Indole, sodium salt, preparation

Indole, sodium salt, preparation of, 54, 60 Indole, 1-benzyl, 54, 50, 58 Indoles, iV-alkyl-, 54, 58, 60 Iodides, from alcohols, methyl iodide, and triphenyl phosphite, 51, 47 ... 

Derivatives of the related pyrrolo[l,2-a]indole system 137 were prepared either from A -acyl Pro or from the sodium salt of L-Pro and 1,3-cyclohex-anediones (73JOC3487 75JOC1260). 

A second, more versatile, method involves the O-acyl thiohydroxamates. These compounds are generally prepared by reaction of acyl chlorides with the commercial sodium salt (1) of 2-mercapto-pyridine A(-oxide (equation 6 X = Cl). Use of mixed anhydrides formed by reaction of the carboxylic acid with isobutyl chloroformate (equation 6 X = OCC>2CH2CHMe2) renders the procedure compatible with unprotected indoles, phenols, secondary and, presumably, tertiary alcohols. An alternative mode of preparation of the 0-acyl thlohydroxamates involves the s t (2) in reaction with the carboxylic acid (equation 7). 

Reactions with electrophilic reagents take place with substitution at C-3 or by addition at the pyridine nitrogen. All the aza-indoles are much more stable to acid than indole (cf. 20.1.1.9), no doubt due to the diversion of protonation onto the pyridine nitrogen, but the reactivity towards other electrophiles at C-3 is only slightly lower than that of indoles. Bromination and nitration occur cleanly in all four parent systems and are more controllable than in the case of indole. Maniuch and Vilsmeier reactions can be carried out in some cases, but when the latter fails, 3-aldehydes can be prepared by reaction with hexamine, possibly via the anion of the azaindole. Alkylation under neutral conditions results in quatemisation on the pyridine nitrogen and reaction with sodium salts allows A-1-alkylation. Acylation under mild conditions also occurs at N-1. The scheme below summarises these reactions for the most widely studied system - 7-azaindole. Acylation at C-3 in all four systems can be carried out at room temperature in the presence of excess aluminium chloride. ... 

Indole-1-carboxylic acid can be converted by treatment with a carbodiimide to the anhydride (413), which can undergo reaction with amines or the sodium salts of phenols, thiophenols, pyrroles, and indoles. For example, it reacts with the sodium salt of pyrrole-2-carbaldehyde to give the product (414) (Scheme 143) <87JOC3934>. V-Chloroformylcarbazole (415), prepared by the reaction of carbazole with phosgene, has been used effectively for the fluorogenic labeling of amino acids (Equation (118)) <90TL1455>. 

A new, water soluble palladium catalyst was used in the Sonogashira reaction (Pd(OAc)2 triphenylphosphine-trisulfonate sodium salt) [131], and several groups adapted the Sonogashira coupling and subsequent cyclization to the solid-phase synthesis of indoles. Bedeschi and coworkers used this method to prepare a series of 2-substituted-5-indolecarboxylic acids [132], CoUini and Ellingboe extended the technique to l,2,3-trisubstituted-6-indolecarboxylic acids [133]. Zhang and... 

A series of papers have been published by Lounasmaa et al. (122-128) on the synthesis of different alkaloid-like indolo[2,3-a]quinolizidine derivatives by means of reduction and subsequent cyclization of A-[2-(indol-3-yl)ethyl]piridi-nium salts, developed as a general method for indole alkaloid synthesis by Wenkert and co-workers (129, 130). Aimed at the total synthesis of vallesiachotamine (9), valuable model studies were reported (131-133). Reduction of pyridinium salts 183 and 184 with sodium dithionite and subsequent acid-induced cyclization represents a convenient method for preparing val-lesiachotamine-type derivatives 185 and 186, respectively. 

A solution of LAH (1.0 M in ether, 36.5 mL, 36.5 mmol) was cooled to 0 °C, and a solution of the cyanoethyl indole (2.78 g, 16.3 mmol) was added slowly. Then, the solution was heated at reflux for 3 h. It was cooled to 0 °C and quenched by dropwise addition of water (20 mL) followed by 1 N sodium hydroxide (40 mL). The phases were separated, and the aqueous phase was extracted with ether. The combined organic phases were washed with brine and then dried (potassium hydroxide). Evaporation of the solvent gave 2.6 g (92%) of homotryptamine as a yellow oil, which solidified on standing. The hydrochloride was prepared by dissolving the amine in a minimum of ethanol and then a saturated solution of hydrogen chloride in ether was added until no additional salt formation was observed. The hydrochloride was recrystallized from ethanol. 

R Cl) and the hydroxyindolinones (147 R H) and (147 R Cl). The phenylazoindole (148) forms the ipso-substitution product (149) on nitration similarly, 3-hydroxymethyl-l-methyl-2-phenylindole (150) affords the azocompound (148) on treatment with benzenediazonium salts.The 3H-indole (151), prepared by the action of <>-nitropheny1sulpheny1 chloride on 2,3-dimethylindole, rearranges to the indole (152) at 95 °C. Carbon monoxide reacts with IJ-acyl-indoles in the presence of palladium(II) acetate and sodium peroxydisulphate, Na2S2°8 to N- Undole-3-carboxylie acids.The iminoindoline (153)... 

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