Lewis acids catalysed Fries rearrangement of isopropylcresol esters

Summary In the course of the Fries rearrangement, aluminium chloride frequently induces migration or elimination of alkyl groups. The results obtained with titanium tetrachloride for the synthesis of vicinalo-hydroxyketones are compared with those obtained with aluminium chloride for some aliphatic and aromatic esters of isopropylcresols. In order to understand the migration and elimination processes occurring, the stabilities of theo-hydroxyketones are studied in the presence of aluminium chloride at different temperatures. Furthermore, all-vicinalo-hydroxyketones were prepared by the Fries rearrangement of 6-tert-butyl-p-thymol with titanium tetrachloride.

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Lewis-Säure-katalysierte Fries-Umlagerung von Isopropylkresolestern

Zusammenfassung Im Verlauf der Fries-Umlagerung induziert Aluminiumchlorid des öfteren eine Wanderung oder Eliminierung von Alkylgruppen. Die Resultate mit Titantetrachlorid bei der Synthese von vicinaleno-Hydroxyketonen werden mit denen mit Aluminiumchlorid für einige aliphatische und aromatische Ester des Isopropylkresols verglichen. Um zu einem Verständnis der auftretenden Wanderungs-und Eliminierungsprozesse zu gelangen, wurden die Stabilitäten vono-Hydroxyketonen bei verschiedenen Temperaturen in der Gegenwart von Aluminiumchlorid untersucht. Außerdem wurden all-vicinaleo-Hydroxyketone mittels Fries-Umlagerung von 6-tert-Butyl-p-thymol mit Titantetrachlorid hergestellt.

     

Fries rearrangement: scalable synthesis of key fluoro building blocks 3-fluoro-4-methoxybenzoyl chloride and 1,2-diethoxy-3-fluorobenzene

Lewis acid catalyzed Fries rearrangement of 2-fluorophenyl acetate (3) was performed on kg scale. The ortho5 and para4 isomers obtained were separated in an industrially feasible way. Compound 4 was then converted into fluorinated building block 3-fluoro-4-methoxybenzoyl chloride (1) while compound 5 was converted into 1,2-diethoxy-3-fluorobenzene (2) in high yields.     

A re-investigation of the Fries rearrangement of 3-chlorophenyl acetate and synthesis of 2-azido-1-(4-(benzyloxy)-2-chlorophenyl)ethanone from 4-bromo-3-chlorophenol

The Fries rearrangement of 3-chlorophenyl acetate provided the expected 4-chloro-2-hydroxy-acetophenone as the major product and 2,4-diacetyl resorcinol and 2-chloro-4-hydroxy-acetophenone as minor products. 4-Benzyloxy-2-chloroacetophenone was prepared by a Heck reaction and then elaborated to 4-benzyloxy-2-chlorophenacyl azide.     

Comparisons of O-acylation and Friedel-Crafts acylation of phenols and acyl chlorides and Fries rearrangement of phenyl esters in trifluoromethanesulfonic acid: effective synthesis of optically active homotyrosines

Reactions involving phenol derivatives and acyl chlorides have to be controlled for competitive O-acylations and C-acylations (Friedel-Crafts acylations and Fries rearrangements) in acidic condition. The extent for these reactions in trifluoromethanesulfonic acid (TfOH), which is used as catalyst and solvent, is examined. Although diluted TfOH was needed for effective O-acylation, concentrated TfOH was required for effective C-acylations in mild condition. These results have been applied to the novel synthesis of homotyrosine derivatives. Both Fries rearrangement of N-TFA-Asp(OBn)-OMe and Friedel-Crafts acylation of phenol with N-TFA-Asp(Cl)-OMe in TfOH afforded the homotyrosine skeleton, followed by reduction and deprotection afforded homotyrosines maintaining stereochemistry of Asp as an optically pure form.     

Direct amination of pyrimidin-2-yl tosylates with aqueous ammonia under metal-free and mild conditions

Ametal-free synthesis of pyrimidine functionalized primary amines via direct amination of pyrimidin-2-yl tosylate with aqueous ammonia has been developed under mild conditions. The desired products pyrimidin-2-amines can be generated in excellent yields in PEG-400, without any catalysts or other additives.     

Chemo- and Regioselective Anionic Fries Rearrangement Promoted by Lithium Amides under Aerobic Conditions in Sustainable Reaction Media

A straightforward and efficient protocol to promote the metalation/anionic Fries rearrangements of O-aryl carbamates, using for the first time a lithium amide as metalating agent under aerobic/ambient-friendly reaction conditions, is reported. This approach enables the sustainable preparation of salicylamide derivatives with high levels of chemoselectivity within ultrafast reaction times, working at room temperature in the presence of air/moisture, and using environmentally responsible cyclopentyl methyl ether as a solvent. Furthermore, the regioselective manipulation of O-2-tolyl carbamates has been accomplished using interchangeably alkyllithiums or lithium amides, with an unexpected beneficial contribution from the employment of biorenewable protic eutectic mixtures as non-innocent reaction media.     

Liquid-liquid equilibria of water + 3-hydroxy-2-butanone + ethyl ethanoate

(Liquid-liquid) equilibrium (LLE) data of the solubility curves and tie-line compositions have been determined for mixtures of (water + 3-hydroxy-2-butanone + ethyl ethanoate) at 298.15 K, 308.15 K and 318.15 K and 101.3 kPa. Distribution coefficients and separation factors have been evaluated for the immiscibility region. The reliability of the experimental tie-lines has been confirmed by using Othmer-Tobias correlation. The LLE data of the ternary systems have been predicted by UNIFAC method.     

o-Phthalic Anhydride/Zn(OTf)2 co-catalyzed Beckmann rearrangement under mild conditions

o-Phthalic anhydride/Zn(OTf)₂ co-catalyzed Beckmann rearrangement was developed, producing the corresponding amide in up to 99% yield with acid-sensitive functionalities tolerated well, and the scale of the reaction could be enlarged to 77 mmol and the excellent yield was maintained. A successive procedure was developed. Moreover, the reaction was carried out at rt under nearly neutral conditions, and the workup was concise. These features illustrated the potential of the protocol in amide synthesis.     

Thermal and photochemical Wallach rearrangement of azoxybenzene in zeolite cages

Acidic zeolites HY and CaY catalyse the Wallach rearrangement of azoxybenzene (I) leading mainly to the formation of para-hydroxyazobenzene (II) and ortho-hydroxyazobenzene (III). In this transformation, increasing the loading level of I results in the formation of a larger amount of para-isomer. As observed in isotropic media, photochemical Wallach rearrangement in the presence of various cation-exchanged faujasites results in the predominant formation of the ortho-isomer from the S₁ state and this rules out any appreciable heavy atom effect.     

Photochemical versus aluminium chloride-catalyzed fries rearrangement of aryl hydrogen succinates. synthesis of 2(3H)-furanones

Summary The photochemical and aluminium chloride-catalyzed Fries rearrangement of a series of aryl hydrogen succinates3 a–f to the corresponding 4-oxoacids1 a–f are compared. Both approaches are complementary: the photochemical process is more general and becomes the method of choice for the succinoylation of phenols supporting alkoxy or hydroxy substituents, while the classical rearrangement is superior in the presence of alkyl or halogen substituents. These results are applied to the preparation of the 2(3H)-furanones2 a–f.

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Photochemische und Aluminiumchlorid-katalysierte Friessche Umlagerung von Bernsteinsäuremonoarylestern. Synthese von 2(3H)-Furanonen

Zusammenfassung Die photochemische und AlCl₃-katalysierte Friessche Umlagerung einer Reihe von Bernsteinsäuremonoarylestern3 a–f zu den entsprechenden 4-Oxosäuren1 a–f werden verglichen. Beide Methoden ergänzen einander: Der photochemische Prozeß ist breiter anwendbar und wird bei Phenolen mit Alkoxy- oder Hydroxy-Substituenten bevorzugt, während die klassische Umlagerung in Gegenwart von Alkyl- oder Halogen-Substituenten vorteilhafter ist. Diese Ergebnisse werden für die Synthese der 2(3H)-Furanone2 a–f angewendet.

     

One-step novel synthesis of methylene bisphenols and methylene bisnaphthols using Lewis acid mediated rearrangement

Mono- and di-substituted isomeric methylene bisphenols and methylene bisnaphthols have been synthesized by rearrangement of the corresponding O-methoxyacetyl derivatives of phenols and naphthols, respectively, in presence of aluminium chloride under dry conditions. The chemistry observed is different from the usual Fries rearrangement reaction and involves an intermolecular rearrangement. The reactions reported here also reflect the influence of substituents present in the substrate as is supported by the substitution of the bridging methylene at a position meta to the phenolic hydroxyl in some of the minor products formed along-side the majorly formed ortho substituted products.     

甲基丙烯酸(2-烷基-2-金刚烷)酯的合成及水解研究

甲基丙烯酸(2-甲基-2-金刚烷)酯和甲基丙烯酸(2-乙基-2-金刚烷)酯是两个重要的193nm光刻胶主体树脂的单体.两个化合物是由2-金刚酮与碘甲烷、碘乙烷的格氏试剂反应得到2-甲基-2-金刚醇、2-乙基-2-金刚醇,然后在氢化钠的作用下与甲基丙烯酰氯发生酯化反应制得.酯化产率50%—60%.产品结构经¹HNMR、IR、MS和元素分析表征.在对甲基苯磺酸-水合物的催化作用下对两个单体进行了水解测试,探讨了水解机理,计算出水解速率常数k,k值分别为-1.52和-3.90.     

Application of the anionic homologous Fries‐rearrangement to the synthesis of 3‐alkylbenzofuran‐2(3H)‐ones

We have developed an effective organometallic‐based procedure allowing the employment of 2‐methylphenols as easily available starting materials in the synthesis of 3‐alkylbenzofuran‐2(3H)‐ones. The first step of this protocol, an anionic homologous Fries‐rearrangement, afforded 2‐(2‐ tert ‐butyldimethylsilyloxyaryl)acetamides, which were selectively metalated and monoalkylated at the benzylic position. Acidic work‐up of crude products afforded the desired heterocycles in satisfactory overall yields. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis and applications of a chiral-oxygenated 3-chloro-3,6-dihydro-2H-pyran obtained under Overman rearrangement conditions

A chlorinated side product was formed under Overman rearrangement conditions from a trichloroacetimidate along with the expected allylic amide. The chlorinated product derived from a hex-2-enopyranoside was obtained in a totally stereoselective manner, and it can be a useful synthetic intermediate for chlorinated sugars. In order to improve the isolated yields of either the expected Overman rearrangement product or the chlorinated compound, we carried out a thorough study on the experimental conditions. The application of the latter for the synthesis of potential calpain inhibitors is also reported.     

An Efficient,Mild and Scalable Synthesis of Bioactive Compounds Containing the Angelicin Scaffold

An efficient, mild and scalable synthesis of angelicin scaffold based compounds was developed. Particularly, the new synthetic route described here circumvents the need for the previously reported key Fries rearrangement step, which uses impractically harsh conditions. The new methodology is applied to the synthesis of several, previously reported analogs of angelicin which have potent anti‐influenza and anti‐cancer activities.     

Synthesis and crystal structure of ethyl benzimidazole-2-yl phosphonate

When N-cyanoimido-( O,O-diethyl)phosphonyl/S-methyl thiocarbonate (1) was treated with o-phenylenediamine in the presence of Et3N in ethanol,diethyl benzimidazole-2-yl phos-phonate (2) was obtained and hydrolyzed during the recrys-tallization in MeOH/H2O,generating ethyl benzimidazole-2-yl phosphonate (3).Hie crystal structure of compound 3 was determined by X-ray diffraction method.The crystals belong to monoclinic,space group C2/c,a = 1.78408(18) ,6 = 0.83725(9),c= 1.67401(18) nm,β= 118.997(2),V = 2.1870(4) nm3,Z = 8,Dc=1.374 g/cm3,F(000)=944.The final R and wR are 0.0499 and 0.1436,respectively.The mechanism of the above reaction is also discussed.     

Synthesis of 2-(3-amino-2-oxoindolin-3-yl)-3-hydroxynaphthalene-1,4-dione derivatives via a one-pot,three-component reaction under catalyst-free conditions

A concise, facile and straightforward synthetic method has been described for the synthesis of 2-(3-amino-2-oxoindolin-3-yl)-3-hydroxynaphthalene-1,4-dione derivatives by a one-pot, three-component reaction of isatins, 2-hydroxy-1,4-naphthoquinone and ammonium acetate under catalyst-free conditions in ethanol. This protocol becomes highly efficient due to its mild reaction conditions, operational simplicity, and overall good to excellent yields (80–99%).     

Experimental and theoretical evidences of 2-aza-Cope rearrangement of nitrones

Both the intramolecular cycloaddition of diastereomeric homochiral N-alkenyl nitrones and the corresponding theoretical calculations using DFT and ab initio methods provided evidences of a thermal [3,3] sigmatropic rearrangement of the nitrones with a complete chirality transfer.     

新的吡啶基硫醚苯甲酸的原位合成及其铜配合物

在氧化铜和溴化铜存在的条件下, 4-[1,2-(2-吡啶基)亚甲硫基]-苯甲酸(L′)经原位消去反应, 形成了一个新的有机配体4-[1,2,2-(2-吡啶基)-(2-吡啶亚甲基)亚甲硫基]-苯甲酸(L), 并与铜形成配位聚合物[Cu₂(L)Br₂]_n(1){L=4-[1,2,2-(2-吡啶基)-(2-吡啶亚甲基)亚甲硫基]-苯甲酸}, 通过红外光谱、元素分析和X射线单晶衍射等手段对其结构进行了表征.     

Di(4,5,6,7-tetrafluorobenzothiazol-2-yl) disulfide: synthesis and reactions with amines

Di(4,5,6,7-tetrafluorobenzothiazol-2-yl) disulfide, obtained by oxidation of 2-mercapto-4,5,6,7-tetrafluorobenzothiazole, readily reacts with aliphatic and alicyclic amines to form the corresponding sulfenyl amides. Dedicated to the memory of Academician N. N. Vorozhtsov on the 100th anniversary of his birth. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1225–1226, June, 2007.