Synthesis of some new Spiro(Pyran-4,2′- Oxazolidine) and Pyridoxazolidine Derivatives

Ketene S,S-acetal 2 reacts with aminoethanol to afford 2-(1-acetal -2-oxo propylldine)oxazolldine 3 which was allowed to react with some active methylene compounds having an α- cyano or α-keto group to give spiro(pyran -4,2′-oxazolldine) derivatives 6-11. Compound 3 reacted with some α, β -unsaturated nltriles to afford the corresponding pyrldoxazolldine derivatives 12a-h through a nucleophillc addition and cyclization.     

Base Promoted Rearrangement of Carbonate Esters Derived from Aldehyde Cyanohydrins: Application to the Synthesis of α-Keto Esters

Acylation of the cyanohydrin derivative (2) of representative aldehydes with ethyl chloroformate, followed by treatment of the corresponding mixed carbonate esters (3) with lithium hexamethyldisilazide, afforded the cyanohydrin derivative (4) of α-keto esters. Cleavage of the latter (4) with 2,6-lutidine in the presence of silver nitrate led to the procurement of α-keto esters in >50% overall yield.     

Selective Hydrolysis of Thioacetals with Thallium(III) Nitrate

In connection with research at present being pursued in these laboratories we required quantities of thioacetal (1) for study. Reaction of Wieland-Miescher ketone (2) with one equivalent of 1,2-ethanedithiol gave only (3) resulting from reaction at the α,β-unsaturated carbonyl group. The structure for (3) was deduced primarily from C n. m. r. which showed a saturated carbonyl absorption (δ212.6)¹. The preferential reaction of 1,2-ethanedithiol with α,β-unsaturated ketone     

Stereoselective Synthesis of 3-C-Branched-Chain Sugars by Aldol Reaction of Furanos-3-Uloses with Acetone

Abstract

Aldol reaction of 1,2-O-isopropylidene-5-O-tertbutyl-dimethylsilyl-α-D-erythro-pentofuranos-3-ulose (1) with acetone in the presence of aqueous K₂CO₃ afforded 3-C-acetonyl-1,2-O-isopropylidene-5-O-tertbutyl-dimethylsilyl-α-D-ribofuranose(2). Similar reaction of 1,2:5, 6-di-o-isopropylidene- α-D-ribo-hexofuranos-3-ulose (3) afforded 3-C-acetonyl-1,2:5, 6-di-o-isopropylidene- α-D-allofuranose (4) and (1R, 3R, 7R, 8S, 10R)-perhydro-8-hydroxy-5,5,10-trimethyl-2,4,6,11,14-pentaoxatetracyclo[8,3,1,0^1,8,0^3,7] tetradecane. The stereochemistry of the new chiral centers were determined by ¹H NOE experiments.     

Halogenotropy in Phosphorus-Carbon Diad

Abstract

NMR and chemical studies have shown that α-halogenoalkyl-phosphines 1 and P-halogenoylids 2 exist as halogenotropic tautoineric systems. The position of the equilibrium depends on the used solvent, temperatures and substituents at the α-carbon atom. For example, the equilibrium 1 2 shifts towards the phosphine from 1 if the substituents at the α-carbon atom are electron-donating (R = H, Me, Pr, i-Pr). These compunds, existing preferably in the phosphine form, undergo typical reactions both for tervalent phosphorus compounds and P-halogenoylids. Tervalent phosphorus compounds, α-halogenoalkylphosphines 1 add sulfur and react with anhydrous HCl to convert into the dichlorophosphines -4. Like the P-halogenoylids, they add alcohols and phenols forming the phosphonium salts 5, 6, react with primary amines and aniline to yield the iminophosphonates 7 They also form the 2-halogenoalkylphosphonates 8 in the reaction with aldehydes.     

Synthesis of Heterobicycles of δ-Lactam Fused with 1,3-Diazaheterocycles by the Reaction of Heterocyclic Ketene Aminals with α,β-Unsaturated Carboxylic Esters

Heterobicycles of δ-lactam fused with imidazolidine (4, 7), hexahydropyrimidine (5, 8), or hexahydro-1, 3-diazepine (6, 9) were synthesized by the reaction of heterocyclic ketene aminals 1, 2 or 3 with ester of α,β-unsaturated carboxylic acids.     

Synthesis of C-Glycosyl α-Glycines

Abstract

A scheme of asymmetric synthesis of C-glycosyl α-glycines is described. Reductive hydrolysis of 2-deoxy-3,5-di-O-p-toluoyl-β D-erythropentofuranose 1-cyanide (4) in the presence of N,N-diphenylethylenediamine gave the imidazolidine 5, which was converted to 2,5-anhydro-3-deoxy-4,6-di-O-p-toluoyl-β-D-allose (3)by acid hydrolysis. The aldehyde (3), chiralamine, benzoic acid and t-butyl isocyanide four component condensation afforded in good yield two diastereomeric adducts (6a and 6b), which were separated by column chromatography and deblocked to furnish 2-deoxy-β-D-erythropentofuranosyl R and S-glycines (1a) and (1b).     

Synthesis of γ-Lactone of 1R-CIS 2,2-Dimethyl-3-(2,2,2-tribromo-1-hydroxyethyl)cyclopropane Carboxylic Acid,A Key Intermediate for Deltamethrin,From (+)-3-Carene

1R-cis-2,2-Dimethyl-3-(2,2-dibromovinyl)cyclopropane carboxylic acid¹ (1), the acid moiety of the highly potent photostable pyrethroid deltamethrin (2) has been obtained either by a Wittig reaction on 1R-cis-caronaldehyde ester (3) employing 1, 1-dibromomethylenetriphenylphosphorane or from the bicyclic tribromo-lactone^2,3 (4) by reaction with zinc and acetic acid. Lactone (4) is thus an important intermediate in the deltamethrin synthesis.     

Synthesis and Stereochemistry of Some new Derivatives of 1,2-O-Cyclohexylidene-α-D-Xylofuranuronic Acid

Abstract

1,2-O-Cyclohexylidene-α-d-xylofuranuronic acid (2) has been converted into its 3-O-acetyl derivative and consecutively to the corresponding acid chloride and ethyl ester. Direct reaction of 2 with ethanol in the presence of p-to-luene sulphonic acid gave the ethyl ester. Reaction of 2 with phosphorus pentachloride in dry ether gave the acid chloride of 1,2-O-cyclohexylidene-3-O-dichlorophosphoryl–α-d-xylofuranuronic acid. Conformational data have been obtained from ¹H and ¹³C NMR measurements.     

A General Method for Stepwise Elongation of the (1→5)-α-D-Arabinofuranan Chain

Condensation reaction of 3,5-di-O-benzoyl-1,2-O-(1-cyanoben-zylidene)-β-D-arabinofuranose (2) with benzyl and allyl 2,3-di-O-benzoyl-5-O-triphenylmethyl-α-L-arabinofuranosides (5a and 5b) in methylene chloride in the presence of triphenylcarbenium tetrafluoroborate as catalyst under high vacuum gave α-(1→5)-linked dimeric D-arabinofuranoside derivatives (6a and 6b). One of the dimeric compounds (6a) was debenzoylated, triphenylmethylated, and rebenzoylated to give a dimeric homolog of 5a (8). Similarly for the preparation of 6a, 8 was condensed with 2 to provide an α-(1→5)-linked trimeric D-arabinofuranoside derivative (9). Further elongation of the glycoside chain might be possible in the same way.     

Nonreducing-Sugar Subunit Analogs of Bacterial Lipid a Carrying the Ester-Bound (3R)-3-(Acyloxy)Tetradecanoyl Group

Abstract

In order to elucidate further the relationship between the composition of the fatty acyl groups in the nonreducing-sugar subunit of bacterial lipid A and its biological activity, 3-O-[(3R)-3-(acyloxy)tetradecanoyl]-2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-4-O-phosphono-D-glucose [GLA-63(R, R) and GLA-64(R, R)], and 3-O-[(3R)-3-(acyloxy)tetradecanoyl]-2-deoxy-4-O-phosphono-2-tetradecanamido-D-glucose [GLA-67(R), GLA-68(R) and GLA-69(R)] have been synthesized. Benzyl 2-[(3R)-3-(benzyloxymethoxy)tetradecanamido]-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside (5) and benzyl 2-deoxy-4,6-O-isopropylidene-2-tetradecanamido-β-D-glucopyranoside (6) were each esterified with (3R)-3-dodecanoyloxytetradecanoic acid (1), (3R)-3-tetradecanoyloxytetradecanoic acid (2) or (3R)-3-hexadecanoyloxy-tetradecanoic acid (3), to give 7-11, which were then transformed, by the sequence of deisopropylidenation, 6-O-tritylation and 4-O-phosphorylation, into a series of desired compounds.     

N-(Chlorosulfinyl)-Imidazole as a New Imidazole Transfer Reagent1

The usefulness of diimidazoles² such as N, N′-carbonyldi-imidazole (1), and N, N′-thionyldiimidazole (2) in organic synthesis has been accumulated recently. In connection with the continuing our studies on the reaction using 1 or 2 ³ (carbonyl, thionyl, and imidazole transfer reactions), our particular interest was focused on the synthesis of N-(chlorosulfinyl)-imidazole (3) in which one imidazole group in 2 was replaced by the other leaving group (Cl). Also, 3 was interesting for preparative purposes as a chlorine atom could be introduced via the addition reaction of 3 to carbonyl compounds as known in the reaction of 1 or 2 with ketones.     

A New Heptanuclear Tin Cluster Containing Sulfur and Oxygen in the Framework

Abstract

We have recently reported that new structural forms having the cube, (n-BuSn(O)O₂PPh₂)₄, and oxygen-capped, [(n-BuSn(OH)O₂PPh₂)₃O] [O₂PPh₂], formulations can be prepared by the reaction of n-butylstannonic acid with the corresponding diorganophosphinic acid. In new work exploring the effects of the bulky mesityl group bound to phosphorus, a cube formulation was also obtained. When n-butylstannonic acid was reacted with dicyclohexylphosphinic acid in the presence of nitric acid an oxygen-capped cluster having nitrate as the anion was obtained, demonstrating that the phosphinate anion is not required to stabilize the o-capped cation. In an attempt to generate similar structural forms, with sulfur replacing oxygen in the framework, the reaction of n-butylstannonic acid with diphenylphosphine oxide in the presence of elemental sulfur has been explored. From this reaction, a new structural form, containing seven hexacoordinate tin atoms and incorporating sulfur into the framework, [(n-BuSn(S)O₂PPh₂)₃O]₂Sn, was obtained in a mixture of products. A comparison of the crystal structures of the three compounds indicates that the new form has structural features in common with both the cube and the o-capped cluster.     

A Facile Method for the Bishomologation of Ketones to α,β-Unsaturated Aldehydes: Application to the Synthesis of the Cyclohexanoid Components of the Boll Weevil Sex Attractant

The acid-catalyzed isomerization of tertiary vinyl carbinols (2) to the corresponding primary allylic alcohols (5) has been reported numerous times in the chemical literature.¹ In addition, the corresponding acetylenic carbinols (3) have been shown² to rearrange to α,β-unsaturated aldehydes (6) when treated with aqueous acid. Since yields are generally low under the conditions required for the latter transformation, a better method³ involves the isomerization of the corresponding tertiary acetylenic acetate (4) in the presence of silver ion to an allenic acetate, followed by hydrolysis to the desired α,β-unsaturated aldehyde (6).     

New Homologation Procedures of Carbonyl Compounds by Means of Diethyl[trimethylsilylethoxymethyl]phosphonate

Abstract

The lithiated carbanion of the phosphonate 1 prepared by means of s-BuLi at -78°C in THF can be treated with C1Si(CH₃)₃ transforming 1 into its α-Si(CH₃₎₃ substituted derivative 2. Whereas the anion of 1 is thermally unstable at temperatures exceeding -70°C the preparation of the corresponding carbanion of 2 by means of s-BuLi and the subsequent reaction with carbonyl compounds can be carried out at temperatures about -30°C illustrating the carbanion stabilizing effect of the α - silyl group. The phosphonate 2 is very suitable to effect conversion of many aldehydes and ketones via the vinylphosphonate-type 3 (applying a Peterson elimination) either to the homolocles esters 4 or the special α -hydroxyesters 5.     

Reaction of Aziridinones with 2-Lithio-1, 3-Dithiane: Selective Cleavage of the Aziridinone Ring

The reaction of aziridinones (1a-1d) with tert-butyllithium at room temperature affords α-hydroxy imines (5ax-5dx).¹ One possible pathway leading to these products involves the formation of 2 as an intermediate, followed by rearrangement to 3. In fact, under carefully controlled conditions that prevent the rearrange-of 2 to 3, α-amino ketones (4ax-4dx), which arise from the protonation of 2, can be isolated. Other α-amino ketones were synthesized in a like manner from aziridinones by treatment with a variety of alkyllithium reagents.² Baumgarten and co-workers³ subsequently reported similar products from the reaction of phenyllithium and methyllithium with an aziridinone. In an attempt to extend this study to other organolithium reagents, especially those bearing functional groups, we have investigated the reaction of     

Crystalline Methyl β-L-Pfamnofuranqside From Fischer Glycqsidatiok of L-Rhamnose

Flash chromatography of the mixture obtained by reaction of L-rhamnose with methanol in the presence of cation-exchange resin, in addition to methyl α-L-rhamnofuranoside (3) and methyl rhamnopyranosides 1 and 2 gave methyl β-L-rhamnofuranoside (4) in 8% yield. ¹³C and ¹H NMR spectra of 3 and 4 as well as their calculated conformation in solution are discussed.     

The structure of cis and trans lsomers of 1-(p-Bromobenzylidene)-2-indanone

Abstract

In this communication we wish to report an interesting case of the isolation and characterization of the cis and trans isomers of 1-(p-bromobenzylidene)-2-indanone and their ketals. Prior to this work, Hoogstreen and Trenner² had reported on the cis and trans isomers of 1-(p-chlorobenzylidene)-2-methyl-5-methoxyindenylacetic acid. The condensation of 2-(N-morpholinyl)-indene (1, prepared by the reaction of 2-indanone³ and morpholine) with P-bromobenzaldehyde was conducted by refluxing them in the presence of acetic acid for 4 hours. Acid hydrolysis of the reaction mixture followed by dry column chrcmatography over sillica gel using a fraction collector afforded two iscmeric monobenzylidenes, compounds 2(36.6%, mp 110–111°)and 3(1.3%, mp 115–116°) and a dibenylidene, compound 4 (8.7%, mp 205°). The relative rations of the mono- and dibenzylidenes seemed to depend on the reaction conditions. Higher yields of the monobenzylidenes 2 and 3 were obtained by conducting the reaction in the presence of UV light. The structures of these monobenzylidenes were established as cis and trans isomers of 1-(p-bromobenzylidenes)-2-indanone on the Basis of elemental analyses and ir and nmr spectroscopy. The ir spectra⁴ (CHCl₃)

of compounds 2 [1725 (c=0), 1620 (c=c)cm^?1] and 3[1710 (c=o), 1570, 1600 (c=c) cm^?1] were consistent with the structures. The molecular ion peaks as well as the fragmentation patterns in the mass spectra of both these compounds were consistent with the assigned structures. Before going into the omr discussion it should be pointed out that treatment of compound 2 with athylene glycol in the presence of p-toluene sulfonic acid produced two ketals, 5 (38.3% mp, 118–120°) and 6 (30.6% mp, 125–126°). As depicted; the ketals 5and 6 were also found (by omr) to be related to each other as cis and trans isomers. Furthermore, each of them could be hydrolyzed with acid to the corresponding monobenzylidenes 2 and 3 without any isomerization. However, UV irradiation of compounds 2 and 3 gave equilibrium mixtures containing both the isomers, indicating isomerization had occurred under photolytic conditions.     

Hypochlorous Acid. A Synthesis of α-Chloro-β-Lactones

Herein we report that the reaction of hypochlorous acid with certain α,β-unsaturated acids in a two phase system^1,2 affords α-chloro-β-lactones^3,4 in poor to fair yield. Thus, β-lactones 4, 5, and 6 are obtained from acids 1, 2 and 3, respectively, where the β-carbon of the acid is disubstituted.     

SULFONATION OF 9-ALKYLANTHRACENES

Abstract

The reaction of anthracene, 9-phenylanthracene and some 9-alkylanthracenes with dioxan-SO₃ has been studied. Anthracene yields the 1-, 2- and 9-sulfonic acid in a ratio of 24 : 6 : 70. 9-Phenyl- and 9-neopentyl-anthracene both yield a mixture of the 4- and 10-sulfonic acids in a ratio of 33 : 67 and 15 : 85 respectively. Unexpectedly, 9-methylanthracene yields, in a more rapid reaction, exclusively 9-anthrylmethanesulfonic acid (1, R[dbnd]H) 9-Alkylanthracenes of which the alkyl group contains at least one α-H yield as main product (s) the α-sulfonic acids 1 and/or (depending on the further structure of the alkyl group) the sulfonic acids 2–4.