kamal
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Imine Reduction with NaBH4
This is in continuation to my earlier posting for C=O to CH2 reduction :
What do you think, if I reduce the Imine formed by reaction between these two reactants with NaBH4 ?
Imine formation :
----------------------
Ph-CO-CH=CH-COOC2H5
+
CH3
l
CH-H2N COOC7H7
to
Ph-CO-CH2-CH(COOC2H5)-NH-CH(CH3)-COOC7H7
Now reducing the Imine formed above with NaBH4 in Methanol to get the final product :
Ph-CH2-CH2-CH(COOC2H5)-NH-CH(CH3)-COOH
i.e. : getting C=O to CH2 & C7H7 to COOH.
May it work ? If yes, then can I get some experimental & work-up suggetions for this ?
Awaiting your suggetions !
Thanks in advance,
Kamal
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chochu3
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to reduce a carbonyl one could use wolf kishner reaction or clemmenson reaction. To get your ester back to a carboxylic acid you need to boild in
acidic water.
\"Abiding in the midst of ignorance, thinking themselves wise and learned, fools go aimlessly hither and thither, like blind led by the blind.\" -
Katha Upanishad
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solo
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I would think to return the ester to a carboxylic acid one would need to boil in a NaOH solution as oppose to an acidic solution being that the esters
are usually made by refluxing with an alcohol and acid...hence the return trip is by means of a base......solo
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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Endo
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Look up Saponification.
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Nicodem
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Kamal, where do you see an imine formed in any of your equations?
All I can see is a Michael addition of the benzyl ester of alanine on an unsaturated ketone/ester!
And how the hell do you expect NaBH4 to reduce a ketone all the way to the methylene?
Anyway, the only reasonable way is to reduce the ketone group of the Michael addition product to the alcohol, acetylate it and hydrogenolize both
benzylic positions (that is, I asume that by "-C7H7" you mean -CH2Ph). All the classical methods like Wolf-Kishner, Clemmensen etc. will fuck up the
rest of the molecule (ester groups!).
PS: Asking a qustion means nothing if one does not give all the information necessary for a reasonable answer!
Edit:
Nevermind, I just noticed it is a dead thread brought up.
[Edited on 10-5-2006 by Nicodem]
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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kamal
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sorry nicodem !
you're right.
my posting was wrong................
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Sandmeyer
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| Quote: | Originally posted by Nicodem
All the classical methods like Wolf-Kishner, Clemmensen etc. will fuck up the rest of the molecule (ester groups!). |
Actually Clemmansen reduction has seen improvements since it's discovery, it can efficiently be done in 30 min in ether and simillar saturated with
dry HCl and activated (not amalgamated) zinc, see:
Yamamura et al, Zinc reductions of oxo steroids Chem. Commun. 1967, 1049-50.
Yamamura et al, Zinc reductions of keto groups to methylene groups. J. Chem. Soc. C 1968, 2887-2889.
Yamamura et al, Modified Clemmensen reductions of keto groups to methylene groups. Bull. Chem. Soc. Jap. 1972, 45, 264-266.
Application of modified Clemmensen in natural product synthesis, Zn dust/Et2O/HCl -5 Celsius: 
Naruse et al, Total Synthesis of [-]-pumiliotoxin C by aqueous intramolecular Diels-Alder approach. Tetrahedron Letters 1994, 35, 9213-9216
As a side-note, something really cool was done by K. Krohn during his total synthesis of (+/-)-lacinilene C methyl ether. First a intermolecular
Friedel-Crafts acylation, between succinic anhydride and aromatic substrate, then followed a intramolecular F-C acylation, but after the first
acylation the 4-keto arylbutyric acid was reduced under Clemmensen conditions, yield for both steps (reduction followed by intramol. F-C) was 72%:
Transition-Metal-Catalyzed Oxidations. 11.1 Total Synthesis of (±)-Lacinilene C Methyl Ether by -Naphthol to -Ketol Oxidation
Krohn, K.; Zimmermann, G.
J. Org. Chem.; (Note); 1998; 63(12); 4140-4142. DOI: 10.1021/jo9801566
http://rapidshare.de/files/20249588/krohn.pdf.html
Supporting info:
http://rapidshare.de/files/20249643/support_krohn.pdf.html
Other papers are out of my reach...
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kamal
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Reduction references
Thanks a lot dear for the references !
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Sandmeyer
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In case the above papers are inacsessible here is at least one reliable method, sorry if this is somewhat off-topic as I didn't fully read the
original post:
MODIFIED CLEMMENSEN REDUCTION: CHOLESTANE
Org., Synth, Coll. Vol. 6, p.289 (1988); Vol. 53, p.86 (1973)
Submitted by Shosuke Yamamura1, Masaaki Toda2, and Yoshimasa Hirata2.
Checked by A. Laurenzano, L. A. Dolan, and A. Brossi.
1. Procedure
A 500-ml., four-necked, round-bottomed flask (Note 1) equipped with a sealed mechanical stirrer (Note 2), a gas-inlet tube, a low-temperature
thermometer, and a calcium chloride tube is charged with 250 ml. of dry diethyl ether. With an acetone–dry ice bath the temperature of the ether is
lowered to −10 to −15° and maintained within this range while a slow stream (Note 3) of hydrogen chloride is introduced, with slow
stirring, for about 45 minutes. The gas-inlet tube is replaced with a glass stopper, and 10.0 g. (0.0259 mole) of cholestan-3-one (Note 4) is added
while the temperature of the stirred solution (Note 5) is kept below −15°. The reaction mixture is cooled to −20°, and 12.3 g. (0.188
g.-atom) of activated zinc (Note 6) is added over a 2–3 minute period. The temperature of the reaction mixture is allowed to rise to −5°
(Note 7), and it is maintained between −4° and 0° (Note 8) for 2 hours. Stirring is not interrupted for the duration of the reaction. The
mixture is finally cooled to −15° and poured slowly onto about 130 g. of crushed ice. The ethereal layer is separated, and the aqueous layer is
extracted with 100 ml. of ether that had been used to rinse the reaction vessel. The ethereal solutions are combined, washed with saturated aqueous
sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The ether is distilled under reduced pressure with a 50° water bath, leaving
9.3–9.5 g. of a colorless, liquid residue that solidifies on cooling. This solid is dissolved in 30–40 ml. of n-hexane (Note 9). The solution is
poured onto a 3.5 cm. by 17 cm. column of silica gel (Note 10) and eluted with 80–90 ml. of n-hexane. Distillation of the solvent under reduced
pressure with a 50° water bath leaves 8.0–8.2 g. (82–84%) of cholestane (Note 11), which, after recrystallization from ethanol-ether (Note 12),
yields 7.3–7.5 g. (76–77%) of product as plates m.p. 78–79° (lit., m.p. 80°)3 (Note 13).
2. Notes
1. A standard, three-necked flask fitted with a Y-tube may be used.
2. An efficient magnetic stirrer may be substituted.
3. Approximately one bubble per second can be spot-checked periodically by connecting the calcium chloride tube to an oil-filled bubble counter.
4. Cholestan-3-one was prepared according to Org. Synth., Coll. Vol. 2, 139 (1943); single spot on TLC with the system described in (Note 11).
5. The cholestanone does not dissolve completely at this low temperature, but the reaction is not affected.
6. The submitters prepared activated zinc by the following procedure. Commercial zinc powder (16 g.), special grade, ca. 300 mesh, obtained from
either Kishida Chemical Company Ltd. or Hayashi Pure Chemical Company Ltd., is added with stirring to a 300-ml., round-bottomed flask containing 100
ml. of 2% hydrochloric acid. Vigorous stirring is continued until the surface of the zinc becomes bright (ca. 4 minutes). The aqueous solution is
decanted, and the zinc powder in the flask is washed by decantation with four 200-ml. portions of distilled water. The activated zinc powder is
transferred to a suction filter with 200 ml. of distilled water and washed successively with 50 ml. of ethanol, 100 ml. of acetone, and 50 ml. of dry
ether. Filtration and washing should be done as rapidly as possible to minimize exposure of the activated zinc to air. The zinc is finally dried at
85–90° for 10 minutes in a vacuum oven (ca. 15 mm.), cooled, and used immediately; the yield is 13–14 g.
The checkers used this procedure with certified zinc powder, 325 mesh, obtained from Fisher Scientific Company.
7. This requires ca. 20 minutes.
8. The temperature is regulated by adding pieces of dry ice to the cooling bath as required. As the reduction proceeds, the solution separates into
two phases.
9. The solution is decanted from any insoluble matter.
10. Silicic acid, 100 mesh (Mallinckrodt), was used.
11. This material melts at 78–79°. On TLC [silica, development with n-hexane, visualization with sulfuric acid-methanol (1:1) and heating] the
product had Rf = 0.74. An impurity, Rf = 0.65, was present.
12. The cholestane is dissolved in 50 ml. of ether. Ether is distilled until the volume is 25 ml., 200 ml. of ethanol is added, and the mixture is
refrigerated.
13. Recovery is 92%. Recrystallization has no effect on the quality of the product as judged by m.p. and TLC (Note 11).
3. Discussion
The well-known Clemmensen reduction4 is a general method by which aralkyl ketones are readily converted to the corresponding hydrocarbons with
amalgamated zinc and hydrochloric acid. It is not particularly effective, however, with alicyclic and aliphatic ketones. The procedure
described herein provides a simple method of reducing a variety of ketones to their desoxy derivatives in high yields under much milder conditions
(0°, 1–2 hours) than those normally used in the Clemmensen reaction.4 This permits selective deoxygenation of ketones in polyfunctional
molecules5 containing groups such as cyano, amido, acetoxy, and carboalkoxy, which are stable under the mild reaction conditions. For example, the
following reduction6 has been carried out successfully by the modification of our procedure, using acetic anhydride as the solvent.5
Wide latitude is permitted in choosing the solvent for the reaction. Several organic solvents (tetrahydrofuran, benzene, n-hexane)7 and particularly
acetic anhydride5,8 may be used instead of dry ether. α-Halo- and α-acetoxycholestanone5 are converted to cholestane with Zn-HCl-Et2O and
also with Zn-HCl-Ac2O.7,8 These reduction systems, however, have given different results with α,β-unsaturated ketones.9 With Zn-HCl-Et2O,
cholest-1-en-3-one gave cholestane in 88% yield, while cholest-4-en-3-one gave an 88% yield of a mixture of 1.2 parts of cholestane and 1 part of
coprostane. By contrast, reaction of Zn-HCl-Ac2O with cholest-1-en-3-one afforded a mixture of three compounds: cholestane (30–32%),
3-acetoxycholest-2-ene (10–24%), and cholestan-3-one (30–40%). Cholestan-3-one appears to be formed from the corresponding cyclopropanol acetate10
during the work up. The mechanism of this reduction is probably similar to that of the Clemmensen reaction.11
[Edited on 12-5-2006 by Sandmeyer]
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