, after which its formation declined.In contrast, TMP formation gradually increased before it leveled out in 15-20 days.At the end of this experiment, only TMP remained as the product, while OXZ was not found.Mechanistically, it is proposed that condensation of acetoin and ammonia generates α-hydroxyimine or α-amino ketone by tautomerism, which may lead to product formation via two pathways.One of the pathways is to form TMP via self-condensation of the α-amino ketone, dehydration, and dehydrogenation, which is well-known.The other pathway may be that the α-hydroxyimine condenses with a second molecule of acetoin and then is cyclized by Schiff base formation to OXZ.These storage results also indicate that the second pathway may be reversible, so that OXZ initially formed is able to be converted back to α-hydroxyimine, which, in turn, was tautomerized to α-amino ketone, so that the first pathway to form TMP could be followed. - Keywords: Acyloins; ammonia precursor; 2-(1-hydroxyalkyl)-3-oxazolines; 2,4,5-trimethyl-2-(1-hydroxyethyl)-3-oxazoline; 2,4-dimethyl-2-(hydroxymethyl)-3-oxazoline; 2,4,5-triethyl-2-(1-hydroxypropyl)-3-oxazoline; acetoin; acetol; 4-hydroxy-3-hexanone; diammonium hydrogen phosphate
Mechanistic Studies of Tetramethylpyrazine Formation under Weak Acidic Conditions and High Hydrostatic Pressure
Huang, Tzou-Chi,Fu, Hui-Yin,Ho, Chi-Tang
, p. 240 - 246 (1996)
A significant enhancement of the tetramethylpyrazine (TMP) formation at high pressure was observed in the 3-hydroxy-2-butanone/ammonium acetate model system. In a water system, the activation volume of TMP formation under high pressure was found to be -6.82 mL/mol. A mechanism was proposed to elucidate the formation of TMP under a weak acidic condition and high hydrostatic pressure. Solvents such as propylene glycol (PG), glycerol, methanol, ethanol, propanol, and butanol were found to enhance TMP formation. Kinetic analyses indicated that TMP formation in aqueous, 80% PG, and ethanol systems followed pseudo-zero-order reaction kinetics. The activation energies were found to be 18.84 ± 1.3, 14.19 ± 7.1, and 13.09 ± 4.7 kcal/mol, respectively. The intermediate of TMP formation was characterized as tetramethyldihdyropyrazine using gas chromatography-mass spectrometry. A 15N-labeled ammonium acetate/3-hydroxy-2-butanone model system was used to confirm the incorporation of a nitrogen atom in the molecule of tetramethyldihydropyrazine. Hydrogen acceptors such as nicotinamide adenine dinucleotide and flavin adenine dinucleotide were found to increase TMP formation, and the formation of TMP from tetramethyldihydropyrazine through dehydrogenation was shown.
Chemo-Enzymatic Synthesis of Pyrazines and Pyrroles
Xu, Jin,Green, Anthony P.,Turner, Nicholas J.
, p. 16760 - 16763 (2018)
Herein we report the biocatalytic synthesis of substituted pyrazines and pyrroles using a transaminase (ATA) to mediate the key amination step of the ketone precursors. Treatment of α-diketones with ATA-113 in the presence of a suitable amine donor yielded the corresponding α-amino ketones which underwent oxidative dimerization to the pyrazines. Selective amination of α-diketones in the presence of β-keto esters afforded substituted pyrroles in a biocatalytic equivalent of the classical Knorr pyrrole synthesis. Finally we have shown that pyrroles can be prepared by internal amine transfer catalyzed by a transaminase in which no external amine donor is required.
Characterization of volatile compounds from the reaction of 3-hydroxy- 2-butanone and ammonium sulfide model system
Xi, Junwu,Huang, Tzou-Chi,Ho, Chi-Tang
, p. 245 - 248 (1999)
The reactions between 3-hydroxy-2-butanone and ammoniun sulfide at 25, 50, 75, 100, 125, and 150 °C were studied. Four well-known flavor compounds, 2,4,5-trimethyloxazole, 2,4,5-trimethyl-3-oxazoline, 2,4,5-trimethylthiazole, and 2,4,5-trimethyl-3-thiazoline, were identified. Another four interesting intermediate compounds, 2-(1-hydroxyethyl)-2,4,5-trimethyl-3-oxazoline, 2- (1-mercaptoethyl)-2,4,5-trimethyl-3-oxazoline, 2-(1-hydroxyethyl)-2,4,5- trimethyl-3-thiazoline, and 2-(1-mercaptoethyl)-2,4,5-trimethyl-3-thiazoline, were also identified by GC-EIMS and GC-CIMS. All these intermediate compounds were formed at 25 °C. On the other hand, tetramethylpyrazine was the major product with a reaction temperature higher than 100 °C.
Novel Ligustrazine-Based Analogs of Piperlongumine Potently Suppress Proliferation and Metastasis of Colorectal Cancer Cells in Vitro and in Vivo
Zou, Yu,Zhao, Di,Yan, Chang,Ji, Yanpeng,Liu, Jin,Xu, Jinyi,Lai, Yisheng,Tian, Jide,Zhang, Yihua,Huang, Zhangjian
, p. 1821 - 1832 (2018)
Piperlongumine 1 increases reactive oxygen species (ROS) levels and preferably induces cancer cell apoptosis by triggering different pathways. However, the poor solubility of 1 limits its intensive investigation and clinical application. Ligustrazine possesses a water-soluble pyrazine skeleton and can inhibit proliferation and metastasis of cancer cells. We synthesized compound 3 by replacement of the trimethoxyphenyl of 1 with ligustrazine moiety and further introduced 2-Cl, -Br, and -I to 3 for synthesis of 4-6, respectively. Compound 4 possessed 14-fold greater aqueous solubility than 1 and increased ROS levels in colorectal cancer HCT-116 cells. Additionally, 4 preferably inhibited proliferation, migration, invasion, and heteroadhesion of HCT-116 cells. Treatment with 4 suppressed tumor growth and lung metastasis in vivo and prolonged the survival of tumor-bearing mice. Furthermore, 4 mitigated TGF-β1-induced epithelial-mesenchymal transition and Wnt/β-catenin activation by inhibiting the Akt and GSK-3β phosphorylation in HCT-116 cells. Collectively, 4 displayed significant antiproliferation and antimetastasis activities, superior to 1.
Acceptorless Dehydrogenative Coupling Using Ammonia: Direct Synthesis of N-Heteroaromatics from Diols Catalyzed by Ruthenium
Daw, Prosenjit,Ben-David, Yehoshoa,Milstein, David
supporting information, p. 11931 - 11934 (2018/09/27)
The synthesis of N-heteroaromatic compounds via an acceptorless dehydrogenative coupling process involving direct use of ammonia as the nitrogen source was explored. We report the synthesis of pyrazine derivatives from 1,2-diols and the synthesis of N-substituted pyrroles by a multicomponent dehydrogenative coupling of 1,4-diols and primary alcohols with ammonia. The acridine-based Ru-pincer complex 1 is an effective catalyst for these transformations, in which the acridine backbone is converted to an anionic dearomatized PNP-pincer ligand framework.
A four-methyl pyrazine preparation method (by machine translation)
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Paragraph 0021; 0027; 0028; 0029; 0030; 0031; 0032, (2017/07/01)
The invention relates to a medicine intermediate four methyl pyrazine synthesis method, the method comprising: in order to diacetyl monoxime as raw materials, the addition of water as the solvent, palladium carbon as a catalyst, in backflow state by adding ammonium formate, after adding continue to stir at reflux 4 hours, filtering to remove the catalyst, the temperature and then the methylene chloride extraction, pressure reducing and concentrated to obtain four a [...]. The invention production four-methyl pyrazine mild reaction conditions, easy post treatment, the conversion is 95% or more, the yield is 80% or more, and the cost is low, and is favorable for industrial production. (by machine translation)
A preparation method of Rhizoma Chuanxiong hydrochlorothizide
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Paragraph 0044-0049; 0053-0058; 0062-0067; 0071-0076, (2017/07/04)
The invention discloses a preparation method of ligustrazine, wherein the preparation method comprises the following steps: adding 3-hydroxy-2-butanone and ammonium acetate as main materials into a reaction vessel, then adding anhydrous ethanol, introducing nitrogen, carrying out water bath heating on the reaction vessel, stirring, stropping introduction of the nitrogen, and waiting the temperature to be dropped to room temperature; adding an aromatization catalyst, then stirring, and filtering to obtain a filtrate A; concentrating the filtrate A to obtain a solution B; adding water and an extraction agent into the B solution, extracting, and taking an upper-layer solution to obtain a solution C; carrying out reduced pressure distillation on the solution C to obtain a solution D; adding water into the solution D, and carrying out cooling crystallization to obtain a mixed material E; and filtering the mixed material E to obtain ligustrazine crystals. The reaction time is greatly shortened, the purification processing is more convenient, the method has the advantages of energy conservation and environmental protection, the prepared ligustrazine is in a needle-shaped crystal form, and the yield can reach 87%.
