Rhodium
(Chief Bee)
06-02-04 16:19
No 510951
       Novel route to dialkyltryptamines
(Rated as: good idea!) 		    

Conversions of Michael Adducts to Nitroolefins
Preparation of Carbonyl Compounds, 1,4-Diaminobutanes, Indoles, and Isoquinolines
Dieter Seebach, Volker Ehrig, Herbert F. Leitz und Rainer Henning
Chem. Ber. 108, 1946-1960 (1975) (../rhodium/pdf /dmt.michael.nitroalkene.pdf)



Abstract
Derivatives of 1,3- and 1,4-dicarbonyl-systems (3,5) are prepared from the Michael adducts of masked acyl anion equivalents or enolates, respectively, to nitroolefins (2,4) using Nef-type reactions. The same adducts (6,8) are reduced with lithium aluminium hydride in THF/dioxane to give amines (7,9) which are convenient precursors to indoles (cf. bufotenin, 10) or isoquinolines (cf. 4-dithianyl derivatives 15,17) if subjected to standard reactions such as the Bischler-Napieralski-, the Pictet-Spengler-, and oxidative indole-ring closures. An access to 1-dithianylisoquinolines (e.g. 25) is also described. All these transformations can be done on a preparative scale and in good to excellent yields. The effects of 1- and 4-dithianyl substituents on the n.m.r. spectral shifts of peri-hydrogens at C-5 and C-8 in di- and tetrahydroisoquinolines are discussed.

Could someone translate the experimental for the preparation of tryptamines from nitrostyrenes? (german)
The Hive - Clandestine Chemists Without Borders 		 
 
 
 
    Lego
(Hive Bee)
06-03-04 23:39
No 511287
       Translation of Chem. Ber., 1975, 108, 1946-1960
(Rated as: excellent) 		    

Grmph, this article is on Lego's harddisk for almost a year......
We need reference 3 as soon as possible, otherwise sleep will be hard to find!



Reduction of nitroalkanes 6 and 8 to the amines 7 or 9:
A suspension of 10-20 g LiAlH4 in 250-350 ml THF and 30-100 ml dioxane is heated to reflux. A solution of 50 mmol nitroalkane in 100-150 ml THF or dioxane is added dropwise and the solution is refluxed for further 5-8 h. After careful addition of water to the ice-cooled reaction mixture the formed precipitate is removed by filtration and refluxed for 2 h with ether. The pooled filtrates were dried over potassium carbonate and evaporated on a rotary evaporator. The mono- or dihydrochlorides, hydrogenoxalates or pikrates were synthesized in the usual manner, the m.p. or decomposition points are given in table 2 and data of the elemental analysis in table 3. The yields given in table 2 are isolated ammonium salts, based on used nitroalkane 6 or 8. [...]

2-(2,5-Dimethoxyphenyl)-N4,N4-dimethyl-1,4-butandiamine (7b):
A solution of 14.8 g (50 mmol) 3-(2,5-dimethoxyphenyl)-N,N-dimethyl-4-nitrobutyramid (6b)3 in 100 ml dioxane was added over a period of 30 min to a refluxing solution of 19 g LiAlH4, 350 ml THF and 50 ml dioxane. After 8 h of reflux the solution is hydrolysed with 75 ml while cooled with ice and worked-up as described above. 8.4 of a yellow oil are obtained which is dissovled in ether and a saturated solution of HCl in ether is added dropwise. Yield of dihydrochloride: 10.8 g (67%); m.p. 149-151 °C (EtOH/ether)

Bufotenine (10):
3.25 g (10 mmol) of 7b dihydrochlorid were heated to reflux with 48% HBr for 30 min in a inert gas atmosphere. The solution was diluted with 90 ml water and evaporated to dryness. The aqeuous solution of the residue was heated to reflux with activated carbon and evaporated. The residue is dried until no more weight is lost over P4O10 and NaOH in an evacuated descicator.
To the solution of the hydroquinone derivative (3.8 g) in 120 ml water a solution of 6.4 g K3Fe(CN)6 and 3.3 g NaHCO3 in 120 ml are added dropwise over a period of 10 min. After 30 min a very little amount of sodium dithionite is added. After removal of the precipitate by filtration the solution is extracted for 2 days with ether which is free of peroxides not sure if '2 d' really means 2 days or perhaps it is a typo and should read '2 x', whatever, extract with ether
The amorphous residue of the etheral solution consists of almost pure 10 (1.1 g, 54%), which could be purified by sublimation at 140 °C/10-4 Torr, m.p. 139 °C (lit. 15 143 °C).

3 D. Seebach, H. F. Leitz and V. Ehrig, Chem. Ber. 108, 1924 (1975) and literature cited therein
The tendency is to push it as far as you can 		 
 
 
 
    Kinetic
(Hive Bee)
06-15-04 19:27
No 513588
       Michael-type additions to nitroolefins
(Rated as: good read) 		    

Here's the looong reference 3 requested by Lego:

Michael-type Addition of Lithium Enolates and Sulfur-substituted Organolithium Reagents to Nitroolefins
Dieter Seebach*, Herbert F. Leitz and Volker Ehrig
Chem. Ber., 108, 1924-1945 (1975)

Abstract
The highly reactive lithium derivatives mentioned in the title (3-9) add smoothly to aliphatic (1a-c) and aliphatic nitroolefins (1d-s) between -70oC and -110oC. The structures of both reactants can be varied within a large scope. A discussion of the n.m.r. spectra of the products (10-22) is included.

  
 
 
 
    Lego
(Hive Bee)
06-20-04 22:27
No 514448
       More on nitrostyrenes and lithium enolates
(Rated as: excellent) 		    

Thanks for the article! Lego converted it to a djvu-file (now it's only 265 kb instead of 7877 kb wink)

The interesting part was translated and some other related articles were scanned and upload (see below).



Michael-type Addition of Lithium Enolates and Sulfur-substituted Organolithium Reagents to Nitroolefines13
Dieter Seebach, Herbert F. Leitz, Volker Ehrig
Chem. Ber., 1975, 108, 1924-1945


Abstract: The highly reactive lithium derivates mentioned in the title(3-9) add smoothly to alipathic (1a-c) and aromatic nitroolefins (1d-s) between -70 and -110 °C. The structures of both reactands can be varied within a large scope. A discussion of the n.m.r. spectra of the products (10-22) is included.





[...]

Table 2
  nitroolefin yield (%) mp [°C]
bp [°C/Torr]		 Lit.
1a nitroethylene 40 50/100 4, 22
b 2-nitropropene 80 50/60 4, 22
c 1-nitropropene 55 54/28 4, 22
d beta-nitrostyrene 80 57/58 4, 23, 24
e 4-methoxy-beta-nitrostyrene 83 87 4, 22, 23, 24
f 2-benzyloxy-beta-nitrostyrene 89 71-73 a, b
g 4-chloro-beta-nitrostyrene 72 115 4, 23, 25, 26
h 3,4-methylendioxy-beta-nitrostyrene 71 158.5 4, 24
i 3,4-dimethoxy-beta-nitrostyrene 84 140-141 4, 24
j 2,5-dimethoxy-beta-nitrostyrene 73 119 4, 26, 27
k 5-chloro-2-methoxy-beta-nitrostyrol 72 121-122 a, c
l 2-benzyloxy-5-chloro-beta-nitrostyrene 86 109-110 a, d
m 2-benzyloxy-5-bromo-beta-nitrostyrene 74 112-113 a, e
n 2,5-dimethoxy-4-methyl-beta-nitrostyrene 67 118-119 28
o 3,4,5-trimethoxy-beta-nitrostyrene 82 120-121 29, 30
p 1-(4-methoxyphenyl)-2-nitro-1-propene 84 48 4, 23, 24
q 1-(3,4-methylendioxyphenyl)-2-nitro-1-propen 60 93-94 4, 23, 24
r 1-(2,5-dimethoxy-4-methyl-phenyl)-2-nitro-1-propene 79 89 28
s beta-bromo-beta-nitrostyrene 70f 63, 6 4, 31, 32

aThese previously unmentioned nitrostyrenes were prepared in the same way as the other nitrostyrenes.
b2-Benzyloxybenzaldehyde: M. Miyano, S. Muraki, T. Nishikubo, M. Matsui, Nippon Nogei-kagaku Kaishi 34, 678 (1960)  [C.A. 59, 13928d (1963)].
c5-Chloro-2-methoxybenzaldehyde: Buu-Hoi, C.R. Acad. Sci. 221, 202 (1945).
d2-Benzyloxy-5-chlorobenzaldehyde: G. Erhardt, J. Hennig, Chem. Ber. 87, 892 (1954)
e2-Benzyloxy-5-bromobenzaldehyde: L. Ch. Raiford, L. K. Tanzer, J. Org. Chem. 6, 722 (1941)
f1s is obtained from 1d by addition of bromine and subsequent HBr-elimination31, 32

[...]

Experimental

[...]

1. Starting products
a) Nitroolefins 1: In Table 2 the used nitroolefins are given with the reaction yields, melting and boilings points and literature references.

[...]

2. Preparation of the enolates
To a solution, cooled to -40 °C and in an argon atmosphere, of 1.4 ml (10 mmol) diisopropylamine in 30-40 ml of absolute THF is added with a syringe the calculated amount (e.g. 6.2 ml of 1.61 M solution) of n-butyllithium in n-hexane. The temperature was allowed to raise to room temperature in 15-20 min (formation of lithium diisopropylamide = LDA).
Depending on the reactivity of the enolate which is prepared the solution of the carbonyl compound is cooled to -40 to -100 °C and stirred for 1 h at -90 to -60 °C (see below, detailed experimental details).

3. Addition of lithium compounds to nitroolefins
5-10 mmol nitroolefin in 30 ml absolute THF are added over a period of 15-30 min to solution cooled to -70 to -100 °C of 10 mmol lithium compound (see 2). The solution is stirred at this temperature for 1-3 h. After addtion of about 1 ml glacial acetic acid the reaction temperature is allowed to raise to -40 to -20 °C within 0.5 h. To the solution the double amount of water is added, extracted several times with dichloromethane, the organic phase is washed with water, dried over Na2SO4 or K2CO3, the solvent is removed on a rotary evaporator and raw product is obtained.

[...]

3-(2,5-Dimethoxyphenyl)-N,N-dimethyl-4-nitrobutyramid (14c): To 150 mmol LDA (see 2.) in 150 ml THF 13.9 ml (150 mmol) N,N-dimethylacetamide are added at -78 °C. The solution is stirred for 1 h and at -78 °C 17.5 g (75 mmol) 2,5-dimethoxy-beta-nitrostyrene (1j) in 180 ml are added dropwise. After 1 h 33 ml glacial acetic acid are added while the solution is still at -78 °C. The solvent is evaporated on a rotary evaporator and slowly crystallizing residue was obtained. From ethanol/pentane 21 g (97%), mp 105-106 °C. An analytical sample melted at 106.4-107.8 °C (from benzene/petane).

N,N-Diethyl-3-(2,5-dimethoxy-4-methylphenyl)-4-nitrobutyramide (15): To a stirred solution of 15 mmol LDA (see 2.) cooled to -78 °C 1.72 g (15 mmol) N,N-diethylacetamide was added. After 1 h 2.23 g (10 mmol) 2,5-dimethethoxy-4-methy-beta-nitrostyrene (1n) in 25 ml THF was added in 30 minutes. After further 30 min the reaction flask was closed under a argon overpressure and stored in the fridge (-20 °C) for 14 h. Then 4 ml glacial aceti acid was added and worked up (see 3.). Yield: 2.88 g (85%), mp 76.4-77.6 °C (ethanol/water).

3-(2-Benzyloxyphenyl)-2-N,N-trimethyl-4-nitrobutyramide (16): To 44 mmol LDA (see 2.) in 100 ml THF cooled to -78 °C 11 ml (50 mmol) N,N-dimethylpropionamide were added. The bath temperature was allowed to raise temporarly (about 30 min) to -50 °C and 5.1 (20 mmol) 2-benzyloxy-beta-nitrostyrene (1f) in 30 ml THF was added at -78 °C. After 12 h at -20 °C (fridge, see above) 8 ml glacial acetic acid was added and worked up (see 3). 6.65 g (95%), mixtures of diastereomeres, mp 83-101 °C (ethanol/petane).

4-Bromo-N,N-dimethyl-4-nitro-3-phenylbutyramide (17): To 20 mmol LDA (see 2.) in 110 ml THF cooled to -78 °C 1.9 ml (20 mmol) N,N-dimethylacetamide was added. The mixture is stirred for 1 h and then (bath temperature: -115 °C) 2.3 g (10 mmol) beta-bromo-beta-nitrostyrene (1s) in 30 ml THF was added dropwise while the mixture was stirred vigorously. After 45 min at -110 °C 2.5 ml glacial acetic acid was added, warmed to -10 °C within 2 hours and worked up (see 3.). 2.9 g of a dark-brown oil are obtained, after careful addition of pentane on the top of the oil it recrystallized and it was recrystallized from the same solvent. Yield: 1.9 (60%); decomposition point 142-144 °C.

[...]

References
[...]
4. Methods of organic chemistry (Houben-Weyl-Müller), volume X/1, Georg Thieme Verlag, Stuttgart 1971; H. O. House, Modern Synthetic Reactions, 2. edition, Benjamin, Palisade 1972; H. Feuer, The Chemistry of the Nitro and Nitroso Groups, Part I, II, Interscience Publishers, New York 1969; V. V. Perekalin, Unsaturated Nitro Compounds, Israel Programm for Scientific Translations, Jerusalem 1964
[...]
22. G. Descotes, Y. Bahurel, M. Bourillot, G. Pingeon, R. Rostaing, Bull. Soc. Chim. France 1970, 282, 290, 295
23. M. Koremura, H. Oku, T. Shono, T. Nakanishi, Takamine Kenkyusho Nempo 13, 205, 212 (1961) [C.A. 57, 16450/51 (1962)]
24. C. B. Gairand, G. R. Lappin, J. Org. Chem. 18, 1 (1953)
25. N. Campbell, W. Anderson, J. Gilmore, J. Chem. Soc. 1940, 446
26. F. G. P. Remfry, J. Chem. Soc. 1911, 282
27. S. Sugasawa, H. Shigehara, Ber. Deut. Chem. Ges. 74, 459 (1941)
28. B. T. Ho, J. Med. Chem. 1, 134 (1957); 13, 26 (1970)
29. E. Späth, Monatsh. Chem. 40, 129 (1919)
30. K. H. Slotta, G. Szyczka, Ber. Deutsch. Chem. Ges. 68, 184 (1935)
31. C. J. Delvin, B. J. Walker, J. C. S. Perkin I 1973, 1428
32. J. Thiele, S. Haeckel, Liebigs. Ann. Chem. 325, 1 (1902)
[...]



Reference 4 from Chem. Ber., 1975, 108, 1946-1960:

Michael-Addition von metallierten Carbonsäureamiden an Nitrostyrole - Ein vereinfachter Zugang zu Tryptaminen
Dieter Seebach, Herbert F. Leitz
Angew. Chem., 1971, 83(14), 542-544




Reference 6 from Angew. Chem., 1971, 83(14), 542-544:

No 226. - Recherches en série indolique. XVII. - Préparation de quelques indolines, indoles et tryptamines oxgénés en positions -4 ou -6 par cyclisation "arynique"
Marc Julia, Hubert Gaston-Breton
Bull. Soc. Chim. Fr., 1966, 1335-1342

The tendency is to push it as far as you can 		 
 
 
 
    Lego
(Hive Bee)
06-23-04 22:12
No 515021
       Bufotenine synthesis by ferricyanide cyclisation
(Rated as: excellent) 		    

Reference 5 from Angew. Chem., 1971, 83(14), 542-544.



Hydroxytryptamines. Part I. Bufotenine, 6-Hydroxybufotenine and Serotonin
John Harley-Mason and A. H. Jackson
J. Chem. Soc., 1954, , 1165-1171


Abstract: Convenient syntheses of bufotenine and serotonin involving the ferricyanide oxidation of 2-(2,5-dihydroxyphenyl)-4-dimethylamino- and -4-amino-butylamine, respectively, are described. A similiar synthesis gave 6-hydroxybufotenine, while attemps to isolated 6-hydroxyserotonin were unsuccessful.



[...]

2-(2,5-Dihydroxyphenyl)-4-dimethylaminobutylamine (III; R = H)
A solution of the amino cyanide (7 g) in ethanol (50 c.c.) saturated with ammonia was hydrogenated over Raney nickel at 100° and 100 atm. for 5 hr. The catalyst was filtered off, the solvent removed, and the residual oil distilled at 145-150°/2.5 mm, giving the diamine (III; R = Me) (5.8 g) as a pale oil. [...]

The dimethoxy-diamine (1.3 g) was refluxed with hydrobromic acid (d 1.49; 8 c.c.) for 45 min., and the resulting solution diluted with water and evaporated to dryness on the waterbath under reduced pressure of hydrogen. The residual dark brown solid was dissolved in water and boiled with charcoal, and the solution again evaporated under hydrogen. The last traces of water and hydrobromic acid were removed by storage in a vacuum desiccator over phosphoric oxide and sodium hydroxide, leaving the dihydroxy-diamine dihydrobromide as a light brown hygroscopic glass which did not crystallise.

Bufotenine (IV)
To a solution of the dihydroxy-diamine dihydrobromide (1.9 g) in water (60 c.c.), a solution of potassium ferricyanide (3.2 g) and sodium hydrogen carbonate (1.65 g) in water (60 c.c.) was added with stirring during 5 min. The mixtured darkened at first, but became paler after 20 min. A little sodium dithionite was added andd, after filtration from a small amount of flocculent precipitate, the light yellowish-brown solution was extracted continuously with peroxide-free ther for 2 days. Removal of the ether and drying of the residue in a vacuum over phosphoric oxide gave bufotenine (0.45 g; 45%) as a hard brown glass, purified by sublimation at 160°/10-4 mm. [...]
The tendency is to push it as far as you can