Author Topic: Imine reduction  (Read 9033 times)

0 Members and 1 Guest are viewing this topic.

Vibrating_Lights

  • Guest
Imine reduction
« on: June 14, 2003, 12:15:00 AM »
Is anhydrous IPA a suitable replacement for MeOH WHen reducing an Imine with NaBH4.  Is MeAm just as soluable in IPa As it is in MeOH?
VL_


Aurelius

  • Guest
IPA
« Reply #1 on: June 14, 2003, 12:32:00 AM »
IPA should do just fine as a substitute.  Don't know about the relative solubility, but it should still be soluble enough.  Try making a concentrated solution at low temperature and then bring to RT outside/in good ventilation.  (if freebase) If HCl salt, just filter off the excess.  Titrate.


LaBTop

  • Guest
No. Wrong.
« Reply #2 on: June 14, 2003, 04:43:00 AM »
"" Sodium borohydride reductions are generally conducted in solvents such as methanol or ethanol due to its high solubility in them.
However, the efficiency of sodium borohydride in these solvents is very poor due to the high rate of decomposition.""
And therefor you add the boro in many small portions, hence the ratio imine to NaBH4 stays always big to tiny.

""In the absence of acid hydrogen evolution slows down due to the increase in pH caused by the formation of the basic metaborate ions. Hence dissolving sodium borohydride in a basic solution prevents initial hydrolysis and permits the reagents to be used or stored in aqueous solution.
Sodium borohydride is soluble in water, lower aliphatic alcohols and amines and not appreciably soluble in diethyl ether, dioxane, hydrocarbons such as benzene, toluene and dichloromethane. The reported values of solubility of sodium borohydride are given in Table I.
Due to the high solubility of sodium borohydride in methanol, most of the borohydride reactions are conducted using methanol as the solvent. However, the great disadvantage of methanol in borohydride reduction is that borohydride undergoes an appreciable rate of decomposition even at -40°C thus releasing 4 moles of hydrogen and inhibiting the formation of hydride ion for the reduction (Equation 3). Therefore, large excess of sodium borohydride (4-5 moles) has to be used for the reduction reaction.

This decomposition reaction is very slow in ethanol and only 33% of the available hydrogen is liberated in 4 h. As the carbon length of the aliphatic alcohol increases, the solubility of the sodium borohydride in it decreases but its stability increases. In isopropyl alcohol and tert-butanol, sodium borohydride exhibits excellent stability and no formation of hydrogen is observed over a period of 24 h, but it has poor solubility in these solvents (Table I).""

See Post 295754 (not existing) for Table I :

Table I - Solubility of sodium borohydride in different solvents (g / 100 g solvent)

Solvent.........................Temperature [°C].....................Solubility
Water..................................20................................55

Methanol..............................-40..........................Highly soluble

Ethanol................................20.........................4 (reacts slowly)

Isopropyl alcohol......................20........................0.25 (reacts slowly)


Use Methanol, never IPA for imine reduction. So next question is irrelevant. LT/


raffike

  • Guest
LaBTop,i've seen many posts saying that rx mix
« Reply #3 on: June 14, 2003, 07:45:00 AM »
LaBTop,i've seen many posts saying that rx mix must be anhydrous and if water is present,yields are low(~30%) while others say(Barium for example) that water doesn't disturb imine formation/reduction.Which is correct?If raf wants to do borohydride reductive amination in one pot,should he keep everything anhydrous?


LaBTop

  • Guest
Ahh, this is the right place and time to
« Reply #4 on: June 14, 2003, 04:28:00 PM »
start this interesting discussion.

Terbium has already told it before, and Barium has luckily for all of us proved then undoubtedly  that aqueous conditions also work for these reductions in acceptable good to very good yields (so much more than 30% !), which is in accordance with many cited references, however, IMHOP, the anhydrous GAS approximation leads to the highests molar yields for the phenethylamines him and I have personally synthesized (Methamphetamine, MDMA and MDA), if I compare his posted molar yields to mine.
I have once cited that I accidentally sucked back approximately 10 liter water out of a wash bottle into my imine reaction vessel while adding NaBH4, and it didn't affect the end yield in desastrous amounts. But it still was about 10% lower.

Raffike, if you want to and can, you can do a 1 mole boro reduction following my procedure and a 1 mole one following Bariums procedure.
Then you and we can compare results.
Please follow instructions to the letter in all your tests.
And tell if you use high grade chems or homemade.
If you don't have commercially grade MeAm gas from a gas supplier firm (which is DRY!), but synth your MeAm gas at home, the comparison becomes already difficult, but if you dry your homemade MeAm gas thoroughly before bubbling it in dry methanol at -10 to -20 Celsius you can compare both methods in a scientific manner.

In fact, I must admit, it is OFCOURSE much easier to work with easy homemade MeAm salt soluted in water, than risking ordering or blackmarketing pure MeAm GAS!
A 10% or perhaps more yield can't outsmart in that case the risks and perhaps smells involved with my anhydrous MeAm-gas procedure.
For small scale production, Bariums method is far better, for BIG scale production my method is far better, IF you posess MeAm gas cylinders.
It's always a simple comparison between risk and GREED.  :P  

 
I'm sure Barium (I hope so), Terbium(I hope so) and many other members who have personally (or from hearsay by a knowledgeable researcher, ynwimean :) ) tested imine reductions with NaBH4 or perhaps even Zincborohydride will joyfully join this highly interesting discussion.

I will post my "Exellent Boro info" from 04-10-02 (that I let read some very important members) in this thread, so everybody can read it at last, I totally forgot to post it in the forums.
Especially the literature list had some good reads in it, which I haven't seen here.

ESPECIALLY  14. T.N. Sorrell and P.S. Pearlman; Tetrahedron Letters 21 3963 (1980)
Reduction of carbonyl compounds by in situ generation of quaternary ammonium borohydrides.  LT/


raffike

  • Guest
SwiRaf was once introduced to some guys.
« Reply #5 on: June 14, 2003, 08:10:00 PM »
SwiRaf was once introduced to some guys.They asked raf how large-scalers do they things.Raf said catalytic hydrogenation with 3 atm H2 pressure or sodium borohydride.They thought that catalytic is bit expensive and also bit dangerous so they wanted to know more about sodium borohydride.
Never saw them again.

Now raf got curious and is testing different methods to come up with one that should work.
If bees are interested,raf may post his test results.He probably starts small-scale as he has never messed with borohydride.


Barium

  • Guest
Imine reduction
« Reply #6 on: June 15, 2003, 02:33:00 PM »
I agree with LabTop that this is a classic interesting topic.

I never tried to optimize the method I posted about, but I'm sure the yields can be pushed up to 80-90%. Especially using phase transfer catalysis. The Hive would appreciate (I think I can speak for most of us here) if someone like Raffike would go through the trouble and run both LabTops and mine reaction parallell since it hasn't been done. A 250 mmol scale would do just fine.

What I would change in mine method though, is to use a higher concentration of the aqueous methylamine solution. E.g. to a solution of the ketone in toluene I would add a saturated solution of methylamine in water, then I would add a 50% aqueous NaOH solution to liberate the amine. This would very effectively push out the liberated methylamine into the ketone solution where we want it. For the borohydride reduction I would optionally use a PTC like Aliquat 336 (this PTC is cheap and easy to handle and still non-watched). When the imine formation is complete the aqeous phase is removed and a stablized aqueous solution of sodium borohydride is added along with 1-5 mol% Aliquat 336. This would presumably lower the need of borohydride tremendously as can be seen in the C=C reduction method. I estimate a yield of 85-90% actually, but this is just my gut feeling.

Damn, I think I'm going to try this myself. Yet again this is a simple modification I havent thought of before.  :P


LaBTop

  • Guest
Excellent Boro info I page 1
« Reply #7 on: June 15, 2003, 10:26:00 PM »
Part I

Merits of sodium borohydride reductions under phase transfer catalysis - Part I

ABSTRACT
Many organic transformations in pharmaceutical and agrochemical industries involve molecules containing multifunctional group, which need to be selectively hydrogenated by using a suitable hydrogen source. In this respect sodium borohydride is found to be highly desirable in comparison with other reducing agent as it is mild and a more selective catalyst. Sodium borohydride selectively reduces functional groups such as aldehydes, ketones, acid chloride and imines in presence of esters, epoxides, amides, nitriles and nitro group. Sodium borohydride reductions are generally conducted in solvents such as methanol or ethanol due to its high solubility in them. However, the efficiency of sodium borohydride in these solvents is very poor due to the high rate of decomposition. Conducting the reaction in two phases using non-polar aprotic solvents such as hydrocarbons and a phase transfer catalyst can alleviate this problem. In hydrocarbon solvents sodium borohydride is stable and does not undergo decomposition reaction and thus its complete utilization can be realized. For the reduction of functional groups such as nitro, ester, amide etc., the reducing power of sodium borohydride can be varied over a wide range by mixing the sodium borohydride with metal salts such as LiCl, AlCl3, CoCl2, MgCl2, TiCl4, BF3, I2, thiols such as ethanethiol, carboxylic acid such as acetic acid, trifluoroacetic acid and quaternary ammonium salts. This paper is published in two parts. Part I delineates the prowess of sodium borohydride reductions under phase transfer catalysis and in situ synthesis of quaternary ammonium borohydrides. Part II will deal with reductions using preformed quaternary ammonium salts and effect of solvents in sodium borohydride reduction.

INTRODUCTION

Many organic transformations in pharmaceutical and agrochemical industries involve molecules containing multifunctional groups, which need to be selectively hydrogenated by a suitable hydrogen source. Sodium borohydride being a milder and a more selective reducing agent than lithium aluminium hydride is found to be ideal to achieve this type of transformations. Sodium borohydride selectively reduces aldehydes, ketones, acid chlorides and imines in presence of esters, epoxides, amides, nitriles or nitro group. Also sodium borohydride is an excellent reducing agent for sugar molecules which are soluble in water and where lithium aluminium hydride cannot be used. Sodium borohydride reductions are usually conducted in methanol as solvent where it reacts vigorously with the solvent at room temperature liberating 4 moles of hydrogen immediately. Therefore, an excess of reducing agent (4-5 moles) per mole of the aldehyde or ketone has to be used. To overcome this problem such reductions can be performed in biphasic medium by using a phase transfer catalyst and a non-polar solvents such as benzene, toluene etc. or a preformed quaternary ammonium borohydride salt and solvents such as higher aliphatic alcohol, dichloromethane and THF etc.


SODIUM BOROHYDRIDE AND ITS MODIFIED VERSIONS

Properties of sodium borohydride
Complex borohydrides are compounds that contain the elemental hydrogen in a reduced or electron rich state. Among the borohydrides, the alkali metal borohydrides, particularly sodium borohydride is the most important for it is specific, easy to handle and highly selective. Sodium borohydride is a stable white crystalline solid and undergoes decomposition above 400°C. It is stable in aqueous alkaline solution and slowly decomposes in water, the rate of which increases with increasing acidity, temperature and presence of transition metal salts such as Ni, Co, Fe and Cu chlorides. Hydrogen gas is generated in situ by two ways as given below:



In the absence of acid hydrogen evolution slows down due to the increase in pH caused by the formation of the basic metaborate ions. Hence dissolving sodium borohydride in a basic solution prevents initial hydrolysis and permits the reagents to be used or stored in aqueous solution.
Sodium borohydride is soluble in water, lower aliphatic alcohols and amines and not appreciably soluble in diethyl ether, dioxane, hydrocarbons such as benzene, toluene and dichloromethane. The reported values of solubility of sodium borohydride are given in Table I.
Due to the high solubility of sodium borohydride in methanol, most of the borohydride reactions are conducted using methanol as the solvent. However, the great disadvantage of methanol in borohydride reduction is that borohydride undergoes an appreciable rate of decomposition even at -40°C thus releasing 4 moles of hydrogen and inhibiting the formation of hydride ion for the reduction (Equation 3). Therefore, large excess of sodium borohydride (4-5 moles) has to be used for the reduction reaction.



This decomposition reaction is very slow in ethanol and only 33% of the available hydrogen is liberated in 4 h. As the carbon length of the aliphatic alcohol increases, the solubility of the sodium borohydride in it decreases but its stability increases. In isopropyl alcohol and tert-butanol, sodium borohydride exhibits excellent stability and no formation of hydrogen is observed over a period of 24 h, but it has poor solubility in these solvents (Table I).


LaBTop

  • Guest
Excellent Boro info I page 5
« Reply #8 on: June 15, 2003, 10:51:00 PM »
Part V

2-Octanone is reduced by aqueous sodium borohydride, yielding 80% of 2-octanol in 6.5 h, at room temperature in benzene solution using tricaprylmethylammonium chloride.
With N-dodecyl-N-methylephedrinium bromide 100% conversion of 2-octanone is obtained in 0.5 h at room temperature whereas the more lipophilic dicyclohexyl-18-crown-6 in boiling benzene solution gave 92% yield in 2.5 h (17).
Phase transfer catalysts such as 18-crown-6 and dibenzo-18-crown-6 catalyzed sodium borohydride reduction of several ketones in boiling toluene solvent. By this method, acetophenone, cyclohexanone and 2-heptanone are reduced in 49%, 50% and 41% yield respectively( 18).

REFERENCES
1. Sreela Sengupta et al; Indian Journal of Chemistry 33B 285 (1994)
2. Atsushi Abiko and Satoru Masamune; Tetrahedron Letters 33 5517 (1992)
3. H.T. Williams et al; Tetrahedron Letters 23 3337 (1982)
4. Sadatoshi Akabon et al; J. Chem. Soc. Perkin Trans 1 3121 (1991)
5. Jean-Louis Luche, J. Am. Chem. Soc. 100 7 (1978)
6. Shinichi Itsuno, Yoshiki Sakurai and Koichi Ito; Synthesis 995 (1998)
7. J.V. Bhaskarkanth and M. Periasamy; J. Org. Chem. 56 5964 (1991)
8. T.E.A. Nieminan and T.A. Hase; Tetrahedron Letters 28 4725 (1987)
9. C.F. Nutaltin; J. Chem. Ed. 66 No.8 (1989)
10. H.C. Brown, E.J. Mead and C.J. Shoaf; J. Am. Chem. Soc. 78 3616 (1956)
11. Ullman; Encyclopedia of Chemical Technology
12. R.O. Hutchim and D. Kandasamy; J. Am. Chem. Soc. 95 6131 (1973)
13. R. O. Hutchim and M. Markowitz; J. Org. Chem. 46 3574 (1981)
14. T.N. Sorrell and P.S. Pearlman; Tetrahedron Letters 21 3963 (1980)
15. R.W. Bragdon, M.D. Banus and T.R.P. Gibb Jr.; J. Am. Chem. Soc. 74 2346 (1952)
16. S. Colonna and R. Fornasier; Synthesis 53 (1975)
17. M. Cinquini, F. Montanari and P. Tundo; J. C.S. Chem. Commun. 393 (1975)
18. T. Matsuda and K. Koida; Bull. Chem. Soc. Jap. 46 2259 (1973)


There are really interesting combinations in that table II.

Please let someone post those references nr's 14 and 15 !!!!

And when your at it, get references nr's 6-8-10-11-12 and 13 also, you definitely will collect a bunch of karma,  :)  LT/

PS: and a real nosy researcher gets ofcourse ALL of them.


Rhodium

  • Guest
Preparation of Quaternary Ammonium Borohydrides
« Reply #9 on: June 16, 2003, 01:43:00 PM »
Ref #15:
Preparation of Quaternary Ammonium Borohydrides from Sodium and Lithium Borohydrides

J. Am. Chem. Soc.; 1952; 74(9); 2346-2348.

(https://www.thevespiary.org/rhodium/Rhodium/pdf/quaternary.ammonium.borohydrides.pdf)

Aurelius

  • Guest
JACS 74(9), 2346-2348 (1952)
« Reply #10 on: June 16, 2003, 09:51:00 PM »
Hey LT, there's one ASCII'd for you- Do you want the others Rhodiums posted to be ASCII'd?

Preparation of Quaternary Ammonium Borohydrides from Sodium and Lithium Borohydride

JACS, (1952), 74(9), 2346-2348.

By M. Douglas Banus, Robert W. Bragdon, and Thomas R.P. Gibb Jr.1

Abstract: 

The metathetical preparation of a new type of borohydride containing a quaternary ammonium cation is described.  Tetramethyl, tetraethyl, and benzyltrimethyl ammonium borohydrides have been prepared by metathetical reactions from sodium borohydride and lithium borohydride.  (Several properties thereof are described.)


The metathetical reaction of alkali metal borohydrides with unsubstituted or partially substituted ammonium salts might be expected to yield ammonium borohydrides.  This reaction, however, evidently gives other products, the nature of which leads in some cases to the supposition that while an ammonium borohydride may be formed momentarily, it decomposes almost immediately.  Thus, ethereal lithium borohydride reacts with ammonium chloride2 and with mono-, di-, and tri-methylammonium chlorides3 according to the over-all equations.

NH4Cl + LiBH4 to NBH4 + LiCl + H2
3CH3NH3Cl + 3LiBH4 to B3N3H3(CH3)3 + 3LiCl + 9H2
(CH3)2NH2Cl + LiBH4 to (CH3)2NBH2 + LiCl + 2H2
(CH3)3NHCl + LiBH4 to (CH3)3N:BH3 + LiCl + H2


The instability of the unsubstituted or partially substituted ammonium borohydrides is due in part to the presence of a hydrogen atom on the nitrogen4 and in part to the weakly basic character of the cation.  Thus, the borohydrides of the more strongly basic alkali metals are far more stable both thermally and toward hydrolysis.  Accordingly, it may be expected that a borohydride having a quaternary ammonium cation, will be more stable than a borohydride having, say, a dimethylammonium cation.  Unfortunately, most quaternary ammonium salts are insoluble in non-aqueous, non-hydroxylic solvents such as ether; and in fact, show appreciable solubility only in a very few highly polar solvents, especially water.  Therefore, it is not feasible to attempt metathetical reaction under the conditions employed previously in the case of partly substituted ammonium compounds.  Moreover, the reactivity of the metal borohydride with water has militated against the use of this medium for preparation of new borohydrides.  However, we have shown that aqueous phase metathesis constitutes an excellent method for the preparation of the quaternary ammonium borohydrides and that hydrolytic losses are less than anticipated.

Aqueous Metathesis with Sodium Borohydride

Aqueous phase reactions were carried out in accordance with the general equation:
R4NX + NaBH4 to R4NBH4 + NaX


Here, X represents hydroxide, halide, phosphate, carbonate, acetate or oxalate.  Both water and dilute ethyl alcohol were employed as solvents and the vacuum dried reaction products were washed with water or 95% ethyl alcohol. 

For tetramethylammonium borohydride, the best procedure was found to be a metathesis involving the quaternary hydroxide, since the resulting dried mixture of borohydride and sodium hydroxide could then be leached with 95% ethanol in which the latter is quite soluble and the former is almost insoluble.  Moreover, sodium borohydride reacts more rapidly with ethyl alcohol than with water and (if present in the reaction product) would thus be removed.  High yields of 99+ % tetramethylammonium borohydride were obtained in this manner.  The tetraethyl compound is more soluble in 95% ethyl alcohol and is also more susceptible to hydrolysis.  Thus it was obtained in variable but considerably poorer yields. 

Similar metathesis employing tetramethylammonium chloride and bromide were successful, but as expected from the solubilites of the four solids involved, none of the reactions gave more than 70-90% yields.  Tetramethylammonium chloride in 95% ethanol gave a crude product containing 76% of the expected quaternary borohydride with evident reaction of the sodium borohydride with the solvent.  Aqueous metathesis of the quaternary fluoride and phosphate appear preferable to those of the chloride or bromide on the basis of the lower solubility of sodium fluoride and triphosphate. ( The latter metathesis is successful only at 0*C)  Neither acetate nor oxalate metathesis offers any apparent advantages.

Aqueous Metathesis with Lithium Borohydride

Although lithium borohydride ordinarily reacts violently with water, it was discovered that if the pure compound is introduced anaerobically at or below 0*C, a solution results with but minor loss of activity.  Air-free distilled water is employed.  The resulting solution is sufficiently stable to permit its use over a period of hours.

The insolubility of lithium fluoride and phosphate permits almost quantitative reaction of the respective quaternary ammonium salts with lithium borohydride.  Of the two metatheses, that employing the fluoride gave better yields in the case of benzyltrimethylammonium borohydride and quantitative yields of tetramethyl- and tetraethylammonium borohydrides.  Various mixtures of lower amines, alcohols, and water were investigated in a rather cursory manner and appear to offer no advantages over water.  Those solvents in which lithium borohydride is soluble, e.g., lower ethers and amines, do not dissolve quaternary ammonium salts.  Aqueous amines are apparently no better than water (90% isopropylamine 10% water dissolves only 0.27g/100g of tetramethylammonium borohydride); aqueous cyclic ethers were not investigated nor were secondary or tertiary alcohols.

Properties:

The three borohydrides prepared are stable hygroscopic microcrystalline solids comparable to sodium borohydride and lithium borohydride.  They burn quietly but rapidly on ignition, leaving a slight ash.  They are not ignited by friction nor by moistening with water or ethyl alcohol.  Spontaneous ignition by pouring or handling in humid air has not been observed although the tetramethyl- and benzyltrimethyl compounds deteriorate very rapidly when so handled.  The materials keep well in an ordinary screw-top bottle, however.  The densities at 25*C of the tetramethyl-, tetraethyl-, and benzyltrimethyl-  compounds are respectively, 0.813, 0.927, 0.638g/cc., all measured by helium displacement.

All three compounds are soluble in water with reaction and they react with methanol.  The tetramethyl compound has the solubilities shown in Table 1 and is insoluble in diethyl ether, isopropylamine, pyridine, chloroform, dioxane, THF, ethyl cellosolve, N-methylmorpholine.  The rate of reaction with water at RT follows approximately the increasing sequence: tetramethyl-, benzyltrimethyl-, tetraethylammonium borohydride, although the pH and presence of trace impurities such as heavy metal ions have profound effect.  The tetramethyl compound is less reactive toward water than sodium borohydride and the tetraethyl compound is considerably less reactive than lithium borohydride.  Hydrolysis yields four mols of hydrogen per mol of borohydride and is presumed to proceed according to the reaction equation:

R4NBH4 + 2H2O to (R)4NBO2 + 4H2


(The resulting quaternary ammonium salt of a weak acid should be capable of further hydrolysis to yield the labile hydroxide which decomposes in boiling water to give volatile ROH and R3N compounds)  The rate of hydrolysis of tetramethylammonium borohydride (5.8M) in water @ 40*C is nearly constant over a period of 100 hours at 0.04% of original weight per hour based on the above equation.  This rate is decreased to 0.02% per hour by the presence of (CH3)4NOH in the amount of 5% of the weight of borohydride.

Solid tetramethylammonium borohydride decomposes slowly in vacuo at 150*C, rapidly at 250*C yielding principally trimethylamineborine and methane.  It does not ignite spontaneously in air at this temperature, but volatilizes leaving no residue.  In an evacuated sealed glass bulb, it decomposes at the average rate of 0.095%/hour @ 150*C, 4.1% @ 175*C, 33.3%@195*C and 41.6%edited from 4.16%
Per minute @ 225*C.  The natural log rate of decomposition is evidently inversely proportional to the reciprocal of the absolute temperature over this range.  At 220-225*C, the trimethylamineborine rapidly sublimes away from the borohydride in the form of pure, acicular crystals (96% yield).  Hydrogen and trimethylamine (4% yield) were observed as decomposition products, indicating two possible courses for the reaction.  The small amount of pure white non-volatile residue (2% of original weight) contained sodium, carbon, hydrogen and nitrogen and presumably boron and oxygen, which could not be determined.  It is thought consist of NaBO2, NaBH4 and possibly polymeric substances.

Experimental:

Commercial sodium and lithium borohydrides were purified by extraction with water and isopropylamine5 and diethyl ether, respectively, to yield products approaching 100% purity as measured by hydrogen evolved from acidified water.  Tetramethyl- and tetraethylammonium chloride, bromide and iodide and hydroxide were obtained from Eastman Kodak Co. and the Paragon Division of the Matheson Co.  Benzyltrimethylammonium chloride was provided by the Commercial Solvents Co.  All were used as received.  (Exposure of the hydroxides to air was kept to a minimum)  The quaternary salts other than those cited above were made by metathesis of by neutralization of the base by the desired acid to the appropriate end-point.  Benzyltrimethylammonium hydroxide was prepared from the aqueous chloride via solid silver oxide.  (it was necessary to stir under an inert atmosphere for four days.)  A preferable method for preparing fluorides from the chlorides or bromides was used subsequently and involved the aqueous reaction with soluble silver fluoride prepared by dissolving silver oxide in dilute HF to a pH of from 6-7.  The quaternary chloride or bromide is added to the solution of silver fluoride until a trace of chloride ion is detected.  After a brief boiling to coagulate the precipitated silver chloride or bromide, the solution is filtered and evaporated.  The crystalline compound (CH3)4NF-2H2O is obtained by evaporation at 80*C.  It is extremely hygroscopic.  Tetramethylammonium carbonate was prepared by saturating the aqueous hydroxide with CO2 to a phenolphthalein end-point and subsequently adding an equal amount of the hydroxide to convert the bicarbonate to carbonate.  The acetates were prepared from the iodides and silver acetate in preference to neutralization of the hydroxide.

Preparation of Tetramethylammonium Borohydride:

Solid sodium borohydride 8.5g (0.22mol) was added to 20g of (CH3)4NOH (0.22mol) dissolved in 90g of water, the mixture giving an almost clear solution.  This was evaporated to dryness in vacuo and the white solid broken up in a dry-box under dry argon.  It was then extracted without precaution to exclude air with 90cc of 95% ethanol and filtered by suction without precaution to exclude air.  The filter cake was washed with two 50cc portions of cold 95% ethanol, the dried in vacuo for 18 hours at 70-80*C.  Yield of 18.5g (93%) of a white, microcystalline solid.  (a similar run in which the product was recrystallized three times from water without extraction with alcohol gave a 61% yield with a 94% purity)

An aqueous metathesis using the quat. Phosphate with filtration at 0-2*C of the precipitated Na2PO4 gave a 90% crude product containing less than 1% phosphate, the balance being borate.  A similar metathesis using the oxalate gavea  79% crude product containing 6.8% sodium oxalate and considerable borate.  Similarly, an acetate metathesis gave an 86% crude product  containing 12% NaBO2.  Metathesis based on the quat. Chloride, bromide and iodide with NaBH4 were shown by solubility considerations not to be feasible in water.  Use of aqueous isopropylamine and aqueous ethyl alcohol as media resulted in no substantial improvement. 

With Lithium Borohydride:

An aqueous solution containing 2.11g (0.97mol) of lithium borohydride was prepared by adding 50cc of distilled, degassed, ice-water to the hydride under argon.  The solution was promptly added to 8.92g of (CH3)4)NF (0.96mol) and stirred.  The precipitated LiF was removed on a sintered glass funnel and the clear filtrate evaporated in vacuo at RT.  The solid was taken up in the minimum amount of water, filtered, evaporated and finally dried 3 hours at 100*C in high vacuum.  Crude yield 98.5% with purity 95%.

Preparation based on metathesis involving the other cations cited were carried out in substantially the same manner using stoichiometric proportions. 

Aqueous phosphate metathesis with filtration of the precipitated Li3PO4 gave a crude product of 78% purity containing borate.  Aqueous carbonate metathesis with filtration of precipitated Li2CO3 gave a product of 89% purity containing 1.1% Li and significant amounts of borate.  Aqueous oxalate metathesis similarly gave a product of 72% purity. 

Preparation of Tetraethylammonium Bromide:

The preparation from the quat. hydroxide and sodium borohydride was complicated by the greater reaction of the product with water.  The preparation from the quat. fluoride and lithium borohydride was carried out exactly as described in the analogous case of the tetramethyl compound.  An 82% yield of the 95% purity product was obtained.

Preparation of Benzyltrimethylammonium Borohydride:

The only preparative method investigated was the aqueous reaction of the quat. fluoride with lithium borohydride.  Stoichiometric proportions of the reactants in water solution were mixed and evaporated to dryness in vacuo as in the case of the tetraethyl compound.  A crude yield of only 100% was obtained, but only 89% purity. (the final product had a slight yellow tinge)


Aurelius

  • Guest
More
« Reply #11 on: June 16, 2003, 09:52:00 PM »
References:

1.  Dept. of Chemistry, Tufts College, Medford, Massachusetts.

2.  H.I. Schlesinger and G.W. Schaffer, et. al. University of Chicago, Final Report, Navy Contract N6ori-20 T.O. 10 (1947-1948)

3.  G.W. Schlesinger and E.R. Anderson, THIS JOURNAL, 71, 2143 (1949)

4.  We are indebted to one of the referees for this observation and the comment that the case is analogous to the increasing ease of formation of N-dimethylaminoborine from trimethylamineborine and dimethylamineborine, respectively.

5.  W. D. Davis, L.S. Mason and G. Stegeman, THIS JOURNAL, 71, 2775 (1949)


Rhodium

  • Guest
Reference 2 & 14 + one related article
« Reply #12 on: June 17, 2003, 01:28:00 AM »
Ref #2:
An Improved, Convenient Procedure for Reduction of Amino Acids to Aminoalcohols: Use of NaBH4-H2SO4

Tet. Lett.; 1992; 33(38); 5517-5518.

(https://www.thevespiary.org/rhodium/Rhodium/pdf/borohydride-h2so4.pdf)

Ref #14:
Selective Reduction of Aldehydes with In Situ Tetraethylammonium Borohydride

Tet. Lett.; 1980; 21; 3963-3964.

(https://www.thevespiary.org/rhodium/Rhodium/pdf/in.situ.et4n-bh4.pdf)

Reductions with Quaternary Ammonium Borohydrides

J. Org. Chem.; 1962; 27(10); 3731-3733.

(https://www.thevespiary.org/rhodium/Rhodium/pdf/reductions.quaternary.ammonium.borohydrides.pdf)

I have copied Ref #3, #4, #8 and #17 too, so they will soon be uploaded too.

Rhodium

  • Guest
Ref #8 & #17 - NaBH4 with Crown Ethers or GAA
« Reply #13 on: June 17, 2003, 03:41:00 PM »
Ref #8:
Selective Reduction of Ketones with Sodium Borohydride-Acetic Acid

Tetrahedron Letters 28(40), 4725-4728 (1987)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/triacetoxyborohydride-ketones.pdf)

Ref #17:
Macrobicyclic Polyethers: Highly Efficient Catalysts In Two-Phase Reactions

J.C.S. Chem. Commun. 393 (1975)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/borohydride.crown-ethers.pdf)

Rhodium

  • Guest
Ref #3 - Tetraalkylammonium Octahydrotriborate(I)
« Reply #14 on: June 18, 2003, 12:48:00 PM »
Ref #3:
Polynyclear Borane Anions as Mild Reducing Agents 1. The Octahydrotriborate(I) Anion

Tetrahedron Letters 23 3337-3340 (1982)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/octahydrotriborate.pdf)

(No need to type this one, Aurelius, I suppose this is a too exotic reagent for most bees...)

Rhodium

  • Guest
Ref #5, #7, #12, and #13 (retrieved by GC_MS)
« Reply #15 on: June 20, 2003, 10:34:00 PM »
Ref #5:
Lanthanides in organic chemistry 1. Selective 1,2-reductions of conjugated ketones

J Am Chem Soc 100(7), 2226 (1978)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/nabh4-lncl3.pdf)

Ref #7:
Selective reduction of carboxylic acids into alcohols using NaBH4 and I2

J Org Chem 56, 5964 (1991)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/borohydrideiodine.pdf)

Ref #12:
Tetrabutylammonium cyanoborohydride - a new, exceptionally selective reducing agent

J Am Chem Soc 95(18), 6132 (1973)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/bu4nbh3cn.pdf)

Ref #13:
Tetraalkylammonium trihydridocyanoborates. Versatile, selective reagents for reductive aminations in nonpolar media

J Org Chem 46, 3571 (1981)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/r4nbh3cn.pdf)

Aurelius

  • Guest
Ref #13- JOC (1981) 46, 3571-3574 R4NBH3CN
« Reply #16 on: July 14, 2003, 07:17:00 PM »
Tetraalkylammonium Trihydridocyanoborates. Versatile, Selective Reagents for Reductive Aminations in Nonpolar Media

JOC (1981), 46, 3571-3574.

Abstract:

Tetrabutylammonium cyanoborohydride or the combination of sodium cyanoborohydride with Aliquat 336 provides useful, convenient reagents for reductive amination of aldehydes and ketones in aprotic or protic media.


Trihydridocyanoborate (cyanoborohydide)1 is well established as a mild, selective, acid-stable reducing agent for a variety of conversions including aldehydes and ketones to alcohols,2 tosylhydrazones,3 polar alkenes,4 and alkyl halides5 to hydrocarbons, and numerous carbon-nitrogen pi-bond derivatives (imines, oximes, enamines) to amines.2  This latter transformation has been particularly exploited as an excellent procedure for the reductive amination of aldehydes and ketones.1,2,6  However, the commercial available sodium derivative suffers the limitation that solubility is restricted to a few polar protic (water, low molecular weight alcohols), aprotic (dimethylsulfate, HMPA), or ether (THF, diglyme) solvent.8  The reagent is almost totally insoluble and unreactive in most other useful solvents including DCM, chloroform, aromatic and aliphatic hydrocarbons, and diethyl ether.

To circumvent the solubility problem and hence augment the utility of cyanoborohydride, we have explored the use of the tetrabutylammonium derivative9 and other phase-transfer techniques10 for typical cyanoborohydride reductions in nonpolar media.5,9,11  This communication reports the successful application of phase transfer to reductive amination, which extends the useful media for these conversions to include most common organic solvents, including DCM, hexane, benzene and diethyl ether.

Tetrabutylammonium cyanoborohydride (TBACB), prepared as previously described,9,11 is an air and moisture-stable crystalline solid (MP 144-145*C) which, in contrast to the sodium counterpart, is not hygroscopic.  Phase transfer was also used to solubilize sodium cyanoborohydride by employing Aliquat 336, an inexpensive liquid reagent composed of methyltrialkylammonium chlorides with C8-C10 chains.  Successful reductive aminations were obtained under a variety of conditions, but the most convenient consisted of simply dissolving the aldehyde or ketone (10mmol), amine (60mmol), and TBACB (7mmol) or sodium cyanoborohydride (7mmol) plus Aliquat 336 (7mmol) in 21ml of solvent followed by addition of HCl (20mmol) conveniently added as a 2.5-5.0N solution in methanol or other solvent.  Approximately 1g of 4A molecular sieves was added (to absorb water formed), and the mixture was stirred at ambient temperature.  Progress of the reactions could be followed by monitoring the disappearance of the carbonyl by IR.  Upon completion, isolations were accomplished in standard fashion (experimental), the products purified by short-path distillation, and identified comparison (IR and/or NMR) with authentic samples.

The results for a range of carbonyls and amines are presented in Table I.  Examples using the standard method (sodium cyanoborohydride, methanol, 2-3days)2 are included for comparisons.  As illustrated, aromatic and aliphatic aldehydes and ketones react readily with unhindered primary and secondary amines to afford respectable to excellent isolated yields of amines in reasonable times, usually 2.5-24 hours for aldehydes and 24-48 hours for ketones.  Two limitations were encountered.  Relatively hindered secondary amines (i.e., diethylamine) reacted only reluctantly with ketones and gave inferior yields (<40%) of amine products.  Also ammonium and tetraalkylammonium salts generally failed to react in aprotic solvents in which solubility is a problem.  In such cases, methanol solvent is clearly superior.2

General Reaction Procedure:

The general reaction procedure is illustrated for the preparation of N-cyclohexylpyrrolidine.  To a solution containing pyrrolidine (4.26g, 60mmol) in 21ml of DCM was added HCl (20mmol, 8ml of a 2.5N solution in methanol) followed by cyclohexanone (0.98g, 10mmol), sodium cyanoborohydide (0.44g, 7mmol), and Aliquat 336 (2.93g, 7mmol).  Approximately 1g of 4A molecular sieves was added, and the mixture was stirred at RT for 48hours.  The mixture was filtered, the filtrate acidified (methyl orange indicator), and the solvent removed on a rotary evaporator.  The residue was taken up with 10ml of water and extracted with 3x20ml portions of ether (discarded).  The aqueous phase was basified (solid KOH, phenolphthalein indicator), 20ml of brine was added, and the mixture was extracted exhaustively with ether.  These combined extracts were dried (magnesium sulfate), concentrated, and distilled in a Kugelrohr apparatus to yield 1.43g (94%) of N-cyclohexylpyrrolidine, identified by comparison (IR) with an authentic sample.  GLC analysis indicated >98% purity.

In conclusion, phase-transfer techniques greatly augment the utility of cyanoborohydride for reductive aminations of carbonyls and complement analogous conversions in protic media.

Acknowledgement:  We gratefully thank The National Science Foundation for support of our programs on hydride chemistry.

Reference:

(1)For reviews of cyanoborohydride chemistry, see (a) Hutchins, R. O.; Natale, N. R. Org. Prep. Proced. Int., (1979), 11, 201. (b) Lane, C.F. Synthesis, (1975), 135; Lane, C.F. Aldrichemica Acta, (1975), 8,3.

(2) Borch, R.F.; Bernstein, M.D.; Durst, H.D. JACS, (1971), 93, 2897. Recently, the intermediacy of iminium ions in certain reductive aminations has been questioned: Tadanier, J.; Hallas, R.; Martin, J.R.; Stanaszek, R.S. Tetrahedron Letters, (1981), 37, 1309; Kapnang, H.; Charles, G.; Sondengam, B.L.; Hemo, J.H. Tetrahedron Letters, (1977), 3469.

(3)Hutchins, R.O.; Maryanoff, B.E.; Milewaki, C.A. JACS, (1975), 40, 923.

(4) Hutchins, R.O.; Rotstein, D.; Natale, N.R.; Fanelli, J.; Dimmel, D. JOC, (1976), 41, 3328.

(5) Hutchins, R.O.; Kandasamy, D.; Maryanoff, C.A.; Masilamani, D.; Maryanoff, B.E. JOC, (1977), 42, 82.

(6) Other reagent systems recently introduced for reductive amination include:

(a)potassium hydridotetracarbonylferrate, Bodrini, G.P.; Panunzio, M.; Umani-Ronchi, A. Synthesis (1974), 261;

(b) NaBH4/H2SO4, Giumanini, A.G.; Chiavari, G.; Musiani, M.M.; Rossi, P. Synthesis, (1980), 743;

(c) the Leukart reaction; see, for example, Baeh, R.D. JOC, (1968), 33, 1647.

(d) NaBH4 in carboxylic solvents, Schellenburg, K.A. JOC, (1963), 28, 3259; Gribble, G.W.; Lord, P.D.; Skotnicki, J; Dietz, S.E.; Eaton, J.T.; Jonson, J.L. JACS, (1974), 96, 7812; Marchini, P.; Liso, G.; Reho, A.; Liborate, F.; Moracci, F.M. JOC, (1975), 40, 3453.

(e) ion-exchange resin supported BH3CN-, Hutchins, R.O.; Natale, N.R.; Taffer, I.M. J. Chem. Soc. Commun., (1978), 1088.

(7) From Alfa or Aldrich Chemical

(8) Wade, R.C.; Sullivan, E.A.; Bershied, J.R.; Purcell, K.F. Inorg. Chem., (1970), 9, 2146.

(9) Hutchins, R.O.; Kandasamy, D. JACS, (1973), 95, 6131; a number of other tetraalkylammonium cyanoborohydrides are also readily available: Reparasky, J.E.; Weidig, C.; Kelly, H.C. Syn. React. Inorg. Met-Org. Chem. , (1975), 5, 337.

(10) For excellent, general reviews of phase-transfer reactions, including reductions, see Weber, W.P.; Gokel, G.W. “Phase Transfer Catalysis in Organic Synthesis”; Springer-Verlag: New York, (1977),; Keller, W.E. “Compendium of Phase-Transfer Reactions and Related Synthetic Methods”; Fluka AG, Ch-9470 Buchs, Switzerland, (1979).

(11) Hutchins, R.O.; Kandasamy, D. JOC, (1975), 40, 2530.


Would somebody please pick up and post the articles in Reference (6) (a) and (e)