US3901899A
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Synthesis of indoles from anilines and intermediates therein
Assignee: Ohio State University Research Foundation
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Filing: 1973-04-27
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Granted: 1975-08-26
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Expires: 1993-04-27
Abstract
Abstract Preparing indoles and intermediates therefor by reacting an Nhaloaniline with a Beta -carbonylic hydrocarbon sulfide to form an azasulfonium halide, reacting the azasulfonium halide with a strong base to form a thio-ether indole derivative, and then reducing the thio-ether indole, e.g. with Raney nickel, to form the indole compound. When an acetal or ketal of the Beta carbonyl hydrocarbon sulfide is used, the azasulfonium salt is treated with a base, and then with an acid to form the thio-ether indole derivative. When an Alpha -ethyl- Beta -carbonylic hydrocarbon sulfide is used, the resulting azosulfonium salt reacts with strong base to form a thio-ether indolenine derivative, which on reduction with Raney nickel or complex metal hydrides yields 3-substituted indoles. The aniline may be an aminopyridine to form an aza-indole compound in the process. The azasulfonium salts and thio-ether indole or thio-ether indolenine derivatives can be isolated and recovered from their respective reaction mixtures. The thio-ether-indole and thio-ether indolenine derivatives are useful as intermediates to make the indoles without the thio-ether group. The indoles are known compounds having a wide variety of uses, e.g., in making perfumes, dyes, amino acids, pharmaceuticals, agricultural chemicals and the like.
Inventors
- 👤 Paul G Gassman
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 17:07
CPC Classifications
C; C07; C07D; C07D471/00; C07D471/02; C07D471/04; C07C; C07C323/00; C07D209/00; C07D209/56; C07D209/80; C07D209/82; C07D209/86; C07D209/88
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
28 words
A PROCESS WHICH COMPRISES REACTING IN AN ORGANIC LIQUID SOLVENT, UNDER SUBSTANTIALLY ANHYDROUS CONDITIONSJAT A TEMPERATURE OF FROM ABOUT -78*C TO ABOUT 2/*C, A COMPOUND OF THE FORMULA
Claim 2
Dependent Claim
28 words
A PROCESS WHICH COMPRISES REACTING IN AN ORGANIC LIQUID SOLVENT, UNDER SUBSTANTIALLY ANHYDROUS CONDITIONSJAT A TEMPERATURE OF FROM ABOUT -78*C TO ABOUT 2/*C, A COMPOUND OF THE FORMULA
Claim 3
Dependent Claim
40 words
A process as defined in claim 1 wherein the azasulfonium salt of formula IV, where R3 H, is reacted with a substantially anhydrous base to effect rearrangement of the azasulfonium salt and to form a thio-ether compound of the formula
Claim 4
Dependent Claim
73 words
A process as defined in claim 1 wherein the azasulfonium salt is one of formula IV wherein X is -CH ; each of Y and Z is hydrogen; R is hydrogen; R2 is hydrogen, lower alkyl or benzyl; R3 is lower alkyl, phenyl or benzyl; and said azasulfonium salt is reacted with a substantially anhydrous base to effect rearrangement of the azasulfonium salt and to form a thio-ether indolenine compound of the formula
Claim 5
Dependent Claim
80 words
A process as defined in claim 1 wherein the aza-sulfonium salt of the formula IV wherein X is -CH ; each of Y and Z is hydrogen; R is hydrogen; R2 and R3 are taken together with the carbon atoms to which they are bonded to complete a ring containing from 5 to 8 carbon atoms; is reacted with a substantially anhydrous base to effect rearrangement of the azasulfonium salt and to form a thio-ether indolenine compound of the formula
Claim 6
Dependent Claim
50 words
A process as defined in claim 2 which further includes the step of treating the thio-ether compound having formula (VI) with a de-sulfurizing reducing agent selected from the group consisting of Raney nickel, an alkali metal aluminum hydride, and an alkali metal borohydride to form a compound of the formula:
Claim 7
Dependent Claim
49 words
A process as defined in claim 3 which further includes the step of treating the thio-ether having formula (VIII) with a de-sulfurizing reducing agent selected from the group consisting of Raney nickel, an alkali metal aluminum hydride, and an alkali metal borohydride to form a compound of the formula:
Claim 8
Dependent Claim
49 words
A process as defined in claim 4 which further includes the step of treating the thio-ether having formula (VIII) with a de-sulfurizing reducing agent selected from the group consisting of Raney nickel, an alkali metal aluminum hydride, and an alkali metal borohydride to form a compound of the formula:
Claim 9
Dependent Claim
75 words
A process as defined in claim 1 wherein X is -CH ; R is lower alkyl; A is chlorine; each of Y and Z is selected from the group consisting of hydrogen and halogen, nitro, cyano, lower alkyl, lower alkyloxy, lower acyloxy, a carbonyloxy-lower alkyl and carbonyloxy-phenyl groups; the sulfide compound has formula II wherein R1 is lower alkyl, R2 is lower alkyl and R3 is hydrogen to form an azasulfonium salt of the formula
Claim 10
Dependent Claim
32 words
A process as defined in claim 8 wherein an N-chloro-aniline is reacted with methylthioacetone, and then the resulting azasulfonium salt is reacted with a tris (lower alkyl) amine to form a 2-methyl-3-methylthioindole.
Claim 11
Dependent Claim
65 words
A process as defined in claim 1 wherein X is -N ; R is hydrogen; A is chlorine; each of Y and Z is selected from the group consisting of hydrogen and halogen, nitro, lower alkyl, lower alkyloxy, lower acyloxy; the sulfide compound has formula II wherein R1 is lower alkyl; R2 is hydrogen, and R3 hydrogen to form an azasulfonium salt of the formula
Claim 12
Dependent Claim
37 words
A process as defined in claim 10 wherein a N-chloro-2-aminopyridine is reacted with thiomethylacetaldehyde to form the azasulfonium chloride salt, and then the azasulfonium chloride salt is reacted with a substantially anhydrous base to form a 3-methylthio-7-azaindole
Claim 13
Dependent Claim
42 words
A process as defined in claim 11 which further includes the step of treating the 3-methylthioindole with a de-sulfurizing reducing agent selected from the group consisting of Raney nickel, an alkali metal aluminum hydride, and an alkali metal borohydride to form indole.
Claim 14
Dependent Claim
14 words
A process as defined in claim 12 wherein the reducing agent is Raney nickel.
Claim 15
Dependent Claim
19 words
A process for preparing indoles which comprises; a. reacting an N-haloaniline with a Beta -carbonyl sulfide having the formula:
Claim 16
Dependent Claim
19 words
A process for preparing indoles which comprises; a. reacting an N-haloaniline with a Beta -carbonyl sulfide having the formula:
Claim 17
Dependent Claim
59 words
A process as defined in claim 14 wherein in step (a) an N-chloroaniline is reacted with a lower alkylthioacetaldehyde to form an azasulfonium chloride salt, in step (b) the azasulfonium chloride salt is treated with a tris (lower alkyl) amine to form a 3-alkylthioindole, and in step (c) the 3-alkylthioindole is treated with Raney nickel to form an indole.
Claim 18
Dependent Claim
50 words
A process as defined in claim 15 wherein in step (a) N-chloroaniline is reacted with methylthioacetaldehyde to form the azasulfonium chloride salt, in step (b) the azasulfonium chloride salt is treated with triethylamine to form 3-methylthioindole; and in step (c) the 3-methylthioindole is treated with Raney nickel to form indole.
Claim 19
Dependent Claim
56 words
A process as defined in claim 14 wherein a 3-thio-ether indolenine is formed by the Procedures of steps (a) and (b) and in step (c) the 3-thio-ether indolenine from step (b) is treated with a hydride selected from the group consisting of lithium aluminum hydride and a sodium borohydride under desulfurizing conditions to form the indole.
Claim 20
Dependent Claim
55 words
A process as defined in step 17 wherein in step (a) a N-chloroaniline is reacted with 2-methylthiocyclohexanone to form an azasulfonium chloride salt; in step (b) the azasulfonium chloride salt is treated with triethylamine to form a 3-thio-ether indolenine; and in step (c) the 3-thio-ether indolenine is treated with lithium aluminum hydride to form tetrahydrocarbazole.
Claim 21
Dependent Claim
55 words
A process as defined in step 17 wherein in step (a) a N-chloroaniline is reacted with 2-methylthiocyclohexanone to form an azasulfonium chloride salt; in step (b) the azasulfonium chloride salt is treated with triethylamine to form a 3-thio-ether indolenine; and in step (c) the 3-thio-ether indolenine is treated with lithium aluminum hydride to form tetrahydrocarbazole.
Claim 22
Dependent Claim
66 words
A process as defined in claim 1 wherein X is -CH , R is hydrogen, A is chlorine, each of Y and Z is selected from the group consisting of hydrogen and halogen, nitro, lower alkyl, lower alkyloxy, lower acyloxy; the sulfide compound has Formula (II) wherein R1 is lower alkyl, R2 is hydrogen and R3 is hydrogen, to form an azasulfonium salt of the formula:
Claim 23
Dependent Claim
38 words
A process as defined in claim 19 wherein an N-chloroaniline is reacted with methylthioacetaldehyde to form the azasulfonium chloride salt, and then the resulting azasulfonium chloride salt is reacted with a substantially anhydrous base to form a 3-methylthioindole.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1978-08-25 | 1979-02-24 | 1979-08-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1982-08-25 | 1983-02-24 | 1983-08-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1986-08-25 | 1987-02-24 | 1987-08-26 | $7700.00 | Window Closed / Lapsed |