Let me proudly present you the absolutely easiest, non-demanding way of turning benzoic acids into corresponding aldehydes. One of the particularly interesting applications of this method would bee, of course, turning gallic acid into 3,4,5-triMeO-BA.
Firstly, a benzoic acid is turned into benzonitrile by treatment w/sulfaminic acid (a very cheap and unsuspicious chemical) and urea.
Secondly, the nitrile is reduced to benzaldehyde with copper-treated Raney Ni/H2 or Al/Ni/formic acid. CTH should also work in this case, but the conditions need to bee adjusted so as not to overreduce the aldehyde.
Step 1. Conversion of benzoic acid into benzonitrile.
Patent GB2151626 (http://l2.espacenet.com/dips/viewer?PN=GB2151626&CY=gb&LG=en&DB=EPD)
Example 2.
A mixture of 396 g /6.6 moles/ of urea, 639 9/ 6.59 moles/ of sulfaminic acid and 700 g /3.30 moles/ of 3,4,5-trimethoxybenzoic acid is heated at 1 90 C for 4 hours.
The reaction mixture is cooled to room temperature, whereupon 1.5 1 of water, 5 1 of toluene and 100 g of calcium carbonate are added. The formed 3,4,5-trimethoxy-benzonitrile enters into the toluene phase. The reaction mixture is heated at 100"C for 20 min
utes, cooled to room temperature, whereupon
200 ml of concentrated aqueous ammonium hydroxide solution and 25 g of activated charcoal are added. The solution is filtered and the filtrate is separated into an organic and aqueous layer. The toluene phase is evaporated in vacuo. The residue is suspended in 1.5 l of acetone, 25 g of activated charcoal are added, the mixture is warned and filtered. The filtrate is poured into water under stirring, the precipitated product is filtered off and dried.
Thus 510 g of 3,4,5-trimethoxybenzonitrile are obtained, yield 80 %, mp.: 93"C.
The pH of the aqueous filtrate is adjusted to 2 by adding concentrated hydrochloric acid under stirring. The mixture is allowed to stand, the precipitated product is filtered off, washed neutral with water and dried. Thus 35 g of 3,4,5-trimethoxy-benzoic acid are obtained; this acid is re-introduced into the manufacture process of 3,4,5-trimethoxy-benzonitrile. The conversion of 3,4,5-trimethoxy-benzonitrile related to the reacted 3,4,5-trimethoxy-benzoic acid amounts to 84.3 %.
Step 2. Reduction of benzonitrile to benzaldehyde.
A) Patent US4500721 (http://l2.espacenet.com/dips/viewer?PN=US4500721&CY=gb&LG=en&DB=EPD)
EXAMPLE 1
(1) 9 g (wet weight) of a commercially available developed Raney nickel was added to 300 ml of a 1% CuSO.sub.4.5H.sub.2 O aqueous solution, and the mixture was stirred for 30 minutes in a nitrogen gas stream. The color of the Raney nickel changed from black to brown. The Raney nickel was collected by filtration and washed with ion-exchanged water to obtain 10.8 g (wet weight) of a copper salt-treated Raney nickel catalyst.
(2) To 50 g of methanol were added under stirring 5.40 g (0.0406 mol) of p-methoxybenzonitrile and 4.1 g of concentrated sulfuric acid. To the resulting solution was added 0.5 g of the copper salt-treated Raney nickel catalyst obtained in (1) above that had been thoroughly washed with methanol. The mixture was then subjected to reduction at room temperature (i.e., 22.degree. to 24.degree. C.) under atmospheric pressure. In 9 hours and 40 minutes, 0.0444 mol of hydrogen was absorbed.
Water (200 g) was added to the reaction solution, and the catalyst was collected by filtration and washed with 100 g of water and 50 g of ethylene dichloride. The mother liquor was combined with the washings, and further mixed with 100 g of ethylene dichloride. The mixture was allowed to stand, and the ethylene dichloride phase was separated. The aqueous phase was extracted twice with 150 g of ethylene dichloride. The ethylene dichloride phases were combined, washed with 100 g of water and concentrated to obtain 5.33 g of an oil with a p-methoxybenzaldehyde content of 95.4%. The yield was 92.1%.
B) Patent US4900859 (http://l2.espacenet.com/dips/viewer?PN=US4900859&CY=gb&LG=en&DB=EPD)
EXAMPLE 3
Preparation of 4-dimethylamino-3,5-dimethoxybenzaldehyde
A mixture of 91 g of the 3,5-dimethoxy-4-methylaminobenzonitrile obtained in Example 2, 726 g of formic acid and 29 g of p-formaldehyde are heated to reflux for 1 hour. The mixture is then cooled to 20 DEG-30 DEG C. and treated with 181 ml of water and 91 g of Raney-nickel alloy. The reaction mixture is heated to reflux for 1.5 hours, whereby the reaction starts vigorously at 80 DEG C. The reaction mixture is cooled to 25 DEG-30 DEG C. and filtered in such a manner that the metal is always covered with solvent. The filter cake is washed with formic acid and the solution is evaporated under reduced pressure and thereafter treated with 360 ml of toluene and 360 ml of water. The pH is adjusted to 5.5 to 6 by adding 30% aqueous sodium hydroxide solution. After adding 7 g of active charcoal, the reaction mixture is filtered. The filter cake is washed with toluene and the organic phase is concentrated under reduced pressure. 80 g of 4-dimethylamino-3,5-dimethoxybenzaldehyde are obtained as an oil.
Note: here they perform in one pot an Eschweiler-Clark methylation followed by reduction. They use 2x molar equivalent of HCHO, so in the beginning of the 2nd step, the sol’n still contains 1 molar eq. of formaldehyde. Is this important for the reduction, or just can bee omitted? Can anyone tell?
And, - dear bees! Can anyone provide us w/other versions of benzonitrile --> benzaldehyde reductions? It seems to bee a fairly common reaction. Please, do if you can!
Antoncho
Chemical name: Aminosulfonic Acid (Sulfamic acid)
Molecular Formula: H2NSO3H
Character: white crystalline, no smell, relative density 2.126. melting point 205, soluble in water liquid ammonia, light soluble in methanol, not soluble in ethyl ester, CS2 liquid sulphite, aqueous solution is high ionization, strong acid, noxious.
Usage: as basic reagent for acid-base litration; used as weedicide, fire-retardant agent; a softener for paper, texitile; sanforizing and bleading and softening for fibre. Cleaning agent for metal and ceramics; catalyst for cascamite; a heavy azotizing for dystuffs and mordanting for plating metal.
It is also important for the retina of cats. So take care kitty gets enough of it! :)
Stephen Reduction Ref:
Post 388559 (https://www.thevespiary.org/talk/index.php?topic=12746.msg38855900#msg38855900)
(Chimimanie: "Hypothetic possibility (+ a synthesis of indol)", Tryptamine Chemistry)
Patent US4383949 (http://l2.espacenet.com/dips/viewer?PN=US4383949&CY=gb&LG=en&DB=EPD)
Example 1.
17.0 g of a 50% strength alkaline suspension of Raney nickel were filtered under a nitrogen atmosphere and the material on the filter was washed until neutral. The Raney nickel obtained by this method was suspended in 150 ml of formic acid. 20.0 g (0.1 mole) of 3-bromo-4-fluoro-benzonitrile were added to this suspension. The mixture was heated at 80 DEG to 90 DEG C. for 3 to 5 hours and the reaction mixture was then cooled and poured into 300 ml of water. After filtering, the filtrate was twice extracted with, in each case, 200 ml of toluene. The toluene phase was dried over sodium sulphate and then concentrated. 17.2 g (85% of theory) of 3-bromo-4-fluoro-benzaldehyde with a boiling point of 63 DEG-65 DEG C./0.3 mm Hg were obtained.
... as well as several other proc's.
Antoncho