Author Topic: propiophenone -drone 342  (Read 3776 times)

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dormouse

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propiophenone -drone 342
« on: April 19, 2000, 01:17:00 PM »
Author  Topic:   propiophenone 
drone 342
Member   posted 10-01-98 02:27 PM          
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By now, chances are that you've looked at the structure of propiophenone, and thought to yourself: truly, *something* good must be able to come out of it. 1-phenyl-1-propanone is far to similar to phenylacetone to let it be innocuous. I agree.
I was sitting in the bath the other day, when I realized that if propiophenone were to react with a strong base, an enolate id formed, rendering the 2-position on the propyl chain active for addition by an electrophile. The question is which electrophile? Clearly, this could yield cathinone, methicathinone, or some other analog, which would be quite interesting. However, by the clemmenson reduction, we got go-go. Any thoughts as to what reagent will do the job?

-drone #342


Osmium
Member   posted 10-01-98 03:51 PM          
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Let me suggest the following: nitrosation of propiophenone should give good yields of the hydroximino ketone (indanone + R-ONO does this in almost quantitative yield). Reduction with Pd/C produces amphetamine in about 70-80% yield. Need refs?
 
drone 342
Member   posted 10-01-98 05:35 PM          
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Though this isn't quite what I was looking for, its certainly interesting. I'd love some ref's, as well if you could a better explaination of what's going on mechanisticly.
-drone #342


Osmium
Member   posted 10-03-98 04:08 PM          
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I'm currently out of town and don't have my notes with me. I'll post it when I'm back home. The procedure comes from a JMC article, the one about indanone analogs of MDMA.
Propiophenone (well, indanone actually) is reacted with an organic nitrite forming Ph-CO-C(=NOH)-R. This apparently can be done with NaNO2/H+, too, but yields are probably higher with the organic nitrite. This intermediate is then reduced with Pd/C to the corresponding amphetamine.


Rhodium
Administrator   posted 10-06-98 04:41 PM          
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Propiophenone is halogenated in the 2-position, forming a 2-halo-propiophenone, which is reduced to the alcohol with Al(iPrO)3 and IPA, turned into the epoxide with the aid of K2CO3, and isomerized to the desired phenylacetone with LiI.
Many steps, yes, but all steps are dirt cheap and very simple, the yields are also high.


drone 342
Member   posted 10-07-98 12:01 AM          
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The following is the product of my strip-mining of Beilstein. Unfortunately, the list was more extensive, with far more goodies in the original version, but it got lost and this is take 2.
This is a really interesting method, since propiophenone is a very cheap, very industrial chemical. Propiophenones are easilt made with propionic acid, polyphosphoric acid, and any number of substituted benzenes -- 2,5-dimethoxypropiophenone's synth is listed in PiHKAL using this method. This would be an excellent means of producing the "DO" series (definately not my ally, but some people love 'em), as well as plenty of other ethereal delights.

The first reaction citations are propiophenones reacting with alkyl nitrites, follwoed by the reduction to amphetamine. The interesting part of this, in my ponion, is the *other* reactions involving the PhCO(C=NOH)Me intermediate -- cyclizations for synthesizing a galaxy of bizarre rigid-bodied and polycyclic analogs -- all uncharted territory in methylenedioxyland (indanes aside.) If there's any need for more information, there's dozens more reactions where these came from detailing even more about these little chemical anomolies.

BTW, I got the JMC article you were talking about -- 33; 2; 1990; 703-710. Actually, I already had this one, but hadn't remembered the chemical similarity.

-drone #342

Reaction

Reaction ID 724478
Reactant BRN 606215 1-phenyl-propan-1-one
1701036 nitrous acid butyl ester
Product BRN 509304 1-phenyl-propane-1,2-dione 2-oxime
-------------------------

Reaction Details

Reaction Classification Preparation
Reagent hydrogen chloride
diethyl ether
Ref. 1 1795343; Journal; Hartung; Crossley; ORSYAT; Org.Synth.; 16; 1936; 46;
Ref. 2 1795341; Journal; Hartung; Munch; JACSAT; J.Amer.Chem.Soc.; 51; 1929; 2264;

Reaction

Reaction ID 724534
Reactant BRN 606215 1-phenyl-propan-1-one
969510 3-methyl-1-nitrosooxy-butane
Product BRN 1908501 2--1-phenyl-propanone-(1)
-------------------------

Reaction Details

Reaction Classification Preparation
Ref. 1 1821372; Journal; Boeeseken; Tellegen; RTCPA3; Recl.Trav.Chim.Pays-Bas; 57; 1938; 133, 142;
Ref. 2 1821370; Journal; Galotti; GCITA9; Gazz.Chim.Ital.; 60; 1930; 866, 869;

Reaction

Reaction ID 724536
Reactant BRN 606215 1-phenyl-propan-1-one
969510 3-methyl-1-nitrosooxy-butane
Product BRN 509304 1-phenyl-propane-1,2-dione 2-oxime
-------------------------

Reaction Details

Reaction Classification Preparation
Reagent hydrochloric acid
Ref. 1 1778601; Journal; Claisen; Manasse; CHBEAM; Chem.Ber.; 22; 1889; 529;

Reaction

Reaction ID 724548
Reactant BRN 606215 1-phenyl-propan-1-one
Product BRN 1908501 2--1-phenyl-propanone-(1)
-------------------------

Reaction Details

Reaction Classification Preparation
Reagent NaCl
concentrated aqueous hydrochloric acid
isopropyl alcohol
NaNO2
Other conditions weiteres Reagens: konz. Schwefelsaeure
Ref. 1 1821373; Patent; Sharp & Dohme Inc.; US 2248035; 1938;

Reaction

Reaction ID 1319864
Reactant BRN 606215 1-phenyl-propan-1-one
Product BRN 509304 1-phenyl-propane-1,2-dione 2-oxime
-------------------------

Reaction Details 1 of 3

Reaction Classification Preparation
Reagent nBuONO, HCl
Solvent diethyl ether
Ref. 1 84368; Journal; Bennett,G.B. et al.; JMCMAR; J.Med.Chem.; EN; 21; 1978; 623-628;

Reaction

Reaction ID 281755
Reactant BRN 1908501 2--1-phenyl-propanone-(1)
Product BRN 507867 1-methyl-2-phenyl-ethylamine
-------------------------

Reaction Details

Reaction Classification Preparation
Reagent palladium
acetic acid
sulfuric acid
Other conditions Hydrogenation
Ref. 1 1934222; Journal; Kindler; Hedemann; Schaerfe; JLACBF; Justus Liebigs Ann. Chem.; 560; 1948; 215,219;


Zero
unregistered   posted 10-22-98 09:15 PM           
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m-chloro-propiophenone is used to make bupropion, an antidepressant & ADHD treatment. m-chloro-propiophenone + Br2 via
alpha-carbonyl bromination makes 2-bromo-propiophenone, then t-butylamine is reacts with that to make bupropion & HBr.
This could be applied to clandestine chem.:
React propiophenone with Br2 (or I2) to make 2-bromo(or iodo)propiophenone. Then react methylamine or ammonia to make the desired final compound. I have no refs.