A Convenient Synthesis of t-butyl p-Aminobenzoate

A convenient one-pot synthesis of t-butyl p-aminobenzoate is described which involves treatment of p-aminobenzoic acid with thionyl chloride, followed by reaction of the resulting p-sulfinylaminobenzoyl chloride with t-butanol.     

Chlorination of 2-Chloroquinoline-3-carbaldehydes

Reactions of 2-chloroquinoline-3-carbaldehydes (1) with chlorine, thionyl chloride and sulphuryl chloride are investigated. Preparation of 2-chloroquinoline-3-carbonyl chlorides (2) and 2-chloro-3-dichloromethylquinolines (5) as products of these reactions is described.     

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 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.     

The Reaction of Benzoyl Substituted Heterocyclic Ketene Aminals with 4-Nitrobenzhydroximic Acid Chloride

Heterocyclic ketene aminals 1 or 2 reacted with 4-nitrobenzhydroximic acid chloride (3) to give the 3,5-diaryl-4-(2-imidazolinyl)-isoxazoles 4 or 3,5-diaryl-4-(2-tetrahydropyrimidinyl)-isoxazoles 5. The mechanism of their formation were also discussed.     

A Facile Synthesis of 2-Aminonicotinaldehyde

A synthesis of 2-aminonicotinaldehyde (1) which does not require chromatography and is easily scaled up has been developed. Bromination of 2-amino-3-picoline, protected as a phthalimide (4), produced the gem-dibromide (5), which was reacted with Nh₄OH. The imine intermediate (7) was hydrolyzed with acid, producing (1) in a 56% conversion from 4.     

Synthesis of the Four Configurational Isomers of N-Benzoyl-2, 3, 6-Trtdeoxy-3-C-Methyl-3-Amino-L-Hexose from the (2S, 3R)-Diol Obtained from α-Methylcinnamaldehyde by Fermentation with Baker'S Yeast

Abstract

The erythro and threo chiral C₅ methyl ketones (4) and (5), prepared from the (2S, 3R)-methyl diel (1b), were converted into the phenylsulfenimines (6) and (7), which, in turn, on reaction with allyl-magnesiutn bromide, yielded after acid hydrolysis and benzoylation, the diastereoisomeric C₈-N-aminodiol derivatives (9) and (11), with threo stereochemistry relative to positions 4 and 5. Ozonolysis of (9) and (11) yielded the l-arabino and l-xylo 3-O-methyl branched aminodeoxysugar derivatives (13) and (15), respectively. Using diallylzinc as the reagent, the diastereoisomeric erythro products (8) and (10) were obtained. The latter materials gave the l-ribo-and l-lyxo-(lL-vancosamine) derivatives (12) and (14) upon oxonolysis. The ¹H and ¹³C NMR spectra of the four isomeric aminodeoxysugar derivatives (12)—(15) were discussed.     

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.     

The Reaction of Phosphonium Ylids with o-Quinones and Triketones

Abstract

The reaction of 1,2-benzo [a] phenazine-8, 9-dione 1 and/or 1,2,3-indantrione 2, with phosphonium ylides has been studied. When 1 was reacted with two molar amounts of methoxy-(3a) and/or ethoxycarbonylmethylenetriphenylphosphorane (3b), in THF, at the reflux temp, for 3 hrs, dimethyl (4a) and/or diethyl 1,2-dihydrobenzo a furo [3,2-h] phenazine-1,2-dicarboxylate (4b), along with triphenylphosphine oxide and triphenylphosphine were obtained. On the other hand, reaction of equimolar amounts of ylides 3 with the red trione 2 in THF at room temp., afforded colourless crys tals of 2′,4′-dihydroxyspiro [indan-2,3′ (2′H)-indeno [1,2-b] pyran]-1,3,5′(4′H)-trione diacetate (5a) or dipropionate (5b), together with triphenylphosphine oxide. Formation of 6-membered dihydro aromatic ring like 5, is considered as a new reaction of phos phoranes. The structure of the new compounds 4 and 5 was confirmed and the reaction mechanisms are discussed.     

One-Pot Synthesis of Tri-Acetalated Aldohexoses with 1,1-Dialkoxycyclohexane–p-Toluenesulfonic Acid

Abstract

2-Deoxy-d-arabino-hexose (1), 2-acetamido-2-deoxy-d-glucose (2), and 2-deoxy-2-trifluoroacetamido-d-glucose (3) were each treated with 1,1-dimethoxycyclohexane or 1,1-dibenzyloxycyclohexane in 1,4-dioxane in the presence of p-toluenesulfonic acid. The major products were the 1,1-dimethyl or 1,1-dibenzyl acetals (4-9) of 3,4:5,6-di-O-cyclohexylidene-2-deoxy-aldehydo-d-arabino-hexose, and of 2- (acylamino)-3,4:5,6-di-O-cyclohexylidene-2-deoxy-aldehydo-D-glucose. The dibenzyl acetal derivatives were converted, by hydro-genolysis, into the corresponding, acyclic aldehydes (10-12) in good yields.     

Reactions of Cyclic Anhydrides XIV. Facile Syntheses of Fused Heterocycles via Anilic Acids Pyridobenzoxazinones,Isoquinolinobenzoxazinones and Isocoumarinoquinolines

o-Carboxyhomomaleanilic acids (5) and o-carboxyhomophthalanilic acids (6) on treatment with sodium acetate-acetic anhydride furnished pyridobenzoxazinones (8) and isoquinolinobenzoxazinones (9) respectively in quantitative yields. Conversion of o-formylhomophthalanilic acid (7) to isocoumarinoquinoline (11) via 2-axo-3(o-carboxyphenyl)quinoline (10) is also described.     

Reaction Pathways upon Interaction of Allenic Phosphonates with Selenyl Chlorides

Abstract

Studies were performed on the reaction between alkyl- and arylselenyl chlorides with esters of allenic phosphonic acids, variously substituted at their terminal C-atom. With the esters of the C-3 diasubstituted acids the reaction is highly regioselective and only oxaphosphol heterocyclization occurs to 2,5-dihydro-1,2-oxaphosphols 21-e. With the esters of the propadiene phosphonic acid the reaction is regio- and (Z)-stereoselective: only the 2,3-adducts 3a-b are formed, where the (Z)-isomer and the allenic phosphonates 4a-b are prevalent, as a result of 1,3-sigmatropic isomerization of 3a-b. With the esters of the C-3 monosubstituted acids, complex reaction mixtures are formed. From them were isolated: (E)- and (Z)-isomers of 2,5-dihydro-1,2-oxaphosphols 2f-j; (E)-and (Z)-isomers of the 2,3-adducts 3c-h; (E)-and (Z)-isomers of 4c-f; and (E)-and (Z)-isomers of the 1,2-adducts 5a-d. The reaction partially loses its regioselectivity, but the (Z)-stereoselectivity is preserved:     

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.     

An Unusual Aminal Derivative from a Misdirected Gabriel Synthesis

N-(2-Bromoethyl)phthalimide (1) was reacted with sodium imidazolate in DMF to give the novel aminal N-[1-(1H-imidazol-1-yl)ethyl]phthalimide (4a) as well as N-vinylphthalimide (3) and the desired Gabriel intermediate 2. Aminal 4a as well as heterologues 4b - d form directly from reaction of 3 with the appropriate heterocyclic sodium salt.     

Synthesis of Benzopyran Derivatives,XIV: New Procedure for the Preparation of 2,2-Dimethyl-2H-chromenes

2,2-Dimethyl-4-methoxychromans (1–12) have been converted into 2,2-dimethyl-2H-chromenes (13–24) in acidic media.     

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.     

Reactions of Per-O-Acetylated Carbohydrate Triflates With Halide Ions

Abstract

The reactions of bromide, chloride, and iodide ions with 1,3,4, 6-tetra-O-acetyl-2-O-(trifluoromethylsulfonyl) -α-D-glucopyranose (2) and with 1, 3, 4, 6-tetra-O-acetyl-2-O-(trifluoromethylsulfonyl)-β-D-mannopyranose (3) gave good to excellent yields of the corresponding deoxyhalogeno sugars. In contrast, when the gluco triflate 2 and tetra-butylammonium fluoride were heated under reflux in benzene, only 5-(acetoxymethyl)-2-formylfuran (13) was formed. Reaction of the manno triflate 3 under similar conditions produced 1, 3,4, 6-tetra-O-acetyl-2-deoxy-2-fluoro-β-D-gluco-pyranose (17), 1. 3, 4. 6-tetra-O-acetyl-2-deoxy-β-D-erythro-hex-2-eno-pyranose (18), 4,6-di-O-acetyl-1, 5-anhydro-2-deoxy-D-erythro-hex-l-enitol-3-ulose (19), and 1, 2, 3, 4, 6-penta-O-acetyl-β-D-glucopyranose (20). The mechanisms of the reactions of The triflates 2 and 3 with fluoride ion are discussed.     

An Efficient Synthesis of 3,4-Dihydro-4-Imino-2(1H)-Quinazolinones

A new one-pot convenient preparation of 3,4-dihydro-4-imino-2(1H)-quinazolinones (4) is described by the reaction of 2-aminobenzonitriles (1) with chlorosulfonyl isocyanate (2), while the reaction of 1 with chlorocarbonyl isocyanate (6) affords ureidobenzonitriles (7), which on thermal cyclization gives 4.     

Chemical Modification of Kanamycin A. II. Nucleophilic Displacement Reactions of Kanamycin-A-4″-sulfonates

Abstract

Reactions of 2′,3′,4′,2″,6″-penta-O-acetyl-tetra-N-tert-butyloxycarbonyl-kanamycin-A-4″-brosylate (4b) or-4″-triflate (4c) with acetate, thiolacetate, azide, and fluoride, respectively, result in the formation of the corresponding derivatives of 4″-epi-kanamycin A (5a-d). While 4b invariably forms an elimination byproduct (9), the only side—reaction of 4c consists in a neighboring group attack with formation of a 3″-epi-4″-cyclic urethane (7). Removal of the protecting groups yields 4″-epi-(6a), 4″-thio-4″-epi-(6b), 4″-deoxy-4″-fluoro-4″-epi-(6d), 4″-azido-4″-deoxy-4″-epi-(6c), and after hydrogenation of the latter, 4″-amino-4″-deoxy-4″-epi-kanamycin A (6f).

Methyl 2,6-di-O-acetyl-3-amino-3-N-tert-butyloxycarbonyl-3-deoxy-4-O-triflyl-β-D-glucopyranoside (1b) served as a model to anticipate preparation, handling, and reactivity of 4c.