Books
in black and white
Main menu
Home About us Share a book
Books
Biology Business Chemistry Computers Culture Economics Fiction Games Guide History Management Mathematical Medicine Mental Fitnes Physics Psychology Scince Sport Technics
Ads

Indoles - Sundberg R.J.

Sundberg R.J. Indoles - Academic press, 1996. - 95 p.
ISBN 0-12-676945-1
Download (direct link): indoles1996.djvu
Previous << 1 .. 20 21 22 23 24 25 < 26 > 27 28 29 30 31 32 .. 68 >> Next

17. R. Sarges, H. K. Howard, В. К. Кос and A. Weissman. J. Med. Chem. 32, 437 (1989).
18. Y. Tamura, J. Uenishi, H. Macda, H. Choi and H. Ishibashi, Synthesis 534 (1981).
19. Y. Tamura, J. Uenishi, H. D. Choi, J. Haruta and H. Ishibashi, Chem. Pharm. Bull. 32, 1995 (3984).
20. H. Ishibashi. M. Okada, A. Akiyama, K. Nomura and M. Ikeda. J. Heterocyci Chem. 23 1163
(1986).
Category I/ Cyclizations-The Hemetsberger Synthesis
The main example of a category I; indole synthesis is the Hemetsberger procedure for preparation of indole-2-carboxylate esters from a-azidocinna-mates[l]. The procedure involves condensation of an aromatic aldehyde with an azidoacetate ester, followed by thermolysis of the resulting a-azidocinna-mate. The conditions used for the base-catalysed condensation are critical since the azidoacetate enolate can decompose by elimination of nitrogen. Conditions developed by Moody usually give good yields[2]. This involves slow addition of the aldehyde and 3-5 equiv. of the azide to a cold solution of sodium ethoxide. While the thermolysis might be viewed as a nitrene insertion reaction, it has been demonstrated that azirine intermediates can be isolated at intermediate temperatures[3].
The procedure has been found to be compatible with a variety of carbocyclic substituents. Table 5.1 provides some examples of the reaction.
Procedure
Methyl 2,4,5-trimethoxy-y. -azidocinnamate[ 11 ]
A solution of sodium methoxide (25% w, 115 ml, 532 mmol) in methanol (187 ml) was cooled to — 8°C under nitrogen. A solution of 2,4,5-trimethoxy-benzaldehyde (25 g, 128 mmol) and methyl azidoacetate (59 g, 513 mmol) in a 1:2 mixture of methanol-THF (50 ml + 100ml) was added dropwisc to the sodium methoxide solution with stirring at — 8°C over a period of 45 min. The solution was stirred and kept below 5°C for 2 h. The mixture was then poured onto ice (1 kg) and stirred. The precipitate which resulted was collected by filtration, washed with water and dried over CaCl2 in a vacuum desiccator. The dried precipitate was dissolved in EtOAc (600 ml) and dried over Na2S04.
&
Tf m О СЧ t"- 00 O'.
тэ
о

* * х з х р * * х
35 ЗС 3 3 3
т: ^ q=; идее
чэ
с
о
CJ
о
___4}
и с г>
О) 0) 0)
Ijj ^
С £Г £Г 0J~
2> с с с
S аз аз о
>. О >. О >»>•.>•» X X Н X X X
Э 3 сс «д г» г»
аз- аГ я а jj jj ’>•>’>% X X
»о
л
Н
>-» >•> >« ?*■<
■5 ">»'5 "^•*’5 ■£ ’S
аз л аз л аз аз аз
Ж й S ш S 2 2
аз аз -й cj
!S2«2
О
тз
с
g
aj
Он
03
£
Xt
3
сл
С
О
X
" «5
X —
g С
4,» Л
&о S'

х Я >•* с
о ^х.Е
■>. S' 2 (5 “ е
n о •£ I *s с С л г> —„ ^ £
ео ш 2 wC-eo
4 4 'О 'О f^-
S | .
С u
*3 ^ ’H'CL
s о со с
Л х 1-1
г»
« и & § о S3
^‘•5
Т>чо
5 ^
* v -L
■ill! 41? £
*“| -—« с, N Н >».-С I ДЛ
г» г- +з [-.
СО W fi
ri- гг ri- и-T
о
г»

UJ
| r-i m ^ ir> \о Г--
со о О —
С
СЛ
5 CATEGORY Ii CYCLIZATIONS THE HEMETSBERGER SYNTHESIS
47
Evaporation of the solvent gave the product as bright yellow crystals (27.6 g) in 74% yield.
Methyl 4,6,7-trimethoxyindole-2-carboxylate[ 11]
The cinnamate ester prepared as above (23.2 g, 79 mmol) was added as a solid slowly to refluxing xylene (500 ml) over a period of 3 h at a rate that prevented accumulation of unreacted azidocinnamate in the solution (monitored by gas evolution through a gas bubbler). The solution was refluxed for an additional
2 h after gas evolution ceased. The reaction mixture was cooled and the solvent removed in vacuo. The residue was recrystallized from methanol to give pure product (20.7 g, 99% yield).
References
1. H. Hemetsberger, D. Knittel and H, Weidmann, Monatsh. Chem. 100, 1599 (1969); H. Hemetsberger, D. Knittel and H. Weidmann, Monatsh. Chem. 101, 161 (1970); H. Hemetsberger, D. Knittel and H. Weidmann, Monatsh Chem. 103, 194 (1972).
2. C. J. Moody, J. Chem. Soc., Perkin Trans., /, 1333 (1984).
3. D. Knittel, Synthesis 186 (1985),
4. G. W. Hardy, D. Bull, H. T. Jones, G. Mills and G. Allan, Tetrahedron Lett. 29, 799 (1988).
5. D. М. B. Hickey, A. R. MacKenzie, C. i. Moody and C. W. Rees, J. Chem. Soc., Perkin Trans. /,921 (1987).
6. M. S. Allen, L. K. Hamaker, A. J. La Loggia and J. M. Cook, Synth. Commun. 22, 2077 (1992).
7. P. T. Kim, R. Guilard, P. Dodey and R. Sornay, J. Heterocycl. Chem. 18, 1365 (1981).
8. P. T. Kim, R. Guilard, S. Samreth and R. Sornay, J. Heterocycl. Chem. 18, 1373 (1981).
9. M. D. Ennis, М. E. Baze, M. W. Smith, С. К Lawson, R. B. McCall, R. A Lahti and M. F. Piercey, J. Med. Chem. 35, 3058 (1992).
10. CJ. B. Jones and C. J. Moody, J. Chem. Soc., Perkin Trans. /, 2455 (1989).
11. E V. Sadanandan, S. K. Pillai, М. V. Lakshmikanatham, А. Г). Billimoria, J. S. Culpepper and M. P. Cava, J. Org. Chem. 60, 1K00 (1995).
12. J. K. MacLeod and L. C. Monahan, Aust. ./. Chem. 43, 329 (1990).
Previous << 1 .. 20 21 22 23 24 25 < 26 > 27 28 29 30 31 32 .. 68 >> Next