Unsubstituted 5-positions

The soda/AQ hardwood lignin is constituted of both guaiacyl (2) and syringylpropanoid (3) units, of which the former have been condensed extensively during pulping (17). This is indicated by the low number of unsubstituted 5-positions (Table II). 

Oxidation of 3-methoxy- or 3-phenoxy-1,2,4-triazines (228) with perbenzoic acid converted them into the appropriate 1-oxides (229) (71JOC787). Peracid treatment of 1,2,4-triazin-3-ones with an unsubstituted 5-position (84 R5 = H) gave l,2,4-triazine-3,5-diones (182) (69JHC403), while 5-substituted l,2,4-triazin-3-ones (84) afforded the appropriate 1-oxides (230) (66JOC3914). 3-Amino-l,2,4-triazines with an unsubstituted (86a) or a monosubstituted amino group (86b) were oxidized by peracids to give the 2-oxides (231), while the 3-dialkylamino compounds (86c) afforded the 1-oxides (232) (77JOC546). 

Of particular interest is the observation that in certain cases products such as 24 resulting from domino processes are obtained After the formation of the furan, evidently a double Michael-type addition of these intermediates to the remaining starting material 23 can take place at the unsubstituted 5-position. Preliminary experiments to investigate scope and limitations of such addition reactions in the presence of gold salts also confirm the applicability to the functionalization of other electron-rich arenes (Scheme 6) Besides furans, azulene 28 and di- and trialkoxybenzene are suitable as nucleophiles for the reaction with unsaturated carbonyl compounds [14]. For instance, 2-methylfuran (25) reacts at the reactive 5-position with methyl vinyl ketone 26 to give the addition product 27, and with azulene 28 a twofold... 

Bulka et al.,22 during the attempted preparation of selenazole formazans, found that the hydrazones of the selenazoles with unsubstituted 5-positions reacted with diazonium salts to give 5-azo derivatives preferentially. Thus coupling 2-benzylidenehydrazino-4-phenyl-selenazole with diazotized o-phenetidine afforded two compounds that could be separated chromatographically on aluminum oxide. The main product (67%) was 2-benzylidenehydrazino-4-phenyl-5-(o-ethoxybenzeneazo) selenazole (7), which formed ruby red prisms with a green surface sheen, mp 206°C.29 The desired formazan formed the minor product (see Section II,B,6). 

The addition of enolate anions to 1,2,4-triazines with an unsubstituted 5-position followed by oxidation with oxygen is also known, e.g. formation of I.160... 

Triazine 4-oxides react with l-ethoxy-7V,7V-dimethylalk-l-enylamines (ketene 0,N-acetals) in two different ways. 1,2,4-Triazine 4-oxides with an unsubstituted 5-position and without a methyl group in the 6-position react with the ketene 0, TV-acetals by 1,3-dipolar cycloaddition to yield isoxazolo[2,3-ci]-l,2,4-triazines as nonisolable intermediates. 5-Methyl-... 

There are several routes to a,c-biladienes. One was mentioned at the start of this section of porphyrin synthesis, i.e. condensation of two dipyrromethenes (one of which has an unsubstituted 5-position). Another route, to symmetrically substituted a,c-biladienes in particular, is by condensation of dipyrrylmethane-5,5 -dicarboxylic acids with two moles of a 2-formyl-5-pyrrole. This method can be used to construct the most unsymmetric porphyrins, e.g. isocoproporphyrin. ... 

Another pharmaceutically important fused-imidazole ring system is the popular sleeping aid medication zolpidem. Bromination of 4-methylacetophenone and condensation with methylated 2-amino pyridine provides the fused-imidazole in good overall yield. Note that the ring nitrogen on the aminopyridine reaction reacts with the bromide carbon. Mannich-type alkylation at the unsubstituted 5-position provides the dimethylaminomethyl substituent in good yield. Further elaboration yields zolpidem. ... 

Synthesis All by standard steps. Though the Michael addition on A could in the ciy occur at either double bond, the unsubstituted position out of the ring is much more reactive than the disubstituted position in the ring and only the wanted reaction occurs. Bull. Soc. Chim. France. 1955, 8. 

Free-radical reactivity of thiazole has been calculated by semiempirical methods, and results free valence and localization energy) have been compared with experimental data. For mono- and dimethylthiazoles the radical localization energy of the unsubstituted position may be correlated with the logarithm of experimental reactivity (180, 200). The value of the slope shows that a Wheland-type complex is involved in the transition state. 

Sodium borohydride and 3-isoxazolium salts with a 3-unsubstituted position also give isoxazolines, as do the 3-substituted 5-unsubstituted derivatives. With the latter group, further reduction occurs to the isoxazolidines (74CPB70). 

This type of addition process is particularly likely to be observed when the electrophile attacks a position that is already substituted, since facile rearomatization by deprotonation is then blocked. Reaction at a substituted position is called ipso attack. Addition products have also been isolated, however, when initial electrophilic attack has occurred at an unsubstituted position. The extent of addition in competition with substitution tends to increase on going to naphthalene and the larger polycyclic aromatic ring systems. ... 

Unsubstituted positions inpolyfluonnated aromatics are nitrated under vigorous conditions 1,3 5-Tnfluorobenzene reacts with oleum and a metal nitrate at elevated temperature to provide l,3,5-trifluoro-2,4,6 tnnitrobenzene [11] (equation 12)... 

In general, electron donating substituents tend to direct the cyclization to the substituted position instead of the unsubstituted position, especially when there is no steric hindrance to cyclization arising from the ketone portion of the hydrazone. In contrast, when an electron withdrawing group such as CF3 or Cl is present in the orthoposition, indolization is then favored at the unsubstituted position (58). ... 

Reaction of the potassium salt of salicylaldehyde with chlo-roacetone affords first the corresponding phenolic ether aldol cyclization of the aldehyde with the ketonic side chain affords the benzofuran (1). Reduction of the carbonyl group by means of the Wolf-Kischner reaction affords 2-ethyl-benzofuran. Friedel-Crafts acylation with anisoyl chloride proceeds on the remaining unsubstituted position on the furan ring (2). The methyl ether is then cleaved by means of pyridine hydrochloride (3). lodina-tion of the phenol is accomplished by means of an alkaline solution of iodine and potassium iodide. There is thus obtained benziodarone (4)... 

In summary, in order to reduce the content of toluene in gasoline while keeping a high octane number, toluene must undergo hydrogenation and ring contraction followed by SRO. The RC step can proceed via bifunctional catalysts and the SRO must use a metal catalyst (e.g. Ir/Si02) that is selective towards the dicarbene mechanism to cleave C-C bonds at unsubstituted positions. 

The acylation of asymmetrical ketones takes place mainly at the more unsubstituted position. 

Sulfite is an extremely good nucleophile for activated aromatic systems and reaction with l-substituted-2,4,6-trinitrobenzenes (1) may result in cr-adduct formation or in displacement of the 1-substiment as shown in Scheme 1. When X = OEt or SEt, adducts (2) and (3) formed by reaction at unsubstituted positions are long-lived. 

Nucleophilic attack at carbon in pteridines can be expected at any of the unsubstituted positions because all are activated by adjacent nitrogen atoms. Such reactions are of limited synthetic use unless a leaving group is present (see Section 10.18.7.2). 

The acid condensation reaction of the aromatic and phenolic units is a typical reaction of lignin. The presence of acids results in resonance stabilized carbonium ion structures formed in the lignin macromolecule. These car-bonium ion structures react further, e.g., with unsubstituted positions in the lignin macromolecule. Thus, thermal treatment of powdered wood in acidic conditions causes condensation, the coniferyl aldehyde and coniferyl alcohol groups being especially reactive. In addition, other inter- and/or intramolecular condensations may occur. 

Trimethylsilyl groups in these compounds are cleaved with hydrochloric acid giving the first cobalt-cyclobutadiene complexes with unsubstituted positions in the four-membered ring. The protecting role of SiMe3 groups (see also Section III, A) is important here, since phenylacetylene does not give cyclobutadiene complexes under similar conditions, but trimerizes instead. 

The second situation in which ipso attack is favoured is when the addition at the ipso position affords a cr-complex intermediate of considerably greater stability than those arising from the addition at the unsubstituted positions. This can happen with electroneutral radicals also. An example is the reaction of the dinitrothiophene (236) with methyl radicals. Here the intermediate (237) is the most stable radical which can be formed from (236) this therefore leads to the ipso substituted product (238) in 35% yield. 

Explain why ethyl formate condenses with 2-methylcyclohexanone in the presence of base at the unsubstituted position ... 

Carbon nucleophiles of type (iii) add to the arene ligand and do not rearrange examples include the very reactive anions, such as 2-lithio-2-methyl-l,3-dithiane, and the less sterically encumbered anions, such as lithio acetonitrile and /-butyl lithioacetate. In these cases, the anion adds to an unsubstituted position (mainly ortho or meta to Cl, as in 22) and does not rearrange. Then iodine quenching, even after a long period at 25 °C, gives almost exclusively the products from formal substitution for hydrogen, as from (22) in Scheme 8. 

Analysis of published data on the kinetics of halogenation of toluene and polymethylbenzenes led Condon (1948) to the conclusion that if there are a number of substituents in the benzene ring, then each of them has an independent effect on the reactivity of the unsubstituted positions in the ring. 

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