Indole acetic simple

From the cinnamic acids or phenyl propanoids described above, / -oxidation and truncation of side chains yields a variety of benzoic or simple phenolic acids [28], Rao et al., [22] identified gallic acid (18), gentisic acid (19), protocatechuic acid (20), />-hydroxybenzoic acid (21), oc-resorcyclic acid (22), vanillic acid (23) and salicylic acid (24) in C. arietinum and showed that overall, leaf content of all phenolic compounds was much greater than in roots and stem. They postulated that the production of these compounds may enhance the activity of indole acetic acid oxidase or may express antimicrobial properties when leached into the soil. However, Singh et al. [24] showed that the production of both 18 and 24 by C. arietinum was induced when treated by the culture filtrate of Sclerotium rolfsii along with the phenyl propanoids 14, 15 and 17 mentioned above. 

Several derivatives of indolo[3,2-fi]carbazole, such as the system 185, have been claimed to arise from the reaction of suitably substituted simple indoles on treatment with thallium triacetate in acetic acid. A compound having the purported structure of 185 was thus isolated when 2,3-dimethylindole was used as the substrate [78UC(B)422]. Many years later, it was demonstrated that this product is in fact a derivative of indolo[2,3-c]carbazole (cf. Section VI) (99T12595). 

The next three procedures provide useful synthetic intermediates. A stereospecific synthesis of ETHYL (Z)-3-BROMO-2-PROPENOATE affords an alternative vinyl bromide partner for the coupling chemistry in the preceding procedure. A very simple but elegant illustration of the flash vacuum pyrolysis technique is used to prepare BENZOCYCLOBUTENONE from o-toluoyl chloride. Another member of the functionalized indole family of synthetic intermediates is presented in a four-step procedure for 5-METHOXYINDOLE-2-ACETIC ACID METHYL ESTER. 

As shown in Table 2, reaction of heteroaromatic compounds with alkynoates occurs under very mild conditions [4, 6]. Heteroaromatic compounds such as pyrroles, furans, and indoles readily hydroarylate alkynoates at room temperature in the presence of a catalytic amount of Pd(OAc)2 in acetic acid or CH2C12, usually affording ds-heteroarylalkenes. This reaction provides a synthetic route to hetero-arylalkenes, especially ds-alkenes, from simple heteroaromatic compounds. 

Indoles can be 3-alkylated by allyl alcohols in the presence of lithium perchlorate and acetic acid 101 is an example (Scheme 42). Pyrrole -alkylation can be achieved with simple alkyl halides [1-bromopentadecane, l-(bromomethyl)-, l-(3-chloropropyl)- and l-(3-iodopropyl)benzenes, 2-(2-bromoethyl)- and 2-(3-bromopropyl)naphthalenes] and mesylates [3-phenylpropyl-, l-methyl-3-phenylpropyl-, 2-(2-naphthyl)ethyl- and 3-(2-naphthyl)propyl methanesulfonates] selectively at C(2) and C(5) positions via reaction in various ionic liquids (e.g., Scheme 43) <20050L1231>. 

Peroxidic reagents may dehydrogenate C-8-Na. The example of this involves the conversion of isostrychnic acid (XXXIII) by hydrogen peroxide in formic or acetic acids in the presence of catalytic quantity of cobalt salt or by potassium nitrosodisulfonate, into the lactone bases CLXXIV (R = H and OH) (144, 145). In both cases, the initially formed simple 3-H indole is oxidized further, probably by way of the tautomeric enamine, to the 13-oxy derivative, which then lactonizes. 

We have studied the reaction of similar cyclic -substituted enaminones which yielded indolones when the reaction was carried out in acetic acid and the quinones had lower oxidation potential, thus preventing prior oxidation of the enaminones. Secondary aminomethylene derivatives of cyclopentanone, cyclohexanone and cycloheptanone reacted with the quinones to presumably form intermediate spiro compounds, as a consequence of normal enaminone chemistry. However, this was unexpectedly followed by rearrangement with ring expansion to indolones (equation 158). In this way carba-zoles, cycloheptindoles and cyclooctindoles can be obtained by a simple entry to this class of indoles, although partially in low yields222-224. Due to their bifunction-ality the produced indol-2-ones are versatile synthons for fused heterocycles (e.g. triazepino- and pyrazino-carbazoles) which become easily accessible225,226. 

The indole group of compounds is conveniently divided into the so-called simple indole derivatives and the indole alkaloids, which often have complicated stmctures, and indole dyes. Thus it was demonstrated that not all compounds are completely separated by either the basic eluent, methyl acetate-isopropanol-25% ammonia (45 35 20, v/v), or the acidic eluent, chloroform-96% acetic acid (95 5, v/v). Therefore one combines the effects of both of these eluent systems in the 2-D TLC method in this way, 14 simple indole derivatives and anthranilic acid can be separated. Compounds are separated into groups according to their polarities. ... 

The UV spectrum of roxburghine-D is not the simple summation of two independent indole chromophores since it exhibits additional absorption at 290 nm. Because an unsaturated carbonyl group is known to be present an attempt was made to hydrogenate the double bond or to reduce it by means of zinc and acetic acid but only very low yields of a reduction product could be obtained. The product, however, exhibited a typical indole spectrum and subtraction of the spectrum of this product from that of roxburghine-D gave a chromophore having Ajnax 290 nm (e 25,500) which could be explained only by the presence of... 

Treatment of tabersonine hydrochloride (28) with zinc and copper sulfate at 100° in glacial acetic acid afforded three products (163). One of these, 274 (1% yield), is the result of simple reduction the major indole... 

Non-tryptamines.—The simple indoles in barley and tomato shoots have been identifiedamongst others, 3-formylindole, 5-hydroxytryptamine, and of course indole-3-acetic acid were common to both only barley had 3-aminomethyl- and 3-methylaminomethyl-indoles, gramine, iV -methyltryptamine, and 5-hydroxy-A(,-methyltryptamine. The seeds of Monodora tenuifolia, which are used to flavour food in West Africa, contain 6-(3-methylbuta-l,3-dienyl)indole. 

This reaction presumably proceeds by electrophilic substitution at C3 and dehydration of the resulting carbinol, followed by cycloaddition. The reaction also involves the decarboxylation of an indole-2-acetic acid, which is known to be facile. Similarly, reaction of indole, a carbonyl compound and 7V-phenylmaleimide generates tetrahydrocarbazoles of structure (68). The yields vary from 15-20% for simple aldehydes to 70% and above for cyclic ketones <93JHC8l>. The stereochemistry, which is predominantly all-cw, arises as the result of an endo addition followed by protonation from the less hindered side of the molecule in the step resulting in aromatization (Scheme 145). 

Another indication of the high reactivity of the indole ring toward acylation is its conversion to the 1,3-diacetyl derivative in refluxing acetic anhydride (24 h), and the isolation of 3-acetylindole in 40% yield after hydrolysis of the A-acetyl group [373]. A simple procedure for cyanoacetylation of indole and its 1-, 2-methyl and other derivatives has been reported. The indole is added to a warm (85°C) 10 1 solution of acetic anhydride cyanoacetic acid. The reaction presumably proceeds via the mixed anhydride and the enhanced reactivity of the cyano-substituted group leads to complete selectivity [374]. 

Zhang s interest in addition of heteroatom radicals to aromatic rings was extended recently to indoles [18]. Using ammonium thiocyanate and manganese (111) acetate in acetic acid at room temperature, a simple intermolecular thiocyana-tion of the 3-position of a variety of substituted indoles (24) was realized. The highest yield of 93% was obtained with 7-methylindole. 

Carbonyl ylides, most often in the form of isomunchnones (formed by decomposition of diketo diazo compounds in the presence of rhodium (II) acetate, and subsequent cyclization of the intermediate rhodium carbenoid species) are by far the most studied 1,3-dipolar cycloaddition partners for indole derivatives. These cycloadditions have been employed in elegant examples of complex ring construction en route to a number of polycyclic indole-containing natural products. Preliminary work by Pirrung [54, 55] (Scheme 23) on simple intermolecular cycloadditions was followed shortly by the utilization of intramolecular examples by Padwa, Boger and others. 

Muthusamy and coworkers [67, 68] have examined the regioselectivity (with respect to dipole orientation) of intermolecular cycloadditions of carbonyl ylides with a variety of N-substituted indoles. l-Diazo-3,3-dimethylpentane-2,4-dione (126), upon treatment with rhodium (11) acetate and simple indole derivatives (125), might be expected to give a mixture of regioisomers 127 and 128 however, only hexahydro-2//-carbazol-2-ones 127 were observed in 86-97% (Scheme 31). 

A cross-coupling reaction of an o-iodoaniline and an alkyne is a key step in Merck s synthesis of MK-0462, a 5-HTid receptor agonist and potential antimigraine drug (Scheme 11). As a catalyst, simple palladium(ll) acetate, although in relative high concentrations (2 mol %), is used without any ligand. Under these conditions, 80% of the (partially de-O-protected) substituted indole is formed in DMF at 100... 

Much less commonly found are a few other Fischer-type variations that will be briefly mentioned. The Piloty-Robinson indole synthesis is a simple variation of the Piloty pyrrole synthesis, where the [3,3] sigmatropic event is triggered by acetic anhydride or methyl iodide (Scheme 26) [142,143]. An example is shown in equation 2 [143]. 

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