CHLOROSULFONATION OF N-PHENYLMORPHOLINE,BENZOTHIAZOLE, 2-METHYL BENZOTHIAZOLE AND TRIPHENYLOXAZOLE

Abstract

N-Phenylmorpholine (1) reacted with chlorosulfonic acid to give the p-sulfonyl chloride (2), which was characterized as the sulfonamides (3–5). Benzothiazole (6) was converted into the sulfonyl chloride (7) by sequential treatment with hot chlorosulfonic acid and thionyl chloride. Reaction of (7) with amines afforded the derivatives (8–10); NMR spectral analysis of the dimethylamide (8) indicated that it was a mixture of the 4- and 7-isomers. Chlorosulfonation of 2-methylbenzothiazole (11) was achieved by heating with chlorosulfonic acid with or without thionyl chloride. The chloride (12) was converted into amides (13–19). Study of the NMR spectra indicated that mixtures of the 5- and 6-isomers were formed. 2,4,5-Triphenyloxazole (20) reacted with chlorosulfonic acid to give either the mono-(21), bis (23) or bis-tris sulfonylchlorides (23, 34); these were converted into 14 sulfonamides. 2-(p-Nitrophenyl)-4,5-diphenyloxazole (41) reacted with hot chlorosulfonic acid to give the bis-sulfonyl chloride (42), characterized as the dimethylsulfonamide (43). Attempts to form the pure monosulfonyl chloride and to mono nitrate 2,4,5-triphenyloxazole (20) were unsuccessful.     

Six-Membered Nitrogen Heterocycles from Xylaramide and Ribaramide

Abstract

N,N'-Diacetyl-tri-O-acetylxylaramide (8) and N,N'-diacetyl-tri-O-acetylribaramide (20) were directly converted to the nitrogen heterocycle 6-acetamido-2,6-diacetyloxy-aza-1,4-cyclohexadlen-3-one (9) with sodium acetate in acetic anhydride. Treatment of tri-O-acetylxylaramide (7) or tri-O-acetylribaramide (19) with the same solvent-base combination gave the highly crystalline 2,3,5,6-tetraacetyloxypyridlne (30) as the principal product. Mechanistic considerations for the formation of these nitrogen heterocycles are presented.     

A THEORETICAL TREATMENT OF THE SULFUR-CONTAINING ANALOGS OF CYCLOBUTADIENE,CYCLOOCTATETRAENE, BUTALENE,AND OCTALENE

Abstract

Several coordination complexes of cyclobutadiene (I) have been prepared (e.g., cyclobutadiene iron tricarbonyl [1]) and cyclooctatetraene (II) is a well-known compound (for a potentially planar form of cyclooctatetraene, see [2]). Although butalene [3] (III) has not been synthesized so far, octalene (IV) has been obtained by Vogel and co-workers [4,5]. Recently we have carried out a theoretical study of the physical and chemical properties of butalene (III) and octalene (IV), and of the various annelated butalenes and octalenes [6,7] using the HMO and SCF-MO (PPP) quantum-chemical methods as well as the structure-resonance theory and graph theoretical methods. Numerous theoretical data are available in the literature on cyclobutadiene (I) and cyclooctatetraene (II).     

Two Efficient Methods for Replacement of Sulfur by Oxygen in a Thionolactone

Abstract

Selective methods for conversion of thionoesters or thiono-lactones to the corresponding ordinary esters or lactones through replacement of sulfur by oxygen are generally lacking, apart from the long known reaction using aqueous silver nitrate¹ and related processes with lead¹ or mercury² carboxylates. Our recent preparation of bicyclic thionolactone 1 ³ affords a convenient substrate for examination of possible reagents for this transformation. A particularly useful property of 1 is that tetrahedral intermediates 2 and 3, formed on nucleophilic addition of Nu^? to 1, have a stereoelectronically favored^3,4 pathway for cleavage of the lactone bridge. Such cleavage in 1 is effectively irreversible, since it will be quickly followed by inversion to the stable diequatorial conformer of cis-3-hydroxycyclohexaneacetic acid (4) or an appropriate derivative, depending on the specific nature of Nu^?. This feature makes 1 a sensitive test of methods for replacement of sulfur by oxygen without competing rupture of the lactone ring.     

New and Stereospecific Synthesis of α-Ethylenic Ketones

Abstract

H. Kise et al¹ have shown that the reaction of β-propiolactones 1 with ylides 2 give phosphonium carboxylate betaïne 3. We now report that, carried out under different conditions, reaction of lactones 1 with the same ylides proceeds through pathway (b). Thermolysis of 4 affords α-ethylenic ketones 5. The mecanism of this new extrusion reaction of triphenylphosphine oxyde probably involves the generation of an oxaphosphene as an intermediate.     

P,Se-Heterocycles From the Quasi-Binary System PhP/Se

Abstract

Contrary to statements in the literature the PhP/Se system does contain a compound with a PhP/Se ratio lower than 1. The reaction of pentaphenyl-cyclopentaphosphane and elemental selenium yields depending on the molar ratio the heterocyclic compounds (PhP)₄Se (1), (PhP)₃Se₃ (2), or (PhP)₂Se₄ (3). 1, 2, and 3 are yellow to orange-red crystalline stable compounds. Their molecular structures, as shown by the ³¹P- and ⁷⁷Se-NMR data as well as by the X-ray crystal structure determination of 2, parallel those of the corresponding sulfur derivatives. Nucleophiles add easily to the phosphorus in 3 splitting the P₂Se₂-ring.     

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.     

REACTIONS WITH 3-CHLORO-1,2-BENZISOTHIAZOLIUM CHLORIDES: A NEW SYNTHESIS OF 3-AMINO-BENZO [B] THIOPHENES

Abstract

3-Chloro-1,2-benzisothiazolium chlorides 1 react with activated methylene groups of ketones. Via a ring-opened intermediate 2, 2,3-dihydro-3-imino-benzo [b] thiophenes 3 are obtained, which may be cleaved to the 3-amino-benzo [b] thiophenes 4 and 5.     

The Simple Synthesis of Tetra-Alkyl Sym-Monothiopyrophosphates

Abstract

This poster is a part of our continuing interest in the synthesis and properties of phosphorus acid anhydride analogs, particulary those containing sulfur bridge between two phosphorus atoms (1). Recently we have found that sulfur dichloride reacts with dialkyl trimethylsilyl phosphites 1 to form the tetra-alkyl sym-monothiopyrophosphates 2 in high yield.     

Synthesis of N-[2-S -(2-Acetamido-2,3-dideoxy-D-glucopyranose-3-y1)-2-Thio-D-Lactoyl]-L-alanyl-D-isoglutamine

Abstract

N-[2-S-(2-Acetamido-2,3-dideoxy-D-glucopyranose-3-y1)-2-thio-D-lactoyl]-L-alanyl-D-isoglutamine, in which the oxygen atom at C-3 of N-acetylmuramoic acid moiety in N-acetylmuramoyl-L-alanyl-D-isoglutamine (MDP) has been replaced by sulfur, was synthesized from allyl 2-acetamido-2-deoxy-β-D-glucopyranoside (1).

Treatment with sodium acetate of the 3-O-mesylate, derived from 1 by 4,6-O-isopropylidenation and subsequent mesylation, gave allyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-allopyranoside (4). When treated with potassium thioacetate, the 3-O-mesylate, derived from 4, afforded allyl 2-acetamido-3-S-acetyl-2-deoxy-4,6-0-isopropylidence-β-D-glucopyranoside (6). S-Deacetylation of 6, condensation with 2-L-chloropropanoic acid, and subsequent esterification, gave the 3-s[D-1(methoxycarbonyl)ethyl]-3-thio-glucopyranoside derivative (7). Coupling of the acid, derived from 7, with the methyl ester of L-alanyl-D-isoglutamine, and subsequent hydrolysis, yielded the title compound.     

Synthesis of the Oligosaccharide Moieties of Musettamycin,Marcellomycin and Aclacinomycin A,Antitumor Antibiotics

Abstract

Condensation of benzyl 2,3,6-trideoxy-3-trifluoroacetamido-α-L-lyxo-hexopyranoside (5) with 4-O-acetyl-3-O-benzyl-2,6-dideoxy-α-L-lyxo-hexopyranosyl bromide (10) carried out under Koenigs-Knorr conditions gave 12. Total deprotection of 12 and N-dimethylation at C-3 led to 17 while selective removal of the 4-O-acetyl group led to 13, a synthetic intermediate for preparing 24 and 33. Condensation of 13 with di-O-acetyl-L-fucal (18) or 4-O-acetyl-L-amicetal (25) in the presence of N-iodosuccinimide followed by hydrogenolysis of the C-2-I bond gave 20 and 27 respectively. The trisaccharide 24 then was obtained from 20 by the same sequence of reactions used to convert 12 into 17. After deacetylation and oxidation, this set of reactions also transformed 27 into 33.     

Synthesis of the 3-0, 4-0 and 6-0 Sulfates of Methyl 2-amino-2-deoxy-α-D-Glucopyranoside

Abstract

Starting with methyl 2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (1), the isomeric methyl 2-amino-2-deoxy-α-D-glucopyranoside 3-, 4-, and 6-sulfates have each been prepared by sulfation of suitably blocked intermediates. Tritylation and acetylation of 1 followed by detritylation gave methyl 3,4-di-0-acetyl-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (3), having a free 6-hydroxyl group. Base catalyzed 0–4→0–6 acetyl migration provided the corresponding 3,6 di-O-acetyl derivative (4) posessing a free 4-hydroxyl group. Preparation of methyl 4,6-0-benzylidene-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (9) provided the intermediate bearing a free 3-hydroxyl group. 0-sulfation of 3, 4, and 9 was effected with the pyridine sulfur trioxide complex in dry pyridine.     

1,1-DIANIONS OF ALKYL PHENYL SULPHONES AS SYNTHETIC INTERMEDIATES IN CYCLIZATION REACTIONS

Abstract

α-Sulphonyl carbanions are known to be good nucleophiles both in intermolecular and in intramolecular reactions¹. In the same way gem-dimetalloderivatives of alkyl phenyl sulphones I a,b readily add to aldehydes and ketones to give the (β-hydroxy compounds II in the case of dilithioderivatives Ia, while from dimagnesioderivatives Ib α, β-unsaturated sulphones III are also obtained².     

NOUVELLE SYNTHÈSE DE [1,2-A]BENZIMIDAZOLO-1,3,5,2-TRIAZAPHOSPHORINES ET DE [1,2-A]BENZIMIDAZOLO-1,3,5,2- TRIAZAPHOSPHORINE-2-THIONES

The condensation of N₁-benzimidazolyl amidines 1 with tris(dimethy- lamino)phosphine leads to the corresponding [1,2a]Benzimidazolo-1,3,5,2-triazaphosphorines 3 . The N₂-phosphoroamidine intermediates 2′ are isolated and yielded the corresponding cyclic compounds 4 upon heating. The oxidation by sulfur of the compounds 3 gives the thiooxide derivatives 4 .

The structure of these compounds is unambiguously confirmed by IR, ¹H, ³¹P, and ¹³C NMR spectroscopy and by MS for some products.     

Photochemical Reactions in Carbohydrate Synthesis. Conversion of L-Arabinose Into L-Streptose

Abstract

A synthesis for L-streptose (1) is described. This synthesis differs from those previously reported in several ways, one of which is the use of photochemical reactions in two important steps. These reactions are part of a sequence leading from L-arabinose (2) to 5-deoxy-1,2-O-isopropylidene-β-L-threo-pentofuranos-3-ulose (3). Two other photochemical reactions are considered as a part of the conversion of 3 into L-streptose (1) but neither proved useful. L-Streptose (1) is synthesized from 3 by a sequence of reactions which involves formation of 5-deoxy-l,2-O-isopropylidene-3-C-nitromethyl-β-L-lyxo-furanose (10) and subsequent reaction of 10 with titanium(III) chloride.     

SYNTHÉSE DE THIOÉTHERS D'ACIDES PROPYLBORONIQUES S - BENZYLÉS

The protection of the hydroxy group of p-cresol 1 by o-silylation gives derivatives 2 and 3 , the methyl group of which can be brominated by NBS. The phase transfer catalysis applied to 4 and 5 is a good way which permits the mild introduction of the allylthio group ( 6 and 7 ). Hydroboration applied to silylated compounds 8 and 9 , followed by methanolysis and hydrolysis leads to target acids 10 and 11 in a good yield.

La protection du groupement hydroxy du p-crésol 1 par o-silylation donne les dérivés 2 et 3 ce qui permet de bromer le substituant méthyle par le N-bromosuccinimide (NBS). La catalyse par transfert de phase (CTP) appliquée aux produits 4 et 5 est une bonne méthode pour introduire un groupement allylthio (composés 6 , 7 ). L'hydroboration des composés silylés 8 et 9 , suivie d'une méthanolyse et d'une hydrolyse permet d'accéder aux acides cibles 10 et 11 avec de bons rendements.     

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).     

Directional Specificity in the Boronate Cleavage of Unsaturated 1,3-Diol Derivatives

Recently Miyashita, Yanami, and Yoshikoshi reported an apparent case of peripheral bond cleavage in the fragmentation of the boronate 2 derived from octalin 1 to give aldehyde 4 (Scheme I, Path a).¹ Since previous examples of related fragmentations had been shown to proceed with exclusive cleavage of the more highly substituted carbon-carbon bond² (i.e. 2 → 3) it was of interest to examine the above system in greater detail to determine if the neighboring hydroxyl substituent caused the unexpected bond cleavage or if an alternative pathway (Scheme I, Path b) might be operative in this case.³ To that end, we first examined the behavior of the methyl ether derivative (5) of alcohol 1 which was prepared along the lines described below for ether 15 (Scheme II). However hydroboration of unsaturated ether 5 followed by base treatment led to no identifiable product. Evidently steric factors retard the hydroboration and / or basic cleavage of the intermediate boronate.     

Synthesis of Deoxy and Deoxyhalogeno Analogues of myo-Inositol

Abstract

A number of deoxy and deoxyhalogeno analogues of moyo-inositol of Interest 1n Investigating the biochemical processes of the phosphoinositide pathway were synthesized. Syntheses Include those deoxyinositols (cyclohexane pentols) which correspond to myo-inositol deoxygenated at positions 1, 4 and 5, as well as a set of 5-deoxyhalogeno (F, Cl, Br, I) myo- and epimeric neo-inositols. Configurational assignments are based primarily on ¹H NMR spectroscopy.     

ZUR SYNTHESE UND REAKTIVITÄT METHYLENVERBRÜCKTER DIPHOSPHORYLVERBINDUNGEN

Abstract

An improved high-yield Arbusov-type synthesis for diphosphorylmethanes with different substituents on both phosphorus atoms ( 4 , 5 , 7 ) by the reaction of isopropyl diphenylphosphinite or diisopropyl phenylphosphonite with diisopropyl bromomethylphosphonate ( 1 ) or isopropyl phenyl-bromomethyl-phosphinate ( 2 ), respectively, is described. 1 and 2 are available in yields of about 50% by the reaction of an excess of methylene bromide with triisopropylphosphite or diisopropyl phenylphosphonite, respectively.

The metalation of the symmetrical and unsymmetrical diphosphorylmethanes 3–8 with NaH in toluene yields the corresponding carbanionic salts 3A–8A . Their structure und reactivity are investigated by means of ³¹P NMR spectroscopy and Horner-reactions with benzaldehyde.

Regioselective monomethylation at the central carbon atom of 3–7 is performed using the phase-transfer technique. With exception of the phosphono-phosphinate derivative 14 , on this way the appropriate 1,1-diphosphorylethanes 13 and 15–17 are obtained in high yield.