Chloroindole

Nitroindole (ARf 40—45), 5-chloroindole (jiRf 60 — 65) and indole QiRf 70—75) yielded orange-yellow chromatogram zones on a pale yellow background. If the chromatogram was exposed to ammonia vapor for 15 s the color was intensified. The detection limits were 10 ng substance per chromatogram zone. 

Fig. 1 Reflectance scan of a chromatogram track with 80 ng substance per chromatogram zone 5-nitroindole (1), 5-chloroindole (2) and indole (3).

Jensen JB, H Egsgaard, H van Onckelen, BU Jochknsen (1995) Catabolism of indole-3-acetic acid and 4- and 5-chloroindole-3-acetic acid in Bradyrhizobium japonicum. J Bacterial 111 5762-5766. 

In the following year, this method was also applied to the total synthesis of tjipanazole FI (371) (784). For this synthesis, the required bisindole 1444 was obtained starting from 5-chloroindole (1440) in three steps and 47% overall yield. Acylation of 1440 with oxalyl chloride led to the glyoxylic acid chloride 1441. Transmetalation of indolylmagnesium bromide with zinc chloride, followed by addition of the acid chloride, provided the ot-diketone 1443. Exhaustive reduction of 1443 with lithium aluminum hydride (LiAlFl4) afforded the corresponding bisindolylethane 1444. Executing a similar reaction sequence as shown for the synthesis of tjipanazole F2 (372) (see Scheme 5.243), the chloroindoline (+ )-1445 was transformed to tjipanazole FI (371) in two steps and 50% overall yield (784) (Scheme 5.244). 

Nitroso derivatives (120) are obtained from indoles they exist largely in oximino forms (121) (80IJC(B)767). The N-nitrosation of 5-chloroindole is followed by a migration of the nitroso group from N to C-3, to give an indolenine-3-oxime (122) hydrolysis and recyclization leads to a indazole carbaldehyde (123) (86JA4115). 

The highly substituted indole, ecopladib (82), which shares many structural elements with the phospholipase inhibitor varespladib (37), shows similar biological activity. Alkylation of hydroxy benzoate (72) with the dimethyl acetal from bromoacetaldehyde (73) affords the ether (74). Acid-catalyzed reaction of this intermediate with 2-methyl-5-chloroindole (75) in the presence of triethylsilane leads in effect to condensation of the acetal with the activated 3 position on the indole ring to afford 76. The nature of the reduction of the aldehyde carbon is not immediately apparent. Alkylation of the anion on nitrogen from reaction of the indole with sodium hydride and bromodiphenylmethane then adds the third... 

C9H6CIN02 5-chloroindole-2-carboxylic acid 10517-21-2 25.00 1.3706 2 15968 C9H7CI02 trans-O Chlorocinnamic acid 939-58-2 25.00 1.2772 2... 

This ring is formed by reaction of a 3-amino-5-chloroindole-2-carboxylic acid with DEAD (review of addition to alkynes [2816]) in alkaline solution when the chlorine atom was replaced by other substituents, a mixture of products was obtained. 

Another type of structure which has been examined are [RuCp]" complexes of 5-chloroindoles <88OM660>. These complexes undergo nucleophilic substitution by amine, alkoxide, thiolate and malonate nucleophiles (Scheme 133). 

Indoles bearing chloro groups at different positions could also be synthesized by this method. A -Tosylated 2,4-dichloroaniline and 2,5-dichloroaniUne were successfully converted into the corresponding 5-chloroindoles and 6-chIoroindoles, respectively, in moderate to high yields (Scheme 26). 

Nunthaboot N, Pianwanit S, Parasuk V, Kokpol S, Wolschann P (2007) Theoretical study on the HIV-1 integrase inhibitor l-(5-chloroindol-3-yl)-3-hydroxy-3-(2H-tetrazol-5-yl)-propenone (5CITEP). J Mol Struct 844-845 208-214. doi 10.1016/j.molstruc.2007.06.026... 

---