Author Topic: FC alkylation with oxiranes vs. aziridines  (Read 2777 times)

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Rhodium

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FC alkylation with oxiranes vs. aziridines
« on: January 15, 2004, 08:05:00 PM »
Friedel-Crafts alkylation of benzene only gives 2-phenyl-1-propanol and no 1-phenyl-2-propanol (P2Pol), this in contrast to the same reaction between benzene and propyleneimine (2-methyl-aziridine), which depending on the reaction conditions gives different ratios between 2-phenyl-2-aminopropane and 1-phenyl-2-aminopropane (amphetamine). The reaction of aziridine with substituted benzenes give moderate yields of phenethylamines.

Friedel Crafts Reactions of Three-Member Heterocycles I. Reaction of Propylene Oxide with Benzene
Norman Milstein

J. Het. Chem. 5, 337-338 (1968)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/friedel-craft.oxirane.pdf)

Abstract
The Friedel Crafts reaction of propylene oxide with benzene has been reinvestigated, and under anhydrous conditions the product is 2-phenyl-1-propanol.
____ ___ __ _

Friedel Crafts Reactions of Three-Member Heterocycles II. Alkylation of Aromatic Compounds with Aziridines
Norman Milstein

J. Het. Chem. 5, 339-341 (1968)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/friedel-craft.aziridine.pdf)

Abstract
The Friedel Crafts reaction of propylenimine with symmetrical arenes in the presence of aluminum chloride was investigated. Electron donating substituents increase the alpha-methyl-beta-phenethylamine/beta-methyl-beta-phenethylamine ratio, while increasing the temperature has the opposite effect. In the reaction of chlorobenzene or toluene with aziridine, the nature of the substituent has little effect on the ortho/para ratio.


josef_k

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Friedel-Crafts alkylation of benzene only...
« Reply #1 on: January 16, 2004, 01:08:00 AM »
Friedel-Crafts alkylation of benzene only gives 2-phenyl-2-propanol and no 1-phenyl-2-propanol (P2Pol)

But our russian comrades found a way (or is that a bunk patent?)

Post 310648 (missing)

(Chemikaze: "Translation", Russian HyperLab)

Rhodium

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The difference is in the details, apparently
« Reply #2 on: January 16, 2004, 01:38:00 AM »
It seems like the Russians have managed to circumvent the problem mentioned in the article above - that the propylene oxide is hydrolyzed before the alkylation takes place - by blowing dry helium gas through the reaction mixture to carry away any formed HCl.

Intact propylene oxide complexed with AlCl3 is alkylated by benzene in the least hindered position, yielding 1-phenyl-2-propanol.

If the propylene oxide first undergoes acid-catalyzed ring-opening, an isopropylic carbocation (carbonium ion) forms, which then attacks the benzene to form 2-phenyl-1-propanol.

So - by eliminating protic acids from the reaction mixture, the epoxide stays intact, and the more interesting of the isomeric alcohols can form. This is probably the explanation for the patent mentioning that "During this reaction HCl gas evolves, leading to low yields and an impure product, therefore He gas is allowed to flow through the reaction mixture."


yinga

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Re: Friedel-Crafts alkylation of benzene only...
« Reply #3 on: January 16, 2004, 02:58:00 AM »

Friedel-Crafts alkylation of benzene only gives 2-phenyl-2-propanol



Should this be 2-phenylpropanol?


Friedel-Crafts alkylation of benzene only gives 2-phenyl-2-propanol and no 1-phenyl-2-propanol (P2Pol),



Doesn't it sometimes give the 1-phenyl-2-propanol (up to 41% in the article)?  It was only reported to give exclusively the primary alcohol in one of the references and under the "strictly anhydrous" conditions of the reported experiment.  And then the translated patent above claims it gives the 1-phenyl also (not under anhydrous conditions).


Rhodium

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Yup
« Reply #4 on: January 16, 2004, 03:29:00 AM »
Should this be 2-phenylpropanol?

Yes, or more precisely 2-phenyl-1-propanol. I have edited my typos above.

Doesn't it sometimes give the 1-phenyl-2-propanol (up to 41% in the article)?

I'm just quoting their abstract. And as we can see ourselves by comparing the article and the russian patent, different experimental techniques gives different end products in the same general reactions.


yinga

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Re: If the propylene oxide first undergoes...
« Reply #5 on: January 24, 2004, 06:46:00 PM »

If the propylene oxide first undergoes acid-catalyzed ring-opening, an isopropylic carbocation (carbonium ion) forms, which then attacks the benzene to form 2-phenyl-1-propanol.

So - by eliminating protic acids from the reaction mixture, the epoxide stays intact, and the more interesting of the isomeric alcohols can form




Where does the acid come from?  I can understand where it comes from if water was present to react with the AlCl3, but  the anhydrous conditions of the article reported exclusive 2-phenyl anyways.


amine

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For those seeking the phenethylamine product.
« Reply #6 on: April 26, 2004, 05:39:00 PM »
Heres a synthesis for ethylenimine.
It worth noting that this compound is listed as "ACUTELY TOXIC" and also has been found to be a carcinogen by OSHA.
It has a boiling point around 60C which makes it pretty volatile. The p-aminoethylsulfuric acid (CAS# 926-39-6)
can be obtained from a few chemical suppliers. (Swim doesn't have the synthesis.).




        In a 5-l. flask surmounted by a water-cooled still head connected to a 30-in. spiral condenser set for downward distillation and connected to a well-cooled receiver (Note 1), 564 g. (4 moles) of ?-aminoethylsulfuric acid (Note 2) is mixed with 1760 g. (1230 ml.) of 40% sodium hydroxide solution (704 g. of sodium hydroxide in 1056 ml. of water). The mixture is heated with a free flame until it just begins to boil. At this point external heating is discontinued (Note 3). The reaction that begins at the boiling point keeps the mixture boiling for several minutes. When this initial reaction has subsided, heating is resumed and about 500 ml. of distillate is collected as quickly as possible in the well-cooled receiver. To the chilled distillate 450–500 g. of potassium hydroxide pellets is added gradually, whereupon the imine separates as an upper layer. The organic layers from four such 4-mole runs are combined and left overnight in a refrigerator over about 400 g. of potassium hydroxide pellets. The aqueous layers are combined and distilled through a wrapped 10-in. Vigreux column attached to a 30-in. spiral condenser. The distillate boiling at 50–100° is chilled thoroughly, and 200–250 g. of potassium hydroxide pellets is added gradually. The upper layer of crude ethylenimine is separated and combined with the larger portion of base (Note 4) and (Note 5).


If an aqueous layer appears during drying of the combined organic layers, the upper layer (about 575–600 g.) is again separated, 200 g. of potassium hydroxide pellets is added, and the whole is distilled through the same apparatus as that used for distilling the aqueous portion. If no layer appears, the base is decanted from the hydroxide and distilled from a fresh 200-g. portion of potassium hydroxide. The fraction boiling at 50–100° (about 350 g.) is collected and dried over 100 g. of potassium hydroxide pellets.


The crude ethylenimine is separated and dried over fresh 100-g. portions of potassium hydroxide until an aqueous layer no longer appears (Note 6). It is then decanted from the drying agent and redistilled from 100 g. of potassium hydroxide.


The yield of ethylenimine (b.p. 56–58°) is 235–250 g. (34–37%). A stick of sodium hydroxide is added to act as a preservative, and the material is best stored in sealed bottles in a refrigerator (Note 7), (Note 8), and (Note 9).

2. Notes
1. Cooling the receiver in a freezing mixture will cut the loss of the distillate to a minimum.
2. ?-Aminoethylsulfuric acid of excellent quality is available from the B. F. Goodrich Company.
3. It is well to have an ice bath available to control the exothermic reaction, which may become quite violent.
4. The use of an efficient distilling column is recommended because the crude base contains higher-boiling by-products. One of these is the dimer, N-?-aminoethylethylenimine; b.p. 126–127.5°.
5. It has been suggested that the portion of ethylenimine, boiling at 50–100°, might be collected directly on distillation without separating the organic layer from the aqueous potassium hydroxide layer. This is not advisable, because heating ethylenimine in the presence of a base appears to increase polymerization. The quantity of the organic base contained in the concentrated aqueous solution of potassium hydroxide is sufficient, however, to warrant this distillation of the aqueous layer.
6. If the original separation is done carefully and if sufficient potassium hydroxide is used, an aqueous layer will separate during the first drying only. Should this not be the case, it may be worth while to combine all aqueous portions obtained and redistil them to obtain any material boiling at 50–100°.
7. Yields of 26.5% and 32% of ethylenimine have been reported.2,3
8. Ethylenimine is strongly caustic and burns the skin. Inhalation of the vapor causes acute inflammation of the eyes, nose, and throat, with symptoms resembling those of bronchitis. After two or three days, the irritation subsides and the tissues return to normal, without suffering any apparent permanent injury. Continued exposure to the vapor may cause an individual to acquire an extreme sensitivity to it. Ethylenimine is also very inflammable and polymerizes with explosive violence under certain conditions.4,5
9. Redistillation over fresh potassium hydroxide of the residue from this final distillation gives an additional 10–15 g. of ethylenimine, boiling at 56–58°. This redistillation is advisable when the residues from three to four 16-mole batches are combined.


3. Discussion

Ethylenimine has been prepared from ?-bromoethylamine hydrobromide by reaction with silver oxide,6 potassium hydroxide,7 or sodium methoxide;8 from ?-chloroethylamine hydrochloride by reaction with sodium methoxide8 or sodium hydroxide;9 from ?-aminoethylsulfuric acid by reaction with sodium hydroxide;2,3,4,10,11 and by heating oxazolidone, or substances yielding it, to 100–300°.12


References and Notes

   1. Eastman Kodak Company, Rochester, New York.
   2. Wenker, J. Am. Chem. Soc., 57, 2328 (1935); Leighton, Perkins, and Renquist, J. Am. Chem. Soc., 69, 1540 (1947).
   3. Jones, Langsjoen, Neumann, and Zomlefer, J. Org. Chem., 9, 125 (1944).
   4. Mills and Bogert, J. Am. Chem. Soc., 62, 1177 (1940).
   5. Pingree, Am. Dyestuff Reptr., 35, 124 (1946).
   6. Gabriel, Ber., 21, 1049 (1888).
   7. Gabriel, Ber., 21, 2665 (1888); Gabriel and Stelzner, Ber., 28, 2929 (1895).
   8. Knorr and Meyer, Ber., 38, 3130 (1905).
   9. U. S. pat. 2,212,146 [C. A., 35, 463 (1941)].
  10. Brit. pat. 460,888 [C. A., 31, 4676 (1937)].
  11. Reeves, Drake, and Hoffpauir, J. Am. Chem. Soc., 73, 3522 (1951).
  12. Sundén (to Stockholms Superfosfat Fabriks A/B), Swed. pat. 148,559 [C. A., 50, 2679 (1956)].

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0433


ning

  • Guest
Hey guys
« Reply #7 on: April 26, 2004, 08:58:00 PM »
If HCl generated by FC alkylation is skrewing up yields, remember I posted an article on "High yielding allylation of benzene" or something like that?

They had exactly the same problem in alkylating benzenes with allyl chloride, because the formed HCl would react with the allyl group immediately and give a phenyl-2-propyl chloride. Their solution was to grind ZnCl2 with silica gel (their alkylation catalyst), and grind K2CO3 with alumina (HCl scrubber). Apparently, when this was done, the carbonate wouldn't bee able to destroy the lewis acid, and the alkylation gave allylbenzenes in high yields.

Perhaps this methodology could bee adapted to the problem at hand?


amine

  • Guest
Easier Ethylenimine Synthesis.
« Reply #8 on: April 29, 2004, 11:48:00 PM »
Can't find the specifics, but its called the "Gabriel Ethylenimine Method" which basically involved reacting the bromoethylamine with KOH.

Bromoethylamine can be made by reacting the cheap aminoethanol with HBr. The methods look easy, but this is chemistry not for the kitchen.

ethylenimine is very carginogenic according to swims research and is currently being tested in disturbing viral dna replication. The compound is also toxic and explosive. Be careful when if someone does attempt to make this aziridine.

Offline nomud2.0

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Re: FC alkylation with oxiranes vs. aziridines
« Reply #9 on: August 11, 2017, 08:31:16 PM »
Ber 66,p1100(1933)

Allychloride w/FeCl3 gave b-chloro-n-propylbenzene*.That should oxidize to something useful.
There are so many variations to the F/C schemes that eventually someone likely will get
a-hydroxypropanone to an extremely useful reagent in a general scheme.

At least it isn't nasty stuff like it's halo cousins.I think it's used in flavorings.
Funny thing is the alcohols are more reactive than the haloalkyls,just have to
keep in mind the carbonyl is reactive too.Maybe mask it eg; ketol etc.
Aziridines are really very nasty.

*PhCH2CHClCH3
All that and a bag of chips too ;)