Author Topic: 3 syntheses  (Read 690 times)

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zero_nrg

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3 syntheses
« on: October 29, 2003, 07:35:00 PM »
I've been reading the threads/patent/book regarding the syntheses numbered 1,2,3 below and have a few questions.  I'm hoping that wise bees might provide some speculative/theoretical ideas.

SYNTHESIS 1: Bromine + propionic acid +  phosphorus trichloride  ---> alpha-bromopropionic acid as per Vogel pg 430

https://www.thevespiary.org/rhodium/Rhodium/chemistry/vogel3.html



Questions:

A) With regard to Fig. III,2,1 pg. 272 (Vogel 3rd ed.) in this apparatus set-up (flask and condenser inclined slightly) for the synth on pg. 430 why does Vogel indicate (pg 273) "the flask must be inclined during the refluxing period as shown in the figure"?  What difference would this make?  Just curious about this - I hope to understand the principle here.

B) If Vogel had scaled this reaction to 20 moles or more, would he have changed any molar ratios in the reaction?


SYNTHESIS 2: alpha-bromopropionic acid + sodium nitrite + magesium ion, DMSO as solvent--> nitroethane as per USP 4319059 

http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=/netahtml/search-bool.html&r=1&f=G&l=50&co1=AND&d=ptxt&s1=4319059.WKU.&OS=PN/4319059&RS=PN/4319059



Questions:

A) If the researchers had scaled this reaction to 20 moles or more would they have changed any molar ratios or the solvent to reactant ratio?

B) Would inexpensive pharmacy grade MgSO4 have been suitable for this reaction?

C) In post

Post 212002

(Rhodium: "Easy nitroethane in quantitative yield", Methods Discourse)
&

Post 212032

(Osmium: "Re: Easy nitroethane in quantitative yield", Methods Discourse)
the two chemists proposed post reaction work-ups for this synthesis.  If the intent of the inventors of the patent was to produce a reasonably pure product while minimizing solvent usage, work-up time, complexity, etc. Would they have chosen one of the 2 procedures below or are there other options?

1)the procedure in

Post 212002

(Rhodium: "Easy nitroethane in quantitative yield", Methods Discourse)
wherein the post reaction mix is flooded with a large amount of water, extracted with DCM or ether, washed with NaCl solution, dried, and distilled.  Or perhaps...

2)the procedure in

Post 212032

(Osmium: "Re: Easy nitroethane in quantitative yield", Methods Discourse)
wherein the alkane is distilled directly out of the mix with vacuum when using DMSO as solvent or w/o vacuum when using DMF as solvent?  I’m confused by this as my merck says DMSO (cas# 67-68-5)has b.p. of 189 at 760mm  while DMF (cas# 68-12-2) has b.p. of 153C at 760mm.  Why couldn’t a simple distillation be used with either one of these solvents?

E) If the researchers had increased the reaction time beyond that necessary to convert all alpha-bromo acid would the mix yield anything negative as a result e.g. 8 hrs max. beyond total conversion?  At elevated temperatures (less than 100C)?  Would  answers to the two previous questions differ if DMF were used interchangeably?

SYNTHESIS 3: alpha-bromopropionic acid + methanol + H2SO4 --> 2-brompropionic acid methyl ester as per: methyl chloroacetate

https://www.thevespiary.org/rhodium/Rhodium/chemistry/2ch.darzen.html


Questions:

A) If the researchers had scaled this reaction to 20 moles or more do you believe they would have changed the molar ratios?
----------------------

With regard to TLC and all the reactions mentioned above, do you think that the scientists/researchers would have considered the eluatropic series mentioned in Zubrick's book sufficient to cover the range of reactions? From Zubrick: (in order of increasing polarity):
Pet. Ether
Cyclohexane
Toluene
Chloroform
Acetone
Ethanol
Methanol. 

 If not, what other eluents should be added to the list?

I realize this is alot to ask in one sitting and any theoretical/speculative info. is appreciated.         -zero