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          Notes on the use of 1-dimethylamino-2-nitroethylene (DMANE)
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If you direct your attention to J. Org. Chem. 42, 1784 (1977), you will
discover the reagent 1-dimethylamino-2-nitroethylene (DMANE), which is easily
prepared from the inexpensive reagents DMF, dimethylsulfate, nitromethane and
sodium ethoxide. The reagent is capable of directly adding the 2-nitrovinyl
(-CH=CH2-NO2) side chain to the 3-position of indole, as well as a variety of 
substituted benzenes. Do you have some 4-acetoxyindole lying around, but don't 
want to go through the hassle of using oxalyl chloride when making a 4-hydroxy 
tryptamine out of it? Then turn to DMANE, which is dissolved in TFAA, and the 
4-acetoxyindole dumped right in. Ten minutes later you return, remove the 
solvent and let your product 3-(2-Nitrovinyl)-4-acetoxyindole crystallize in 
almost 80% yield, ready to become reduced to 4-hydroxytryptamine. We can also 
imagine that you are sitting with some 2,5-dimethoxyphenyl propyl sulfide, and 
want to turn it into a juicy phenethylamine. You can either subject it to a
vilsmeyer formylation, followed by a Knoevenagel condensation with nitromethane
to give you the nitrostyrene, or - you can simply get it in one step with this 
reagent. If you turn down this reagent with the excuse that you don't want any 
low potency phenethylamines, I can tell you about the homolog you can use to 
create phenylnitropropenes just as easy - 1-Dimethylamino-2-nitropropene. 

Below, I have included a few examples of the reagent, applied to various indole
substrates, and even further down, you'll find preparation details of both the 
above-mentioned nitro reagents, as well as how to prepare a DMF/Me2SO4 complex 
needed for doing it. 

There is one downside to the procedure, and that is that the preferred solvent 
for the reaction seems to be trifluoroacetic acid. The authors of the above 
article mentions some italians who were using the reagent in ethanolic HCl 
(but with relatively low yields), so TFAA is at least not ubiquitous. 
Do anyone have an educated guess as to what could be a decent substitute for 
TFAA as solvent in a reaction like this? And one more thing, could someone 
with access to Beilstein or something run a search on these two nitro reagents
for possible later articles dealing with them than the ones I've already found. 


3-(2-Nitrovinyl)indole 
----------------------
To a stirred solution of 1-dimethylamino-2-nitroethylene in trifluoroacetic 
acid (15 mL) at ice-bath temperature was added 3.51 g (30 mmol) of indole and 
the mixture was stirred in a nitrogen atmosphere for 10 min. During this time 
the color of the solution changed from light yellow to dark. The mixture was 
then allowed to warm up to room temperature and was poured into ice water 
(300 mL), from which a yellow semisolid precipitated. The aqueous solution was 
extracted with ethyl acetate (350 mL) and then twice with the same solvent 
(100 mL). The combined organic phases were washed with saturated NaHCO3 
solution (150 mL) and with saturated NaCl solution (100 mL) and dried (Na2SO4). 
Removal of solvent in vacuo afforded 5.40 g (96%) of a yellow solid. 
Recrystallization from hot methanol gave yellow prisms: mp 172°C (lit 171°C).

Ref: JOC 42, 1784 (1977)


3-(2-Nitrovinyl)-5-methoxyindole 
--------------------------------
A 15-mL flask equipped with reflux condenser was charged with 580 mg (5 mmol) 
of 1-dimethylamino-2-nitroethene and 3 mL of trifluoroacetic acid. To this 
stirred solution was added 735 mg (5 mmol) of 5-methoxyindole. The resulting 
suspension was heated to 30-45°C for 10 min and the solution was then allowed 
to cool. The dark slurry was poured into ice water. Extraction with ethyl 
acetate was followed by washing of the organic layer with saturated NaHCO3 and 
saturated NaCl solution. After drying (Na2SO4), the solvent was evaporated, 
yielding 1.1 g of dark green crystals. Purification by column chromatography 
(100 g, silica gel, CH2Cl2) yielded 60 mg (8%) of unreacted
5-methoxyindole 
and 697 mg (64%) of 3-(2-nitrovinyl)-5-methoxyindole. Recrystallization from 
acetone/hexane gave yellow needles: mp 162-165°C (lit 157-158°C).

Ref: JOC 42, 1784 (1977)


3-(2-Nitrovinyl)-4-acetoxyindole 
--------------------------------
To a solution of 175 mg (1.0 mmole) of 4-acetoxyindole in 1 ml of trifluoro-
acetic acid was added 116 mg (1 mmole) of 1-dimethylamino-2-nitroethylene. 
The reaction mixture was heated at 55°C under a nitrogen atmosphere for 10 
minutes during which time the light yellow solution became dark red. The 
reaction was cooled to room temperature and the solvent distilled under 
reduced pressure. The resulting red oil was dissolved in 2 ml of chloroform 
and the solvent removed in vacuo. This was repeated with 3 ml of dioxane. 
Addition of 1 ml of ethyl acetate and scratching induced crystallization of 
the residue. Hexane (0.25 ml) was added and the yellow needles collected by 
filtration and dried in vacuo to give 191 mg of 3-(2-Nitrovinyl)-4-acetoxy-
indole (78%), mp 200-203°C (dec).

Ref: J. Heterocyclic. Chem. 18, 175 (1981)


N,O-Diacetyl-4-hydroxytryptamine 
--------------------------------
3-(2-Nitrovinyl)-4-acetoxyindole (335 mg, 1.36 mmoles) was dissolved in 4 ml 
of tetrahydrofuran and added to a stirred suspension of 300 mg (7.89 mmoles) 
of lithium aluminum hydride in 5 ml of tetrahydrofuran. After the addition 
the reaction was refluxed for 20 minutes, cooled to room temperature, and 
water added dropwise until gas evolution ceased. The mixture was filtered 
(Celite, dry nitrogen atmosphere) and the filtrate concentrated under 
reduced pressure. The resulting clear syrup (slight blue tinge) was dissolved 
in a mixture of 5 ml of pyridine and 3 ml of acetic anhydride. After standing 
overnight at room temperature the solvents were distilled under reduced 
pressure and the residue purified by preparative thin-layer chromatography in 
5% methanol in chloroform. The eluted (ethyl acetate) product was crystallized 
from ethyl acetate/hexane to give 94 mg (26%), mp 150°C.

Ref: J. Heterocyclic. Chem. 18, 175 (1981)


N,N-dimethylformamide and dimethylsulfate complex
-------------------------------------------------
The reaction between N,N-dimethylformamide and an equimolar amount of dimethyl-
sulfate (which takes two days at room temp, and two hours at 60-80°C, with no 
solvent added) furnishes the O-methyl complex of the amide. The formation of the 
complex is revealed through a change in viscosity and refraction index. Both DMF 
and Me2SO4 are soluble in ether, benzene and ethyl acetate, but their complex 
isn't. Upon attempted distillation of the complex, the components are re-formed. 

Ref: Angew. Chem. 73, 493 (1961)


1-Dimethylamino-2-nitroethylene
-------------------------------
To a solution of 2.3 grams of sodium metal in 100 ml of absolute ethanol, 
20g of DMF/Me2SO4 complex and 6.1 grams of nitromethane is added. The 
mixture is heated to a boil for 1-2 minutes, cooled to room temperature, 
and the solvent was then evaporated in vacuum. The mixture is then extracted 
with methylene chloride, the solvent is again evaporated in vacuum, and the 
residue is washed with cold isopropanol, and then recrystallized from the 
same solvent. The yield is 60% of melting point 104°C. 

Ref: Ber 98, 3847 (1965)


1-Dimethylamino-2-nitropropene
------------------------------
A solution of 10 grams of sodium metal in 500ml of absolute ethanol is cooled
to 10°C and 90 grams of DMF/Me2SO4 complex and 47.5 grams of nitroethane is 
added. The solution is shaken with cooling for five minutes, and the solution 
takes on a orange-red color. The solvent is removed at 30-35°C in a rotavap, 
and the solid yellow residue is extracted with methylene chloride, and the 
solvent is again removed under vacuum. The orange-red oily residue is cooled
in the fridge, whereupon it crystallizes. The crystals are washed with a small
amount of cold ether, and are recrystallized from ethanol to give yellow 
crystals with a melting point of 78°C in a yield of 73% of theory. 

Ref: Ber 107, 1499 (1974)

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Cesium:

1-dimethylamino-2-nitroethylene CA SEARCH 1982-7/2000

100:22856
The chemistry of indoles. XIX. Synthetic study directed toward cyclopiazonic acid.
Chem. Pharm. Bull., 31(6), 2153-6 (English) 1983.

97:216537
Psilocine analogs. III. Synthesis of 5-methoxy- and 
5-hydroxy-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indoles.
J. Heterocycl. Chem., 19(4), 845-8 (English) 1982.

96:104201
Synthesis of 1H-[1,2]diazepino[4,5-b]indole derivatives.
J. Heterocycl. Chem., 18(5), 889-92 (English) 1981.

120:77615
2-Substituted 5-methoxy-N-acyltryptamines: synthesis, binding affinity for the 
melatonin receptor, and evaluation of the biological activity.
J. Med. Chem., 36(25), 4069-74 (English) 1993.

121:9157
Tryptamines for treatment of circadian rhythm disorders.
EP 93-830269 24 Jun 1993

Unfortunatelly, all with trifluoroacetic a. as a solvent :-(                                                                              

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