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All 9 posts Subject: LAH alternatives refs Please login to post Down

Rhodium
(Chief Bee)
05-25-00 21:39
No 9315
User Picture       LAH alternatives refs
(Rated as: excellent)

Copied from an old Usenet post:

I was wondering if anybody has born witness to, or heard of thru trusted sources, an effective way of reducing 2,5-dimethoxy-beta-nitrostyrene to its corresponding amine without using LAH? I've read a couple decent methods using NaBH4, but they sound either poorly tested or the folks doing them can afford to sit around and watch their reaction for six days!

There are some variations of the NaBH4 method: 3 to 5 h reflux in THF:
Synth. Commun. 15 (9) 1985, 843-848;
J. Heterocycl. Chem. 24, 1987, 767-772;
Heterocycles 41 (11), 1995, 2441-2458.

Anybody know about the real-world effectiveness of Zwit's Zinc/HCl method? How about a good way of activating the NaBH3 reaction? Maybe suggestions for different catalysts that don't require an H2 atmosphere or don't use household aluminum foil (I don't really trust the oxidation state or metallurgical purity of said foil)? Any ideas, comments, references, or places to look would be appreciated. Thanks and Have Joy!

Of course, Red-Al (DIBAH) and AlH3 are also working but suffer from the same disadvantages as LAH.

Zn-aq. HCl is disclosed in:
Chem. Pharm. Bull. 16 (2), 1968, 217-226;
Bull. Soc. Chim. Fr. 1960, 231-239;
Arch. Pharm. 322, 1989, 477-482 (2 min reflux in THF!),
J. Chem. Res. Miniprint, 1, 1988, 0157-0177;
Tetrahedron Lett. 33 (45), 1992, 6883-6884;
Ann. Pharm. Fr., 10, 1952, 276-281;
Ann. Pharm. Fr., 7, 1949, 733;
Acta Chim. Acad. Sci. Hung., 14, 1958, 325;
Monatsh. Chem., 40, 1919, 144.

Aluminum is used in Monatsh. Chem., 79, 1948, 72.

The use of LiBH4/Me3SiCl in THF (24 h room temperature) as disclosed in Angew. Chem. 101 (2), 1989, 220-222, might also be of interest.

There are a lot of electrochemical reductions reported (e.g., MeOH, H2SO4, lead cathode) but obviously require special equipment.

You might also consider stepwise reaction to the ketone with subsequent amination as described in PIHKAL for #68, DOM (MeOH, NH4OAc, NaCNBH3).

IMHO, catalytic hydrogenation (e.g., Pd-C, MeOH, aq. HCl, atmospheric pressure, room temperature) constitutes the most efficient procedure for the preparation of this class of compounds.

obituary
(Hive Bee)
05-27-00 11:58
No 9956
User Picture       Re: LAH alternatives refs

swim's read a lot of stuff and have not seen any procedures using atmospheric pressure (maybe a balloon) and room temperature for hydrogenation- references? links?

zooligan
(Hive Bee)
05-28-00 00:06
No 10161
User Picture       Re: LAH alternatives refs

Yes, Rhod! References, links, synth notes perhaps????

zool

zooligan
(Hive Bee)
08-02-00 15:28
No 35787
      Re: LAH alternatives refs
(Rated as: good read)

Tips for Hydrogenation Experiment (http://ice.chem.umbc.edu/Chem351l/exp9_tips.html)

KrZ
(Hive Bee)
08-03-00 05:12
No 36071
User Picture       Re: LAH alternatives refs
(Rated as: good read)

Rhodium, recent experiments at my monkey laboratory have notice some fascintaing behavious here is a very interesting example:

100g 2,5-Dimethoxynitrostyrene
150ml H2SO4 98% (2.84 mol)
2000ml Glacial Acetic Acid
15g Pd/C 5%
75psi (6 atmospheres)

Reactor charge and shaken, 100% absorption was encountered after 45 minutes!!!!!

Add 1,200 ml of 5M NaOH with stirring to cooled post reaction mix
Add 1L of MeOH, instant precipitation of all the former Na2SO4
Filter off the Na2SO4
Remove the GAA, H2O, and MeOH at reduced pressure

Take the residue in the distillation flask, add 500ml 5M NaOH
Add 125ml DCM and stir
Seperate and rextract 3x 125ml
Pool the DCM extracts, dry over Na2SO4, and distill

Yield: 92%

This was the animals first experience with the GAA/H2SO4 system and it was quite impressive indeed, solvation is comparable to that of using alcohol solvents but yields and reaction times are greatly improved. It may be possible to add undissolved NS to the mix which would dissolve over the course of the reaction, we will have to observe the animals further to see how that goes.

Rhodium
(Chief Bee)
08-03-00 19:34
No 36273
User Picture       Re: LAH alternatives refs

KrZ, Thanks for your contribution! (BTW, I didn't write any of the above, it was just cut-n-paste fron usenet)

http://rhodium.lycaeum.org

Rhodium
(Chief Bee)
05-15-04 16:17
No 507331
User Picture       Clemmensen reduction of nitrostyrenes
(Rated as: excellent)

_{This artience has been mentioned before in:
Post 9315 (Rhodium: "LAH alternatives refs", Methods Discourse)
Post 108634 (dormouse: "The Good Reverend's nitrostyrene reduction contest -rev drone", Novel Discourse)
Post 78688 (PolytheneSam: "Re: References on nitrostyrene reduction", Chemistry Discourse)}

_{Studies on the Alkaloids of Menispermaceous Plants. CCXLIV.}
Synthesis of dl-Cepharanthine
Masao Tomita, Kazuyoshi Fujitani, Yoshiaki Aoyagi, and Yasumichi Kajita
Chem. Pharm. Bull. 16(2) 217-226 (1968) (https://www.rhodium.ws/pdf/cepharantine.ns2pea.zn-hg.pdf)

5-Bromopiperonal (VI) obtained in relatively high yield (42-64%) from 5-bromoprotocatechuic aldehyde (V) through methylenation reaction catalysed by cupric oxide¹⁰ was condensed with nitromethane in the presence of ammonium acetate in acetic acid to afford a nitrostyrene (VII), which was reduced to a phenethylamine (VIII) under Clemmensen condition. Preparation of VIII starting with 5-bromoprotocatechuic aldehyde was already reported by Erne and Ramirez,¹¹ but the modification adopted by the present authors raised the yield in every step of the reaction sequence. [...] 3-methoxy-4-hydroxy-β-nitrostyrene (X)¹² was treated with ethyl chloroformate in pyridine and the resulted O-carbethoxy derivative (XI) was reduced under Clemmensen condition to give a phenethylamine (XII).

Experimental

3-Bromo-4,5-methylenedioxy-β-nitrostyrene (VII)
The solution of 5-bromopiperonal (64 g), nitromethane (65 g), and NH₄OAc (30 g) in AcOH (400 ml) was heated to reflux for 2 hr. After cooling, the mixture was poured into water (1 liter); a precipitated crystalline solid was collected by filtration. Recrystallization of the above crystalline substance from 50% (by vol.) CHCl₃-EtOH afforded the product. Yield 55 g. Yellow needles, mp 160-162°C (lit.¹¹ mp 160-161°C).

3-Bromo-4,5-methylenedioxy-β-phenethylamine (VIII)
The foregoing nitrostyrene (VII, 53 g) and amalgamated zinc prepared from zinc powder (200 g) and HgCl₂ (20 g) were suspended on EtOH (2 liter). Under vigorous stirring, conc. HCl was added portionwise into the above mixture until the yellow coloring of the reaction mixture disappeared. After the decolorization was completed, the reaction mixture was further stirred for 30 min. An excess Zn-Hg was filtered off; EtOH was evaporated in vacuo, and the residue was poured into water (1 liter). The aqueous solution was made alkaline with conc. NH₄OH after washed with ether; then the basic product was extracted into CHCl₃, and the washed CHCl₃ extracts were evaporated to give the product. Light-brown viscous oily substance, yield 32 g. Hydrochloride: Recrystallized from EtOH-acetone, colorless platelets, mp 238-240°C (dec.) (lit.¹¹ mp 250-251°C).

3-Methoxy-4-O-carbethoxy-β-nitrostyrene (XI)
To a solution of 3-methoxy-4-hydroxy-β-nitrostyrene (15 g) in pyridine (100 ml), ethyl chloroformate (15 ml) was added dropwise with stirring on an ice bath. After the addition was completed, the mixture was further stirred for 3 hr at room temperature, then poured into water (1 liter). The precipitated crystals were collected by filtration, then washed with water and MeOH. Yellow needles, mp 125-126°C. Yield 20 g.

3-Methoxy-4-O-carbethoxy-β-phenethylamine (XII)
Amalgamated zinc prepared from zinc powder (50 g) and HgCl₂ (5 g) was agitated with MeOH (100 ml) on an ice bath. To the above mixture, conc. HCl and a solution of the foregoing nitrostyrene (19 g) in tetrahydrofuran (200 ml) were added alternately. The temperature of the reaction mixture was kept below 50°C during the reaction. After the addition of the nitrostyrene solution was completed and the yellow coloring of the reaction mixture disappeared, an excess Zn-Hg was filtered off, and MeOH and tetrahydrofuran were removed by distillation in vacuo; then the residue was poured into water (500 ml), washed with ether, and the basic product was extracted into CHCl₃ after basification with conc. NH₄OH. Evaporation of the solvent gave the product as a pale yellow oily material. Yield 9.5 g. Oxalate: Recrystallized from EtOH; colorless microcrystals, mp 135-191°C (decomp.).

References
[10] M. Tomita, K. Fujitani, and Y. Aoyagi, Chem. Pharm. Bull. (Tokyo), Vol. 16, No. 3, 523-526 (1968)
[11] M. Erne and F. Ramirez, Helv. Chim. Acta, 33, 912 (1950). Post 506993 (Rhodium: "Mescaline, Amphetamine etc. by LAH reduction", Novel Discourse)
[12] G. Hahn and K. Stiehl, Ber., 71, 2154 (1938).

^{The Hive - Clandestine Chemists Without Borders}

Rhodium
(Chief Bee)
06-03-04 22:37
No 511296
User Picture       Nitroalkenes to Amines w/ BH3·THF made in situ
(Rated as: excellent)

Synthesis of Alkylamines via Reduction of Nitroalkenes using in situ Prepared BH₃·THF
Rajender S. Varma and George W. Kabalka
Synthetic Communications 15(9), 843-847 (1985) (https://www.rhodium.ws/chemistry/nitroalkenes2amines.bf3-nabh4.html)

Abstract
α,β-Unsaturated nitroalkenes are readily reduced to alkylamines by in situ generated BH₃·THF in refluxing THF.

^{The Hive - Clandestine Chemists Without Borders}

armageddon
(Hive Bee)
06-09-04 01:10
No 512266
      NaBH4 for LAH?

I know countries where LAH is somewhat difficult to obtain - but it's easier aquired than NaBH₄...

I think the most easiest way from nitrostyrenes to phenetylamines would bee the Leminger style reduction (Post 245040 (Rhodium: "O Leminger's Phenethylamines - posted by Karel", Novel Discourse) - and of course UTFSE) (zinc/HCl) or maybe an electrochemical reduction а la Zlotta (on Rhod's page)

(hey rhod - already drank some milk today? It is said to be VEEEEERY healthy, without those PUS... laugh ) (just jokin)

Greetz A

"..ein Trank von unterschiedlicher Farbe, in ihm ist Heilung für die Menschen."

	https://the-hive.archive.erowid.org	the-hive@erowid.org



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	All 9 posts		Subject: LAH alternatives refs		Please login to post		Down


		Rhodium (Chief Bee) 05-25-00 21:39 No 9315				LAH alternatives refs (Rated as: excellent)
						Copied from an old Usenet post: I was wondering if anybody has born witness to, or heard of thru trusted sources, an effective way of reducing 2,5-dimethoxy-beta-nitrostyrene to its corresponding amine without using LAH? I've read a couple decent methods using NaBH4, but they sound either poorly tested or the folks doing them can afford to sit around and watch their reaction for six days! There are some variations of the NaBH4 method: 3 to 5 h reflux in THF: Synth. Commun. 15 (9) 1985, 843-848; J. Heterocycl. Chem. 24, 1987, 767-772; Heterocycles 41 (11), 1995, 2441-2458. Anybody know about the real-world effectiveness of Zwit's Zinc/HCl method? How about a good way of activating the NaBH3 reaction? Maybe suggestions for different catalysts that don't require an H2 atmosphere or don't use household aluminum foil (I don't really trust the oxidation state or metallurgical purity of said foil)? Any ideas, comments, references, or places to look would be appreciated. Thanks and Have Joy! Of course, Red-Al (DIBAH) and AlH3 are also working but suffer from the same disadvantages as LAH. Zn-aq. HCl is disclosed in: Chem. Pharm. Bull. 16 (2), 1968, 217-226; Bull. Soc. Chim. Fr. 1960, 231-239; Arch. Pharm. 322, 1989, 477-482 (2 min reflux in THF!), J. Chem. Res. Miniprint, 1, 1988, 0157-0177; Tetrahedron Lett. 33 (45), 1992, 6883-6884; Ann. Pharm. Fr., 10, 1952, 276-281; Ann. Pharm. Fr., 7, 1949, 733; Acta Chim. Acad. Sci. Hung., 14, 1958, 325; Monatsh. Chem., 40, 1919, 144. Aluminum is used in Monatsh. Chem., 79, 1948, 72. The use of LiBH4/Me3SiCl in THF (24 h room temperature) as disclosed in Angew. Chem. 101 (2), 1989, 220-222, might also be of interest. There are a lot of electrochemical reductions reported (e.g., MeOH, H2SO4, lead cathode) but obviously require special equipment. You might also consider stepwise reaction to the ketone with subsequent amination as described in PIHKAL for #68, DOM (MeOH, NH4OAc, NaCNBH3). IMHO, catalytic hydrogenation (e.g., Pd-C, MeOH, aq. HCl, atmospheric pressure, room temperature) constitutes the most efficient procedure for the preparation of this class of compounds.



		obituary (Hive Bee) 05-27-00 11:58 No 9956				Re: LAH alternatives refs
						swim's read a lot of stuff and have not seen any procedures using atmospheric pressure (maybe a balloon) and room temperature for hydrogenation- references? links?



		zooligan (Hive Bee) 05-28-00 00:06 No 10161				Re: LAH alternatives refs
						Yes, Rhod! References, links, synth notes perhaps???? zool



		zooligan (Hive Bee) 08-02-00 15:28 No 35787				Re: LAH alternatives refs (Rated as: good read)
						Tips for Hydrogenation Experiment (http://ice.chem.umbc.edu/Chem351l/exp9_tips.html)



		KrZ (Hive Bee) 08-03-00 05:12 No 36071				Re: LAH alternatives refs (Rated as: good read)
						Rhodium, recent experiments at my monkey laboratory have notice some fascintaing behavious here is a very interesting example: 100g 2,5-Dimethoxynitrostyrene 150ml H2SO4 98% (2.84 mol) 2000ml Glacial Acetic Acid 15g Pd/C 5% 75psi (6 atmospheres) Reactor charge and shaken, 100% absorption was encountered after 45 minutes!!!!! Add 1,200 ml of 5M NaOH with stirring to cooled post reaction mix Add 1L of MeOH, instant precipitation of all the former Na2SO4 Filter off the Na2SO4 Remove the GAA, H2O, and MeOH at reduced pressure Take the residue in the distillation flask, add 500ml 5M NaOH Add 125ml DCM and stir Seperate and rextract 3x 125ml Pool the DCM extracts, dry over Na2SO4, and distill Yield: 92% This was the animals first experience with the GAA/H2SO4 system and it was quite impressive indeed, solvation is comparable to that of using alcohol solvents but yields and reaction times are greatly improved. It may be possible to add undissolved NS to the mix which would dissolve over the course of the reaction, we will have to observe the animals further to see how that goes.



		Rhodium (Chief Bee) 08-03-00 19:34 No 36273				Re: LAH alternatives refs
						KrZ, Thanks for your contribution! (BTW, I didn't write any of the above, it was just cut-n-paste fron usenet) http://rhodium.lycaeum.org



		Rhodium (Chief Bee) 05-15-04 16:17 No 507331				Clemmensen reduction of nitrostyrenes (Rated as: excellent)
						_{This artience has been mentioned before in: Post 9315 (Rhodium: "LAH alternatives refs", Methods Discourse) Post 108634 (dormouse: "The Good Reverend's nitrostyrene reduction contest -rev drone", Novel Discourse) Post 78688 (PolytheneSam: "Re: References on nitrostyrene reduction", Chemistry Discourse)} _{Studies on the Alkaloids of Menispermaceous Plants. CCXLIV.} Synthesis of dl-Cepharanthine Masao Tomita, Kazuyoshi Fujitani, Yoshiaki Aoyagi, and Yasumichi Kajita Chem. Pharm. Bull. 16(2) 217-226 (1968) (https://www.rhodium.ws/pdf/cepharantine.ns2pea.zn-hg.pdf) 5-Bromopiperonal (VI) obtained in relatively high yield (42-64%) from 5-bromoprotocatechuic aldehyde (V) through methylenation reaction catalysed by cupric oxide¹⁰ was condensed with nitromethane in the presence of ammonium acetate in acetic acid to afford a nitrostyrene (VII), which was reduced to a phenethylamine (VIII) under Clemmensen condition. Preparation of VIII starting with 5-bromoprotocatechuic aldehyde was already reported by Erne and Ramirez,¹¹ but the modification adopted by the present authors raised the yield in every step of the reaction sequence. [...] 3-methoxy-4-hydroxy-β-nitrostyrene (X)¹² was treated with ethyl chloroformate in pyridine and the resulted O-carbethoxy derivative (XI) was reduced under Clemmensen condition to give a phenethylamine (XII). Experimental 3-Bromo-4,5-methylenedioxy-β-nitrostyrene (VII) The solution of 5-bromopiperonal (64 g), nitromethane (65 g), and NH₄OAc (30 g) in AcOH (400 ml) was heated to reflux for 2 hr. After cooling, the mixture was poured into water (1 liter); a precipitated crystalline solid was collected by filtration. Recrystallization of the above crystalline substance from 50% (by vol.) CHCl₃-EtOH afforded the product. Yield 55 g. Yellow needles, mp 160-162°C (lit.¹¹ mp 160-161°C). 3-Bromo-4,5-methylenedioxy-β-phenethylamine (VIII) The foregoing nitrostyrene (VII, 53 g) and amalgamated zinc prepared from zinc powder (200 g) and HgCl₂ (20 g) were suspended on EtOH (2 liter). Under vigorous stirring, conc. HCl was added portionwise into the above mixture until the yellow coloring of the reaction mixture disappeared. After the decolorization was completed, the reaction mixture was further stirred for 30 min. An excess Zn-Hg was filtered off; EtOH was evaporated in vacuo, and the residue was poured into water (1 liter). The aqueous solution was made alkaline with conc. NH₄OH after washed with ether; then the basic product was extracted into CHCl₃, and the washed CHCl₃ extracts were evaporated to give the product. Light-brown viscous oily substance, yield 32 g. Hydrochloride: Recrystallized from EtOH-acetone, colorless platelets, mp 238-240°C (dec.) (lit.¹¹ mp 250-251°C). 3-Methoxy-4-O-carbethoxy-β-nitrostyrene (XI) To a solution of 3-methoxy-4-hydroxy-β-nitrostyrene (15 g) in pyridine (100 ml), ethyl chloroformate (15 ml) was added dropwise with stirring on an ice bath. After the addition was completed, the mixture was further stirred for 3 hr at room temperature, then poured into water (1 liter). The precipitated crystals were collected by filtration, then washed with water and MeOH. Yellow needles, mp 125-126°C. Yield 20 g. 3-Methoxy-4-O-carbethoxy-β-phenethylamine (XII) Amalgamated zinc prepared from zinc powder (50 g) and HgCl₂ (5 g) was agitated with MeOH (100 ml) on an ice bath. To the above mixture, conc. HCl and a solution of the foregoing nitrostyrene (19 g) in tetrahydrofuran (200 ml) were added alternately. The temperature of the reaction mixture was kept below 50°C during the reaction. After the addition of the nitrostyrene solution was completed and the yellow coloring of the reaction mixture disappeared, an excess Zn-Hg was filtered off, and MeOH and tetrahydrofuran were removed by distillation in vacuo; then the residue was poured into water (500 ml), washed with ether, and the basic product was extracted into CHCl₃ after basification with conc. NH₄OH. Evaporation of the solvent gave the product as a pale yellow oily material. Yield 9.5 g. Oxalate: Recrystallized from EtOH; colorless microcrystals, mp 135-191°C (decomp.). References [10] M. Tomita, K. Fujitani, and Y. Aoyagi, Chem. Pharm. Bull. (Tokyo), Vol. 16, No. 3, 523-526 (1968) [11] M. Erne and F. Ramirez, Helv. Chim. Acta, 33, 912 (1950). Post 506993 (Rhodium: "Mescaline, Amphetamine etc. by LAH reduction", Novel Discourse) [12] G. Hahn and K. Stiehl, Ber., 71, 2154 (1938). ^{The Hive - Clandestine Chemists Without Borders}



		Rhodium (Chief Bee) 06-03-04 22:37 No 511296				Nitroalkenes to Amines w/ BH3·THF made in situ (Rated as: excellent)
						*Synthesis of Alkylamines via Reduction of Nitroalkenes using in situ* Prepared BH₃·THF** Rajender S. Varma and George W. Kabalka Synthetic Communications 15(9), 843-847 (1985) (https://www.rhodium.ws/chemistry/nitroalkenes2amines.bf3-nabh4.html) Abstract α,β-Unsaturated nitroalkenes are readily reduced to alkylamines by in situ generated BH₃·THF in refluxing THF. ^{The Hive - Clandestine Chemists Without Borders}



		armageddon (Hive Bee) 06-09-04 01:10 No 512266				NaBH4 for LAH?
						I know countries where LAH is somewhat difficult to obtain - but it's easier aquired than NaBH₄... I think the most easiest way from nitrostyrenes to phenetylamines would bee the Leminger style reduction (Post 245040 (Rhodium: "O Leminger's Phenethylamines - posted by Karel", Novel Discourse) - and of course UTFSE) (zinc/HCl) or maybe an electrochemical reduction а la Zlotta (on Rhod's page) (hey rhod - already drank some milk today? It is said to be VEEEEERY healthy, without those PUS...) (just jokin) Greetz A "..ein Trank von unterschiedlicher Farbe, in ihm ist Heilung für die Menschen."

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