demorol
(Hive Bee)
12-13-02 22:27
No 389178
      Acid chlorides -> aldehydes
(Rated as: excellent)
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Acid chlorides can be easily converted to aldehydes by reductive oxidation using LAH and Pyridinum chlorochromate (PCC) or Pyridinum dichromate (PDC). Since this procedure uses no exotic or watched chemicals and since yields are pretty good, this might be another way to our beloved aldehydes.

Experimental section

All reaction were performed under a dry N2 atmosphere. All chemicals used were commercial products of the highest purity available; THF was dried over 4 A molecular sieve and distilled from sodium-benzophenone ketyl prior to use. Methylene chloride was also dried over P4O10 and distilled. 1H NMR spectra were recorded on a Bruker AMX 300 spectrometer. Gas chromatographic analyses were carried out with a Varian 3300 Chromatograph.

Reductive Oxidation of Acid Chlorides to Aldehydes

The following reaction is typical of the procedure utilized in such conversion with PCC. A solution of lithium aluminum hydride (1.0 M, 31mL, 31 mmol) in THF was placed in an oven-dried, 500-mL flask fitted with a side-arm and a reflux condenser leading to a mercury bubbler. To this solution 8.57g (61 mmol) of benzoyl chloride was added dropwise with vigorous stirring at 0C and the mixture was stirred further for 3 hours at room temperature. To a well stirred solution of PCC (14.5g, 67 mmol) in methylene chloride (120mL) taken in a 500-mL flask equipped as described above, was added dropwise the above reaction mixture in THF using a cannula. The mixture was stirred for 3 hours at room temperature. GC analysis of aliquot using tridecane as an internal standard indicated a yield of 98%.

Isolation of Aldehyde Products

The rest of reaction mixture (60 mmol) was diluted with ethyl ether (120mL) and the supernatant liquid is then filtered through Florisil (120g) contained in a 300-mL sintered glass funnel. The solid residue was triturated with ethyl ether (3 30mL) and passed through the same Florisil column. The filtrate is concentrated and distilled under reduced pressure to give 5.2g (82%) of pure benzaldehyde, bp 62-63C (14 mmHg, np22 1.5450).


Benzoyl chloride -> Benzaldehyde, 82% w/PCC (79% w/PDC), reaction time: 3h;

4-Chlorobenzoyl chloride -> 4-Chlorobenzaldehyde, 97% w/PCC (97% w/PDC), reaction time: 3h;

o-Toluoyl chloride -> o-Tolualdehyde, 96% w/PCC (95% w/PDC), reaction time: 3h;

p-Toluoyl chloride -> p-tolualdehyde, 95% w/PCC (95% w/PDC), reaction time: 3h;

o-Anisoyl chloride -> o-Anisaldehyde, 96% w/PCC (94% w/PDC), reaction time: 3h;

p-Anisoyl chloride -> p-Anisaldehyde, 96% w/PCC (95% w/PDC), reaction time: 3h.


Reference
Bull. Korean Chem. Soc. 2000, Vol. 21, No. 4, pp 375

I'm dreaming of the white crystals.
 
 
 
 
    El_Zorro
(Hive Addict)
12-14-02 03:23
No 389283
      So LAH is unwatched? When was I gonna be told ...  Bookmark   

So LAH is unwatched?  When was I gonna be told about this?

It is seductive, way too seductive.             -Eleusis
 
 
 
 
    Antoncho
(Official Hive Translator)
12-14-02 05:22
No 389327
      Anyway,...  Bookmark   

...this is the 1st reduction of an acid chloride to ALDEHYDE with LAH ever documented on this site, i dare say.

Very interesting - thanx, Demorol!


Antoncho
 
 
 
 
    demorol
(Hive Bee)
12-19-02 19:58
No 390832
      More procedures
(Rated as: excellent)
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Conversion of Alcohols to Aldehydes and Ketones by Oxidation of Trialkoxyaluminum with Pyridinum Chlorochromate (PCC), Bull. Korean Chem. Soc., 1998, Vol. 19, No. 7, pp 724

Experimental procedure

The following experimental procedure is illustrative. To an oven-dried, nitrogen-flushed 100-mL RB flask, fitted with a septum inlet, a magnetic stirring bar, and a reflux condenser leading to a mercury bubbler, a 1.10 M solution of aluminum hydride (18.2mL, 20 mmol) in THF was injected and the solution was kept at 0C with aid of an ice-water bath. The mixture was stirred at 0C and a 3.0 M solution of 1-octanol (20mL, 60 mmol) was added dropwise with a syringe. After the addition was complete, the mixture was then allowed to room temperature and stirred for 3 h. In another oven-dried, nitrogen-flushed 500-mL RB flask, fitted with a septum inlet, a magnetic stirring bar, and reflux condenser leading to a mercury bubbler, are placed powdered PCC (26g, 120 mmol) and methylene chloride (200mL). To the well-stirred suspension, a solution of trioctylaluminum in THF thus prepared was added with the aid of a double-ended needle. The mixture was stirred at room temperature for 1 h. Then, ethyl ether (200mL) was added and the mixture was filtered through a column containing Florisil. The solid residue in the flask was triturated with ethyl ether (3 50mL) and filtered through the same Florisil column. The combined filtrate was concentrated and distilled to afford 6.04g of pure octanal (78%); bp 170-172C/761 mmHg. The purity was further confirmed by GC analysis.
A small scale of same reaction (trioctylaluminum, 1 mmol) was also performed and tridecane was added as an internal standard. The product aldehyde was analyzed by GC with use of a Carbowax TAP capillary column (25 m) to show 97% octanal formation.

Alkyl group of (RO)3Al   Product
Ph-CH2-                 BA* (98%)
4-Me-Ph-CH2-            4-Me-BA (97%)
4-MeO-Ph-CH2-           4-MeO-BA (97%)
4-Cl-Ph-CH2-            4-Cl-BA (98%)


*BA = Benzaldehyde

Conversion of Carboxylic Acids into Aldehydes by Oxidation of Alkoxyaluminum Intermediate with Pyridinum Chlorochromate or Pyridinum Dichromate, Bull. Korean Chem. Soc., 1998, Vol. 19, No.7, pp 730

Experimental procedure

This method provides another convenient procedure for the direct conversion of carboxylic acids to corresponding aldehydes. The following procedure for the reaction of hexanoic acid is representative. An oven-dried, 250-mL RB flask with sidearm, equipped with a magnetic stirring bar and a reflux condenser, was attached to a mercury bubbler. The flask was flushed with dry nitrogen and then maintained under a static pressure of nitrogen. The flask was charged with hexanoic acid (6.97g, 60 mmol) and 30mL of THF. The flask was immersed in an ice-water bath and a pre-cooled 1.0 M solution of aluminum hydride (30mL, 30 mmol) in THF was added dropwise with vigorous stirring. After the complete evolution of the hydrogen, the ice-water bath was removed and the reaction mixture was stirred for 30 min at room temperature.

To a well-stirred suspension of PCC (14.3g, 66 mmol) in methylene chloride (100mL) taken in a 500-mL RB flask equipped as described above, is added dropwise the above solution of alkoxyaluminum intermediate in THF using a cannula. The mixture was stirred for 12 h at room temperature. The small portion of this mixture was transfered to a vial and dodecane was added as an internal standard. GC analysis using a Carbowax 20 M capillary column (20 m) showed a presence of hexanal in a yield of 96%. The reaction mixture was diluted with 200mL of diethyl ether and the supernatant liquid is filtered through Florisil (100g) contained in a 300-mL sintered glass funnel. The solid residue is washed with diethyl ether (3 50mL) and passed through the same Florisil column. The filtrate was concentrated and distilled to afford pure hexanal (4.93g, 82% yield); bp 129-130C (754 mmHg).

Analogous procedures are used for the synthesis of the other aldehydes listed in Table 1. In the case of PDC as an oxidant used, actually the same procedure was adopted except the oxidation time.

Cinnamic acid -> Cinnamaldehyde, 95% w/PCC (98% w/PDC), reaction time: 12h;

Benzoic acid -> Benzaldehyde, 85%* w/PCC (99% w/PDC), reaction time: 6h;

o-Toluic acid -> o-Tolualdehyde, 99% w/PCC (99% w/PDC), reaction time: 6h;

m-Toluic acid -> m-Tolualdehyde, 98% w/PCC (99% w/PDC), reaction time: 6h;

p-Toluic acid -> p-Tolualdehyde, 99% w/PCC (99% w/PDC), reaction time: 6h;

p-Anisic acid -> p-Anisaldehyde, 98% w/PCC (98% w/PDC), reaction time: 6h;

4-Chlorobenzoic acid -> 4-Chlorobenzaldehyde, 99% w/PCC (98% w/PDC), reaction time: 6h.

*Isolated yield


I'm dreaming of the white crystals.
 
 
 
 
    demorol
(Hive Bee)
12-20-02 19:37
No 391098
      Carboxylic Esters -> Aldehydes  Bookmark   

Convenient Conversion of Carboxylic Esters to Aldehydes by Oxidation of Alkoxyaluminum Intermediate with Pyridinum Chlorochromate or Pyridinum Dichromate, Bull. Korean Chem. Soc., 1998, Vol.19, No. 12, pp 1301

This method provides another convenient procedure, which is superior to many of the procedures previously utilized.

Experimental procedure

The following procedure for the reaction of ethyl benzoate with PCC is representative. An oven-dried, 250-mL RB flask, fitted with a side arm and a reflux condenser connected to a mercury bubbler, was flushed with dry nitrogen and then maintained under a static pressure of nitrogen. The flask was charged with 1.0 M solution of aluminum hydride (61mL, 61 mmol) in THF. To the stirred solution at room temperature, ethyl benzoate (9.61g, 61 mmol) was added dropwise and the reaction mixture was stirred for 1 hour. To a well stirred suspension of PCC (28.5g, 132 mmol) in methylene chloride (200mL) taken in a 500-mL flask equipped as described above, was added dropwise to the above solution of alkoxyaluminum intermediate in THF using a cannula. The mixture was stirred for 3 h at room temperature. The small portion of this mixture was transferred to a vial and dodecane was added as an internal standard. GC using a capillary column of Carbowax 20 M indicated the presence of benzaldehyde in a yield of 99%.
The rest of the reaction mixture (60 mmol) was diluted with diethyl ether (200mL). The supernatant liquid was filtered through Florisil (200g) contained in a 300-mL sintered glass funnel; the solid was triturated with ethyl ether (3 50mL) and passed through the same column. The filtrate was concentrated and distilled under reduced pressure to give pure benzaldehyde (5.22g, 82%), bp 62-63 C (15 mmHg).

Analogous procedure is used for the synthesis of the other aldehydes. In the case of PDC as an oxidant used, actually the same procedure was adopted.

Ethyl butyrate -> Butyraldehyde, 94% w/PCC (93% w/PDC), reaction time: 6h;

Ethyl cinnamate -> Cinnamaldehyde, 96% w/PCC (95% w/PDC), reaction time: 3h;

Methyl benzoate -> Benzaldehyde, 99% w/PCC (98% w/PDC), reaction time: 3h;

Ethyl benzoate -> Benzaldehyde, 82% w/PCC (81% w/PDC), reaction time: 3h;

Ethyl 4-methylbenzoate -> 4-Methylbenzaldehyde, 97% w/PCC (98% w/PDC), reaction time: 3h;

Methyl 4-chlorobenzoate -> 4-Chlorobenzaldehyde, 98% w/PCC (96% w/PDC), reaction time: 3h.


I'm dreaming of the white crystals.
 
 
 
 
    pHarmacist
(Hive Bee)
12-20-02 19:39
No 391100
      Yet another excellent post from demorol  Bookmark   

Wow demorol! Outstanding work in this area... Great findings! >90% Excellent!


"Turn on, Tune in and Drop Out"
 
 
 
 
    demorol
(Hive Bee)
12-20-02 19:59
No 391106
      Actually, I think yields are not that high.  Bookmark   

Actually, I think yields are not that high. I think isolated yields are around 80-85%, but that is also good, IMO.

I'm dreaming of the white crystals.
 
 
 
 
    demorol
(Hive Bee)
02-07-03 17:33
No 405313
      Acyl chlorides -> aldehydes
(Rated as: excellent)
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Aldehydes from Acyl Chlorides; General Procedure:

Reduction at atmospheric pressure

The acyl chloride is added over a period of 3-5 min to a well-stirred suspension of hydrogen-equilibrated catalyst (see Notes) under dry hydrogen in dry THF containing 1 equiv of 2,6-dimethylpyridine per acyl chloride function. Best results are obtained when the concentration of acyl chloride does no exceed 0.25 M. With 10-15mg of 10% Pd/C or 20-30mg of 5% Pd/BaSO4 catalyst per mmol of acyl chloride, hydrogen uptake occurs at a steady rate and is usually complete in 1-2 h.

Upon completition of the reduction, the solvent is removed under vacuum, ether or petroleum ether added, the mixture filtered, and the filtrate concentrated to give nearly pure aldehyde. Alternatively, the product is recovered by filtration, concentration of the filtrate, addition of ether, and washing with dilute HCl and then aqueous NaHCO3. After drying over anhydrous MgSO4 the ether solution is evaporated and the residue distilled or recrystallized.

Reduction at slightly elevated pressure

Low-pressure hydrogenations (2-4 atm) are conducted as described above except that the acyl chloride is added before exposure of the suspension to hydrogen.

Yields:

Benzaldehyde*, 93%
4-Chlorobenzaldehyde*, 77%

* Reduction conducted in benzene at 40-50 C

Notes:

1.) Catalysts used were: 10% Pd/C, 5% Pd/BaSO4, 10% Pd/C Quinoline S.

2.) Except when commercially available, the acyl chlorides were prepared by the action of redistilled oxalyl chloride on a 1 M solution or suspension of the anhydrous acid in benzene at 25-30 C. One microdrom of DMF accelerated the reaction to completition within 20 min or less, except in the case of dicarboxylic acids, which required more time. After 30 min, the solvent and excess reagent were removed under vacuum. Fresh benzene was added, and the solution was treated with dry Nuchar, filtered and reconcentrated. Generally, the acyl chloride was suitable for use without further purification, although whenever possible, it was redistilled or recrystallized.

Reference: Synthesis, 1976, pp 767

I'm dreaming of the white crystals.