A New Synthesis of Polysubstituted Cyclopropanes

Polysubstituted cyclopropane derivatives (3a-3h) could be obtained by reaction of activate olefinic compounds (2) with the cyanophosphates (1) aldehydes (benzaldehyde, cinnamaldehyde and croton-aldehyde) in the presence of butyllithium and tetra-methylethylenediamine in tetrahydrofuran via a Michael addition followed by 1,3-elimination.     

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in which the oxygen atom at C-3 of N-acetylmuramoic acid moiety in N-acetylmuramoyl-L-alanyl-D-isoglutamine (MDP) has been replaced by sulfur, was synthesized from allyl 2-acetamido-2-deoxy-β-D-glucopyranoside (1).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 2, 3-dideoxy-4-O-p-methoxybenzyl-L-erythro-hex-2-enono-1, 5-lactone

The synthesis of 2, 3-dideoxy-4-O-p-methoxy-benzyl-L-erythro-hex-2-enono-1, 5-lactone 9 from L-serine, using (1RS, 3S)-3, 4-isopropylidene-1-methoxy-1-phenylthio-butan-2-one 2 as key chiral intermediate, is described. Compound 9 is an interesting chiral precursor for the synthesis of L-sugars.     

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     

Convenient Synthesis of 2-Vinylindoles

A convenient, two-step synthesis of 2-vinylindoles is described from the easily accessible (E)-ethyl-α-allyl-2-nitrocinnamates. Ethylcinnamates (1a and 1b) on reaction with triethylphosphite provide ethyl-2-allylindole-3carboxylates (2a and 2b ) along with minor amounts of their N-ethoxyderivatives (4a and 4b). Alkaline hydrolysis of 2a and 2b provide (E)-2-vinylindoles 3a and 3b in 60 and 67% yield respectively.     

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.     

Dioscorone. Regioselective Oxxmercuration of 2-Azabicyclo[2. 2]oct-5-ene

Oxymercuration of 2-azabicylo[2.2.2]oct-5-ane 1 occurs regioselectively to give a50:50 mixture of 5-syn-and 5-anti-isoquinculidinols 2 which can be converted to dioscorone 5.     

Synthesis of Flavones from the Hypervalent Iodine Oxidation of Flavanones Using [Hydroxy(tosyloxy)iodo]benzene in Methanol

Hypervalent iodine oxidation of several flavanones (1a-1f) using (hydroxy(tosyloxy)iodo] benzene in methanol offers a new method for the synthesis of flavones (2a-2f).     

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.     

Synthesis of 2-Carbamoyl-2-Deoxy Glycosides

Abstract

Recently we have reported the addition of trichloracetyl isocuyanate to glycals 1 _1,2,3. The reaction led to the highly stereoselective formation of a mixture of unstable [2+2] and [4+2] cycloadducts 2 and 3. The isocyanate adds to the glycal moiety anti to the substituent at C-3. The addition of benzylamine to the reac6tion mixture led to N-deprotection of 2 and allowed us to isolate stable bicyclic β-lactams 4 _1-3. We have shown also that 2 (a mixture of α-L-gluco and β-L-manno isomers) obtained from L-rhamnal 1 (R¹[dbnd]Ac, R²[dbnd]CH₃ under high pressure, when treated with methanol, underwent a rapid trans opening of the four-membered ring to give respective glycosides 5(β-L-gluco and α-L-manno isomers). On the other hand 3 (R¹[dbnd]Ac, R²[dbnd]CH₃) under the same conditions added a molecule of methanol to the C[dbnd]N double bond affording 6.     

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.     

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.     

Synthetic Mucin Fragments: Methyl-3-O-(2-Acetamido-2-Deoxy-4-O- and 6-O-β-D-Galactopyranosyl-β-D-Glucopyranosyl)-β-D-Galactopyranoside and Methyl 3-O-(2-Acetamido-2-Deoxy-4-O- and 3-O-Methyl-β-D-Glucopyranosyl-3-D-Galactopyranoside

Abstract

Glycosylation of methyl 3-O-(2-acetamido-3, 6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (2) with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide (1), catalyzed by mercuric cyanide, afforded a trisaccharide derivative, which was not separated, but directly O-deacetylated to give methyl 3-O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-β-D-giucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (8). Hydrogenolysls of the benzyl groups of 8 then furnished the title trisaccharide (9). A similar pflyccsylation of methyl 3-O-(2-acetamido-3-O-acetyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl- β-D-galactopyranoside (obtained by acetylation of 4, followed by hydrolysis of the benzylidene acetal group) with bromide 1 gave a tribenzyl trisaccharide, which, on catalytic hydrogenolysls, furnished the isomeric trisaccharide (12). Methylation of 4 and 2 with methyl iodide-silver oxide in 1:1 dichloro-methane-N, N-dimethylformamide gave the 3-O- and 4-O-monomethyl ethers (13) and (15), respectively. Hydrogenolysis of the benzyl groups of 13 and 15 then provided the title monomethylated disaechartdes (15) and (16), respectively. The structures of trisacchacides 9 and 12, and disaccharides 14 and 16 were all established by ¹³C MMR spectroscopy.     

Synthesis of 2-Aryl-1H-s-Triazolo[1, 5-a] Benzimidazoles

2-Aroylaminobenzimidazoles (2) have been converted into 1(2-benzimidazolyl)-5-aryl-1H-tetrazoles (4) by treatment with PCl₅ followed by azidation with NaN₃ in aqueous acetone solution. Pyrolysis of 4 in diphenylether yielded 2-aryl-1H-s-triazolo [1,5-a] benzimidazoles (6). The product of benzylation of 6a has been characterised. A reasonable pathway for the formation of 6 from 4 has been suggested.     

The Reaction of Diethanolamine with 2-Chloronitrobenzene-A Reinvestigation

In a report on the reaction of 2-chloronitrobenzene (1) with diethanolamine (2), Meltsner et al ¹ claim that the expected S_NAr product, N-(2-nitrophenyl)diethanolamine (3), is not formed; rather that the products are 2,2′-dichloroazobenzene (4), 2-nitrophenol (5), 2-chloroaniline (6) and 4-(2-aminophenyl)morpholine (7). Similar products in which the nitro function is reduced are also reported² for the corresponding reaction with ethanolamine. In this laboratory, in an attempted preparation of 2,2′-dichloroazobenzene (4) for reference purposes in photochemical studies on the antineoplastic agent 5-(3-azido-4-chlorophenyl)-6-ethyl-pyrimidin-2,4-diamine³, the expected S_NAr product (3) was obtained along with other products.     

Synthesis of the Pheromones, (E)-3, 7-Dimethyl-2, 7-Octadienyl Propionate, (E)-3, 7-Dimethyl-2-Octene-1, 8-Diol and Frontalin from a Common Intermediate1

Ketal ester 9 has been prepared in five steps from methyl levulinate 4 (scheme 1). The propionate 1, diol 2 and (±) frontalin 3 were prepared from ester 9 employing the routes shown in scheme 2,3 and 4 respectively. The branched chain alkenes 13 and 20 were prepared conveniently from the primary alcohols 11 and 10 following the procedure of S.Wolff. Triethyl phosphonopropionate 7 has been prepared by methylating triethylphosphonoacetate with methyl iodide in the presence of sodium hydride.     

Synthetic Application of Partially Protected Fructopyranoses

Partial deacetonation of 1-O-benzoyl-2,3:4,5-di-O-isopropylidene-β-D-fructopyranose (2) yielded the related 2,3-O-isopropylidene derivative (3) that was subsequently transformed into the corresponding 1-O-benzoyl-4,5-O-dibutylstannylene-2,3-O-isopropylidene-β-D-fructopyranose (4). Reaction of 4 with benzyl bromide proceeded with high regioselectivity to afford 1-O-benzoyl-5-O-benzyl-2/3-O-isopropylidene-β-D-fruc-topyranose (5) together with a small quantity of the 4-O-benzyl derivative (6). Oxidation of 5 gave the 4-oxo derivative (10) which was reduced to yield a mixture of 5 and its 4-epimer (11). Debenzylation of 11, followed by a debenzoylation reaction produced 2,3-O-isopropylidene-β-O-tagatopyranose (13). Aceto-nation of 13 yielded 1,2:3,4-di-O-isopropylidene-α-D-tagatofuranose (14). Structures and configurations of the above compounds were established on the basis of their analytical and spectroscopic data.     

Synthesis of (3-Ethoxycarbonyl But-3-en-2-yl)phenyl Sulfone and (2-Ethoxycarbonyl But-2-en-1-yl)phenyl Sulfone from Ethyl 2-Bromomethyl But-2-enoate

The synthetic usefullness of “acrylic” tin compounds has been largely demonstrated by BALDWIN and coworkers¹. We wanted to apply this methodology to prepare the peroxide precursors. Thus, we needed to synthesize (2-ethoxycarbonyl prop-2-enyl) phenyl sulfone 1, (2-ethoxycarbonyl but-2-en-1-yl) phenyl sulfone 2 and (3-ethoxycarbonyl but-3-en-2-yl) phenyl sulfone 3. We wish to report the synthesis of such compounds using the advantage of the complexing effect of Polyethyleneoxide 400 (PEO 400) on alkali cations. We also must to report the isomerisation of 2 to 3 in presence of traces of sodium sulfinate which make access to 2 difficult.     

1-Thioglycopyranosyl Esters of N-Acylamino Acids

Abstract

Fully protected 1-thioglycopyranosyl esters of N-acylamino acids (5, 6, and 7) were prepared by condensation of methyl 2, 3, 4-tri-O-acetyl-1-thio-β-d–glucopyranuronate (1), 2, 3, 4-tri-O-acetyl-1-thio-l–arabinopyranose (2), and 2, 3, 4-tri-O-acetyl-1-thio-D-arabinopyranose (3) with pentachlorophenyl esters of N-acylamino acids in the presence of imidazole. The ¹³C NMR chemical shifts of the starting 1-thio sugars and the 1-thiol ester products are reported.     

Reaktionen Mit Trimethylsilylhalogeniden an Derivaten Der Digitoxose

Abstract

Treatment of methyl 3,4-di-O-acyl-2,6-dideoxy-α-D-ribo-hexo-pyranoside 1 or 2 with trimethylsilyl halide leads to the formation of a complex mixture of α-D-ribo-hexopyranosyl halides 3 or 5 together with the educts 1 or 2 as well as their β-anomers 8 or 9. The bromides 3 and 5, suitable for glycosidations, are preferably obtained by reaction of the digitoxose acetate derivatives 6 and 7, respectively, which in turn are prepared from 1 and 2 by mild acetolysis. Further reaction of the halides 3 to 5 with trimethylsilyl halides gives rise to a quantitative formation of the 2,3,6-trideoxy-4-0-acyl-3-halo-α-D -arabino-hexopyranosyl halides 10 to 12. In another reaction sequence starting with the olivose triacetate 20 the formation of 10 via the halide 13 is demonstrated. Structural evidence for the halides 10 to 12 is given by ¹H NMR data as well as by analyses of their glycosides 14 to 19. The results support a mechanistic interpretation for the formation of 10 to 12 via a 3,4-acetoxonium ion as the key intermediate obtained from 3 by an S_Nfi and from 13 and S_N2i step. Final conversion into the terminal halodeoxy compounds 10 to 12 proceeds by and S_N2 reaction with the halide ion.