A study of the acylation of 4-hydroxy-6-methyl-2-pyrone and 4 hy(lroxy-6-phenyl-2-pyrone

The acylation of 4-hydroxy-6-melhyl-2-pyrone (1) and 4-hydroxy-6-phenyl-2-pyrone (XXII) with aliphatic acid anhydrides, or with aliphatic acid chlorides in trifluoroacetic acid, has been found to product; first the corresponding ester, which then rearranges, partially or wholly, depending on the conditions and on the nature of the acyl moiety, to form the corresponding 3-acylpyrone. With aromatic acid chlorides in pyridine or in trichloroacetic acid only the corresponding ester was obtained. These esters, however, could be rearranged to the corresponding 3-acylpyrones with aluminum chloride. Acetoaeetylation of 1 and 4-hydroxycoumarin (XXIX) with diketene gave, in both cases, the C-acetoacetylated product.     

Formylation of 5-hydroxybenzofuran derivatives and synthesis of furo-[3,2-<Emphasis Type="Italic">f</Emphasis>]coumarins based on them*

The formylation of esters of 5-hydroxy-1-benzofuran-3-carboxylic acid has been studied. The interaction of the synthesized aldehydes with esters of β-keto acids and hetarylacetonitriles gave furo[3,2-f]coumarin-1-carboxylic acids derivatives.     

Elektrochemische Oxidation von (S)-Äpfelsäure-Derivaten: ein Weg zu enantiomerenreinen alkylierten Malonaldehydsäure-estern

Electrochemical Oxidation of (S)-Malic-Acid Derivatives: a Route to Enantiomerically Pure Alkylmalonaldehydic Esters The 3,3-dialkymalic-acid diesters, prepared by the previously described diastereoselective alkylations through dilithium alkoxide enolates, are saponified to the monoesters containing a free α-hydroxycarboxylic-acid moiety(Scheme 3). The monoesters are subjected to electrochemical oxidative decarboxylation in MeOH . If the intermediate monoacids are purified, the malonaldehydic esters (2-formy1-2-alkylcaroxylates) Obtained by this procedure are enantiomerically pure; they have the same structural features, i.e. two enantiotopic functionalized branches on the (persubstituted) stereogenic center, as the well known 3-hydroxy-2-methylpropanoic acid (‘Roche acid’) which was employed frequently as a starting material for the preparation of either enantiomer of various target molecules.     

Synthese und Reaktionen von Bicyclo[6.4.0]dodecan-3-carbonsäure-Derivaten

Synthesis and Reactions of the Bicyclo[6.4.0]dodecane-3-carboxylic Acid Derivatives The synthesis and some consecutive reactions of the compounds 5-8 , derivatives of bicyclo[6.4.0]dodecane-3-carboxylic acid ( 1 ), are described. The esters 7 and 8 can be obtained by Baeyer-Villiger oxidation of 2-hydroxy-8-methyltricyclo[7.3.1.0^2,7]tridecan-13-one ( 4 ) and subsequent hydrolysis of the lactone 5 . The structure and configuration of these compounds has been evaluated by spectroscopic techniques (mainly 2D-NMR methods). The formation of 7 via 1,2-H shift and subsequent isomerization to 8 has been studied. The esters 11 and 13 are formed stereospecifically from 7 and 8 .     

NMR.-spektroskopische Methoden als Reinheitskriterien isomerer Weinsäuren und Weinsäureester

NMR.-spectroscopic Methods as Criteria of the Purity of Isomeric Tartaric Acids and Their Esters meso-Tartaric acid ( 2 ) can be distinguished either from the natural (+)-(2R, 3R)-tartaric acid ( 1 ) or the ‘unnatural’ (?)-(2S, 3S)-tartaric acid ( 1 ′) or their racemic mixture, by ¹H-NMR.-spectral resolution using europium chloride in aqueous solution. Diastereomeric esters have been prepared from different esters of tartaric acid 3 and the Mosher reagent 4 and the purities of the enantiomers of 3 have been checked by ¹H-NMR. spectroscopy.     

Efficient synthesis of 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters

A general procedure is described for the preparation of 6-substituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters (6-substituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters). These compounds are shown to undergo selective alkylation at the 2-position in moderate to good yields (19-77%) to afford 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters (2,6-disubstituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters).     

Cyclic hydroxamic acids derived from quinazoliue

The action of various acylating agents on 2-aminobenzohydroxamic acid afforded 3-hydroxy-4(3H)quinazolinones (hydroxamic acids) as well as several ethers and esters from them were prepared and their spectroscopic properties analyzed. Secondary amines, as well as one equivalent of alkali, on 2-halomethyl-3-hydroxy-4(3H)quinazolinone lead to the formation of a dimer(XI). In this respect the behaviour of secondary amines is different from that of primary amines. Some new 3-hydroxy-2-4(1H,3H)-quinazolidinediones are described.     

Cyclocondensation of 3-amino-2-hydrazino-4(3H)-pyrimidinones with dimethyl acetylenedicarboxylate. Formation of 1-amino-2,6-dihydro-2,6-dioxo-1H-pyrimido[1,2-b][1,2,4]triazine-3-acetic acid esters

[(1-Amino-6-hydroxy-2(1H)-pyrimidinylidene)hydrazone]butanedioic acid dimethyl esters 3 , formed from 3-amino-2-hydrazino-4(3H)-pyrimidinones and dimethyl acetylenedicarboxylate in acetic acid at room temperature, underwent a facile, thermal rearrangement to 1-amino-2,6-dihydro-2,6-dioxo-1H-pyrimido-[1,2-b]-[1,2,4]triazine-3-acetic acid methyl esters 6 in hot acetic acid.     

Structural reassignment of the alleged 6-hydroxy-1,2,4-triazine-3,5-(2H,4H)dione

The reaction of 6-amino-1,2,4-triazine-3,5-(2H,4H)clione with sodium hydroxide or nitrous acid has been shown to give 5-hydroxy-1,2,4-triazole-3-carboxylic acid instead of 6-hydroxy-1,2,4-triazine-3,5-(2H,4H)dione as reported in the literature. The triazolecarboxylic acid was also obtained from the aminotriazine and hydrochloric acid.     

Arbeiten über Phosphorsäure- und Thiophosphorsäureester mit einem heterocyclischen Substituenten. 7. Mitteilung. Thio- und Dithiophosphorsäureester von der Art des GS 13005 mit einem analogen oder homologen heterocyclischen Ring

To complete results presented in this and in previous papers of this series as well as published in patents of other authors a review is given on known and new variations of the heterocyclic moiety in GS 13005 type thio- and dithiophosphoric acid esters ( 1, 2 ) by modification of the 1,3,4-thiadiazol-2(3H)-one ring 5 and by its replacement by analogue five- and homologue six-membered rings. Among new esters of this type some containing the pyrazolinone ring 3 or a 2-alkoxy-4H, 6H-1,3,4-thiadiazin-5-one ring 10 (homologue of the original 5-methoxy-1,3,4-thiadiazol-2(3H)-one ring in GS 13005) show no remarkable pesticidal activity, some others containing a pyrazolering 7 or a 3(2H)-pyridazinonc ring 8 are moderately to highly active but toxic to inauinials in the same proportion. Attempts to prepare seven-membered 2-alkoxy- and 2-alkylthio-6,7-dihydro-l, 3,4-thiadiazepin-S(4H)-ones 11 , Z-rnethoxy-l,3,4-thiadiazepin-S(4H)-one 12 (ring vinylogue of the original 5-methoxy-l,3,4-thiadIazol-2(3H)-one ring in GS 13005) and its 7-methyl-derivative have been unsuccessful due to unexpected side reactions, such as: five-ring closure of 3-(3-chloropropionyl)-thio- and -dithiocarbazic acid esters 22 to pyrazolidinone derivatives 23 , pyrazolinone ring closure of a 3-(acetoacety1)-thiocarbazic acid O-methyl ester derivative 26 , bromine attack on sulfur in 3-(2-alkenoyl)-thiocarbazic O-methyl esters 29 instead of bromine addition at the double bond, and halogen splitting off without ring closure in 3-(2,3-dihalogeno-alkanoyl) -thiocarbazic O-methyl esters 30 prepared by acylation of thiocarbazic acid O-methyl ester with dihalogeno-alkanoyl-chlorides.     

Trading N and O: asymmetric syntheses of β-hydroxy-α-amino acids via α-hydroxy-β-amino esters

Both diastereoisomers of 2-amino-3-hydroxybutanoic acid and 2-amino-3-hydroxy-3-phenylpropanoic acid have been prepared from enantiopure α-hydroxy-β-amino esters via the intermediacy of the corresponding cis- and trans-aziridines. Aminohydroxylation of two α,β-unsaturated esters produced enantiopure 2,3-anti-α-hydroxy-β-amino esters in >99:1 dr. Subsequent epimerisation at the C(2)-position via a sequential oxidation/diastereoselective reduction protocol gave the corresponding enantiopure 2,3-syn-α-hydroxy-β-amino esters in >99:1 dr. These syn- and anti-substrates were then converted into the corresponding N-Boc protected cis- and trans-aziridines, respectively, via a three step reaction sequence: (i) hydrogenolysis and in situ N-Boc protection; (ii) OH-activation; and (iii) aziridine formation. Subsequent regioselective ring-opening of the C(3)-methyl-aziridines with Cl₃CCO₂H proceeded with inversion of configuration to give the corresponding 2-amino-3-trichloroacetate esters, whereas the analogous reaction with the C(3)-phenyl-aziridines resulted in rearrangement to the corresponding oxazolidin-2-ones with retention of configuration. In each case, hydrolysis of the products from these ring-opening reactions produced the corresponding enantiopure β-hydroxy-α-amino acids as single diastereoisomers.     

Synthesis of novel 1-phenyl-1H-indole-2-carboxylic Acids. I. Utilization of ullmann and dieckmann reactions for the preparation of 3-hydroxy, 3-alkoxy,and 3-alkyl derivatives

Methods for the synthesis of novel 3-hydroxy, 3-alkoxy, and 3-alkyl indole-2-carboxylic acids and esters are described. Dieckmann cyclization of various 2-[(carboxymethyl)amino]benzoic acid diesters yielded 1-unsubstituted-, 1-methyl-, and 1-phenyl-3-hydroxy-1H-indole-2-carboxylic acid esters. An Ullmann reaction with bromobenzene converted 1H-indoles to 1-phenylindoles.     

Transformations in the 2-quinolone series

The treatment of 1-substituted-1,2-dihydro-4-hydroxy-2-oxo-3-quinoline carboxylic acid esters and 4-hydroxy-1-methyl-3-nitro-2-(1H)quinolinone with phosphorus oxychloride resulted in the formation of the corresponding 4-chloro-2-quinolones. Their reactions with a variety of carbon, nitrogen, oxygen, and sulfur nucleophiles is described.     

Reaction of the Reformatskii reagent obtained from bromotetrahydrofuran-2-one with 2-oxochromene-3-carboxylic or 3-oxo-3<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">f</Emphasis>]chromene-2-carboxylic acid derivatives

The Reformatskii reagent obtained from 3-bromotetrahydrofuran-2-one reacts with alkyl esters of 6-bromo- and 6,8-dibromo-2-oxochromene-3-carboxylic acid or alkyl esters and N-benzylamide of 3-oxo-3H-benzo[f]chromene-2-carboxylic acid to form alkyl esters of 6-bromo- and 6,8-dibromo-2-oxo-4-(2-oxotetrahydrofuran-3-yl)chroman-3-carboxylic acid or alkyl esters and N-benzylamide of 2,3- dihydro-3-oxo-1-(2-oxotetrahdrofuran-3-yl)-1H-benzo[f]chromene-2-carboxylic acid as a mixture of two diastereomers.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 9, 2004, pp. 1513–1515.Original Russian Text Copyright © 2004 by Shchepin, Fotin, Shurov.This revised version was published online in April 2005 with a corrected cover date.     

Preparation of 4-hydroxy-3-substituted, 2H-1-benzopyran-2-ones and 2H-1-benzothiopyran-2-ones from carboxylic esters and methyl salicylates or methyl thiosalicylate

C(α)-Carboxylic acid esters were treated with excess lithium diisopropylamide, condensed with methyl salicylates or methyl thiosalicylate, followed by acid cyclization to either 4-hydroxy-3-substituted, 2H-1-benzopyran-2-ones (coumarins), or 2H-1-benzothiopyran-2-ones (thiocoumarins).     

4-hydroxy-2- quinolones 199*. use of <Emphasis Type="Italic">N,N</Emphasis>'-dicyclohexylcarbodiimide in the synthesis of ethyl 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylates

A novel method has been developed for the synthesis of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids esters based on the use of monoethyl malonate as an acylating agent in the presence of N,N'-dicyclohexylcarbodiimide and characterized by high yields and purity for the final products. Practical recommendations are given for the removal of specific admixtures.     

3-Oxo-1,2-benzoisothiazoline-2-acetic acid 1,1-dioxide derivatives. I. Reaction of esters with alkoxides

Reaction of 3-oxo-1,2-benzoisothiazoline-2-acetic acid alkyl esters 1,1-dioxide ( 1a-d ) with alkaline alkoxides was carried out under various conditions. Under mild conditions, o-(N-carboxymethylsulfamyl)benzoic acids dialkyl esters ( 2a-d ) were obtained with good yields. Reaction of 1a-d or 2a-d with sodium alkoxides under drastic conditions afforded 4-hydroxy-2H-1,2-benzothiazine-3-carboxylic acid alkyl esters 1,1-dioxide ( 3a-d ). Transesterification was observed when esters 1b-d were treated with sodium methoxide in methanol. Esters 3a-d were hydrolyzed in concentrated aqueous sodium hydroxide affording the acid 6 . Attempts to recrystallize 6 from water resulted in its decarboxylation to give 2H-1,2-benzothiazine-4-(3H)one 1,1-dioxide (7). Compound 6 could not be obtained by acid hydrolysis of esters 3a-d or by rearrangement of 3-oxo-1,2-benzoisothiazoline-2-acetic acid 1,1-dioxide ( 8 ). Different experimental evidence supports the suggestion that rearrangement took place by ethanolysis of the carboxamide linkage affording the open sulfonamides (fast step) followed by a Dieckmann cyclization (slow step). It was demonstrated that transesterification took place in the open sulfonamides 2 .     

Synthesis of aldehyde and carboxylic acid derivatives from 2-hydroxymethyl-3-hydroxy-4H-pyran-4-one (α-hydroxymaltol)

α-Hydroxymaltol (2-hydroxymethyl-3-hydroxy-4H-pyran-4-one) ( 1 ) has been converted to the 3-O-methyl ether 2 and 3-O-p-nitrobenzyl ether 4 by standard methods. The ethers 2 and 4 have been oxidized by barium manganate to the corresponding aldehydes, 3 and 5 , in 91 and 77% yields respectively. Long-term reaction of 5 with hydrogen bromide in acetic acid gives 3-hydroxy-4H-pyran-4-one-2-carboxaldehyde ( 6 ). The aldehyde 3 is readily oxidized by short-term reaction with silver oxide to the corresponding acid 7 .     

Interaction of Hydroxylamine with Esters of 2-Oxobutenoic Acids. Synthesis of 1-Hydroxy-3-hydroximino-2-pyrrolidinones

New 3-hydroximino-1-hydroxy-2-pyrrolidinones have been synthesized by the interaction of NH₂OH and NH₂OBn with the methyl esters of 2-oxo-3-butenoic acid derivatives. Some intermediate compounds have been isolated and identified and the reaction mechanism is discussed.     

Benzylidène-5-hydroxy-4-dihydro-2,5-thiophènecarboxanilides-3-(Z): Synthèse et isomérisation en benzyl-5-hydroxy-4-thiophènecarboxanilides-3

(Z)-5-Benzylidene-2,5-dihydro-4-hydroxy-3-thiophenecarboxanilides: Synthesis and Isomerization into 5-Benzyl-4-hydroxy-3-thiophenecarboxanilides Upon treatment with an arylamine in boiling xylene, the esters I yield predominantly the corresponding anilides II, along with a small but variable amount of the isomeric thiophene derivatives III (Table 1). On the other hand, the derivatives III can be readily prepared by base- or acid-catalyzed isomerization of II . Esters I can also be isomerized to the corresponding thiophene derivatives IV (Scheme 6), but only in the presence of a strong acid (Table 4). The two series of isomers reported in Tables 2 and 3 present spectral differences which allow unambiguous structural assignments. The (Z)-configuration for compounds of Table 2 is confirmed by a NOE study carried out on the O-methyl derivatives 6a and 7a .