foxy2 (Distinctive Doe)
09-08-01 13:50
No 211342
      Novel o-toluidine synthesis  Bookmark   

Hofmann-Martius Rearrangement.

N-methyl Aniline --> o-toluidine + p-toluidine





A. W. Hofmann, C. A. Martius, Ber. 4, 742 (1871)
A. W. Hofmann, ibid. 5, 720 (1872)
Howard, Derick, J. Am. Chem. Soc. 46, 166 (1924)
Hickinbottom, Ryder, J. Chern. Soc. 1931, 1281
Thesing, Mayer er. 87, 1084 (1954).
Mechanism: Hart, Kosak, J. Org. Chem. 27, 116 (1962)
Ogata et al., Tetrahedron 20, 2717 (1964).

Cf. Reilly-Hickinbottom Rearrangement.


Keywords: o-toluidine, Methaqualone, Quaalude

Do Your Part To Win The War
 
 
 
 
    foxy2
(Distinctive Doe)
09-08-01 13:56
No 211344
      Re: Novel o-toluidine synthesis  Bookmark   

Reilly-Hickinbottom Rearrangement.





J. Reilly and W. J. Hickinbottom, J. Chem. Soc. 117, 103 (1920).
Ingold, Structure and Mechanism in Organic Chemistry (New York, 1953), p 615. (1962).
Hart, Kosac, J. Org. Chem. 27, 116(1962)



Do Your Part To Win The War
 
 
 
 
    PrimoPyro
(Hive Prodigy)
05-08-02 01:57
No 305963
      TFSE Is God  Bookmark   

Well, well! blush

I'll have you all know that I was just about to make a brand new thread, in this very forum about just this subject: the Hofmann-Martius Rearrangement, on N-phenyl methylamine (upon heating) to a mixture of ortho and para toluidine.

I decided at the last moment to UTFSE for this, and lo and behold, foxy2 beat me to it by several months. You bastard. tongue

So I will be content to merely bump this back up for re-recognition of the possibility, and perhaps add a little extra info, if I may.

http://themerckindex.chemfinder.com/TheMerckIndex/NameReactions/ONR193.htm

and http://www.chemfinder states that:

p-Toluidine CASRN: 106-49-0
m.p.43C b.p.201C r.d.0.962 water solubility 0.664 g/100 mL

o-Toluidine CASRN: 95-53-4
m.p.-14.7C b.p.200.2C r.d.1.008 water solubility Slightly soluble. 1.66 g/100 mL

Notice the ~50C difference in melting points, allowing for a method of seperation.

One could easily prepare the N-phenyl methylamine by condensing aniline (easy to get chemical from a supplier) with trioxane (a formaldehyde trimer) in an aluminum amalgam to reduce the imine. Formation of a crude HCl salt and thermal transformation would yield your mix of p- and o- toluidines, ready for seperation. smile

                                                 PrimoPyro

Vivent Longtemps La Ruche!
 
 
 
 
    halfapint
(Ubiquitous Precursor Medal Winner)
05-08-02 11:40
No 306164
      o-toluidine for my quinoline  Bookmark   

Could I carbonylate this o-toluidine to get o-amino benzaldehyde, I'd bee but a baby step (condensation with acetaldehyde) away from the o-amino cinnamaldehyde needed to make quinoline. Quinoline is used with copper to decarboxylate aromatic acids, which is something I need to do. Also, this ring geometry has got to bee a step toward indole, say it quietly or PolySam will get in here shoveling patent numbers on us.

a half a pints a half a pound a half a world a half a round
Sidearm n. Flask neck tube.
 
 
 
 
    Mountain_Girl
(Hive Bee)
05-08-02 12:01
No 306171
      Quinoline ?  Bookmark   

halfapint:

Surely you do know that quinoline can be prepared from aniline, glycerol & iodine ?
I'm rather interested in this idea of decarboxylating aromatic acids with quinoline/Cu - some details, references (or should I just UTFSE?)?
 
 
 
 
    halfapint
(Ubiquitous Precursor Medal Winner)
05-08-02 17:00
No 306254
      Not so surely I do know  Bookmark   

Post 305141 (halfapint: "Decarboxylating Benzoic", Chemistry Discourse) has my current grumbles about Decarboxylating Benzoic. Among the Organic Synthesis refs are mentions of aniline, glycerol and various other oxidants, but iodine is not among them. If you got a clue, shoot it to us.

For quinoline decarboxylation refs, I can only repeat Jerry March's list from Advanced Organic Chemistry. That's the only place I ever heard of it!

Cohen and Schambach, J. Am. Chem. Soc. 92, 3189 (1970)
Chowdowska-Palicka and Nilson, Acta Chem. Scand. 24, 3353 (1970)
Cairncross, Roland, Henderson and Sheppard, J. Am. Chem. Soc. 92, 3187 (1970)
Cohen, Berninger, and Wood, J. Org. Chem. 43, 837 (1978)

"In certain cases the carboxyl group can be replaced by groups other than hydrogen, e.g., NO"
Ibne-Rasa, J. Am. Chem. Soc. 84, 4962 (1962)
Tedder and Theaker, J. Chem. Soc. 257 (1959)
"or Br."
Grovenstein and Ropp, J. Am. Chem. Soc. 78, 2560 (1956)

JM has a few clues: "The reaction proceeds much faster if the acid is heated in quinoline with cuprous oxide instead of copper, provided that atmospheric oxygen is rigorously excluded... It has been shown that cuprous salts of aromatic acids are easily decarboxylated by heating in quinoline."

The real place to find information is interactively here at Hive. Last night I absorbed osmotically that I had prepared my benzoic batches wrong: I should have started with the salt, and then added another equivalent of lye, instead of starting with the free acid.

a half a pints a half a pound a half a world a half a round
Sidearm n. Flask neck tube.
 
 
 
 
    Mountain_Girl
(Hive Bee)
05-09-02 15:07
No 306695
      Quinoline from aniline,glycerol & iodine
(Rated as: excellent)
 Bookmark   

Preparation of Quinoline using aniline, glycerol and iodine:
Yields in this prep are not as good as the one using nitrobenzene (50% vs ~80%)

Preparation of Quinoline
(Source: Vogel's Textbook of Practical Organic Chemistry, 4th ed.,pg. 910)

This preparation should be done in a fume cupboard.

1) CH2OH.CHOH.CH2OH __> CH2=CH.CHO
2) C6H5.NH2 + CH2=CH.CHO __>  'hydroquinoline' __> quinoline

Equip a 250ml three-necked flask with a double surface condenser, a sealed stirrer unit and a screw-capped adapter carrying a thermometer positioned so that subsequently the temperature of the reaction mixture may be noted. Place 10g (9.8ml, 107mmol) of pure aniline, 15g (163mmol) of glycerol (*) and 0.5g iodine in the flask. Stir the reaction mixture and add down the condenser from a dropping funnel 30g (16.4ml, 306mmol) of conc. sulphuric acid. Reaction soon commences, the temp. rises to 100-105C. Heat the flask gradually, with stirring, in an air or oil bath to 140C; the reaction proceeds with the evolution of SO2 and a little iodine vapour and the liquid refluxes. Continue heating at 170C for 1 hr, allow to cool and then add cautiously with stirring sufficient 5 M NaOH soln (~ 85ml) to render the mixture alkaline. Rearrange the apparatus for steam distillation and steam distil until no more oily drops pass over. The distillate contains quinoline and a little aniline. Extract the distillate with 3x25ml portions of ether, combine the ethereal extracts and remove the ether on a rotary evaporator.

To remove the aniline present in the residual crude quinoline, advantage is taken of the fact that bis-quinolinium tetrachlorozincate(II) [(C9H8N)2+(ZnCl4)-2] is almost insoluble in water and crystallises out, whilst under the same experimental conditions, bis-anilinium tetrachlorozincate(II) [(C6H5.NH4)2+(ZnCl4)-2] remains in solution (**). Dissolve the crude quinoline in 100ml of dilute hydrochloric acid (1:4 by volume), warm the solution to 60C and add, with stirring, a solution of 13g (95mmol) of zinc chloride in a 22ml portion of the diluted hydrochloric acid. Cool the well stirred mixture thoroughly in ice-water and, when crystallisation is complete, filter the bis-quinolinium tetrachlorozincate(II) with suction, wash with two 10ml portions of dilute hydrochloric acid and drain well. Transfer the solid to a 250ml beaker, add a little water and then 10% NaOH soln until the initial precipitate of zinc hydroxide dissolves completely. Extract the quinoline with 3x25ml portions of ether in a separatory funnel and dry the combined ethereal extracts with calcium sulphate. Remove the ether by flash distillation using a 10ml flask and finally distil the residue from an air bath using an air condenser. Collect the quinoline at 236-238C as a colourless liquid: the yield is 6.9g (50%). If distilled under reduced pressure the b.p. is 118-120C/20 mm Hg.

(*)Lab grade glycerol may be used since anhydrous glycerol is not necessary when iodine is used as the oxidising agent. Anhydrous glycerol may be prepared by heating commercial grade glycerol in a porcelain evaporating dish carfully over a wire guaze (preferably in a fume cupboard), stirring it steadily with a thermometer until the temperature rises to 180C, allowing it to cool to about 100C, pouring it into a pyrex beaker and transferring the beaker to a dessicator containing conc. sulphuric acid. It must be remembered that glycerol is a very hygroscopic substance.

(**)An alternative method of removing aniline is to add 8ml of conc. sulphuric acid carefully to the steam distillate, cool the soln to 0-5C and add a concentrated soln of sodium nitrite until a drop of the reaction mixture colours potassium iodide-starch paper a deep blue instantly. As the diazotisation approaches completion, the reaction becomes slow; it will therefore be necessary to test for the excess of nitrous acid after an interval of five minutes, stirring all the while. About 3g of sodium nitrite are usually required.
The diazotised soln is then heated on a boiling water bath for an hour (or until active evlution of N2 ceases), treated with a solution of 15g of NaOH in 50ml water, the mixture steam-distilled and the quinoline isolated from the distillate by extraction with ether as above.