Thiophenes 2-nitro

Benzo[6]thiophene, 4-N-methylcarbamoyl-biological activity, 4, 913 Benzo[6]thiophene, 2-methyl-3-vinyl-cycloaddition reactions, 4, 795 Benzo[fc]thiophene, 2-( 1 -naphthyl)-synthesis, 4, 915 Benzo[6]thiophene, 2-nitro-reduction, 4, 815 synthesis, 4, 923 Benzo[6]thiophene, 3-nitro-cycloaddition reactions, 4, 789 Benzo[6]thiophene, 4-nitro-synthesis, 4, 923 Benzo[6]thiophene, 5-nitro-synthesis, 4, 923... 

Thiophene, 3-methyl-4-phenyl-phototranspositions, 4, 743 Thiophene, 2-(methylthio)-3,4-disubstituted synthesis, 4, 876, 931 Thiophene, nitro-... 

The effect of substituents on the reactivity of heterocyclic nuclei is broadly similar to that on benzene. Thus mem-directing groups such as methoxycarbonyl and nitro are deactivating. The effects of strongly activating groups such as amino and hydroxy are difficult to assess since simple amino compounds are unstable and hydroxy compounds exist in an alternative tautomeric form. Comparison of the rates of formylation and trifiuoroacetylation of the parent heterocycle and its 2-methyl derivative indicate the following order of sensitivity to substituent effects furan > tellurophene > selenophene = thiophene... 

Nitration of benzo[6]thiophene (HNOs/AcOH) yields mainly the 3-nitro derivative. Under these conditions the /3 to a ratio of substitution is approximately 5 1, which is... 

Mercury(II) acetate tends to mercurate all the free nuclear positions in pyrrole, furan and thiophene to give derivatives of type (74). The acetoxymercuration of thiophene has been estimated to proceed ca. 10 times faster than that of benzene. Mercuration of rings with deactivating substituents such as ethoxycarbonyl and nitro is still possible with this reagent, as shown by the formation of compounds (75) and (76). Mercury(II) chloride is a milder mercurating agent, as illustrated by the chloromercuration of thiophene to give either the 2- or 2,5-disubstituted product (Scheme 25). 

The validity of the Hammett relationship log K/Ko = pa- has been extensively investigated for five-membered heteroaromatic compounds and their benzo analogues. The ratio Pheterocycie/Pbenzene is closest to Unity for thiophene. Judged from work on the polarographic reduction of nitro compounds, the ability to transmit electronic effects is HC=CH = S < O < NH. 

Nitration of 4-(2-thienyl)- (301) and 4-(3-thienyl)-pyrazoles (302) mainly occurs on the thiophene ring, but when acetyl nitrate is used as the nitration agent small quantities of products nitrated on the pyrazole ring are isolated (position of the nitro group uncertain) (80CS( 15)102). Pyrazol-l -ylpyridines (303) undergo electrophilic reactions (bromination, chlorination and nitration) preferentially in the pyrazole ring. Thus, the nitration of (303 R = R = = H) either with a mixture of nitric acid and sulfuric acid at 10-15 °C or with... 

Thiophene, 3-acetamido-5-methyl-JV-di(2-hydroxyethyl)aniline-4,2 -azo-5 -acetyl-3 -nitro-... 

Benzo[6]thiophene, 3-acetamido-2-nitro-reactions, 4, 818-819 Benzo[6]thiophene, 3-acetoxy-... 

Benzo[b]thiophene-2-carboxylic acid, 5-nitro-synthesis, 4, 923... 

Ethylene, /3-(dimethylamino)-nitro-in pyrrole synthesis, 4, 334 Ethylene, dithienyl-in photochromic processes, 1, 387 Ethylene, furyl-2-nitro-dipole moments, 4, 555 Ethylene, l-(3-indolyl)-2-(pyridyl)-photocyclization, 4, 285 Ethylene, l-(2-methyl-3-indolyl)-l,2-diphenyl-synthesis, 4, 232 Ethylene, (phenylthio)-photocyclization thiophenes from, 4, 880 Ethylene carbonate C NMR, 6, 754 microwave spectroscopy, 6, 751 photochemical chlorination, 6, 769 synthesis, 6, 780 Ethylene oxide as pharmaceutical, 1, 157 thiophene synthesis from, 4, 899 Ethylene sulfate — see 2,2-dioxide under 1,3,2-Dioxathiolane... 

Thiophene, 2-amino-3-cyano-5-phenyl-synthesis, 4, 888-889 Thiophene, 3-amino-4,5-dihydro-cycloaddition reactions, 4, 848 Thiophene, 2-amino-3-ethoxycarbonyl-ring opening, 4, 73 Thiophene, 2-amino-5-methyl-synthesis, 4, 73 Thiophene, 2-anilino-synthesis, 4, 923-924 Thiophene, aryl-synthesis, 4, 836, 914-916 Thiophene, 2-(arylamino)-3-nitro-synthesis, 4, 892 Thiophene, azido-nitrenes, 4, 818-820 reactions, 4, 818-820 thermal fragmentation, 4, 819-820 Thiophene, 3-azido-4-formyl-reactions... 

Thiophene, 2-methyl-5-(mesitylsulfonyl)-Truce-Smiles rearrangement, 4, 825 Thiophene, 2-methyl-3-nitro-acidity, 4, 799... 

Thiophene, 3-nitro-4-(phenylsulfonyl)-cine substitution, 4, 817, 825 Thiophene, oxo-synthesis, 4, 125... 

Finally, certain 3-substituted compounds can be prepared by utilizing the - meta) directing powet (cf. Section IV,B) of some groups in the 2-position which afterward can be removed. 3-Nitrothiophene is prepared by nitration of 2-thiophenesulfonyl chloride and by removal of the sulfonic acid group of the 4-nitro-2-sulfonyl chloride formed with superheated steam. Another approach to 3-nitrothio-phene is to nitrate 2-cyanothiophene, separate the 4-nitro-2-cyano-thiophene from the 5-isomer, hydrolyze, and decarboxylate. A final method of preparation of 3-nitrothiophene is by simultaneous de-bromination and decarboxylation of 5-bromo-4-nitro-2-thiophene-carboxylic acid obtained through the nitration of methyl 5-bromo-2-thiophenecarboxylate. 

From resonance structure (12) it is obvious that a —I—M-substit-uent strongly deactivates the 2-position toward electrophilic substitution, and one would thus expect that monosubstitution occurs exclusively in the 5-position. This has also been found to be the case in the chlorination, bromination, and nitration of 3-thiophenecarboxylic acid. Upon chlorination and bromination a second halogen could be introduced in the 2-position, although further nitration of 5-nitro-3-thiopheneearboxylic acid could not be achieved. Similarly, 3-thiophene aldehyde has been nitrated to 5-nitro-3-thiophene aldehyde, and it is further claimed that 5-bromo-3-thiopheneboronic acid is obtained upon bromination of 3-thiopheneboronic acid. ... 

The position of substitution in disubstituted thiophenes can, in most cases, easily be deduced from the directing effect of each substituent. Thus with a - -M-substituent in the 2-position and a —M-substituent in the 5-position, both substituents direct the entering group to the 3-position as is exemplified by the nitration of methyl 2-bromo-5-thiophenecarboxylate to methyl 2-bromo-3-nitro-5-thio-phenecarboxylate (109) or in the chlororaethylation of methyl 2-methyl-5-thiophenecarboxylate to methyl 2-methyl-3-chloromethyl-5-thiophenecarboxylate (110). °... 

Radicaloid substitution has not been extensively studied in the thiophene series. Molecular orbital calculations indicate that substitution should occur in the a-position. This has been found to be the case in the Gomberg-Bachmann coupling of diazohydroxides with thiophenes which has been used for the preparation of 2-(o-nitro-phenyl) thiophene, 2-(p-toluyl) thiophene, " " and 2-(p-chloro-phenyl)thiophene. " Coupling in the /8-position has been used for the preparation of 1,3-dimethyl-4,5-benzisothionaphthene (148) from 2-amino-tt-(2,5-dimethyl-3-thienyl)cinnamic acid (149). A recent investigation describes the homolytic phenylation of 2- and 3-phenyl-... 

Nucleophilic substitution has been used for the preparation of many thiophenes. For instance, 2-phenylthio-3,4-dinitro-5-piperidino-thiophene (155) has been prepared " through stepwise reaction of (150) with different nucleophiles. Nitrothienols and derivatives of them have been obtained from halogenated nitrothiophenes. " Allyl ethers have been prepared by the reaction of 5-chJoro-4-nitro-2-acetylthiophene, 3-nitro-2-chlorothiophene, and 2-nitro-3-bromothio-... 

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