Sciencemadness Discussion Board - Dehalogenation an Aliphatic Hydrocarbon

Dehalogenation an Aliphatic Hydrocarbon

solo - 16-10-2005 at 17:31

Need a method to dehalogenate a chlorinated primary non -benzylic amino alcohol.....want to avoid the HgAl a well known OTC method.....also the catalytic hydrogenation is out of the option, hence have thought of using Hypophosphorous Acid for the dehalogenation. I would welcome more suggestions as I've thought of ZnCl +HCl but the yields are very low...........solo

BromicAcid - 16-10-2005 at 21:00

How about reduction with a nickel-aluminum alloy? Quote from the handbook of destructive procedures of hazardous chemicals in the lab.

Quote:

The halogenated compounds are reductively dehalogenated with nickel-aluminum (Ni-Al) alloy in dillute base to give the corresponding compound without the halogen. When the products are soluble in H2O the yield of product is good, but when they are not (for example, toluene from benzyl chloride) they are lost from solution and accountances are not complete. The product from chloronitrobenzenes is analine (concomitant reduction of the nitro group) and the product from the reduction of 3-chloropyridine is piperidine in 87% yield(concomitant reduction of the inital product pyridine).

Organic chem isn't really my thing and you probably thought of this already but I'm just trying to add to the discussion.

grignard

the alchemist - 17-10-2005 at 06:40

Make a grignard with Mg metal in diethyl ether and react the Grignard with plain 'ol water.

Marvin - 17-10-2005 at 07:27

Its an alcohol, so a grignard would fail. The information given is too sparse for me to suggest anything helpful. Sounds like you need to visit a university library solo.

solo - 17-10-2005 at 08:22

C6H5-CH2-CH(NH2)-CH2-CL-->>>>>>>>C6H5-CH2-CH(NH2)-CH3
Note:
An example of a chlorinated, former non-benzylic primary amino alcohol

As noted a primary halogen on an aliphatic compound..........solo

Sandmeyer - 17-10-2005 at 08:46

Quote:

Originally posted by Marvin
Its an alcohol, so a grignard would fail. The information given is too sparse for me to suggest anything helpful. Sounds like you need to visit a university library solo.

There is an amine there, but it dosen't matter in this case - as soon as Grignard is formed it will react with the amino group, giving:

C6H5-CH2-CH(NH2)-CH2-Cl + Mg --> [C6H5-CH2-CH(NH2)-CH2-MgCl] --> C6H5-CH2-CH(NHMgCl)-CH3

This could then be worked up to amphetamine, at least in theory.

[Edited on 17-10-2005 by Sandmeyer]

Nicodem - 17-10-2005 at 09:45

The problem is that the Grignard reaction don't initialize on protic substrate as far as I know. Though there might be some trick make it work.

But anyway, dear Solo, haven’t you been explained in the now unfortunately gone forum that your substrate of eternal interest does not exists as such. It can only exist in equilibrium with 2-benzylaziridine hydrochloride.
You can only have the stable salts of the compound you wrote down, like Ph-CH2-CH(NH2)-CH2Cl×HCl for example. This makes a big difference, making only the reductions in acidic environment feasible. If you want to use basic conditions (like Zn-Ni/ammonia for example) than you should consider the 2-benzylaziridine form and check the literature which product, either Ph-CH2-CH(NH2)-Me or Ph-CH2-CH2-CH2-NH2 would form after the reduction of this aziridine using the selected method.

[Edited on 17-10-2005 by Nicodem]

solo - 17-10-2005 at 18:34

Yes, I stand corrected its the HCl in the example.........its a long effort to make things easier and OTC for those that have run out of matches and have had their dreams
put out of reach, as for me catalytic hydrogenation with Pd works just fine...............solo

[Edited on 9-11-2007 by solo]

Nicodem - 18-10-2005 at 10:18

Solo, perhaps you will find the attached file interesting for your OTC optimization.
However, I hope you know that the hydrogenation of 2-benzylaziridine results in a controlled substance and is thus a reaction not allowed in most if not all countries of the world.
You might consider a much simpler diversion: doi:10.1016/S0022-1139(00)85218-5

[Edited on 18-10-2005 by Nicodem]

Attachment: 2-Benzylaziridines_Cyclic Analogs of A.pdf (277kB)
This file has been downloaded 1083 times

Sandmeyer - 24-11-2005 at 16:22

Speaking of aziridines. There is a nice method for the preparation of N-tosyl aziridines: http://www.organic-chemistry.org/pdf/mol/Molecules,2002,7,90...

These could serve for a conveniant preparation of phentermines, by ring opening with a ArMgX. Since aziridines are such unstable molecules (see below), I wonder if not arylzinc would be enough to open up the ring to corresponding N-tosyl phentermine. This route woeld be interesting particulary for DOI phentermine as the tosyl would possibly function as a protection group during some inexpensive iodination procedures.

Damn, I just saw that isobutanolamine (2-Amino-2-methyl-1-propanol) is dirt-cheap. Next week I could dig in litterature for such ring openings in case there is interest.

Typical Synthetic Procedures

Method A: Tosyl chloride (2.2 mmol) was added portionwise at r.t. to a stirred mixture of 3 (1.0 mmol), K2CO3 (4.0 mmol) and acetonitrile (2.0 mL). After 6 h, toluene (5 mL) was added, the solid was filtered off and the solvents evaporated.

Method B: Tosyl chloride (2.5 mmol) was added portionwise at r.t. under vigorous stirring to a mixture of KOH (2.0 g), 3 (1.0 mmol), water (2.0 mL) and CH2Cl2 (2.0 mL). After 30 min, ice and water were added, the organic layer was separated, washed with water, dried over MgSO4 and evaporated. The crude products were purified by crystallization, short-path distillation or column chromatography. The optical purities of all products were proven to be identical with those of the starting materials. The pure aziridines polymerize at r.t. within a few days, but can be stored at –30º for months.

[Edited on 25-11-2005 by Sandmeyer]

solo - 21-12-2005 at 18:03

As I recall aziridines are decomposed with hydrogenation using Pd as a catalyst however I don't recal if methanol was the solvent used.......as I recall Rhodium posted a method to make azaridines and the reduction to meth was by catalytic hydrogenation, I just can't locate the post.....solo

[Edited on 22-12-2005 by solo]

Sandmeyer - 21-12-2005 at 19:27

2-hexyl-1-(toluene-4-sulfonyl)-aziridine + phenylmagnesium bromide ----> (+/-)-N-(1-phenyloctan-2-yl)toluene-p-sulfonamide

Yield 94 percent
Solvent tetrahydrofuran
diethyl ether
Time 18 hour(s)
Other Conditions: Ambient temperature

Toshimitsu, Akio; Abe, Hideyuki; Hirosawa, Chitaru; Tamao, Kohei; J. Chem. Soc. Perkin Trans. 1; 23; 1994; 3465-3472.

--------------------------------------------------------

2-methyl-1-N-p-toluenesulfonylaziridine + phenylmagnesium bromide ----> N-(1-methyl-2-phenyl-ethyl)-toluene-4-sulfonamide

Yield 82 percent
Solvent tetrahydrofuran
Time 5 hour(s)
Other Conditions Heating

Lin, Pen-Yuan; Bentz, Gunther; Stamm, Helmut; J. Prakt. Chem./Chem.-Ztg.; 335; 1; 1993; 23-34. (in english)

------------------------------------------------

Too bad that those papers are out of my reach, could someone get them? Nice is that reaction is done at or above the room temperature, there are other refs where this is done at - 30 C...

-------------------------------------------------

General procedure for desulfonylation

To a suspension of Mg (0.45 g, 20 mmol) in MeOH (5 mL) was added a solution of the corresponding N-tosylalkyl-2-aryl (heteroaryl)amine (2 mmol) in MeOH (10 mL). The resulting suspension was sonicated for 1 h until consumption of the starting material was complete. The reaction mixture was then diluted with aqueous NH4Cl and extracted with ether (3×5 mL). The organic layer was dried over MgSO4 and evaporated. To resulting oil ethanolic solution HCl (0.5 mL, c 2 M) was added. Hydrochloride was precipitated, filtered and
washed with ether.

The method is from V. G. Nenajdenko et al. /Tetrahedron : Asymmetry 12 (2001) 2517–2527

A new convenient approach to chiral β-aryl(heteroaryl)alkylamines

Abstract

Chiral β-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)-α-amino acids, so this method is the first effective route to asymmetric β-aryl(heteroaryl)alkylamines.

Paper: http://rapidshare.de/files/9612711/A_new_convenient_approach...

------------------------------------

Selective removal of electron-accepting p-toluene- and naphthalenesulfonyl protecting groups for amino function via photoinduced donor acceptor ion pairs with electron-donating aromatics

Tatsuo Hamada, Atsushi Nishida, Osamu Yonemitsu;
J. Am. Chem. Soc.; 1986; 108(1); 140-145.

Abstract: When N-tosylamines (3a, 3b, 7, 17a, 17b, 21,23) in aqueous ethanol were irradiated with a high-pressure mercury lamp in the presence of an electron-donating aromatic such as 1,2- (6) and 1,4-dimethoxybenzenes (10) and 1,5-dimethoxynaphthalene (14) and a reductant (sodium borohydride, ascorbic acid, ammonia borane, hydrazine), a photochemical detosylation proceeded quite easily to give the corresponding amines (4a, 4b, 8, 18a, 18b, 22,24) in the high yields. On irradiation in the presence of 10 and sodium borohydride, N-(naphthalenesulfonyl)phenethylamine (19) also gave 4a. Mechanistic studies based on fluorescence quenching, quantum yield measurement, and free energy change calculation show that this photoreaction involves an electron transfer from an electron-donating aromatic to an electron-accepting sulfonamide. A preliminary application for the synthesis of lysine peptides was also described.

Paper: http://rapidshare.de/files/9612979/desulfonylation.pdf.html

----------------------------

There is also a paper describing preparation of N-tosyl aziridines from cheap alpha-amino acids: Berry, M.; Craig, D. Synlett 1992, 41.

[Edited on 22-12-2005 by Sandmeyer]

[Edited on 22-12-2005 by Sandmeyer]

solo - 3-6-2006 at 12:18

Aziridine reference material.....

Regio- and Stereocontrolled Nucleophilic Ring Opening of Chiral Oxazolidines by
Diethylaluminum Cyanide. A Short and Efficient Route to Enantiomerically Enriched a-Amino Esters
Celia Andrh Alicia Maestro, Rafael Pedrosa,* Alfonso Perez-Encabo, Martina Vicente
Synlett 1992, pg.47

Abstract: i-Amino esters 7 are prepared in good chemical yield and enantiomeric excess (53-86%) by ethanolysis and subsequent debenzylation of the &amino nitriles 5 obtained by regio- and stereocontrolled ring opening of N-benzyl-2-phenylglycinolderived oxazolidines 4 (2-alkyl-3-benzyl-4-phenyloxazolidines) with diethylaluminum cyanide.

Attachment: regio and stereocontrolled neuclophilic ring opening of chiral oxazolidines by diethylaluminum cyanide....pdf (176kB)
This file has been downloaded 1127 times

solo - 18-7-2006 at 12:30

Quote:

Originally posted by Nicodem
Solo, perhaps you will find the attached file interesting for your OTC optimization.
However, I hope you know that the hydrogenation of 2-benzylaziridine results in a controlled substance and is thus a reaction not allowed in most if not all countries of the world.
You might consider a much simpler diversion: doi:10.1016/S0022-1139(00)85218-5

Attachment: 2-Benzylaziridines_Cyclic Analogs of A.pdf (277.41kb)
This file has been downloaded 85 times

In the procedure of recovering the 2-benzylaziridine , why is it necessary to have ether and NaOH pellets in the receiving vessel can on just have ethanol or is ether necessary as the product will be dissolved in ethanol for further RX to the amine ?

Also will hydrogenation give the correct configuration for the desired amine ? any suggestions on where to look for the answer?

Enclosed the original study referenced in the article Nicodem so kindly provided and gave so much insight.........solo

--------------------------------------------------------------------------------------------

Chemistry of Ethylenimine. VIII. Stereospecificity in the Pyrolytic Rearrangement of 1-(p-Nitrobenzoyl)-Z-benzylaziridinel
D. V. KASHELIKAARN D PAULE . FANTA
J. Amer. Chem. Soc., 82, 4930, (1960)

Abstract
Refluxing a solution of l-(p-nitrobenzoyl)-2-benzylaziridiinne toluene for twenty-four hours gave a 91 yo yield of KThe observation is best explained in terms of an intramolecular reaction mechanism. The rearrangement is therefore (Irans-cinnamy1)-p-nitrobenzamide. in which the cis-elimination of a proton is concerted with the opening of the aziridine ring. Analogous in facility and stereospecificity to the Chugaev reaction and the Cope reaction of tertiary amine oxides.

[Edited on 18-7-2006 by solo]

Attachment: Chemistry of Ethylenimine.pdf (245kB)
This file has been downloaded 960 times

solo - 19-7-2006 at 05:35

Although this thread started out to be about dehalogenation of aliphatic hydrocarbons , the premise was the downside of removing an OH site via halogenation then reductive dehalogenation. However it was suggested perhaps tosylating or making an aziridine would be an easier method hence an easier leaving group.

With this in mind I then provide this article dealing with the removal of the aziridine via ring opening to the amine.

--------------------------------------------------------------------------------------------

NEW SYNTHETIC “TRICKS”. [Et3NH][Sn(SPh)d AND Bu2SnH2, TWO USEFUL REAGENTS FOR THE REDUCTION OF AZIDES TO AMINES
Mart1 Ebrtra, Felix Urpl. and Jaume Vilarrasa
Tetrahedron Letters Volume 28, Issue 47 , 1987, Pages 594-5944

Abstract
Treatment of Sn(SPh)z with PhSH and Et3N affords a tin(II) complex, soluble in organic solvents, which is the best reducing agent for azides reported so far. Bu2SnH2. although not so reactive, also shows several advantages with regard to the standard reducing agents for azides. such as its solubility in most solvents or its scarce reactivity with water.

[Edited on 19-7-2006 by solo]

Attachment: NEW SYNTHETIC TRICKS FOR THE REDUCTION OF AZIDES TO AMINES.pdf (326kB)
This file has been downloaded 1161 times

solo - 24-7-2006 at 08:51

A Novel, Simple, Chemoselective and Practical Protocol for the Reduction of Azides Using In / NH4CI
G. Vidyasagar Reddy*, G. Venkat Rao and D.S. Iyengar
Tetrahedron Letters 40 (1999) 3937-3938

Abstract : A simple, mild and efficient method for the reduction of azides to
amines using In / NH4C1 is described. © 1999 Elsevier Science Ltd. All rights reserved.

Note: I wonder if the Indium powder can be reused? since it's quite expensive 5gr. $66.40....if so this would be a nice method to reduce aziridines to amines

Note: I stand corrected as I mis-assumed that azides would cover the azaradines but as noted azaridines=/= azides......I will nevertheless leave the post as it's a good article for reference in reduction of azides...............solo

Note: additional reference from,

---------------------------------------------------------------------------------

Chemistry of Ethylenimine. VIII. Stereospecificity in the Pyrolytic Rearrangement of 1-(p-Nitrobenzoyl)-Z-benzylaziridinel
D. V. Kashelikar and P. E. Fanta
J. Amer. Chem. Soc., 82, 4930, (1960)

http://rapidshare.de/files/26905399/Chemistry_of_Ethylenimin...

Abstract
Refluxing a solution of l-(p-nitrobenzoyl)-2-benzylaziridiinne toluene for twenty-four hours gave a 91 yo yield of KThe observation is best explained in terms of an intramolecular reaction mechanism The rearrangement is therefore (Irans-cinnamy1)-p-nitrobenzamide. in which the cis-elimination of a proton is concerted with the opening of the aziridine ring. analogous in facility and stereospecificity to the Chugaev reaction and the Cope reaction of tertiary amine oxides.

Excerp
Experimental6
( *)-Phenylalaninol (IIIa) was prepared as previously
described.' Treatment of the amino alcohol with phenyl
isothiocyanate gave the N-phenylthiocarbamyl derivative,
shining, colorless plates from ethanol, m.p. 17O-1ilo.
Anal. Calcd. for C16H18XLOS: C, 67.10; H, 6.33; IC,
9.78. Found: C, 67.18; H, 6.80; S, 9.82.
(=I=)-Phenylalaninyl Hydrogen Sulfate (IIIb) .-To a cold
suspension of phenylalaninol(l2.0 9.) in 30 ml. of water was
added 10.0 g. of cold 95% sulfuric acid. The light yellow
solution was heated in a metal-bath at 120' to remove water,
first at atmospheric pressure and finally at 130-140' (15
mm.). The brown residue was recrystallized from 100 ml.
of 407; aqueous ethanol with concentration of the mother
liquors to give a total crop of 14.5 g. (79';

of shining, elongated
needles. Xn additional recr)-stallization from 956;,
ethanol gave the analytical sample, m.p., becomes brown at
250' and decomposes at 266-270' (uncor.).
Anal. Calcd. for CsHlaA-08: C, 46.74; H, 5.66; S,
6.06. Found: C, 46.84; H, 5.63; S, 5.66.
(&-Z-Benzylaziridine (IVa).-.k solution of 11 .0 g. of the
sulfate ester and 10.0 g. of sodium hi-droxide in 35 ml. of
water was heated in a distilling flask, and the distillate was
collected in a cooled receiver containing 50 ml. of ether over
sodium hydroxide pellets. During the distillation, water
was added intermittently to the distilling flask whenever the
residue began to crystallize. When the condensate no
longer contained oily drops, the ether layer was separated
and the aqueous layer was extracted with three 30-ml. portions
of ether. The combined ether solution was dried cver
sodium hydroxide pellets, concentrated, and distilled through
a short column, giving 4.8 g. (76'3,) of colorless imine with a
characteristic sharp odor, b.p. 73-75' (1 mm.), %*OD 1.5431,
,,,A, 3 . 1(~N -H band).
Anal. Calcd. for CSH~INC: , 81.15; H, 8.33; S, 10.52.
Found: C,81.03; H,8.75; N, 10.05.

[Edited on 25-7-2006 by solo]

Attachment: A Novel Simple Chemoselective and Practical Protocol for the Reduction of Azides Using In -NH4CI.pdf (114kB)
This file has been downloaded 955 times

solo - 24-7-2006 at 08:55

Note: As a side note and observation not to deviate from the topic of the thread ......

I'm wondering if the method of making azidirines would work in benzyl type amino alcohols....following the approach used in the primary non benzylic amino alcohol used in the synthesis of 2-benzylaziridine. If this is so then it would be a great way to convert benzyl type amino alcohols to the respective amines .....in theory of course........solo

[Edited on 24-7-2006 by solo]

Sandmeyer - 24-7-2006 at 11:08

Quote:

Originally posted by solo
A Novel, Simple, Chemoselective and Practical Protocol for the Reduction of Azides Using In / NH4CI
G. Vidyasagar Reddy*, G. Venkat Rao and D.S. Iyengar
Tetrahedron Letters 40 (1999) 3937-3938

Abstract : A simple, mild and efficient method for the reduction of azides to
amines using In / NH4C1 is described. © 1999 Elsevier Science Ltd. All rights reserved.

Note: I wonder if the Indium powder can be reused? since it's quite expensive 5gr. $66.40....if so this would be a nice method to reduce aziridines to amines

I wouldn't be surprised to see a synthesis of acetic acid from acetic anhydride using 10 eq. gold under 10000 atm pressure with no experimental details in the comming issue of tetrahedron Letters, it's pure crap, like reading chemistry gossips. I was even stupid enough to waste some precious starting materials by following methods (or better hints) published in that journal, they sounded wonderful but there was a catch - they simply don't work. I'd guess that from the late 1980-ies the quality became worse and worse. Anyways, azides can be reduced with a number of different agents, but I see no relevance, are you maybee misstaking aziridines for azides?

[Edited on 24-7-2006 by Sandmeyer]

solo - 24-7-2006 at 11:25

Quote:

Originally posted by Sandmeyer

Quote:

I think you're right Sandmeyer I have made a false assumption in equating aziridines with azides , thinking azides as a general term for the former......I guess closer reading is in order...thanks for the point of reference I will need to read some more......................solo

Nicodem - 24-7-2006 at 11:40

???

AZIDES =/= AZIRIDINES

Edit:
Solo, sorry for repeating what Sandmeyer already told you. I only noticed today. Do you have access to chemistry databases (Beilstein, SciFinder)? If so, do a search on the transformation R-CH2-CH(NH)CH2 => R-CH2-CH(NH2)-CH2 and I’m sure you will find a regioselective enough reagent for your reduction. Remember to use a terminal aziridine as an example. This is most important, especially with reductions based on the hydride addition mechanism. Also, N-tosyl- or N-acyl- aziridines may behave differently so find examples on N-unsubstituted or N-alkyl aziridines first.

[Edited on 25-7-2006 by Nicodem]

not_important - 24-7-2006 at 14:32

The indium gets oxidized in that reaction, similar to using Al, it would have to be recovered from the aq portion. Electrolytic recovery would likely work.

Getting it back to a powder might be tricky, it's pretty soft. Perhaps melting it under mineral oil or kerosene, stirring like crazy, and letting it cool; finally filter it off and wash with pet ether. I don't remember if there are any reductions that would let you take the hydroxide or chloride to the metal below the melting point.

A related reduction using In/NH4Cl, for aromatic nitro compounds
http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=v81...

solo - 26-7-2006 at 18:09

Sorry to say Nicodem I live in a remote area , I'm lucky to have acquired access to some data bases from friends but no access to the research data bases you mentioned. I must admit aziridines are interesting quite unlike azides,which they have their own story to tell, , as it was brough to my attention ......thanks,............

while on the subject of ring closed amph......would anybody know if any of this compounds listed are restricted......

Closed Ring Amph Analogs

2-benzylaziridine
2-benzylazetidine
2-benzylpiperidine
3,4-dichloro-methylphenidate
ethylphenidate
N3-methyl-4-methylaminorex
3-methyl-(1-phenylcyclobutyl)butanamine
N-ethylcathinone

Had been looking for this article on the catalytic hydrogenation reduction of aziridines ......and found it over at Rhodiums archives............solo
----------------------------------------------------------------------------------------------

[Edited on 27-7-2006 by solo]

Attachment: (S)-fenfluramine.pdf (634kB)
This file has been downloaded 1696 times

Nicodem - 27-7-2006 at 11:47

Solo, attached is another paper on the reduction of terminal aziridines to secondary amines:

Hwang, Chung, and Lee. Efficient Synthesis of Ephedra Alkaloid Analogues Using an Enantiomerically Pure N-[(R)-(+)-r-Methylbenzyl]aziridine-2-carboxaldehyde. J. Org. Chem., 1996, 61, 6183-6188.

Several 2-benzylaziridines having an OH group on the benzylic position were reduced to the appropriate 1-aryl-1-hydroxy-2-aminopropanes with H2 and Pd(OH)2 at ambient temperature and pressure. The amount of catalyst used is a bit exaggerated, but it should be possible to lower it by increasing H2 pressure.

PS: Get yourself also the following reference in case you still don’t have it. It isn't about reduction of aziridines, instead it is about using 2-methylaziridine in Friedel-Crafts reactions:
Milstein, N. Friedel-Crafts reactions of three-member heterocycles. II. Alkylation of aromatic compounds with aziridines. Journal of Heterocyclic Chemistry, 1968, 5(3), 339-341.

Attachment: J_Org_ Chem_61_ 6183-6188.pdf (211kB)
This file has been downloaded 947 times

solo - 24-8-2006 at 07:51

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:

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.

--------------------------------------------------------------------------------------------------

[Edited on 24-8-2006 by solo]

Attachment: Friedel Crafts Reactions of Three-Member Heterocycles II. Alkylation of Aromatic Compounds with Aziridines.pdf (149kB)
This file has been downloaded 882 times

solo - 3-9-2006 at 11:54

In March's text 5th edition on page 1328 the following..................

----------------------------------------------------------------------------------------------------

When proton acids catalyze alcohol dehydration, the mechanism is El.(160 )The
principal process involves conversion of ROH to ROH^ and cleavage of the latter to
R+ and H2O, though with some acids a secondary process probably involves
conversion of the alcohol to an inorganic ester and ionization of this (illustrated for
H2SO4):

..........................H2SO4
ROH ••>>>>>>>>>>>>> ROSO2OH •--------->.• R+ + HSO4

Note that these mechanisms are the reverse of those involved in the acid-catalyzed
hydration of double bonds (15-3), in accord with the principle of microscopic
reversibility. With anhydrides (e.g., P2O5, phthalic anhydride) as well as with some
other reagents such as HMPA,(161) it is likely that an ester is formed, and the leaving
group is the conjugate base of the corresponding acid. In these cases, the mechanism
can be El or E2. The mechanism with A12O3 and other solid catalysts has been
studied extensively but is poorly understood.(162)
Magnesium alkoxides (formed by ROH + Me2Mg —>ROMgMe) have been
decomposed thermally, by heating at 195-340°C to give the alkene, CH4, and
MgO.(163) Syn elimination is found and an Ei mechanism is likely. Similar
decomposition of aluminum and zinc alkoxides has also been accomplished.(164)

REF:
(160) For reviews of dehydration mechanisms, see Vinnik, M.I.; Obraztsov, PA. Russ. Chem.
Rev., 1990,59,63; Saunders Jr., W.H.; Cockerill, A.F. Ref. 3, pp. 221, 317; Knozinger, H. in
Patai The Chemistry of the Hydwxyl Group, pt. 2; Wiley: NY, 1971, p. 641.

(161) See, for example, Kawanisi, M; Arimatsu, S.; Yamaguchi, R.; Kimoto, K. Chem. Lett.,
1972, 881.

(162) For reviews, see Beranek, L.; Kraus, M. in Bamford; Tipper, Ref. 3, vol. 20, 1978, p. 274;
Pines, H. Intra-Sci. Chem. Rep., 1972, 6(2), 1; see pp. 17-21; Noller, H.; Andreu, P.;
Hunger, M. Angew. Chem. Int. Ed Engl, 1971,10, 172; Knozinger, H. Angew. Chem. Int.
Ed. Engl., 1968, 7,791. See also Berteau, P.; Ruwet, M.; Delmon, B. Bull. Soc. Chim. Belg.,
1985, 94, 859.

(1 6 3)Ashby, E.C.; Willard, G.F.; Goel, A.B. J. Org. Chem., 1979, 44, 1221.

(1 6 4)Reference 163; Brieger, G.; Watson, S.W.; Barar, D.G.; Shene, A.L. J. Org. Chem., 1979,
44, 1340.
------------------------------------------------------------------------------------------------------------

..............so the alcohol converts to the ester, then the ester is reduced to the hydrocarbon and HSO4:Noting that when applied to a primary non benzylic amino alcohol the amine won't be affected by the acidic environment, ...........through thermal decomposition( pyrolysis) ........but is it too high to destroy a phenylalaninol?

................I guess I better check the references next................solo

cuprate - 5-9-2006 at 16:19

I understand catalytic hydrogenation is not an option for you. How about other sources other than hydrogen gas? For example, NH4Cl/Pd/C in refluxing methanol or hexadiene/Pd/C?

other option will be butyl lithium. Although you have alcohol in your molecule, you just need waste one extra equivalent butyl lithium, and then quench it with water. However, depend on your molecule, elimination to ether might happen.

Quote:

Originally posted by solo
Need a method to dehalogenate a chlorinated primary non -benzylic amino alcohol.....want to avoid the HgAl a well known OTC method.....also the catalytic hydrogenation is out of the option, hence have thought of using Hypophosphorous Acid for the dehalogenation. I would welcome more suggestions as I've thought of ZnCl +HCl but the yields are very low...........solo

Sandmeyer - 15-9-2006 at 15:29

I stated in another speed thread that afromentioned dehalogenation will probably work if you reflux the hydrochloride salt of the chloride in formic containing excess zinc. To skip one extra (albeit very easy) step the amino acid can be taken down directly with boran, and by UTFSE you'll find a paper for in situ preparation of it from relatively OTC chemicals.

[Edited on 16-9-2006 by Sandmeyer]

LSD25 - 21-1-2008 at 06:38

Quote:

Originally posted by solo
In March's text 5th edition on page 1328 the following..................

----------------------------------------------------------------------------------------------------

When proton acids catalyze alcohol dehydration, the mechanism is El.(160 )The
principal process involves conversion of ROH to ROH^ and cleavage of the latter to
R+ and H2O, though with some acids a secondary process probably involves
conversion of the alcohol to an inorganic ester and ionization of this (illustrated for
H2SO4):

..........................H2SO4
ROH ••>>>>>>>>>>>>> ROSO2OH •--------->.• R+ + HSO4

Note that these mechanisms are the reverse of those involved in the acid-catalyzed
hydration of double bonds (15-3), in accord with the principle of microscopic
reversibility. With anhydrides (e.g., P2O5, phthalic anhydride) as well as with some
other reagents such as HMPA,(161) it is likely that an ester is formed, and the leaving
group is the conjugate base of the corresponding acid. In these cases, the mechanism
can be El or E2. The mechanism with A12O3 and other solid catalysts has been
studied extensively but is poorly understood.(162)
Magnesium alkoxides (formed by ROH + Me2Mg —>ROMgMe) have been
decomposed thermally, by heating at 195-340°C to give the alkene, CH4, and
MgO.(163) Syn elimination is found and an Ei mechanism is likely. Similar
decomposition of aluminum and zinc alkoxides has also been accomplished.(164)

REF:
(160) For reviews of dehydration mechanisms, see Vinnik, M.I.; Obraztsov, PA. Russ. Chem.
Rev., 1990,59,63; Saunders Jr., W.H.; Cockerill, A.F. Ref. 3, pp. 221, 317; Knozinger, H. in
Patai The Chemistry of the Hydwxyl Group, pt. 2; Wiley: NY, 1971, p. 641.

(161) See, for example, Kawanisi, M; Arimatsu, S.; Yamaguchi, R.; Kimoto, K. Chem. Lett.,
1972, 881.

(162) For reviews, see Beranek, L.; Kraus, M. in Bamford; Tipper, Ref. 3, vol. 20, 1978, p. 274;
Pines, H. Intra-Sci. Chem. Rep., 1972, 6(2), 1; see pp. 17-21; Noller, H.; Andreu, P.;
Hunger, M. Angew. Chem. Int. Ed Engl, 1971,10, 172; Knozinger, H. Angew. Chem. Int.
Ed. Engl., 1968, 7,791. See also Berteau, P.; Ruwet, M.; Delmon, B. Bull. Soc. Chim. Belg.,
1985, 94, 859.

(1 6 3)Ashby, E.C.; Willard, G.F.; Goel, A.B. J. Org. Chem., 1979, 44, 1221.

(1 6 4)Reference 163; Brieger, G.; Watson, S.W.; Barar, D.G.; Shene, A.L. J. Org. Chem., 1979,
44, 1340.
------------------------------------------------------------------------------------------------------------

..............so the alcohol converts to the ester, then the ester is reduced to the hydrocarbon and HSO4:Noting that when applied to a primary non benzylic amino alcohol the amine won't be affected by the acidic environment, ...........through thermal decomposition( pyrolysis) ........but is it too high to destroy a phenylalaninol?

................I guess I better check the references next................solo

There are patents (ho, ho, ho and so on) where the sulfate ester is formed by heating the amino alcohol with ammonium sulfate or ammonium bisulfate (eg. http://www.wikipatents.com/4597911.html), but it is unclear (to say the least) whether this works and of course also as to whether this is applicable to either the primary amino alcohol or the corresponding benzylic variant.

solo - 21-1-2008 at 07:10

There was some interesting stuff posted here i.e. 2-benzylaziridines, from primary amino alcohols, the ester with sulfuric acid and the ring made with destillation over NaOH......all but to open the ring and maybe even methylate the amine if that's your pleasure.......solo

https://sciencemadness.org/talk/viewthread.php?tid=4654&...

LSD25 - 21-1-2008 at 07:20

I was thinking this may be of some minor interest:

http://v3.espacenet.com/origdoc?DB=EPODOC&IDX=gb509661&a...

Of course that patent only deals with the benzylic sulfate ester variant, but I was wondering if the same would work with the primary amino alcohol sulfate ester?

dangator - 24-1-2008 at 23:25

Or just using a hydride reductant?

LSD25 - 26-1-2008 at 03:49

What hydride would you suggest?

I expect it is possible that that would only take the amino acid to the alkanolamine? Not to the alkylamine?

I mean, if you have a good reference and it seems legitimate, it 'MIGHT' be possible that some hydride reductant could do this (seems odd that it has escaped notice by several thousand researchers - both serious professionals and interested amateurs), although I for one would probably take some convincing. Nonetheless, if you could point me in the right direction, I am more than interested in sharing in such a momentous discovery.

Solo,

Read that patent, it seems to be a lot more realistic than some I have read. Granted this is no guarantee of reproducibility, but it seems like a possibility. If that doesn't work, it is known that a tosyl group works (removed with ZnI IIRC), so it is entirely possible that a mesyl group would do the job. Given that, the use of a sulfate ester doesn't seem such a stretch - it converts the horribly difficult to remove OH to a sulfate ester, the same leaving group that adheres to the OH group with either tosyl/mesyl addition. Given that this is a good leaving group and doesn't cause cyclization (at least it isn't mentioned in the various articles on the use of these in the reduction of tyrosine/phenylalanine via there amino alcohols), it may be worthwhile looking into how to graft the sulfate ester (rather than the mesyl/tosyl) onto the primary alcohol function.

dangator - 26-1-2008 at 14:28

Whoops, was looking at the original fifth post where we were going from a simple alkyl halide to alkane. My mistake.

[Edited on 26-1-2008 by dangator]