Synthesis of Several Derivatives of Phenyl(2-hydroxy-3-pyrazyl)carbinol

Venturella, Vincent S.; Bianculli, J.A.; Sager, Robert W.

doi:10.1002/jps.2600520208

Cited by 5 publications

(3 citation statements)

References 9 publications

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“…A pH of 12−13 in these reactions is critical; lower pH did not result in aldol reaction, and more basic conditions gave decomposition of the Schiff bases. This decomposition was also seen in our initial attempts to transfer the already available methyl ester 7 into amide 12 ; amidation in concentrated ammonia resulted in decomposition of 7 , as is known from the literature for identical compounds . Under strongly basic conditions, 7 and other 3-phenylserine derivatives dehydrated to the enamine, which subsequently hydrolyzed to methyl 3-[4-(methylthio)phenyl]-2-oxopropionate.…”

Section: Resultssupporting

confidence: 63%

Synthesis of 4-Sulfur-Substituted (2S,3R)-3-Phenylserines by Enzymatic Resolution. Enantiopure Precursors for Thiamphenicol and Florfenicol

Kaptein

Dooren

Boesten

et al. 1998

Org. Process Res. Dev.

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Enantiomerically pure 4-methylthio- and 4-methylsulfonyl-substituted (2S,3R)-3-phenylserines are prepared by enzymatic resolution of the corresponding racemic threo amides using the amidase from Ochrobactrum anthropi NCIMB 40321. The unwanted (2R,3S) enantiomers of the amides are separated from the enantiopure amino acids and easily racemized after Schiff base formation with the corresponding 4-(methylthio)- and 4-(methylsulfonyl)benzaldehyde. The racemization can be combined with the preparation of the racemic amides by aldol reaction under crystallization conditions to yield only the threo isomers. Enantiopure (2S,3R)-3-[4-(methylthio)phenyl]serine and (2S,3R)-3-[4-(methylsulfonyl)phenyl]serine are thus obtained in 78% and 62% overall yields starting from the corresponding substituted benzaldehydes. (2S,3R)-3-[4-(Methylthio)phenyl]serine is reduced to (1R,2R)-2-amino-1-[4-(methylthio)phenyl]propane-1,3-diol with NaBH4/H2SO4 and can be used for the synthesis of thiamphenicol and florfenicol.

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Section: Resultssupporting

confidence: 63%

Synthesis of 4-Sulfur-Substituted (2S,3R)-3-Phenylserines by Enzymatic Resolution. Enantiopure Precursors for Thiamphenicol and Florfenicol

Kaptein

Dooren

Boesten

et al. 1998

Org. Process Res. Dev.

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“…The preparation of 3,5-substituted-2-hydroxypyrazines 3 is usually undertaken [6,13,[18][19][20][21][22][23][25][26][27][28]31] as follows. The α-ketoaldehyde 1 and the hydrochloride salt of the α-aminoamide 2 are dispersed in methanol, the suspension is cooled (usually at −30 °C) and a concentrated solution of sodium hydroxide is added.…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, a fascinating aspect of this reaction is seen when starting from α-ketoaldehydes (1, R 1 = H, R 2 ≠ H). Indeed, if only an average reaction yield is usually obtained, it is the least expected 3,5-substituted-2-hydroxypyrazine isomer (3, R 1 = H, R 2 ≠ H) which is isolated sometimes along with a much smaller amount of the alternative 3,6-substituted-2-hydroxypyrazines (4, R 1 = H, R 2 ≠ H) [6,13,[18][19][20][21][22][23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

On Reuben G. Jones synthesis of 2-hydroxypyrazines

Legrand¹,

Janin²

2022

Beilstein J. Org. Chem.

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In 1949, Reuben G. Jones disclosed an original synthesis of 2-hydroxypyrazines involving a double condensation between 1,2-dicarbonyls and α-aminoamides upon treatment with sodium hydroxide at low temperature. This discovery turned out to be of importance as even today there are no simple alternatives to this preparation. Across the years, it was employed to prepare 2-hydroxypyrazines but some of its limits, notably regioselectivity issues when starting from α-ketoaldehydes, certainly hampered a full-fledged generation of pyrazine-containing new chemical entities of potential interest in medicinal chemistry. The present text describes some insights and improvements, such as the unprecedented use of tetraalkylammonium hydroxide, in the reaction parameters affecting the regioselectivity and yield when starting from phenylglyoxal and two α-aminoamides. We also suggest a mechanism explaining the counterintuitive occurrence of 3,5-substituted-2-hydroxypyrazine as the major reaction product.

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1982

Chemistry of Heterocyclic Compounds: A Series of Monographs

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Synthesis of Several Derivatives of Phenyl(2-hydroxy-3-pyrazyl)carbinol

Cited by 5 publications

References 9 publications

Synthesis of 4-Sulfur-Substituted (2S,3R)-3-Phenylserines by Enzymatic Resolution. Enantiopure Precursors for Thiamphenicol and Florfenicol

Synthesis of 4-Sulfur-Substituted (2S,3R)-3-Phenylserines by Enzymatic Resolution. Enantiopure Precursors for Thiamphenicol and Florfenicol

On Reuben G. Jones synthesis of 2-hydroxypyrazines

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