Hurd-Mori Reaction Research Articles

Synthesis of 4-(2-Fluoro-4-hydroxyphenyl)-1,2,3-thia- and -Selenadiazoles and Glycosides on Their Base

Basing on 2-fluoro-4-methoxyacetophenone 2-fluoro-4-hydroxyphenyl-1,2,3-thiadiazole was synthesized by means of the Hurd-Mori reaction. Under the conditions of phase transfer catalysis in water-chloroform system it was glycosylated with 1-α-bromo-2,3,4-tri-O-acetyl-D-xylopyranose. 2-Fluoro-4-hydroxy-1,2,3-selenadiazole can be prepared by oxidation of 2-fluoro-4-hydroxyacetophenone with selenium dioxide in acetic acid. Glycosylation of 2-fluoro-4-hydroxy-1,2,3-selenadiazole with 1-α-bromo-2,3,4,6-tetra-O-acetyl-D-galactopyranose leads to formation of corresponding glycoside. Alternative pathway for preparing of 1-β-[3-fluoro-4-(1,2,3-selenadiazol-4-yl)-phenyl]-2,3,4-tri-O-acetyl-D-xylopyranose including synthesis of 2-fluoro-4-hydroxyacetophenone xyloside and subsequent formation of selenadiazole ring was developed.

Synthesis and characterization of some new 1,2,3-thiadiazole and 1,2,3-selenadiazole triterpene derivatives from allobetulone and 2-oxoallobetulin

The synthesis of new 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives from triterpenoid ketones has been investigated via the corresponding semicarbazones. The intermediates 5, 8 have also been isolated, separated and their structures identified. The Hurd–Mori reaction and Lalezari method have been applied to synthesize a series of new substances 6 and 7. The regioselectivity of the functionalization mostly was centered at the C-3 position for the products 9 and 10. The structures of these compounds were confirmed by 2D-NMR spectroscopy.

Synthesis of 4-(5-Nitrophenylfur-2-yl)-1,2,3-thia- and Selenadiazoles

Arylation of 2-acetylfuran with o-, m-, and p-nitrophenyldiazonium salts under the conditions of the Gomberg-Bachmann reaction has afforded the corresponding 5-(nitrophenyl)-2-acetylfurans. Their carbo-ethoxyhydrazones have undergone the cyclization into stable 4-(5-nitrophenylfur-2-yl)-1,2,3-thiadiazoles under the conditions of the Hurd-Mori reaction. Analogous semicarbazones have afforded the corresponding selenadiazoles upon oxidation with selenium dioxide. The analysis of electronic absorption spectra of the obtained hybrid heterocycles has shown that the conjugation of the phenyl and the furan ring in o-nitrophenyl derivatives is distorted due to steric hindrance, whereas the effect of direct polar conjugation leading to strong bathochromic shift of the absorption band has been observed in the case of the p-nitro derivatives. The position and intensity of the bands in the electronic absorption spectra of the studied compounds are determined by electronic as well as steric factors. The difference in the length of conjugation chain determined by the position of the nitro group in the phenyl fragment also contributes to the observed trend. The introduction of selenadiazole fragment instead of thiadiazole one has caused slight bathochromic shift of the band in the electron absorption spectra.

Synthesis of the Derivatives of 4-(5-Aryl-3-methylfuran-3-yl)-1,2,3-thiadiazole and Functionalization of 5-Aryl-2- methylfuran via Reactions of Thiadiazole Ring

By arylation of 2-methyl-3-acetylfuran via the Gomberg–Bachmann reaction 5-(4-ethoxycarbonylphenyl)-, 5-(2-nitrophenyl), and 5-(4-nitrophenyl)-2-methyl-3-acetylfurans were synthesized. Carboethoxyhydrazones of 2-methyl-5-phenyl-3-acetylfuran and its phenyl-substituted analogs when treated with thionyl chloride form 4-(5-aryl-2-methylfuran-3-yl)-1,2,3-thiadiazoles by the Hurd–Mori reaction. Thermal stability of obtained compounds increases with the increase in electron-acceptor action of substituent in phenyl ring. Opening of thidiazole ring in the compounds synthesized under the action of potassium tert-butylate in THF in the presence of alkyl iodides leads to the corresponding alkylthioethynylfurans. Performing the reaction with potassium carbonate in DMF in the presence of excess morpholine permits the preparation of (2-methyl-5- arylfuran-3-yl)thioacetylmorpholides.

TBAI-Catalyzed Reaction between N-Tosylhydrazones and Sulfur: A Procedure toward 1,2,3-Thiadiazole

A TBAI-catalyzed reaction between N-tosyl hydrazone and sulfur was developed, leading to 1,2,3-thiadiazoles in moderate to good yields. It represents a facile and practical procedure to access thiadiazole under metal-free conditions. This procedure serves as an improvement for the Hurd-Mori reaction.

Synthesis of ethyl 4-(1,2,3-thiadiazol-4-yl)-5-(bromomethyl)furan-2-carboxylate and its reactions with nucleophiles

By cyclization of carboethoxyhydrazone of ethyl 4-acetyl-5-methylfuran-2-carboxylate under the conditions of Hurd–Mori reaction ethyl 4-(1,2,3-thiadiazol-4-yl)-5-methylfuran-2-carboxylate was synthesized. The ester obtained was brominated with N-bromosuccinimide at the methyl group in the furan ring. This bromide reacts with various N-, S-, O-, and P-nucleophiles to form the corresponding substitution products. Furylthiadiazole fragment remains stable in the course of these transformations.

Synthesis of 5-(1,2,3-thiadiazol-4-yl)2-methylfuran-3-carboxamides

Acetylation of 2-methylfuran-3-carboxamides with acetic anhydride in the presence of magnesium perchlorate yields the corresponding 5-acetyl derivatives; their carboethoxyhydrazones have been synthesized via the reaction with carboethoxyhydrazine. The carboethoxyhydrazones undergo cyclization into the 5-(1,2,3-thiadiazol-4-yl)-2-methylfuran-carboxamides upon treatment with thionyl chloride under conditions of the Hurd–Mori reaction. In the case of (2-methyl-3-furoyl)proline esters, the optical activity is retained after the described transformations.

Synthesis of alkyl 2-aminomethyl-5-(1,2,3-thiadiazol-4-yl)furan-3-carboxylate and pseudopeptides on its basis

Cyclization of alkyl 2-methyl-5-acetylfuran-3-carboxylate carbethoxyhydrazone according to Hurd-Mori reaction afforded alkyl 2-methyl-5-(1,2,3-thiadiazol-4-yl)-3-carboxylate. Its bromination with N-bromosuccinimide yielded 2-bromomethyl derivative. The latter was involved in the Delepine reaction to form alkyl 2-aminomethyl-5-(1,2,3-thiadiazol-4-yl)-3-carboxylate. Acylation of the product synthesized with chloroacetyl chloride and subsequent treatment with morpholine or 4-methylpiperidine gave the corresponding pseudopeptides. In the course of these transformations the furylthiadiazole fragment retained its stability.

Synthesis and some reactions of derivatives of 5-(1,2,3-thiadiazol-4-yl)furan-2-carboxylic and 3-[5-(1,2,3-thiadiazol-4-yl)fur-2-yl]acrylic acids

Alkyl 5-(1,2,3-thiadiazol-4-yl)furan-2-furoate and 3-[5-(1,2,3-thiadiazol-4-yl)fur-2-yl]acrylate were synthesized via cyclization of carbethoxyhydrazones of acetyl derivatives of furan-2-carboxylic and 3-(2-furyl)-acrylic acids under the conditions of the Hurd-Mori reaction. Corresponding acids, acid chlorides, amides, furoyl hydrazide and acryloyl azide were prepared. It was shown that in all above-mentioned substances furylthiadiazole fragment is thermally stable. Treating of methyl 5-(1,2,3-thiadiazol-4-yl)furan-2-furoate with morpholine in the presence of potassium hydroxide leads to the cleavage of thiadiazole ring with the liberation of nitrogen and the formation of [5-(methoxycarbonyl)fur-2-yl]acetic acid morpholide.

ChemInform Abstract: H3PO4/(CF3CO)2O Mediated Acylation Followed by Hurd—Mori Reaction: Synthesis of Novel 1,2,3‐Thiadiazol Derivatives.

AbstractStarting material (I) is prepared in a three step sequence starting from o‐nitrophenol.

H3PO4/(CF3CO)2O Mediated Acylation Followed by Hurd-Mori Reaction: Synthesis of Novel 1,2,3-Thiadiazol Derivatives

The synthesis of novel 1,2,3-thiadiazol derivatives containing 2H-benzo[b][1,4]oxazin-3(4H)-one moiety as one of the substituents has been reported. A combined application of H3PO4/(CF3CO)2O mediated acylation followed by Hurd–Mori reaction has been explored to synthesize these compounds. The scope and limitation of this strategy along with the reaction mechanism of the key step is discussed.

Concerning the Regioselectivity of the Hurd-Mori Reaction for 1,2,3-Thiadiazoles

The work investigates the regio­selectivity of the Hurd-Mori reaction on 1,2,3-thiadiazoles. The success of the described cyclization events is found to be highly dependant on the presence of an electron-withdrawing group. Steric factors are highlighted as critical in the regioselectivity of the process.

Investigation of the regioselectivity of the Hurd–Mori reaction for the formation of bicyclic 1,2,3-thiadiazoles

A series of new pyrrolo[ d][1,2,3]thiadiazole carboxylates and 5,6-dihydro-4 H-cyclopenta[ d][1,2,3]thiadiazoles has been synthesized via the Hurd–Mori reaction. The regioselectivity of the cyclization has been studied and trends were established to predict the cyclization direction to afford bicyclic 1,2,3-thiadiazoles. Effects promoting and disfavoring the reaction have also been investigated to guide the synthesis of scaffolds of this type.

Synthesis of Pyrrolo[2,3-d][1,2,3]thiadiazole-6-carboxylates via the Hurd-Mori Reaction. Investigating the Effect of the N-Protecting Group on the Cyclization

A route to methyl pyrrolo[2,3-d][1,2,3]thiadiazole-6-carboxylates as potential plant activators and inducers of systemic acquired resistance (SAR) is reported. A synthetic strategy based on cyclization of the thiadiazole ring system utilizing thionyl chloride via the Hurd-Mori protocol as key step was developed. Success of the ring closure reaction turned out to be highly dependent on the nature of the N-protecting group of the pyrrolidine precursor. While electron donors such as alkyl gave only poor conversion to the required 1,2,3-thiadiazoles, an electron withdrawing substituent such as methyl carbamate gave superior yields.

Synthesis of 1,2,3‐Thiadiazolo Terpenoids on the Basis of Cyclopentanonopimaric and Betulonic Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of 1,2,3-Thiadiazolo Terpenoids on the Basis of Cyclopentanonopimaric and Betulonic Acids

The Hurd-Mori reaction with derivatives of cyclopentanonopimaric and betulonic acids afforded mostly the corresponding 1,2,3-thiadiazoles and small amounts of thioketone oxides.

1,4-PENTADIEN-3-ONES. A SOURCE FOR SELENANO 1,2,3- SELENA AND THIADIAZOLES

The 4-Selenanols (2,3) and 4-selenanones (4) were obtained by the reaction of 1,4-pentadien-3-ones (1) with sodium hydrogen selenide under different conditions. The fused 1,2,3-selenadiazoles (6) and 1,2,3-thiadiazoles (7) were prepared from 4 on oxidative cyclization with SeO2 and Hurd–Mori reaction with SOCl2.

Synthesis of phosphonyl 1,2,3-thiadiazoles

In accord with the Hurd-Mori reaction conditions, 1- or 2-phosphonyl hydrazones reacted with thionyl chloride to afford 4- or 5-phosphonyl 1,2,3-thiadiazoles in good yields and purity. A synthesis of 1- or 2-phosphonyl hydrazones using two methods is described. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 16:413–416, 2000

A new type of plant activator: thieno[2,3-d][1,2,3]thiadiazole-6-carboxylic acid derivatives

A short and efficient synthesis of a series of the title compounds is presented starting with methylenebutanedioic acid and thioacetic acid. Using the Hurd–Mori reaction in the key step, the optimised reaction sequence allows the large-scale preparation of this new type of plant activator in a few steps with a high overall yield. Additional functionalisation of the 5-position via directed ortho-lithiation methodology is also described. © 1998 Society of Chemical Industry

SYNTHESIS OF SPIRO-TETRAHYDROBENZOTHIENO-1,2,3-SELENN THIADIAZOLES AND SPIRO-TETRA HYDROTHIO-CHROMENO-l,2,3-SELENA/THIADIAZOLES

The title compounds have been prepared by exploiting α-ketomethylene group in spiro-tetrahydrobenzothienones/thiochromenones by oxidative cyclization with SeO2 and Hurd-Mori reaction process with SOCl2. The latter compounds have been obtained by the reaction of mercaptoacetic/propanoic acids with spiro-pyrimidinetriones and isoxazolidinediones followed by cyclodehydration with P2O5.