Vibrating_Lights (Hive Addict)
07-20-02 14:45
No 335201
      Amidomercuration ?  Bookmark   

In an Amidomercuration rxn is there any reducing method(other than a metalhydride) available to percipatate the Hg from the complex.  mabyee Al as in the preperation of a urushibara catalyst.
Vl?
 
 
 
 
    PrimoPyro
(Hive Prodigy)
07-20-02 15:18
No 335221
      Define Amidomercuration  Bookmark   

Please answer this: What do you mean by amidomercuration? Do you mean adding an amide across an olefin using mercuric compounds, or are you referring to adding an amine across the bond, as in aminomercuration?

If you truly mean adding an amide across the olefin, I am intrigued to no end, as I have wanted to do this for some time with a very specific amide.

                                                   PrimoPyro
 
 
 
 
    Rhodium
(Chief Bee)
07-20-02 17:31
No 335280
      Amidomercuration  Bookmark   

But PP, you know you never need to go further than my page to find everyhing you need wink

../rhodium/chemistry /allylamination.html
 
 
 
 
    PrimoPyro
(Hive Prodigy)
07-20-02 18:09
No 335303
      Ive seen it  Bookmark   

And that is precisely what gave me my idea that I oh so dearly hope would work. Im practically foaming at the mouth over the possibility, Im sure Ive blabbed it to you in PM one time or another.

I simply did not take that page to mean a definite yes, because of the difference in structure between that amide and the amide I am thinking of: N-methyl formamide/N-formyl methylamine.

Often times in o-chem, simple assumptions like that are often wrong, at least when I make them, so I held back this time. Are you hinting that amides can indeed be used in amidomercurations? Pleeeeeeease say yes, and you know I mean N-methyl formamide across safrole with appropriate Hg(II) salt.

The reduction with NaBH4 and NaOH would also hydrolyze the formyl function in the presence of water, yielding a one step/one pot safrole --> MDMA freebase. My holy grail.

                                                   PrimoPyro
 
 
 
 
    Rhodium
(Chief Bee)
07-20-02 18:49
No 335321
      I don't know how small amides that can be used, ...  Bookmark   

I don't know how small amides that can be used, but I have a literature example of 2-(Acetylamino)-5-hexene being intramolecularly amidomercurated to N-Acetyl-trans-2,5-dimethylpyrrolidine in 98% yield here: JOC 46, 3920 (1981)
 
 
 
 
    Ritter
(Master Whacker)
07-20-02 19:53
No 335341
      Amidomercuration--Nitriles work too!  Bookmark   

Many moons ago an associate successfully performed an amidomercuration with acetonitrile as source of amide.  Technically I guess this is completely different than a true amidomercuration reaction, however the reaction did indeed produce a good yield of N-acetyl MDA which is indeed an amide and was hydrolyzed to MDA in a good yield.  This reaction is detailed in M.V. Smiths' book.  Safrole is reacted with acetonitrile and Hg(NO3)2 then demercurated with NaBH4.  The resulting acetylamide was hydrolyzed with 4N HCl.  This reaction is good for SMALL batches- scaling above 100mmol can result in a run-away exotherm during the mercuration.  Not to mention no one should be messing with this toxic shit when there are better methods available anyway.
 
 
 
 
    PrimoPyro
(Hive Prodigy)
07-21-02 04:51
No 335456
      Ritter and Nitriles  Bookmark   

Yeah, I saw a ref posted by Osmium about exactly that on Rhodium's website.

Styrofoam and DMSO would be an otc way to allylbenzene, methamphetamine counterpart to safrole.

I like direct amination of alkenes. N-methyl formamide and NaBH4 are the only possible hangups with this, the mercuric salts are easy to make. NMF could be purchased in a gallon or two from a source once and you'd be alright. And PolytheneSam gave us many patents on making NaBH4, one was very cheap and done eletrolytically, with simple NaBO2, NaOH and water.

                                                   PrimoPyro
 
 
 
 
    El_Zorro
(Hive Bee)
07-21-02 13:06
No 335529
      What about the idea you had a while back about ...  Bookmark   

What about the idea you had a while back about reacting mthylamine with formic acid to get methylammonium formate, then heating until the water distills out to get N-methyl formamide, PP?

Who is that masked man?
 
 
 
 
    PrimoPyro
(Hive Prodigy)
07-21-02 17:42
No 335588
      I never tried it myself  Bookmark   

but I know that ammonium formate can be dehydrated by heating to formamide, so methylammonium formate should likely be able to undergo the same.

I dont have a copy of the Merck Index, but if you can locate the entry for methylammonium formate, and locate its boiling point, we can assume that it does not undergo dehydration upon boiling, at least completely anyway.

But if no boiling point is listed, I would assume that to mean that it dehydrates to NMF upon boiling. It should say if it decomposes anyway. I cannot locate the compound methylammonium formate on chemfinder, or any similar named compounds, nor the molecular structure or substructure, so I can't find the answer myself right now.

As for my past question about using ammonium formate and formaldehyde to make methylammonium formate in the same manner methylammonium chloride is made from ammonium chloride, yes I do think it would work, the only additioanal side reaction to those associated with the traditional synthesis possibly being some dehydration to NMF possibly.

                                                   PrimoPyro
 
 
 
 
    Rhodium
(Chief Bee)
07-21-02 19:49
No 335618
      Methylammonium formate will definitely form ...  Bookmark   

Methylammonium formate will definitely form N-methyl-formamide upon dry distillation. It has whole chapters in Fester's books devoted to it.
 
 
 
 
    PrimoPyro
(Hive Prodigy)
07-22-02 06:52
No 335778
      Is That A Reliable Ref?  Bookmark   

tonguewink
 
 
 
 
    Rhodium
(Chief Bee)
07-22-02 12:11
No 335847
      The Preparation of Aliphatic Amides
(Rated as: excellent)
 Bookmark   

No, but I knew that his references for that particular reaction was good. Here it follows:

The Preparation of Aliphatic Amides
by JA Mitchell and EE Reid
J Am Chem Soc 53, 1879-1883 (1931)

The most satisfactory methods of preparing amides have involved dehydration of the ammonium salt of the corresponding acid. Hofmann [1] prepared various amides by heating ammonium salts of aliphatic acids for five or six hours at 230C under pressure. Kundig [2] prepared acetamide by the rapid distillation of ammonium acetate and by heating an alcoholic solution of acetic acid and ammonia in a sealed tube for a long time at 100C. He also obtained a yield of amide greater than 25% by passing dry ammonia through acetic acid and then heating to boiling. Grant and James [3] have prepared amides by saturating the acid with dry ammonia and boiling. Dunlap, [4] Keller [5] and Verley [6] have modified the procedure by heating sodium acetate and ammonium chloride at 240C.

Acetamide is best prepared according to Coleman and Alvarado [7] by heating a mixture of ammonium acetate and acetic acid under a reflux condenser in such a manner that the excess acetic acid and the water formed in the reaction are slowly distilled off [8]. Noyes and Goebel have also shown that acetic acid catalyzes the reaction.

This method is very satisfactory for preparing acetamide, but is not economical for the higher aliphatic acids on account of the cost of the large excess of acid required. This suggested using an excess of the other reactant, ammonia, which is cheap. Instances in which dimethyl amides were prepared in a similar manner are rare. Franchimont and Klobbie [9] prepared dimethyl heptoamide by heating the acid with dimethylamine at 230C in a sealed tube. Verley [6] prepared dimethyl formamide and acetamide by distilling a mixture of an alkali salt of the acid and dimethylamine hydrochloride.

Results

We have found that by passing ammonia gas through aliphatic acids kept at a suitable temperature in such a way that the water formed is continually removed, the equilibrium point of the reaction may be displaced far to the amide side and very high yields of amides obtained. The results with the aliphatic amides are indicated in Table I.

The temperature at which the acid is heated is sufficient to dehydrate a small proportion of the higher amides to form the nitriles. This reaction becomes appreciable with butyric and the higher amides. The reaction velocity is appreciably slower with the higher acids. Heptoic acid reacts much more slowly than caproic and caprylic more slowly than heptoic. Lauric acid was heated at 185C for sixteen hours. Only a small fraction was converted to the amide. No amide was obtained from palmitic or stearic acid upon heating either at 125 or 190C for considerable intervals of time. The ammonium salts of these acids are probably unstable under the conditions of the experiments. Similar experiments were performed in which anhydrous zinc chloride was added to acetic, propionic and caproic acids. No difference in rate of formation of the amide was observed when compared with parallel experiments with no zinc chloride. Zinc chloride is a catalyst, however, for dehydration of the amide to the nitrile. At a temperature higher than that used in the preparation of the amide a considerable proportion of caproic acid is converted to the nitrile. Although small amounts of nitrile are formed in distilling acetamide and propionamide, they are satisfactorily purified by distillation at atmospheric pressure. It is better to fractionate the higher amides at reduced pressures. Acetamide is best recrystallized from methyl alcohol and ether according to the method outlined by Wagner [10]. The amides become increasingly soluble in ether as the molecular weight increases. This furnishes a satisfactory recrystallization medium for all but acetamide. The amides are more effectively recrystallized from hot benzene. The crystals, however, tenaciously absorb the solvent and it is advisable to centrifuge. Dimethyl amides were prepared in the same manner, the ammonia being replaced by dimethylamine. The results are given in Table II. The dimethyl amides obtained were all liquids at ordinary temperatures and were purified by distillation.





Experimental

The apparatus employed. consisted of a flask with a jacketed reflux condenser. The condenser was connected top and bottom with a side tube of the same length, which upon being filled with water could be kept at any desired temperature up to 90C by means of a Bunsen burner placed at the lower end of the side-tube. The flask containing the acid was heated to any desired temperature by an oil-bath. Temperatures were read from a thermometer which was placed inside the flask and extended into the condenser. The ammonia delivery tube entered at the top of the condenser and extended to the bottom of the flask.

For the preparation of the amides a stream of ammonia, taken directly from a cylinder, was passed through the delivery tube and bubbled through the acid the entire duration of the experiment. The water formed in the reaction was swept out through a tube just at the top of the condenser jacket into a bulb.

Samples of amides were carefully purified. After the preliminary vacuum distillation the amides were further purified by crystallization from pure benzene and absolute ether, frequently centrifuging and drying over sulfuric acid in a vacuum desiccator until accurate melting points were obtained, checking for several recrystallizations. The melting points were taken with a calibrated Anschtz thermometer. Every precaution was taken to prevent overheating of the melting point bath and its temperature was kept uniform by efficient stirring. Melting points quoted in Table I are the corrected ones.

Acetamide was purified by recrystallizing four times from methyl alcohol and ether, centrifuging twice. Propionamide was crystallized once from methyl alcohol and ether, followed by centrifuging, and then recrystallized twice from ether. Butyramide (a) was crystallized from benzene, centrifuged and recrystallized three times from ether, followed by centrifuging. Butyramide (b) was crystallized three times from ether, and centrifuged. Valeramide was crystallized three times from ether and centrifuged. Caproamide (c) was crystallized three times from ether and centrifuged twice. Caproamide, (d) heptoamide and caprylamide were crystallized from benzene, centrifuged, and recrystallized twice from ether.

For the preparation of the dimethyl amides, the apparatus was attached to a water pump at the exit side and a current of air mixed with dimethylamine, prepared by dropping an aqueous solution of the amine [11] on solid potassium carbonate, was drawn through the acid during the course of the experiment. The gas was dried by passing it over solid potassium hydroxide. Certain experiments indicated, however, that drying was not essential. The reaction proceeds much faster with dimethylamine than with ammonia.

Summary

A satisfactory and economical method has been described for the prepara- tion of amides and dimethyl amides from the normal acids of the aliphatic series up to caprylic. Accurate melting points of the amides from acetic to caprylic have been determined.

References

1) Hofmann, Ber., 15, 977 (1882).
2) Kundig, Ann., 105, 277 (1858).
3) Grant and James, J. Am. Chem. Soc., 39, 933 (1917).
4) Dunlap, ibid., 24, 762 (1902).
5) Keller, J. prakt. Chem., [2] 31, 364 (1885).
6) Verley, Bull. soc. chim., [3] 9, 691 (1893).
7) Coleman and Alvarado, "Organic Syntheses," 1923, Vol. 3, p. 2.
8) Rosanoff, Gulick and Larkin, J. Am. Chem. Soc., 33, 974 (1911);
   Hitch and Gilbert, ibid., 35, 1780 (1913);
   Noyes and Goebel, ibid., 44, 2286 (1922).
9) Franchimont and Klobbie, Rec. trav. chim., 6, 247 (1887).
10) Wagner, J. Chem. Ed., 7, 1135 (1930).
    Wagner obtained a melting point as high as 83C for acetamide. We obtained a melting point of only 81.5C after a very rigid purification.