Reaction of organozinc reagents prepared from bromomalonic acid esters and zinc with 3-aryl-2-cyanopropenoic acid primary amides

Organozinc compounds prepared from bromomalonic acid esters and zinc react with 3-aryl-2-cyanopropenoic acid primary amides giving a single diastereomer of the corresponding 1-R′-4-aryl-2,6-dioxo-5-cyanopiperidine-3-carboxylic acid esters, or 3-R′-6-aryl-2,4-dioxo-5-cyano-3-azabicyclo[3.1.0]hexene-1-carboxylic acid esters.     

Ferrocene compounds XXIII. Synthesis and reactions of the new type of methyl ferrocyloxyalkanoates

The new types of ferrocenyloxaaliphatic acid ester, FcCHROCHR′COOMe (R = H, Me, Ph; R′ = H, Me) (7) have been prepared by the action of alkoxides derived from methyl glycolate or methyl lactate on the corresponding ferrocenylcarbinyl acetates (2) or N,N,N-trimethylferrocylammonium iodides (4). The esters obtained were accompanied by a small quantity of oligomeric esters, FcCHR(OCHR′CO)_n OMe (9), and with more or less ferrocyl methyl ethers (8). As opposed to the alkaline hydrolysis of the analogous methyl benzoxyacetate (6) into benzoxyacetic acid (5) the acidification of sodium alkanoates 10 obtained by saponification of esters 7 gave unexpectedly the corresponding ferrocenylcarbinols 1. In a similar way the esters 7 were converted into mixtures of the mentioned carbinols and diferrocyl ethers 11 under action of aqueous hydrochloric acid. The mechanisms of the reactions 10 → 1 and 7 → 1, 11 are discussed.     

Oxathiaphospholane approach to N- and O-phosphorothioylation of amino acids

A method of highly efficient synthesis of N- and O-phosphorothioylated amino acids was developed. N- and O-(2-Thiono-1,3,2-oxathiaphospholanyl)amino acid methyl esters (3) were prepared in high yields in reaction of amino acid methyl esters with 2-chloro-1,3,2-oxathiaphospholane in pyridine in the presence of elemental sulfur. Compounds 3 were converted in high yield into the corresponding methyl or benzyl phosphorothioamides 6 and 7 by DBU-assisted treatment with methanol or benzyl alcohol. When 3-hydroxypropionitrile was used instead of methanol or benzyl alcohol, the corresponding 2-cyanoethylphosphorothioamidates 4 were obtained in high yield, from which the 2-cyanoethyl group was removed with concentrated ammonium hydroxide. The oxathiaphospholane methodology was also applied for the phosphorylation of amino acids. Thus, 2-oxo-1,3,2-oxathiaphospholane derivatives 10 were prepared by oxidation of compounds 3 with SeO(2.) Compounds 10 were transformed into the corresponding phosphate diesters or amidoesters upon treatment with 3-hydroxypropionitrile in the presence of DBU. The DBU-assisted oxathiaphospholane ring-opening process in 3 and 10 did not cause any measurable C-racemization of phosphorothioylated/phosphorylated amino acids.     

Acetylenic Esters of Polychlorobicyclo[2.2.1]hept-2-ene-5-carboxylic Acids

Acetylenic esters of polychlorobicyclo[2.2.1]hept-2-ene-5-carboxylic acids were prepared from the corresponding acid chlorides and acetylenic alcohols.     

A Novel Synthesis of Quinazolines by Cyclization of 1‐(2‐Isocyanophenyl)alkylideneamines Generated by the Treatment of 2‐(1‐Azidoalkyl)phenyl Isocyanides with NaH

A new and efficient method for the synthesis of quinazolines has been developed. Thus, N‐[2‐(1‐azidoalkyl)phenyl]formamides 1 are dehydrated with POCl₃ to give the corresponding 2‐(1‐azidoalkyl)phenyl isocyanides 2 , which are then treated with NaH in DMF at 0° to give quinazolines 6 in satisfactory yields via cyclization of 1‐(2‐isocyanophenyl)alkylideneamine intermediates 4 . This methodology can be applied to the synthesis of the 7‐azaanalogs of quinazolines, i.e., pyrido[3,4‐d]pyrimidines 9 .     

Preparation of α,ω-ditriazinylperfluoroalkane derivatives

The synthesis of 2-oxa and 2-thiaperfluoroglutaric acids and their corresponding ethyl esters, amides, nitriles, acid chlorides, and also 2-thiaperfluoroglutaric anhydride are described. These compounds were prepared as precursors to α,ω-ditriazinylperfluoroalkane derivatives containing a heteroatom in the perfluoroalkylene chain. The ditrazinylpropanes were prepared most satisfactorily from the diacid chlorides rather than the dinitriles.     

One-pot preparation of phenylpropanoid esters co-catalyzed by boric acid and piperidine

Phenylpropanoid esters, especially those with hydroxyl and/or methoxy groups on the benzene ring, are important medicinal chemicals or intermediates. They are usually prepared by esterification of their corresponding substituted cinnamic acids with various alcohols. However, the esterification procedures often suffer from environmentally hazardous problems when sulfuric acid is used as a catalyst or suffer from unsatisfactory yields and expensive raw material when enzyme is applied as a catalyst. In this paper, a convenient one-pot process for preparing various phenylpropanoid esters from substituted benzaldehydes bearing hydroxyl and/or methoxyl groups has been developed. The alcohols react first with malonic acid catalyzed by boric acid to form monomalonate, then without separation, let the resultant mixture immediately react with the injected various substituted benzaldehydes in the presence of piperidine to afford the desired esters with moderate to good yields.     

Facile N-derivatization of alpha-amino esters and amides via benzotriazolylmethyl derivatives

Alpha-(N-substituted amino)esters were prepared in a two-step procedure from available unsubstituted alpha-amino esters. alpha-Amino esters are first converted into the corresponding N-benzotriazolylmethyl derivatives; in the second step, the benzotriazole group is substituted by various nucleophiles with or without the presence of a Lewis acid to give substituted alpha-amino esters in high overall yield under mild conditions with no signs of racemization. Boc-protected amino acids were converted into alpha-amino amides; subsequent deprotection allowed the conversion into N-substituted derivatives analogously to the alpha-amino esters, without racemization in high yields under mild conditions.     

Syntheses of some polyunsaturated sulfur- and oxygen-containing fatty acids related to eicosapentaenoic and docosahexaenoic acids.

With the aim of enhancing selectively the beneficial biological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) a number of polyunsaturated fatty acids containing sulfur or oxygen atoms in the chain has been synthesized starting from EPA and DHA, respectively. Oxidative degradation of these acids led to the corresponding aldehydes all-(Z)-3,6,9,12-pentadecatetraenal and all-(Z)-3,6,9,12,15-octadecapentaenal. Reactions with DBU converted these aldehydes quantitatively into the conjugated isomers (2E,6Z,9Z,12Z)-pentadecatetraenal and (2E,6Z,9Z,12Z,15Z)-octadecapentaenal, respectively. The four aldehydes were transformed by a sequence of reactions comprising reduction to the alcohols, halogenation and substitution with mercapto esters into the corresponding sulfur containing polyunsaturated fatty acid esters. The oxygen containing esters were prepared from the respective alcohol by boron trifluoride catalysed reaction with ethyl diazoacetate.     

Esters of 2-iodoxybenzoic acid: hypervalent iodine oxidizing reagents with a pseudobenziodoxole structure

Esters of 2-iodoxybenzoic acid (IBX-esters) were prepared by the hypochlorite oxidation of the corresponding 2-iodobenzoate esters and isolated as chemically stable, microcrystalline products. These hypervalent iodine compounds are potentially valuable oxidizing reagents belonging to a new class of pentavalent iodine compounds with a pseudobenziodoxole structure. Methyl 2-iodoxybenzoate can be further converted to the diacetate or a bis(trifluoroacetate) derivative by treatment with acetic anhydride or trifluoroacetic anhydride, respectively. Single-crystal X-ray diffraction analysis of methyl 2-[(diacetoxy)iodosyl]benzoate 8a reveals a pseudobenziodoxole structure with three relatively weak intramolecular I...O interactions. The dimethyl and diisopropyl esters of 2-iodoxyisophthalic acid were prepared by oxidation of the respective iodoarenes with dimethyldioxirane. Single-crystal X-ray diffraction analysis of diisopropyl 2-iodoxyisophthalate 6b showed intramolecular I...O interaction with the carbonyl oxygen of only one of the two carboxylic groups, while NMR spectra in solution indicated equivalency of both ester groups. IBX-esters, methyl 2-[(diacetoxy)iodosyl]benzoate, and 2-iodoxyisophthalate esters can oxidize alcohols to the respective aldehydes or ketones in the presence of trifluoroacetic acid or boron trifluoride etherate. The bis(trifluoroacetate) derivative can oxidize alcohols to carbonyl compounds without acid catalyst.     

5-氟尿嘧啶N1-甲酰基氨基酸、短肽的合成及抗肿瘤活性

5-氟尿嘧啶N¹-甲酰氯分别与Gly、Val、Leu、Ile、Phe、Asp和Glu的苄酯反应,制备了7种5-氟尿嘧啶-N¹-甲酰基氨基酸苄酯。氢解后得到了相应的5-氟尿嘧啶N¹-甲酰氨基酸。将其进一步与氨基酸甲酯或二肽甲酯缩合,制备了5-氟尿嘧啶N¹-甲酰基二肽甲酯和三肽甲酯。5-氟尿嘧啶-N¹-甲酰基二肽甲酯也可采用5-氟尿嘧啶-N¹-甲酰氯与二肽甲酯直接反应制备。     

Reductive acetylation of nitrocarboxylic acids of the thiophene and furan series or their esters

The corresponding 4-acetylamino-2-thiophenecarboxylic acids or their esters were produced by the action of reduced iron on solutions of 4-nitro-2-thiophenecarboxylic acid, its derivatives, or their esters in a mixture of acetic acid and acetic anhydride. Esters of 5-acetylamino-2-thiophenecarboxylic or 5-acetylamino-2-furancarboxylic acids are formed from esters of 5-nitro-2-thiophenecarboxylic or 5-nitro-2-furancarboxylic acids. Free 5-nitro-2-thiophenecarboxylic and 5-nitro-2-furancarboxylic acids are entirely decomposed under the conditions of reductive acetylation by iron. The ester of 5-acetylamino-3-thiophenecarboxylic acid was obtained from the methyl ester of 5-nitro-3-thiophenecarboxylic acid.     

Efficient lipase-catalyzed synthesis of new lipid antioxidants based on a catechol structure

Lipid antioxidants phenolic saturated fatty acid esters were synthesized in high yields and short reaction times using the corresponding ethyl fatty acid esters, lipase from Candida Antarctica, vacuum and no solvent. Phenolic esters with mono- and polyunsaturated fatty acids (EPA and DHA) were also prepared.     

Selective tert-butyl ester deprotection in the presence of acid labile protecting groups with use of ZnBr2

Chemoselective hydrolysis of tert-butyl esters in the presence of other acid-labile groups has been explored by employing alpha-amino esters and ZnBr(2) in DCM. Although N-Boc and N-trityl groups were found to be labile, PhF protected amines were compatible with these Lewis acid deprotection conditions such that a variety of N-(PhF)amino acids were prepared in good yields from their corresponding tert-butyl esters.     

AlCl3-NaI(NaBr)-t-BuOH: mild, chemo- and stereoselective reagents for hydrohalogenation of propiolic derivatives

(Z)-β-Iodo-propenamides and -β-iodo-propenoic esters were selectively prepared in high yields, at room temperature, through reaction of 2-propynamides and 2-propynoic esters, respectively, with AlCl₃ and NaI in the presence of t-BuOH in dichloromethane. These experimental conditions are compatible with the presence of acid sensitive acetal groups. Alternative use of EtOH or H₂O in place of t-BuOH was investigated. (Z)-Bromo-propenamides and corresponding esters were prepared according to a similar procedure using sodium bromide in refluxing acetonitrile.     

Functional polymers. XLVII. Synthesis of various derivatives of ω-alkenoates

A number of derivatives of ω-alkenoates were synthesized in preparation for the synthesis of functional polymers based on α-olefins. For the preparation of most of the methyl esters, the regular esterification of ω-alkenoic acids, specifically 10-undecenoic acid with methanol and sulfuric acid as the catalyst, was most effective. For the preparation of the tert-butyl- and 2-ethylhexyl esters of 10-undecenoic acid, the acid chloride route was found to be most convenient, whereas for the preparation of the corresponding esters of 5-hexenoic acid, our method of choice was the synthesis via the imidazolyl derivative of the acid. 2,2,2-Trifluoroethyl 10-undecenoate and the 2,2-dimethyloxazolidine derivative of 10-undecenoic acid were prepared from the acid and 2,2,2-trifluoroethanol or 2-amino-2-methyl-propanol with p-toluene sulfonic acid as the catalyst. Esters of phenol, 2,6-dimethylphenol, and 2,6-diphenylphenol were synthesized from 3-butenoic and 10-undecenoic acid with trifluoroacetic anhydride.     

Synthesis and spectroscopic studies of some quinolylmethylphosphonates

Monoethyl esters of 2-quinolylmethylphosphonic acid ( 3 ) and 8-quinolylmethylphosphonic acid ( 6 ) have been prepared. The corresponding diethyl esters 1 and 4 , and sodium salts of monoesters 2 and 5 , respectively, have also been isolated. The properties of the monoethyl esters of 8- and 2-quinolylmethylphosphonic acid are very different. While the former was isolated as the hydrochloride, the latter did not form such a salt. Molecular weight determination indicated a dimeric structure of the monoester 3 , and spectroscopic measurements confirmed the association presumably owing to the hydrogen bonding between the P?O and P-OH groups.     

Synthesis of optically pure (R)- or (S)-α-fluoro-α-methyl-β-ketoesters

A number of optically pure (R)- or (S)-α-fluoro- α-methyl-β-ketoesters were prepared by the reaction of the optically pure acid chlorides made from the corresponding (R)- or (S)-α-fluoro-α-methylmalonic acid monoethyl esters with alkyl (or aryl) cuprates.     

Polymer-bound diazonium salts for the synthesis of diazoacetic esters

Starting from Merrifield resin, various polymer-bound diazonium salts were prepared. Upon treatment with amino acid esters, resulting the appropriate triazenes, the corresponding diazoacetic esters were formed by basic cleavage. Scope and limitation of this transformation were investigated.     

Synthesis of regioisomeric 6,9-(chlorofluoro)-substituted benzo[g]quinoline-5,10-diones,benzo[g] isoquinoline-5,10-diones and 6-chloro-9-fluorobenzo[g]quinoxaline-5,10-dione

Treatment of difluoro or chloro fluoro-substituted benzyl bromides 5a-c with zinc dust in tetrahydro-furan leads to the corresponding benzylic zinc bromides 6a-c. These organometallics on treatment with chlorosubstituted heterocyclic esters 4A and 4B mediated by nickel catalysis undergo couplings to yield dihalobenzyl substituted heterocyclic esters 7Aa-c and 7Ba-c. Treatment of 4c with 6c under Pd catalysis leads to 7Cc. The acids 8, prepared by hydrolysis of these esters, with treatment of fuming sulfuric acid undergo cyclizations and oxidations to yield the desired regioisomeric dihalo-substituted heterocyclic quinones 2.