Furans nitration

An alternative route to 5-nitro-2-furancarboxaldehyde requires nitration of 2-furancarboxaldehyde oxime [1121 -47-7] with mixed acid to give the nitrated oxime [555-15-7] and concomitant hydrolysis (22). Furthermore, 2-furan-carboxaldehyde derivatives with the R-substituent in place have been nitrated to the desired product (23). 

The high reactivity of pyrroles to electrophiles is similar to that of arylamines and is a reflection of the mesomeric release of electrons from nitrogen to ring carbons. Reactions with electrophilic reagents may result in addition rather than substitution. Thus furan reacts with acetyl nitrate to give a 2,5-adduct (33) and in a similar fashion an adduct (34) is obtained from the reaction of ethyl vinyl ether with hydrogen bromide. 

The range of preparatively useful electrophilic substitution reactions is often limited by the acid sensitivity of the substrates. Whereas thiophene can be successfully sulfonated in 95% sulfuric acid at room temperature, such strongly acidic conditions cannot be used for the sulfonation of furan or pyrrole. Attempts to nitrate thiophene, furan or pyrrole under conditions used to nitrate benzene and its derivatives invariably result in failure. In the... 

Thiophene is much more easily nitrated than benzene and it is therefore possible to use mild nitrating agents such as acetyl or benzoyl nitrate. Like pyrrole and furan the principal nitration product is the 2-derivative. The a selectivity decreases with increasing vigour of the reagent and up to 15% of the 3-isomer has been obtained. 

Benzo[b]furan, 2-aryl-2,3-dihydro- H NMR, 4, 570 Benzo[b]furan, 2-bromo-nitration, 4, 604 Benzo[b]furan, 5-cinnamoyl-properties, 4, 708 Benzo[b]furan, 2-cyano-photochemical reactions, 4, 636 Benzo[b]furan, 2,3-dialkyl-synthesis, 4, 710 Benzo[b]furan, 2,3-dihydro-aromaticity... 

Furan, 2,3-dihydro-5-methyl-polymers, 1, 276 Furan, 2,3-dihydro-3-methylene- H NMR, 4, 577 Furan, 2,5-dihydro-2-methylene- H NMR, 4, 577 tautomerism aromaticity and, 4, 595 Furan, 2,5-dihydro-2-nitro-structure, 4, 550 Furan, 2,3-dihydroxy-tautomerism, 4, 37 Furan, 2,4-dihydroxy-tautomerism, 4, 37 Furan, 3,4-dihydroxy-tautomerism, 4, 37 Furan, 2,5-diiodo-nitration, 4, 602 synthesis, 4, 712 Furan, 3,4-diiodo-reactions, 4, 650 Furan, 2,3-dimethoxy-synthesis, 4, 625, 648 Furan, 2,5-dimethoxy-synthesis, 4, 648 Furan, 3,4-dimethoxy-cycloaddition reactions, 4, 64, 625 lithiation, 4, 651 reactions... 

Furan-2-carbonyl chloride, 5-alkyl-3,4-dichloro-synthesis, 4, 690 Furancarboxamides rotational isomerism, 4, 543 Furan-2-carboxylic acid, 5-acetylamino-ethyl ester reactions, 4, 647 Furan-2-carboxylic acid, amino-properties, 4, 708 Furan-2-carboxylic acid, 5-bromo-nitration, 4, 603, 711 Furan-2-carboxylic acid, 3-methyl-methyl ester bromination, 4, 604 Furan-2-carboxylic acid, 5-methyl-nitration, 4, 602... 

Acetyl benzoyl peroxide Furan Inorganic salts of alkyl nitrates... 

Nitration of furfuryl alcohol (2-furylmethanol) in acetic anhydride yields the nitro-nitrate 57 which possesses both a reactive methylene group able to undergo aldol reactions, etc., and also a nitrate ion leaving group for nucleophilic substitutions.137 Detailed studies of the nitration disclose various products resulting from the addition of one or even two acetic acid residues to the furan nucleus in competition with the nitrations.138,139... 

Among heteroaromatic compounds able to react with nitrile oxides as dipo-larophiles, furan, probably, is the best known. Recently, a novel nitrile oxide was generated from a sulfoximine and converted in situ to a cycloadduct with furan (Scheme 1.25) (287). The starting racemic N-methyl-S-nitromethyl-S-phenylsul-foximine 124 was prepared in 87% yield via nitration of N,S-dimethyl-S-phenyl-sulfoximine. Reaction of 124 with p-chlorophenyl isocyanate and a catalytic quantity of triethylamine, in the presence of furan, afforded dihydrofuroisoxazole 125, the product of nitrile oxide cycloaddition, in 42% yield (65 35 diastereomer ratio). The reaction of 125 with phenyllithium and methyllithium afforded compounds 126, which are products formed by replacement of the sulfoximine group by Ph and Me, respectively. 

Allenyl alcohols have been used as starting materials for a different kind of dihydrofuran synthesis. This is a process with great generality and utility in total synthesis. An example of the process is shown in Eq. 13.43 [42]. Treatment of allenyl alcohol 133 with silver nitrate in aqueous acetone at room temperature leads stereospe-cifically to dihydrofuran 134 in excellent yield. A similar reaction occurs with allenyl ketones, leading to furans. The isomerization is known to take place with Rh(I) [43], Ag(I) [44, 45] Pd(II) [46], Au(III) [47, 48] Cu(I) [49] or Hg(II) [50, 51],... 

Changes in intramolecular selectivity in the bromination and nitration of alkyl-benzenes in acidic media have been attributed to changes in medium polarity or changes in electrophile solvation. Mass spectrometric studies of the first stage in the gas-phase reactions of halobenzenes, furan, thiophene and pyrrole with alkyl cations have been rationalized in terms of co-existing a- and tt-complexes. The extent of... 

In order to achieve 2-nitration, acetyl nitrate may be used as the reagent, but unlike pyrrole a semi-stable adduct, 5-acetoxy-2,5-dihydro-2-nitrofuran, is formed as an intermediate product (Scheme 6.22). This eliminates acetic acid when treated with pyridine. Furan also undergoes initial bromination or chlorination (X = Br or Cl) in ethanol at -40 °C, but then addition of two ethoxyl units occurs with the expulsion of halide ion (Scheme 6.23). 

These compounds are less common than indole (benzo[ ]pyrrole). In the case of benzo[i>]furan the aromaticity of the heterocycle is weaker than in indole, and this ring is easily cleaved by reduction or oxidation. Electrophilic reagents tend to react with benzo[Z ]furan at C-2 in preference to C-3 (Scheme 7.21), reflecting the reduced ability of the heteroatom to stabilize the intermediate for 3-substitution. Attack in the heterocycle is often accompanied by substitution in the benzenoid ring. Nitration with nitric acid in acetic acid gives mainly 2-nitrobenzo[Z ]furan, plus the 4-, 6- and 7-isomers. When the reagent is in benzene maintained at 10 °C, both 3- and 2-nitro[ ]furans are formed in the ratio 4 1. Under Vilsmeier reaction conditions (see Section 6.1.2), benzo[Z ]furan gives 2-formylbenzo[6]furan in ca. 40% yield. 

An alternative, but effective, method for preparing furo[2,3-r/ pyrimidines with the potential for polysubstitution in the furan ring is shown in Equation (108). Here -dimethylbarbituric acid 299 is treated with a variety of alkenes in MeCN containing cerium(iv) ammonium nitrate to produce 300 with complete regioselectivity (Equation 108) <2000SC4277>. 

Like 1,3-azoles, due to the presence of a pyridine-like nitrogen atom in the ring, 1,2-azoles are also much less reactive towards electrophilic substitutions than furan, pyrrole or thiophene. However, 1,2-azoles undergo electrophilic substitutions under appropriate reaction conditions, and the main substitution takes place at the C-4 position, for example bromination of 1,2-azoles. Nitration and sulphonation of 1,2-azoles can also be carried out, but only under vigorous reaction conditions. 

NOTE Higher nitrated derivs of Dibenzo-furan were not found in Beil or in CA thru 1961... 

Furan and acetyl nitrate give an addition product which is converted by pyridine into 2-nitrofuran (Scheme 10). The positions in which substituted furans undergo nitration with acetyl nitrate are shown in diagrams (59)-(63) and illustrate the rules of orientation. 

There are examples of ipso attack during the nitration of pyrroles, furans and thiophenes and in the corresponding benzo-fused systems. Reactions resulting in nitro-dealkylation, nitrodeacylation, nitro-decarboxylation and nitro-dehalogenation are to be found in the monograph reactivity chapters of CHEC. Treatment of the 3-azophenylindole (64) with nitric acid in acetic acid at room temperature gives 80% of the 3-nitroindole (65) (81JCS(P2)628). 

---