Regioselective Reaction of N1-Benzyl-N2-(4-nitrophenyl)ethanediamide and Acetylenic Esters

The regioselective reaction of N¹-benzyl-N²-(4-nitrophenyl)ethanediamide with dialkyl acetylenedicarboxylates or alkyl propiolates in the presence of triphenylphosphine leads to dialkyl 4-benzylamino-1-(4-nitrophenyl)-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylates or alkyl 4-benzylamino-1-(4-nitrophenyl)-2-oxo-5-pyrrolidinecarboxylates in good yields.     

Nucleosides. Part LI The 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) and 2-(2,4-dinitrophenyl)ethoxycarbonyl (dnpeoc) groups for protection of hydroxy functions in ribonucleosides and 2′ -deoxyribonucleosides

The Common 2′ -deoxypyrimidine and -purine nucleosides, thymidine ( 4 ), O⁴-[2-(4-nitrophenyl)ethyl]-thymidine ( 17 ), 2′-deoxy-N⁴-[2-(4-nitrophenyl)ethoxycarbonyl]cytidine ( 26 ), 2′-deoxy-N⁶-[2-(4-nitrophenyl)-ethoxycarbonyl]adenosine- 39 , and 2′-deoxy-N²-[2-(4-nitrophenyl)(ethoxycarbonyl]-O⁶-[2–4-nitrophenyl)ethyl]-guanosine ( 52 ) were further protected by the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) and the 2-(2,4-dinitrophenyl)ethoxycarbonyl (dnpeoc) group at the OH functions of the sugar moiety to form new partially and fully blocked intermediates for nucleoside and nucleotide syntheses. The corresponding 5′-O-monomethoxytrityl derivatives 5 , 18 , 30 , 40 , and 56 were also used as starting material to synthesize some other intermediates which were not obtained by direct acylations. In the ribonucleoside series, the 5′ -O-monomethoxytrityl derivatives 14 , 36 , 49 , and 63 reacted with 2-(4-nitrophenyl) ethyl chloroformate ( 1 ) to the corresponding 2′,3′-bis-carbonates 15 , 37 , 50 , and 64 which were either detriylated to 16 , 38 , 51 , and 65 , respectively, or converted by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) treatment to the 2′,3′-cyclic carbonates 66 – 69 . The newly synthesized compounds were characterized by elemental analyses and UV and ¹H-NMR spectra.     

Nucleotides,Part LXIII,New 2-(4-Nitrophenyl)ethyl(Npe)- and 2-(4-Nitrophenyl)ethoxycarbonyl(Npeoc)-Protected 2′-Deoxyribonucleosides and Their 3′-Phosphoramidites – Versatile Building Blocks for Oligonucleotide Synthesis

A series of new base-protected and 5′-O-(4-monomethoxytrityl)- or 5′-O-(4,4′-dimethoxytrityl)-substituted 3′-(2-cyanoethyl diisopropylphosphoramidites) and 3′-[2-(4-nitrophenyl)ethyl diisopropylphosphoramidites] 52 – 66 and 67 – 82 , respectively, are prepared as potential building blocks for oligonucleotide synthesis (see Scheme). Thus, 3′,5′-di-O-acyl- and N ²,3′-O,5′-O-triacyl-2′-deoxyguanosines can easily be converted into the corresponding O⁶-alkyl derivatives 6 , 8 , 10 , 12 , 14 , and 16 by a Mitsunobu reaction using the appropriate alcohol. Mild hydrolysis removes the acyl groups from the sugar moiety (→ 9 , 11 , 13 , 15 , and 19 (via 18 ), resp.) which can then be tritylated (→ 38 – 42 ) and phosphitylated (→ 57 – 61 ) in the usual manner. N ²-[2-(4-nitrophenyl)ethoxycarbonyl]-substituted and N ²-[2-(4-nitrophenyl)ethoxycarbonyl]-O⁶-[2-(4-nitrophenyl)ethyl]-substituted 2′-deoxyguanosines 5 and 7 , respectively, are synthesized as new starting materials for tritylation (→ 28 , 35 , and 37 ) and phosphitylation (→ 54 , 56 , 70 , and 78 ). Various O⁴-alkylthymidines (see 20 – 24 ) are also converted to their 5′-O-dimethoxytrityl derivatives (see 43 – 47) and the corresponding phosphoramidites (see 62 – 66 and 79 – 82 ).     

Thermische Reaktionen mit 3-Phenyl-2H-azirinen; 1, 3-dipolare Cycloadditionen und En-Reaktionen

Benzonitrile p-nitrobenzylide ( 5 ) undergoes 1,3-dipolar cyclo-additions in the presence of 3-phenyl-2H-azirines ( 1 ), yielding in benzene at 0° 2-(p-nitrophenyl)-4,5-diphenyl-1,3-diazabicyclo[3.1.0]hex-3-enes ( 7 , scheme 2). Under the basic conditions of the reaction mixture, 7 a and 7 b are partially converted to 2-(p-nitrophenyl)-4,5-diphenyl-1,6-dihydropyrimidines ( 8a, b ) which are dehydrogenated by oxygen to the corresponding pyrimidines 9a and 9b , respectively. 3-Phenyl-2H-azirines ( 1 ) form, on heating at 145° in xylene in the presence of the azalactone 32 (2,4-diphenyl-Δ²-oxazolin-5-one), 4-(aziridin-2′-yl)-2,4-diphenyl-Δ²-oxazolin-5-ones ( 33 , scheme 11). 33 arises from an ene reaction of the enol form of 32 with 1 . Similar ene reactions are observed with the azirines 1 and dimedone ( 37 , scheme 12). Under the ene reaction conditions (xylene, 145°), the non-isolated intermediate primary adducts ( 38a and 38b ) undergo rearrangements of the vinylcyclopane-cyclopentene type to give 6,6-dimethyl-4-oxo-1,3-diphenyl-4, 5, 6, 7-tetrahydroisoindole ( 40 ) and 6, 6-dimethyl-4-oxo-3-phenyl-4, 5, 6, 7-tetrahedroindole ( 42 ), respectively.     

Diastereoselective reaction of (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol with aromatic aldehydes. Synthesis of (1R,2R,4S,5S,8S)-2,8-diaryl-4-(4-nitrophenyl)-1-aza-3,7-dioxabicyclo[3.3.0]octanes

We have synthesized a series of (1R,2R,4S,5S,8S)-2,8-diaryl-4-(4-nitrophenyl)-1-aza-3,7-dioxabicyclo[3.3.0]octanes as a result of reaction of (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol with aromatic aldehydes. The structure of the compounds obtained was established on the basis of ¹H NMR data. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 757–763, May, 2006.     

Regioselective Reaction of <Emphasis Type="Italic">N</Emphasis><Superscript>1</Superscript>-Benzyl-<Emphasis Type="Italic">N</Emphasis><Superscript>2</Superscript>-(4-nitrophenyl)ethanediamide and Acetylenic Esters

Summary. The regioselective reaction of N¹-benzyl-N²-(4-nitrophenyl)ethanediamide with dialkyl acetylenedicarboxylates or alkyl propiolates in the presence of triphenylphosphine leads to dialkyl 4-benzylamino-1-(4-nitrophenyl)-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylates or alkyl 4-benzylamino-1-(4-nitrophenyl)-2-oxo-5-pyrrolidinecarboxylates in good yields.     

The preparation of some 1-(2-furyl)-2-arylethylenes

Some 1-(2-furyl)-2-arylethylenes, where the furan nucleus is substituted in position 5 with a methyl or p-chlorophenyl group and where the aryl group is phenyl, p-nitrophenyl, α-naphthyl or β-naphthyl, have been prepared by the Perkin reaction and subsequent decarboxylation of the acid. The compounds 1-12 were prepared lor of photochemistry and photoelectron spectroscopy studies. Their geometrical configurations has been established by ¹H nmr and ir spectra.     

Synthesis and Stereochemistry of (1S,3S,4S,7R11R)-3-(4-Nitrophenyl)-11-aza-2,6-dioxatricyclo[5,3,1,04,11]undecane

The reaction of (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol with glutaraldehyde has been studied. It has been established on the basis of AM1 and PM3 calculations and ¹H NMR spectra recorded in the presence of the shift reagent Eu(fod)₃ that (1S,3S,4S,7R,11R)-3-(4-nitrophenyl)-11-aza-2,6-dioxatricyclo[5,3,1,0^4,11]undecane is formed as the result of the reaction.     

Synthesis of isomeric 2-oxazolidinones from (1<Emphasis Type="Italic">R</Emphasis>,2<Emphasis Type="Italic">R</Emphasis>)-and (1<Emphasis Type="Italic">S</Emphasis>,2<Emphasis Type="Italic">S</Emphasis>)-2-amino-1-(4-nitrophenyl)-1,3-propanediols

A synthesis is reported for (4R,5R)-and (4S,5S)-4-hydroxymethyl-5-(4-nitrophenyl)oxazolidin-2-ones and (1′R,4R)-and (1′S,4S)-4-[hydroxy(4-nitrophenyl)methyl]oxazolidin-2-ones from (1R,2R)-and (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediols. The effect of the experimental conditions on the formation of these compounds was studied. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1562–1570, October, 2007.     

Reduktion von 1,2-bis[(Z)-(2-nitrophenyl)-NNO-azoxy]benzol: Synthese von Cyclotrisazobenzol ( = (5E,6aZ,11E,12aZ,17E,18aZ)-5,6,11,12,17,18-Hexaazatribenzo[aei][1,3,5,7,9,11]cyclododeca-hexaen)

Reduction of 1,2-Bis[(Z)-(2-nitrophenyl)-NNO-azoxy]benzene¹: Synthesis of Cyclotrisazobenzene ( = (5E,6aZ,11E,12aZ,17E,18aZ)-5,6,11,12,17,18-Hexaazatribenzo[aei][1,3,5,7,9,11]cyclododeca-hexaene) Na₂S reduction of 1,2-bis[(Z)-(2-nitrophenyl)-NNO-azoxy]benzene ( 2 ) yielded 3 deoxygenated products: the (known) red 2,2′-((E,E)-1,2-phenylenbisazo)dianiline ( 3 , 23%), the orange 2-[2-((E)-2-aminophenylazo)phenyl]-2H-benzotriazol ( 4 , 55%) and the colorless 2,2′-(1,2-phenylene)di-2H-benzotriazol ( 5 , 13%). The constitutions of 3 – 5 and of 6 , the N-acetyl derivative of 4 , were deduced from their ¹H-NMR spectra (chemical shifts, couplings, and symmetry properties), and the configurations of 3 , 4 , and 6 at their N,N-double bonds are assumed to be the same as in 2 . Oxidation of 3 with 2 mol-equiv. of Pb(OAc)₄ afforded 5 (47%) and a novel, highly symmetrical macrocycle, called cyclotrisazobenzene ( 7 , 24%). The constitution of 7 as a tribenzo-hexaaza[12]annulene and its (E)-configuration at the N,N-bonds was confirmed by X-ray analysis. The molecular symmetry expressed by the ¹H-, ¹³C- and ¹⁵N-NMR spectra of 7 reveals a rapid torsional motion around the six N,C bonds. This implies that the N,N-double bonds in the cyclic 12π-electron system (or 24π-electron system if the benzene rings are included) of 7 are highly localized.     

Synthese von rac-threo und rac-erythro-α-(2, 2-Dichloracetamido)-β-hydroxy-p-nitrohydrozimtaldehyd

rac-threo-α-(2, 2-Dichloroacetamido)-β-hydroxy-p-nitrohydrocinnamaldehyde (3) and rac-erythro-α-(2, 2-dichloroacetamido)-β-hydroxy-p-nitrohydrocinnamaldehyde (4) were synthesized starting from α-acetamido-p-nitroacetophenone (7) , and their structures were proved b^n? reduction to rac-chloramphenicol (19) and rac-erythro-2-(2, 2-dichloroacetamido)-1-(p-nitrophenyl)^v 1, 3-propanediol (14) respectively. 3 exhibited only low antibacterial activity compared to rac-chloramphenicol (19) .     

Tautomerism of 2-(o-hydroxyphenyl)-azines

The tautomeric properties ofo-hydroxyphenylazines have been investigated by¹⁷O NMR and UV spectroscopy. 2-(o-Hydroxyphenyl)-pyridine and itsp-nitrophenole analog II exist in chloroform or ethanol as a phenol A. In the case of 2-(2-hydroxy-5-nitrophenyl)-quinoline the NH-tautomer is realized, the content of which increases when going to the dinitro-analog IV.

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Die Tautomerie von 2-(o-Hydroxyphenyl)-azinen (Kurze Mitteilung)

Zusammenfassung Es wurden die tautomeren Eigenschaften vono-Hydroxyphenylazinen mittels¹⁷O-NMR und UV-Spektroskopie untersucht. 2-(o-Hydroxyphenyl)-pyridin und seinp-Nitrophenol-Analog II existieren in Chloroform und Ethanol als Phenol A. Das 2-(2-Hydroxy-5-nitrophenyl)-chinolin liegt als NH-Tautomer vor, dessen Anteil im Dinitro-Analog IV noch steigt.

     

2-(Benzo[d]thiazol-2-yl) phenyl-4-nitrophenyl alkyl/aryl substituted phosphoramidates: Synthesis,characterization and antimicrobial activity evaluation

A series of new 2-(benzo[d]thiazol-2-yl) phenyl-4-nitrophenyl alkyl/aryl substituted phosphoramidate derivatives (7a-j) of biological interest are synthesized in two steps via an in situ process without the isolation of the intermediate. 2-(Benzo[d]thiazol-2-yl) phenol (3) was treated with 4-nitrophenyl phosphorodichloridate(4) to obtain the monochloro intermediate, 2-(benzo[d]thiazol-2-yl)phenyl (4-nitrophenyl) phosphorochloridate(5). It was subsequently reacted with various amines, 6(a-j) to afford the desired title products. IR, NMR (¹H, ¹³C and ³¹P), mass spectral and elemental analysis are used to characterize the structures of the newly synthesized compounds. The antibacterial and antifungal activities are determined by the growth of inhibition of bacteria and fungi of the title compounds at two concentrations, 50 and 100 µg/mL, and minimum inhibitory concentrations to the active compounds. The compounds 7e, 7f and 7j exhibited promising inhibition activity against bacterial strains and 7c, 7e and 7i against A. niger and C. albicans and MIC values are in the range of 10.0–15.0 µg/mL.     

Nucleotides. Part L. Aglycone protection by the (2-dansylethoxy)carbonyl (= {2-{[5-(dimethylamino)naphthalen-l-yl]sulfonyl}ethoxy}carbonyl; dnseoc) group a new variation in oligodeoxyribonucleotide synthesis

The (2-dansylethoxy)carbonyl (= {2-{[5-(dimethylamino)naphthalen-l-yl]sulfonyl}ethoxy}carbonyl; dnseoc) group was employed for protection of the amino functions of the aglycone residues. The lactam function of 2′-deoxyguanosine was on the one hand unprotected and on the other hand alkylated at O⁶ of the aglycone with the 2-(4-nitrophenyl)ethyl (npe) and 2-(phenylsulfonyl)ethyl (pse) group, respectively. The syntheses of monomeric building blocks, both phosphoramidites and nucleoside- functionalized supports, are described for the three common 2′-deoxynucleosides (2′-deoxycytidine, 2′-deoxyadenosine, 2′-deoxyguanosine). As kinetic studies with the tritylated nucleosides showed, the dnseoc group is more labile towards DBU cleavage than the corresponding 2-(4-nitrophenyl)ethyl-(npe) and [2-(4-nitrophenyl)ethoxy]carbonyl(npeoc)-protected analogues (see Table 2). These results were confirmed by the very fast deprotection rate of the dnseoc groups at some oligonucleotides.     

Micelle Effects of Functionalized Surfactants, 1-Cetyl-3-(2-hydroxyiminopropyl)imidazolium Halides,in Reactions with p-Nitrophenyl p-Toluenesulfonate,Diethyl p-Nitrophenyl Phosphate,and Ethyl p-Nitrophenyl Ethylphosphonate

1-Cetyl-3-(2-hydroxyiminopropyl)imidazolium chloride and bromide were synthesized for the first time. These compounds are functionalized zwitterionic surfactants which give rise to micelle formation in aqueous solution. Kinetic and thermodynamic analysis of nucleophilic cleavage of p-nitrophenyl p-toluenesulfonate, diethyl p-nitrophenyl phosphate, and ethyl p-nitrophenyl ethylphosphonate in the presence of 1-cetyl-3-(2-hydroxyiminopropyl)imidazolium halide micelles showed that the latter are powerful nucleophilic reagents whose kinetic behavior can be described in terms of a simple pseudophase distribution model. The efficiency of substrate solubilization with zwitterionic surfactant micelles and the reactivity of the oximate fragment in the micelle phase were estimated on a quantitative level. The observed acceleration of S_N2 reactions with the examined p-nitrophenyl esters relative to analogous reactions of zwitterionic 1-methyl-3-(2-hydroxyiminopropyl)imidazolium halides is, respectively, 12800, 550, and 900 times; it is explained mainly by increased concentration of the reactants in micelles.     

Studies on furan derivatives IV. A simple preparation of α-substituted β-(5-nitro-2-furyl)ethynyls from α-substituted β-(5-nitro-2-furyl)vinylamines

α-Substituted β-(5-nitro-2-furyl)ethynyls were conveniently prepared by the deamination of α-substituted β-(5-nitro-2-furyl)vinylamines. Also the application of this reaction toward α,β-bis(p-nitrophenyl)vinylamine was examined and afforded α,β-bis(p-nitrophenyl)ethynyl as the main product.     

Nitro derivatives of <Emphasis Type="Italic">N</Emphasis>-alkylbenzoaza-15-crown-5: synthesis,structures, and complexation with metal and ammonium cations

A number of N-alkylnitrobenzoaza-15-crown-5 with the macrocycle N atom conjugated with the benzene ring were obtained. The structural and complexing properties of these compounds were compared with those of model nitrobenzo- and N-(4-nitrophenyl)aza-15-crown-5 using X-ray diffraction, ¹H NMR spectroscopy, and DFT calculations. The macrocyclic N atom of benzoazacrown ethers are characterized by a considerable contribution of the sp3-hybridized state and a pronounced pyramidal geometry; the crownlike conformation of the macrocycle is preorganized for cation binding, which facilitates complexation. The stability constants of the complexes of crown ethers with the NH₄ ⁺, EtNH₃ ⁺, Na⁺, K⁺, Ca²⁺, and Ba²⁺ ions were determined by 1H NMR titration in MeCN-d₃. The most stable complexes were obtained with alkaline-earth metal cations, which is due to the higher charge density at these cations. The characteristics of the complexing ability of N-alkylnitrobenzoaza-15-crown-5 toward alkaline earth metal cations are comparable with analogous characteristics of nitrobenzo-15-crown-5 and are much better than those of N-(4-nitrophenyl)aza-15-crown-5.     

Heterocycles with a Bridged Nitrogen Atom. 13. An Anomalous Example of the Sulfonating Action of Dimethyl Sulfate During an Attempt at the Methylation of 5-Aminoindolizine. Crystal Structure of Methyl 5-Morpholyl-2-(p-nitrophenyl)indolizine-1-sulfonate

The reaction of 5-morpholino-2-(p-nitrophenyl)indolizine with dimethyl sulfate gives the sulfonation product - methyl 5-morpholyl-2-(p-nitrophenyl)indolizine-1-sulfonate. Its structure was proved by X-ray crystallographic analysis.     

Reaction of N1, N2-diarylamidines with chloranil and 2,3-dichloro-1,4-naphthoquinone

Nucleophilic attack by N² of N¹ N²-diarylformamides 1a-c on C-2 of chloranil (2) and subsequently by N¹ on C-1 of 2 initiates the formation of benzimidazolinones 8a-c. In contrast, when 1b-e is reacted with 2,3-dichloro-1,4-naphthoquinone (9) , both chlorine atoms are successively substituted by the two nitrogen atoms and 2-(arylamino)-3-(N-formylarylamino)-1,4-naphthoquinones 13b-e result, which (probably via their cyclic tautomers 12b-e ) may be cyclodehydrogenated to form N¹,N³-diarylnaphtho[2,3-d] imidazoline-2,4,9-triones (as 14b,c ). On the other hand, N¹,N²diarylacetamidines 15a-d attack 2 and 9 at C-2 with N² but subsequently exert nucleophilic character at the acetamidine α-carbon attacking C-1 of 2 and 9 , respectively, thus forming 1-aryl-2-(arylimino)-3a-hydroxy-2,3,3a,6-tetrahydro-1N-indol-6-ones 18a-d and 3-aryl-2-(arylimino)-9b-hydroxy-2,3,5,9b-tetrahydro-1-H-benz[e]indol-5-ones 19b,c , respectively. The latter may be thermally dehydrated to the fully conjugated 2,5-dihydro-3H-benz[e]indol-5-ones 20b,c. Unambiguous structural assignments for 18b and 20c are made on the basis of X-ray crystal structure analyses.     

Synthesis of 2-(2-methoxyethyl)- and 2-(2-thiomethoxyethyl)-aniline and related compounds

Summary 2-(2-Nitrophenyl)-ethanol (2) was methylated with dimethyl sulfate to give 2-(2-methoxyethyl)-1-nitrobenzene (3a) which then was reduced with hydrazine hydrate in the presence ofRaney nickel to 2-(2-methoxyethyl)-aniline (1a). Compound1a can be transformed into the N-monosilylated derivative4 by lithiation withn-butyllithium and subsequent reaction with chlorotrimethylsilane. Reaction of2 withp-toluenesulfonyl chloride yields 2-(2-nitrophenyl)-ethylp-toluenesulfonate (5), which reacts with sodium thiomethoxide to give 2-(2-nitrophenyl)-ethylp-toluenesulfonate (5), which reacts with sodium thiomethoxide to give 2-(2-thiomethoxyethyl)-1-nitrobenzene (3b).3b was reduced with hydrazine hydrate in the presence ofRaney nickel to yield 2-(2-thiomethoxyethyl)-aniline (1b). Ethyl (2-nitrophenyl)-acetate (6) could be dimethylated with methyl iodide in the presence of potassiumtert-butoxide and 18-crown-6 to give ethyl 2-methyl-2-(2-nitrophenyl)-propionate (7). Reduction of7 with lithium borohydride yields 2,3-dihydro-3,3-dimethyl-1H-indole (9) and 2-[(1-hydroxy-2-methyl)-2-propyl]-aniline (10).

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Synthese von 2-(2-Methoxyethyl)- und 2-(2-Thiomethoxyethyl)-anilin und verwandten Verbindungen

Zusammenfassung 2-(2-Nitrophenyl)-ethanol (2) wurde mit Dimethylsulfat zu 2-(2-Methoxyethyl)-1-nitrobenzol (3a) methyliert, das sich mit Hydrazinhydrat in Gegenwart vonRaney-Nickel zu 2-(2-Methoxyethyl)-anilin (1a) reduzieren läßt. Verbindung1a kann durch Metallierung mitn-Butyllithium und anschließende Reaktion mit Chlortrimethylsilan in dasN-monosilylierte Derivat4 umgewandelt werden. Reaktion von2 mitp-Toluolsulfonylchlorid ergab 2-(2-Nitrophenyl)-ethyl-p-Toluolsulfonat (5), das mit Natriumthiomethanolat zu 1-Nitro-2-(2-thiomethoxyethyl)-benzol (3b) reagiert.3b wurde mit Hydrazinhydrat in Gegenwart vonRaney-Nickel zu 2-(2-Thiomethoxyethyl)-anilin (1b) reduziert. Ethyl-2-(nitrophenyl)-acetat (6) kann mit Methyliodid in Gegenwart von Kalium-tert-butoxid und 18-Krone-6 zu Ethyl-2-methyl-2-(2-nitrophenyl)-propionat (7) dimethyliert werden. Reduktion von7 mit Lithiumborhydrid lieferte 2,3-Dihydro-3,3-dimethyl-1H-indol (9) und 2-[(1-Hydroxy-2-methyl)-2-propyl]-anilin (10).