Naf1

2-Benzyl aziridines
United States Patent 3925360

Aziridines of the formula (I) and the pharmaceutically acceptable acid addition salts thereof, in which Ar is a phenyl group optionally substituted by one or more hydroxy, halo, lower alkyl, lower alkoxy, halo(lower)alkyl, nitro, amino or mono- or di-(lower)alkyl-amino groups and R is hydrogen or lower alkyl possess anorectic properties. The appetite of a mammal may be inhibited by administering to it an aziridine of formula (I) or a pharmaceutically acceptable acid addition salt thereof. Aziridines of formula (I) in which Ar and R have the above defined meanings with the proviso that R is lower alkyl when Ar is phenyl, p-chlorophenyl or p-methoxyphenyl are novel compounds.
http://www.freepatentsonline.com/3925360.pdf

Quote
We have found that aziridines of the above general formula (I) possess anorectic properties. Accordingly the present invention provides a method of inhibiting the appetite of a mammal by administering to the mammal an anorectic amount of an aziridine of genral formula (I) or a pharmaceutically acceptable acid addition salt thereof. Although the mammal may be non-human, preferably it is a human.

The compounds of general formula (I), including the novel compounds, may be prepared by methods known in the art for preparing aziridines. For example, compounds of formula (I) in which R is hydrogen may be prepared by the Wenker method (see, for example, Brois, J. Org. Chem. 1962, 27, 3532 and Kashelikar et al., J. Amer. Chem. Soc., 1960, 82, 4930) in which a sulphate ester of an amino alcohol of general formula (IIb) is cyclised by treatment with alkali. The alkali may be, for example, sodium hydroxide. The sulphate esters may be prepared by esterification of the amino alcohols with sulphuric acid. The amino alcohol, preferably has the formula (IIb). The amino alcohols are described in the literature or may be prepared by methods known for preparing analogous compounds, for example by reduction of the corresponding amino acids.

In a third method of preparing an aziridine of general formula (I) in which R is hydrogen a haloamine of general formula (IVa) wherein Ar has the meaning given above and Hal is halogen, preferably bromo, may be cyclised with the elimination of hydrogen halide by treatment with a base such as an alkali metal hydroxide, e.g. potassium hydroxide. The haloamines of formulae (IVa) and (IVb) may be prepared by known methods.


"I thought that may interest you, as it would be a potentially interesting compound with an amphetamine like constitution. As aminorex, phenmetrazine, dextroamphetamine ect ect all have a very similar constitution and started life as simple anorectic compounds. Usually one would want to avoid aziridines as most are toxic, but not in this case! Also as a note to be aware of the formation of 2-benzylaziridine as a byproduct after it is iodized, moreso the hydrolysis analogous to ephedrine that causes problems. So a gentle halogenation followed by the procedure from this thread so minimize by-products (being a cleaner reduction with less by products than reducing ephedrine with HI). As the ammonium chloride reductive dehalogenation is very mild in comparison."

.......i have the phenylalaninol and at the moment I don't have the aziridine, however i have discussed this and have given the method to produce the aziridine in question.......and it's interesting that it has those properties...so a HCL salt of such product would be a good anorexic material for all thos fat asses.... java

however i have discussed this and have given the method to produce the aziridine in question.

Oh, I missed that! Sorry...

and it's interesting that it has those properties...so a HCL salt of such product would be a good anorexic material for all thos fat asses..

It is interesting it has those properties, and not only for fat asses! It would be very surprising if it did not have stimulant properties similar to amphetamine, aminorex, phenmetrazine and other anaolgous compounds that have also been used as anorectic agents. The N-methyl compound one would imagine is also analogous with 4-methyl aminorex, Methamphetamine, Phendimetrazine ect. A point that can be seen in the patent quoted above;

"Particularly preferred novel compounds of general formula (I) are those in which Ar is trifluoromethylphenyl, e.g. m-trifluoromethylphenyl, especially such compounds in which R is hydrogen or ethyl. The compounds in which Ar is trifluoromethylphenyl are particularly valuable since, in general, they have very little undesirable stimulant activity as measured by standard pharmacological tests. "

Which would indicate the others have "undesirable stimulant activity", it depends on who is telling the story whether that activity is undesirable or not though. And 2-benzylaziridine may well be just as strong a stimulant as dextroamphetamine, phenmetrazine, aminorex ect all the similar compounds that have also been used as anorectic agents at some stage in the past but ended up being pulled from the shelves for reasons such as increased recreational use and addiction. I would strongly suggest making a gram and testing it out (it may be better than amphetamine!).

The ester is made with sulphuric acid easily, then reaction with sodium hydroxide (done!)

Anorectic from wiki;

"Drugs of this class are frequently stimulants of the phenethylamine family, related to amphetamine (informally known as speed)."

"The German military experimented with issuing amphetamines to soldiers in 1945, when food supplies were very short in Germany. Following the Second World War, amphetamines were re-directed for use on the civilian market. Indeed, amphetamine itself was sold commercially as an appetite suppressant until it was outlawed in most parts of the world in the late 1950s due to increased recreational use."
http://en.wikipedia.org/wiki/Anorectic

@Jon;

1-Phenyl-2-amino-3-bromopropane Hydrobromide(I)-dl-Phenylalanine ethyl ester was converted to dl-Phenylalaninol, m.p.67-68*, by reduction with lithium aluminum hydride.
  A sealed tube containing 1.0 g.(0.006 mole) of dl-phenylalaninol and 25ml. of 48% hydrobromic acid was heated at 170-175* for five hours. The dark colored reaction mixture, in which some carbonized material was present, was diluted with 100ml of water and was decolorized with charcoal (Nuchar). The resulting water-white, strongly acid solution was taken to dryness under reduced pressure on the steam bath. The dry residue after crystallization from absolute alcohol weighed 1.27g (65%) and melted at 173-176*. A second crystallization (from 3ml of absolute alcohol) afforded 0.97 g (49%) of pure 1-phenyl-2-amino-3-bromopropane hydrobromide, m.p. 174-175*.
  When the reaction was carried out at 100* instead of 170*, the hydrobromide of dl-phenylalaninol was the only material isolated. This salt was prepared in a separate experiment by evaporating a mixture of 1.0 g (0.0066 mole) of dl-phenylalaninol and 25 ml of 48% hydrobromic acid under reduced pressure, and crystallizing the dry residual solids from ethyl alcohol. The hydrobromide obtained in this way (1.21 g or 79%) melted at 148-149*, and showed no change in meting point after admixture with the material (m.p. 148-149) obtained from the reaction at 100*
http://pubs.acs.org/doi/abs/10.1021/ja01137a505

That second paper you linked in that WD thread says it all, thanks!

2-Benzylaziridines. Cyclic analogs of amphetamines
Keith Brewster, Roger M. Pinder
J. Med. Chem., 1972, 15 (10), pp 1078–1079
DOI: 10.1021/jm00280a025

"It is likely lack of biological activity compared to amphetamine is due to the conformational restraint placed upon the molecule by incorporation of the amino function into the aziridine moiety, particularly since the analogous phenylcyclopropylamines exhibit considerable amphetamine like activity"

http://servente.area.ge.cnr.it/sds/DbToC/include/file_fr.php?id=3226632&wh=nm

Those things look fucking ugly for in vivo use.

the question is what.....?

My initial question before reading that link you posted was, how active is it as a stimulant compared to amphetamine? It turns out it is not only 0.1 of the activity of amphetamine but as Tsath pointed out it has antineoplastic properties like many other aziridines and as such I would not advise testing for activity....

My next question would be how harsh does the subsequent reduction to open the ring have to be? Obviously you dont want an acidic enviroment to reduce it.

Note: it doesn't get any easier , just using the Fe article to remove the chlorine in case ZnCl is used and the  aziridine doesn't need to be tosylated just make the 2-benzylaziridine and use the info on this article to open it and ............java

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An efficient route to regioselective opening of N-tosylaziridines with zinc(II) halides
Manas K. Ghorai, Kalpataru Dasa, Amit Kumara and Koena Ghosha
Tetrahedron Letters
2005, Volume 46, Issue 23, Pages 4103-4106
doi:10.1016/j.tetlet.2005.04.006;



Abstract
An efficient route for the regio- and stereoselective ring opening of N-tosylaziridines with zinc dihalides (ZnX2, X = Cl, Br, I) is described. Depending on the solvent and Zn(II) halide, ?-halo amines or imidazolines are obtained selectively in good to excellent yields.

Keywords: Aziridine; Zinc(II) halide; ?-Halo amine; [3+2] Cycloaddition

A new convenient approach to chiral beta-aryl(heteroaryl)alkylamines
Valentine G. Nenajdenko,* Alexei S. Karpov and Elizabeth S. Balenkova
Tetrahedron: Asymmetry 12 (2001) 2517–2527

Abstract—Chiral beta-aryl(heteroaryl)alkylamines have been prepared from N-tosyl alkylaziridines via regiospecific nucleophilic ring
opening and subsequent desulfonylation in good to excellent yields. The corresponding aziridines are easily obtained from
commercially available (S)-alpha-amino acids, so this method is the first effective route to asymmetric beta-aryl(heteroaryl)alkylamines.

http://psyhosting.info/Ionium/Rhodium/pdf/aziridine/n-tosyl-alkylaziridines.grignard.pdf

The presence of a suitable electron-withdrawing protecting group is necessary for effective ring opening. There are several protecting groups that could serve as activators of aziridine cleavage such as diphenylphosphinyl (Dpp),6 diethoxyphosphoryl7 and sulfonyl.8 In our synthesis, we chose the tosyl group as the activator. It is known that N-tosyl aziridines could be easily synthesized from commercially available natural alpha-amino acids using a one-pot modification of Craig’s protocol9 and following this procedure, we prepared N-tosyl aziridines from phenylalanine, leucine and valine (Scheme 2).

An efficient synthesis of both enantiomers of cathinone by regioselective reductive ring opening of substituted aziridines
Gweon Hwang, Jae-Ho Chung and Won Koo Lee
PII: S0040-4020(96)00702-8
Tetrahedron Vol 52, No 37 pp 12111-12116, 1996

Both enantiomers of cathinone were prepared as HCl salts from N-(R)-alpha-methylbenzylaziridine-2-(S)-carboxaldehyde and its enantiomer N-(S)-alpha-methylbenzylaziridine-2-(R)-carboxaldehyde in high yield. This process makes it possible to prepare other aromatic and heteroaromatic analogs of cathinone efficiently.

http://www.imagene.co.kr/ScienceTechnology/PDF/AnEfficientSynthesisofBothEantiomersofCathinonebyRegioselectiveReductiveRingOpeningofSubstitutedAziridines.pdf

Aziridines: epoxides’ ugly cousins?
J. B. Sweeney
Chem. Soc. Rev., 2002, 31, 247–258

Aziridines, the nitrogenous analogues of epoxides, have until recently excited far less interest amongst synthetic organic chemists than their oxygenated counterparts, with some justification. A range of reviews concerned with the physical properties,1 synthesis (asymmetric2 and otherwise3), reactions4 and utility of aziridines exists; this review briefly summarizes the similarities and differences between oxiranes and their nitrogenated analogues, concentrating on the underlying properties of aziridines and recent developments
in their chemistry. In addition to descriptions of the physical nature of aziridines, especially those features which underpin their utility as synthetic intermediates, the sections beneath describe reactions involving alkylative ringopening and synthesis of aziridines.

http://www.rsc.org/delivery/_ArticleLinking/DisplayArticleForFree.cfm?doi=b006015l

I posted this long ago at SM......however since the reactin deals with an aziridine i wonder if it will also open and established aziridine , in our case the 2-benzylaziridine.......i guess a test run is in order....java

the reactin below looks nice, save the  compounds used are not friendly.....however told " It isn't about reduction of aziridines, instead it is about using 2-methylaziridine in Friedel-Crafts reactions:
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Reference Information




Friedel crafts Reaction of three -Member Heterocycles II -Alkylation of Aromatic compounds with Aziridines
Norman Milstein
Journal of Heterocyclic Chemistry, pg.339, June 1968




Abstract
The Friedel Craft 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-phenethylaimine ratio, while  increasing the temparature 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.


Ref Information:


http://actrav.itcilo.org/actrav-english/telearn/osh/ic/75558.htm

PROPYLENIMINE
(synonym): 2-methylethylenimine; nist75-55-8; methylaziridine; methylethylenimine; 1,2-propyleneimine; 2-methylazacyclopropane; 2-methylaziridine; propyleneimine; 1,2-propylenimine
Chemical and Use Information
Chemical Abstract Symbol (CAS)
75-55-8
Additional CAS Numbers
None
Use Information
Propyleneimine is used as a chemical intermediate in the modification of latex surface coating resins, polymers in textile and paper industries, dyes, photography, gelatins, oil additives and organic synthesis. It is a comonomer for polymers with methacrylic acid and esters.

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