Sciencemadness Discussion Board

hydrogenolysis with lithium aluminium hydride

alittlebitcrazy - 2-7-2018 at 17:28

LiAlH4 can be used to reduce a formyl(aldehyde) group into a methyl group? and basically do hydrogenolysis by replacing the oxygen attached to the carbon with hydrogen?.
i downloaded an article that talk about turning a formyl group in some compound into methyl group by reduction with LiAlH4 but when reading on reduction with LiAlH4 i only managed to read about reduction of ketons and aldehydes into alcohols. does the scientists behind the article done something special with the LiAlH4?.

sorry if i have some mistakes here, i don't have formal or any serious knowledge in chemistry and i am just an amateur chemist.

SWIM - 2-7-2018 at 20:59

What's that formyl group attached too?
Maybe an amine?

Is the amine beta to an aromatic group by any chance?

By the way, how are you going to get LAH when you have problems getting nitric acid according to your earlier posts?

LAH tends to be harder to get than nitric acid.

At least it is around here.



[Edited on 3-7-2018 by SWIM]

JJay - 2-7-2018 at 22:06

I don't think LiAlH4 reduces typical aldehydes and ketones to alkanes... I think it reduces them to alcohols. The usual means of reducing aldehydes and ketones to alkanes are the Wolff-Kishner reduction and the Clemmensen reduction. Neither requires anything that you can't lay your hands on as an amateur, but both involve rather toxic substances; the Wolff-Kishner is probably more environmentally friendly.

Chemi Pharma - 2-7-2018 at 23:01

I agree with all @JJay have written above, and add that some aryl ketones and alcohols can be reduced to methylenic groups with NaBH4 and TFA, or AlCl3.


[Edited on 3-7-2018 by Chemi Pharma]

alittlebitcrazy - 3-7-2018 at 09:53

Quote: Originally posted by SWIM  
What's that formyl group attached too?
Maybe an amine?

Is the amine beta to an aromatic group by any chance?

By the way, how are you going to get LAH when you have problems getting nitric acid according to your earlier posts?

LAH tends to be harder to get than nitric acid.

At least it is around here.



[Edited on 3-7-2018 by SWIM]

it is attached to amine. it is attached to a nitrogen atom that is attached to another carbon and a hydrogen atom.
can LiAlH4 reduce in some cases formyl group into a methyl group? does it require some special means?.



and for the nitric acid thing, i was a bit affraid to get into some "black list" for buying some nitrate salts/nitrate based fertilizer somewhere or for the "research" i made on google about making some explosives and rocket fuels(for the fun obviously) but i got over it.


[Edited on 3-7-2018 by alittlebitcrazy]

[Edited on 3-7-2018 by alittlebitcrazy]

JJay - 3-7-2018 at 11:16

If there's a carbonyl adjacent to an amine, that's called an amide. Amides can be reduced to amines with LiAlH4 IIRC.

Chemi Pharma - 3-7-2018 at 11:25

You really didn't read what @JJay wrote, I guess.

No, LiAlH4 can't reduce ketones or aldehydes to methylenic groups, just to alcohols.

To do that you need to do a Wolf-Kirshner redution with tosyl hydrazide, to form an hydrazone. Then the hydrazone can be easily reduced to methylenic group with LiAlH4 or NaBH4 in methanol.

Other way is the Clemensen reduction with amalgamated zinc and HCl at 0ºC.

Also bis-aryl alcohols and aryl ketones can be deoxigenated by NaBH4/AlCl3(anhydrous) or NaBH4/TFA couple.

alittlebitcrazy - 3-7-2018 at 11:49

Quote: Originally posted by Chemi Pharma  
You really didn't read what @JJay wrote, I guess.

No, LiAlH4 can't reduce ketones or aldehydes to methylenic groups, just to alcohols.

To do that you need to do a Wolf-Kirshner redution with tosyl hydrazide, to form an hydrazone. Then the hydrazone can be easily reduced to methylenic group with LiAlH4 or NaBH4 in methanol.

Other way is the Clemensen reduction with amalgamated zinc and HCl at 0ºC.

Also bis-aryl alcohols and aryl ketones can be deoxigenated by NaBH4/AlCl3(anhydrous) or NaBH4/TFA couple.


so basically the authors of the article did a wolf-kirshner reduction and used LiAlH4 as you said but without mentioning the wolf-kirshner reduction?.
here is the section i am talking about in the article:

"Reduction of the compound lb, R = CHO (6'9 g; 42·3 mmol) with lithium aluminium hydride (3'21 g) in ether (75 ml) and the usual work-up afforded 4·5 g (67%) of a product, b.p. 48-52°C: : 1 mm-Hg. For C10H15N (149'2) calculated: 80'50% C, 10'08% H, 9·41% N; found: 80·70% C, 10'24% H, 9'44% N. Reported16, b.p. 93°C/15 mm Hg, for the compound lb (R = CH3) obtained by the reduction of the corresponding ketone methylimine. "

the article is a very weird and unclear for me so i hope someone with more experience with reading chemistry-related articles will help me understand this.

[Edited on 3-7-2018 by alittlebitcrazy]

Chemi Pharma - 3-7-2018 at 13:07

Quote: Originally posted by alittlebitcrazy  

"Reduction of the compound lb, R = CHO (6'9 g; 42·3 mmol) with lithium aluminium hydride (3'21 g) in ether (75 ml) and the usual work-up afforded 4·5 g (67%) of a product, b.p. 48-52°C: : 1 mm-Hg. For C10H15N (149'2) calculated: 80'50% C, 10'08% H, 9·41% N; found: 80·70% C, 10'24% H, 9'44% N. Reported16, b.p. 93°C/15 mm Hg, for the compound lb (R = CH3) obtained by the reduction of the corresponding ketone methylimine. "


The Author said that the compound R = CHO were reduced to C-OH with LiAlH4, and R=CH3 were obtained from the imine of the ketone/aldehyde, reduced by LiAlH4. That means the Author reacted the base compound R=CHO with methylamine to get the methylimine CH3-N=C. Then he reduced the imine with LiAlH4. Two steps to the target.

However, I think methylimines reduced by LiAlH4 will give methylamines, never alkanes. Something is wrong in this text and I don't know exactly what the Author wanted to say with this.



[Edited on 3-7-2018 by Chemi Pharma]

zed - 3-7-2018 at 13:20

What article?

Include a link. It is, in fact, kind of a rule.

Start a topic; include a reference!

DDTea - 12-1-2019 at 07:34

I've done something like this, albeit starting from the ester to get down to the alkane (was installing a methyl-d3 group). Ketones and aldehydes can be reduced to aliphatic groups in a three step sequence: reduction to alcohol, halogenation (or tosylation or triflation, etc.) to install a better leaving group, followed by displaced of the leaving group by a nucleophilic hydride.

Lithium aluminum hydride can be and has been used for that last reaction, but it leads to a lot of undesired E2 elimination product. Super hydride (lithium triethylborohydride) gives much cleaner and faster nucleophilic substitution.

Of course, it is also pyrophoric, and is prepared from pyrophoric materials.

Mush - 16-7-2019 at 10:07

R-NH-formyl can be reduced to R-NH-CH3.

I believe this JACS article must have been Shulgin's starting point to his n-methylation reactions with LiAlH4 .

Formylation of Amines with Chloral and Reduction of the N-Formyl Derivatives with Lithium Aluminum Hydride

F. F. Blicke , Chi-Jung Lu

J. Am. Chem. Soc.1952, 74, 15
doi.org/10.1021/ja01135a503

Examples:

1, N-formyltryptamine -> N-methyltryptamine
https://isomerdesign.com/PiHKAL/read.php?domain=tk&id=50

2, N-formyl-1-(2,3-methylenedioxyphenyl)-2-butanamine -> N-methyl-1-(2,3-methylenedioxyphenyl)-2-butanamine
https://www.designer-drug.com/pte/12.162.180.114/dcd/chemist...

3, N-Formyl- 1-(1,3-benzodioxol-5-yl)-2-propanamine-> N-Methyl-1-( 1,3-benzodioxol-5-yl)-2-propanamine

Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class

David E. NicholsAndrew J. HoffmanRobert A. OberlenderPeyton Jacob IIIAlexander T. Shulgin
J. Med. Chem.198629102009-2015


4, non n-me, pyrrole-2-carboxaldehyde -> 2-methylpyrrole
https://www.sciencedirect.com/topics/chemistry/clemmensen-re...
2.03.3.4 Conversion of Acyl Substituents to Alkyl Groups

The reductive deoxygenation of acyl substituents is one of the classic methods for introduction of primary alkyl groups on aromatic rings. For benzene derivatives, the Wolff-Kishner and Clemmensen reactions can be used. In the case of C-acylpyrroles and C-acylindoles, the transformation can also be effected by typical hydride donors because of the lability of the carbinol intermediates. For example, pyrrole-2-carboxaldehyde can be reduced to 2-methylpyrrole by LiAlH4 (Equation (87)) 〈93T1343〉.


[Edited on 16-7-2019 by Mush]

Mush - 17-7-2019 at 09:50

Methyl tert-butyl ether- iodine - Sodium borohydride

9 : Example 9 Preparation of ethyl 3-methoxy-4- (1-methylpiperidin-4-ylmethoxy) benzoate (Compound I)
Ethyl 4- (1- (formyl) piperidin-4-ylmethoxy) -3-methoxybenzoate (1 g, 3.12 mmol) was dissolved in 10 mL of methyl
tert-butyl ether,Sodium borohydride (0.43 g, 11.23 mmol) was added and the mixture was cooled to 0 ° C in an icewater
bath. Methyl tert-butyl ether solution (20 mL, 1.2 g iodine) was slowly added dropwise for 1.5 h. After 6 h reaction,
Reflux overnight.The reaction mixture was spun dry and extracted with ethyl acetate (10 mL). The organic phases
were combined, washed three times with water (10 mL) and twice with saturated brine (10 mL), dried over anhydrous
Na2SO4 and spun dry to obtain 0.8 g of a white solid. Yield 84.2percent.
With sodium tetrahydroborate, iodine in tert-butyl methyl ether, Time= 6.5h, T= 0 °C , Reflux, Industrial scale, Reagent/
catalyst, Solvent
Patent; Shanghai Pharmaceutical Industry Institute; China Pharmaceutical Industry Zongyuan; Zhang Wenqiang;
Cai Zhengyan; Zhou Weicheng; Zhang Qingquan; Li Hongyan; (12 pag.); CN104876852; (2017); (B) Chinese

sodium borohydride - THF - iodine
A Convenient Reduction of Amino Acids and Their Derivatives (Table 2)
https://www.erowid.org/archive/rhodium/pdf/borohydride-iodin...