Indoline ring

The stronger directing effects present in the indoline ring can sometimes be used to advantage to prepare C-substituted indoles. The aniline type of nitrogen present in indoline favours 5,7-substitution. After the substituent is introduced the indoline ring can be aromatized by dehydrogenation (see Section 15.2 for further discussion). A procedure for 7-acylation of indoline... 

Aromatization of indolines is important in completing synthetic sequences in which the directive effects of the indoline ring have been used to achieve selective carbocyclic substitution[l]. Several methods for aromatization have been developed and some of these are illustrated in Table 15.2. A range of reagents is represented. One type of procedure represents use of oxidants which are known to convert amines to imines. Aromatization then provides the indole. Such reagents must not subsequently oxidize the indole. Mereuric acetate (Entry 1) is known to oxidize other types of amines and presumably reacts by an oxidative deprotonation ot- to the complexed nitrogen. 

CEX (ionization potential) = 13.6 eV, Yn = 6.08 eV f°r N atom of indoline ring is used in PPP calculation. The carbon for indoline component is ignored for PPP calculation. Other parameters listed in Ref. 15. Oscillator strength. 

Extension of -conjugation from naphthalene to anthracene and phenanthrene has a small effect on the tmax of the photomerocyanine form. Replacement of the indoline ring with piperidine, benzoxazole, or benzo-thiazole83 has resulted in hypsochromic shift by ca. 10 nm.72... 

The Fischer s bases, 2-alkylidene-l,3,3-trisubstituted indolines, which may be further substituted in the indoline ring, are the most versatile and useful bases for preparing spiropyrans. For convenience, the name Fischer s base will be used hereafter in the general sense indicated above, as well as for the specific compound 2-methylene-l,3,3-trimethylindoline. Substituents in the 1- and 3-positions are methyl unless otherwise specified thus 3-phenylFischer s base denotes the 1,3-dimethyl-3-phenyl compound. 

That all this evidence still did not prove the structure XX was evident from the fact that two further structures were advanced in 1947. A return to structure XX was made when information on the relationship of Nb with the /3-carbon of the indoline ring was derived from the realization... 

The procedure described here offers a general route to 7-substituted indolines.3 The method is based on the directed ortho-lithiation of N-(tert-butoxycarbonyl)aniline derivatives.4 The teri-butoxycarbonyl group seems to be essential for C-7 selective lithiation, since other directing groups so far reported promote C-2 metalation on the Indoline ring.5 The C-7 selective lithiation of 1-(tert-butoxycarbonyl)indoline is in contrast to the C-2 selective lithiation of 1-(tert-butoxycarbonyl)indole.6... 

These cycloadditions can also be extended to pyridazines (87TL6027) and were used to prepare the indoline ring (33) as a part of PDE I and PDE... 

Indapamide is extensively metabolized to at least 15 different metabolites. Only about 52 is excreted as unchanged drug in the urine (25,29). Several workers have suggested that hydroxylation of the indoline ring with conjugation may be a major route of metabolism (25). The glucuronide and sulphate conjugates of indapamide have been detected in the urine of patients (26). 

The efficiency of this hyperconjugation must depend essentially on the geometric configuration of the LEPs of the N(l ) and 0 atoms and the Cspi[O-0 and Cspin,-N(l ) bonds, on the one hand, and on the electronic state ofthe N and 0 atoms, on the other hand. In all of the SPs studied, the spiro center has a sterically strained structure. Because of the rigidity of the tetrahedral structure of the spiro center and the similar conformation of the indoline ring, the Cspiro—O bond makes an angle (t) of 165-171° with the LEP of the N(l) atom (Table 1). 

The crystalline structure of solvated MCI provides a basis for the assumption that replacement of a methyl group by a more bulky group at the N(T) atom in the indoline ring can hinder the solvation of the phenolate oxygen atom. To confirm this assumption, an X-ray diffraction analysis of the pentyl-substituted MC2 (Figure 6) was carried out.37,38 The pentyl substituent at the N(l ) atom is similar to the methyl group in terms of its electronic properties. The MC2 molecules in the crystals are not solvated. MC2 molecules (Figure 6) have an almost planar trans-cis structure, similar to that of MCI. 

Eq. (a) shows the interaction between N-chloroacetyl-N-phenyl-2, 6-dichloroaniline (I) and anhydrous aluminium chloride whereupon the indolin ring closure occurs to yield l-(2, 6-dichlorophenyl)-2-indolinone (II) with the elimination of a mole of HCl. 

Indole forms a dimer and a trimer under various acidic conditions. The dimer is formed by electrophilic attack on indole by the 3-protonated species. The structure of the trimer, first proposed by G. F. Smith [15], was proven by synthesis [16]. Trimer results from acid-catalyzed opening of the indoline ring in the dimer, followed by electrophilic attack on a second indole. The dimerization-trimerization process is evidently reversible in 0.5 M H2SO4. A composition of approximately 1 0.4 0.3 is reached from the indole, the dimer or the trimer [17]. An isomeric trimer 5-C can be... 

Other 3-substituted indoles such as indole-3-acetic acid give 2,2 -dimers [21]. The dimer has trans stereochemistry at the indoline ring, as was determined by X-ray crystallography on a derived lactam [22]. 

Other compounds that give high yields of 2,2 -dimers are the methyl esters of indole-3-acetate, indole-3-butanoate, and the A -acetyl derivative of trypt-amine [23]. For the corresponding tryptophan derivative, the dimerization is stereoselective giving two dimers, each having trans orientation in the indoline ring [24]. 

The intermolecular variant of the above reaction between W-methylphthalimide (74) and a series of W-acylindole derivatives 75a-f was next examined [37, 38]. Compounds 75a and 75d-f produced the corresponding more sterically hindered oxetanes 76a and 76d-f in which the aromatic rings of the isoindolone and indoline moieties overlap (Scheme 19). Interestingly, in the cases of 75b, c, the initially formed oxetanes 76b-d were converted to a variety of products, presumably via the hydrolysis of the oxetanes, followed by ring opening of the indoline ring and subsequent reactions to produce 78-81. 

Investigation into the efforts of introducing a nitrogen hetero atom into the indoline ring to give a 7 aza and a 4,7 diazo SINO revealed a large hypsochromic shift accompanied by an increase in stability. The products were colorless in the bleached state. 

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