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All 13 posts Subject: Oxidations and brominations w/ H2O2/Br2/HBr Please login to post Down

moo
(Hive Bee)
11-01-03 09:05
No 468077
      Oxidations and brominations w/ H2O2/Br2/HBr
(Rated as: excellent)

I ran into a nice article. cool

Too bad they didn't try to oxidise/brominate any toluenes with only electron donating substituents even though it is quite obvious that ring bromination is going to happen. Maybe this "side reaction" could be exploited to get 4-bromo-2,5-dimethoxybenzyl bromide or 4-bromo-2,5-dimethoxybenzaldehyde straight from 2,5-dimethoxytoluene.

Also, it's interesting that cumene yields alpha-methylstyrene and alpha-methyl-beta-bromostyrene. It might be naive to think that the latter product could be hydrolysed to 2-phenylpropanal with an alkali metal hydroxide knowing how stable aldehydes are. In that case one has to settle for only one P2P precursor (https://www.rhodium.ws/chemistry/2-phenylpropanal.html). Maybe the reaction could be tweaked to produce P2P and 2-phenylpropanal from cumene in one pot, who knows? In the end the yields are sure going to suck.

Catalytic Processes of Oxidation by Hydrogen Peroxide in the Presence of Br₂ or HBr. Mechanism and Synthetic Applications
Amati, Alessandro; Dosualdo, Gabriele; Zhao, Lihua; Bravo, Anna; Fontana, Francesca; Minisci, Francesco; Bjorsvik, Hans-Rene
Organic Process Research & Development 2(4), 261-269 (1998) (https://www.rhodium.ws/pdf/br-cat.h2o2-oxidation.pdf)
DOI:10.1021/op980028j

Abstract
The mechanism and the synthetic applications for the oxidation of alcohols ethers, and aldehydes by H₂O₂ catalyzed by Br₂ or Br^- in a liquid two-phase system (aqueous and organic) are reported. Aliphatic and benzylic primary alcohols and ethers show an opposite behavior, which has been rationalized on the ground of the different electronic configurations of the intermediate alkyl (p-type) and acyl (s-type) radicals and their influence on enthalpic and polar effects. A two-phase system is particularly useful also for an efficient benzylic bromination by Br₂ or Br^-; the substitution of the benzyl bromide by OH, OR, and OCOR regenerates Br^-, which can be recycled. The evaluation of the relative reactivities of the involved substrates and intermediates has allowed to develop a variety of simple, facile, convenient, and selective syntheses of alcohols, aldehydes, ketones, esters, and benzyl bromides, which fulfill the conditions for practical applications.

General Oxidation Procedures.

Oxidation of Primary Aliphatic Alcohols to Esters. (I suppose this is procedure A)
Five millimoles of the alcohol, dissolved in 7.5 mL of CH₂Cl₂, was stirred for 2 h at room temperature with 3 mmol of Br₂ and 7.5 mL of water; 6 mmol of H₂O₂ (30% aqueous solution) was added within 2 h. The organic phase was separated, washed with aqueous NaHCO₃ solution, and analyzed by GC (ethyl heptanoate as internal standard). The reaction products were identified by GC-MS analysis and by comparison with authentic samples. The results are reported in Table 1. The aqueous solution, containing HBr, has been utilized for a further oxidation of 5 mmol of alcohol in 7.5 mL of CH₂Cl₂ by the addition of 7.5 mmol of H₂O₂ over 4 h: the results are quite similar.

Oxidation of Secondary Alcohols to Ketones
Procedure A was utilized by employing half of the oxidant. The results are reported in Table 2.

Oxidation of Aliphatic Aldehydes in the Presence of Alcohols
Five millimoles of the aldehyde, 15 mmol of the alcohol, and 2.5 mmol of Br₂ dissolved in a mixture of 7.5 mL of CH₂Cl₂ and 7.5 mL of water were refluxed for 1 h; 2.5 mmol of H₂O₂ was added, and the mixture was refluxed for an additional hour. The organic phase was separated and analyzed by GC and GC-MS; authentic samples were utilized for the identification and analysis of the reaction products. The results are reported in Table 3.

Oxidation of Benzyl Alcohols to Aldehydes
Two millimoles of the alcohol, dissolved in 10 mL of ACOEt and mL of water, together with Br₂ and H₂O₂ in the ratios reported in Table 6, was refluxed for 4 h. The organic phase was separated, washed with aqueous NaHCO₃ solution, and analyzed by GC (p-chlorobenzaldehyde as internal standard; with p-chlorobenzyl alcohol, o-chlorobenzaldehyde was utilized as internal standard). The reaction products were identified by GC-MS analysis and by comparison with authentic samples. The results are reported in Table 6.

Oxidation of Benzyl Alcohols to Methyl Benzoate (Procedure E)
Five millimoles of benzyl alcohol, 20 mmol of CH₃OH, and mmol of Br₂ in 10 mL of CH₂Cl₂ and 10 mL of water were refluxed for 2 h; 6 mmol of H₂O₂ were then added under reflux over a 2 h period. The organic phase was separated and analyzed by GC (ethyl benzoate as internal standard) by using authentic samples and GC-MS analysis for the identification of the reaction products. The results are reported in Table 7.

Oxidation of Benzyl Alcohols to Alkyl Benzoates (Procedure F)
Procedure E has been utilized with benzyl alcohols and tertiary aliphatic alcohols. With primary aliphatic alcohols, the procedure has been modified as follows: 5 mmol of benzyl alcohol, 1 mmol of aliphatic alcohol, and 5 mmol of Br₂ in 10 mL of CH₂Cl₂ and 10 mL of water were refluxed. Over 4 h, 6 mmol of H₂O₂ and 4 mmol of aliphatic alcohol were added. The organic phase was separated and analyzed by GC and GC-MS. The results are reported in Table 8.

Oxidation of Aromatic Aldehydes to Alkyl Benzoates
Procedures E and F were utilized by using half of the oxidant. The results are reported in Table 9.

Oxidation of Ethers
Alkylbenzyl Ethers. Two millimoles of methyl benzyl ether in 7.5 mL of CH₂Cl₂ were stirred for 24 h at room temperature with 0.2 mmol of Br₂ and 4 mmol of H₂O₂ (30% aqueous solution). The mixture was analyzed during the reaction course after 0.5, 1.3, 2, 3, 5.5, and 26.5 h, and the results are reported in Table 10.
Di-n-alkyl Ethers. Two millimoles of di-n-alkyl ether, 0.2 mmol of Br₂, and 4 mmol of H₂O₂ (30% aqueous solution) were stirred for 4 h at room temperature in 7.5 mL of CH₂Cl₂. The organic phase was separated and analyzed. The results are reported in Table 12.

Oxidation of Tetrahydrofuran (THF) to gamma-Butyrolactone
Ten millimoles of THF and 4 mmol of Br₂ were refluxed for 1 h in a mixture of 5 mL of CH₂Cl₂ and 5 mL of water. Four millimoles of H₂O₂ was added, and the mixture was refluxed for 1 h; an additional 4 mmol of H₂O₂ was added, and the mixture was refluxed for 2 h. The mixture was analyzed after 1, 2, and 4 h, and the results are reported in Table 13.

The same procedure was utilized with other ethers, and the results are summarized in Table 13.

Bromination of Alkylbenzenes
Five millimoles of alkylbenzene, dissolved in 15 mL of a CH₂Cl₂/H₂O mixture containing the other reagents in the ratios reported in Tables 14 and 15, were refluxed for 4 h. The CH₂Cl₂ solution was separated from the aqueous phase and directly analyzed by GC and GC-MS, by using p-chlorobenzyl bromide as internal standard (with p-chlorotoluene the internal standard was o-chlorobenzyl bromide) and authentic samples of the benzyl bromides for the characterization. With substrates deactivated by the presence of -NO₂, -CN, and -COOR groups, H₂O₂ was slowly added to the reacting mixture. In competitive bromination of equimolar amounts of o-nitrotoluene and toluene, only the latter is substantially brominated. With cumene, only 5% of cumyl bromide was formed; the main reaction products were alpha-methylstyrene (72%) and a 1:1 mixture of cis- and trans-alpha-methyl-beta-bromostyrenes (21%). The products were characterized by comparison (GC-MS) with authentic samples.

Table 1. Oxidation of primary aliphatic alcohols to esters by H₂O₂, catalyzed by HBr

alcohol solvent time (h) conversion (%) yield (%)^a

1-propanol CH₂Cl₂/H₂O (1:1) 2 56 99

1-propanol CH₂Cl₂/H₂O (1:1) 4 69 98

1-propanol CH₂Cl₂/H₂O (1:1) 6 100 98

1-butanol CH₂Cl₂/H₂O (1:1) 2 58 99

1-butanol CH₂Cl₂/H₂O (1:1) 4 71 98

1-butanol CH₂Cl₂/H₂O (1:1) 6 100 98

1-pentanol CH₂Cl₂/H₂O (1:1) 6 100 97

1-hexanol CH₂Cl₂/H₂O (1:1) 6 100 98

2-methyl-1-pentanol CH₂Cl₂/H₂O (1:1) 6 100 95

1-heptanol CH₂Cl₂/H₂O (1:1) 6 100 98

1-heptanol hexane/H₂O (1:1) 6 61 97

1-heptanol^b hexane/H₂O (4:1) 6 58 95

1-heptanol^c hexane/H₂O (4:1) 24 91 91

1-heptanol AcOEt/H₂O (1:1) 4 20 57

1-decanol CH₂Cl₂/H₂O (1:1) 6 100 97

^a Based on the converted alcohol. ^b 5% of heptanal is formed. ^c 9% of heptanal is formed.

Table 2. Oxidation of secondary alcohols to ketones by H₂O₂, catalyzed by Br₂

alcohol conversion (%) yield (%)^a

2-hexanol 100 96

2-heptanol 98 99

2-decanol 99 98

cyclohexanol 94 87

cyclopentanol 96 91

2-adamantanol 100 96

Ph-CHOH-CH₃ 100 95

Ph-CHOH-Ph 98 88

^a Based on the converted alcohol.

Table 3. Oxidation of aliphatic aldehydes to esters in the presence of primary and tertiary alcohols

aldehyde alcohol conversion (%)^a yield (%)^b

1-heptanal n-BuOH 96 92

1-heptanal 1-AdOH 89 87

1-heptanal t-BuOH 92 84

1-pentanal n-PrOH 87 91

1-pentanal n-BuOH 91 89

1-pentanal t-BuOH 83 87

^a Converted aldehyde. ^b Based on the converted aldehyde.

Table 6. Synthesis of aldehydes X-C₆H₄-CHO from X-C₆H₄-CH₂OH by bromine-catalyzed H₂O₂ oxidation

X ratio (alcohol:Br₂:H₂O₂) conversion (%)^a yields (%)^b

H 1:0.05:2 92 98

H 1:0.15:1.5 100 93

o-Me 1:0.15:2 97 91

m-Me 1:0.15:2 94 96

p-Me 1:0.15:2 98 90

o-Cl 1:0.15:2 98 93

p-Cl 1:0.05:2 99 97

p-Cl 1:0.15:1 94 93

p-Br 1:0.05:2 98 98

p-COOEt 1:0.15:2 93 94

p-CN 1:0.2:2 94 92

o-NO₂ 1:0.2:2 94 96

p-NO₂ 1:0.15:2 81 95

p-Ph 1:0.15:2 98 94

^a Conversion of the benzyl alcohol. ^b Yields based on the converted alcohol.

Table 7. Oxidation of benzyl alcohols X-C₆H₄-CH₂OH to the corresponding methyl benzoates

X conversion (%) yields (%)^a

H 100 87

o-Me 100 83

p-Me 100 88

o-Cl 93 83

p-Cl 92 86

^a Based on the converted benzyl alcohol.

Table 8. Oxidation of benzyl alcohols X-C₆H₄-CH₂OH to alkyl benzoates X-C₆H₄-COOR

X R-OH conversion (%)^a yields (%)^b

H EtOH 93 84

H n-BuOH 86 82

H t-BuOH 91 93

o-Cl n-BuOH 97 83

p-Cl n-BuOH 92 88

o-Me n-BuOH 98 81

o-Me t-BuOH 78 94

p-Me t-BuOH 81 96

^a Conversion of benzyl alcohol. ^b Yields based on the converted benzyl alcohol.

_{fear fear hate hate}

moo
(Hive Bee)
11-01-03 09:13
No 468078
      Oxidations and brominations w/ H2O2/Br2/HBr
(Rated as: good read)

Table 9. Oxidation of aromatic aldehydes, X-C₆H₄-CHO, to alkyl benzoates X-C₆H₄-COOR

X R-OH conversion (%)^a yields (%)^b

H MeOH 92 96

H EtOH 94 84

H n-BuOH 87 83

H t-BuOH 72 94

o-Cl MeOH 93 9

p-Cl MeOH 91 89

o-Me MeOH 92 87

p-Me MeOH 89 91

p-Me n-BuOH 91 78

p-Me t-BuOH 81 96

^a Conversion of aldehyde. ^b Yields based on the converted aldehyde.

Table 10. Oxidation of benzyl methyl ether to benzaldehyde (I), methyl benzoate (II), and mixed anhydride between benzoic and formic acids (III)

T (°C) reaction time (h) conversion^a (%) I (%)^b II (%)^b III (%)^b

18 0.5 18 87 0 0

18 1.3 32 91 2.1 0

18 2 48 89 5.3 0

18 3 70 87 9.1 0

18 5.5 99.5 81 18.3 0

18 26.5 100 20 60 0

42 2 100 33 40 25

42 4 100 0 61 32

^a Conversion of benzyl ether. ^b Yields based on the converted benzyl ether.

Table 11. Oxidation of secondary benzyl ethers, X-C₆H₄-CH(R)-OMe, to the corresponding ketones, X-C₆H₄-CO-R

X R conversion^a (%) yields^b (%)

H Me 98 94

H Et 96 97

o-Cl Me 97 92

p-Cl Et 99 89

o-Me Me 96 91

p-Me Me 92 94

p-Me Et 96 98

^a Conversion of benzyl ether. ^b Yields based on the converted benzyl ether.

Table 12. Oxidation of dialkyl ethers, R-CH₂-O-CH₂-R, to the corresponding esters, R-COOCH₂R (IV)

R conversion (%) IV^a (%) R-CH₂OH^a (%) R-COOH^a (%)

n-Pr 94 65 10 8

n-Bu 92 73 7 6

n-hexyl 91 71 8 7

2-Me-pentyl 87 70 6 9

n-heptyl 89 71 9 8

^a Yields based on the converted ether.

Table 13. Oxidation of THF and other ethers

ether product time (h) conversion (%)^a yield (%)^b

THF gamma-butyrolactone 1 34.2 98

THF gamma-butyrolactone 2 64.6 87

THF gamma-butyrolactone 4 92.4 81

methyl cyclooctyl ether cyclooctanone 4 87 92

methyl cyclooctyl etherc cyclooctanone 4 96 97

dicyclohexyl ether cyclohexanone 4 98 93

methyl cyclohexyl ether cyclohexanone 4 91 96

^a Conversions based on the oxidant. ^b Yields based on the conversion. ^c The procedure is the same, with the difference that a stoichiometric amount of Br₂ was used in a two-phase system in the absence of H₂O₂.

Table 14. Bromination of 2-nitrotoluene (Ar-CH₃)

brominating agent ArCH₃:Br:H₂O₂ solvent conversion (%) yields (%) of ArCH₂Br^a

Br₂ 1:1:0 CH₂Cl₂ traces traces

Br₂ 1:0.5:0 CH₂Cl₂/H₂O 1:1 20 99

Br₂ 1:1.2:0 CH₂Cl₂/H₂O 1:2 91 89

Br₂/H₂O₂ b 1:0.7:0 CH₂Cl₂ 93 94

Br₂/H₂O₂ 1:0.5:0.5 CH₂Cl₂/H₂O 1:1 34 98

Br₂/H₂O₂ 1:0.7:10 CH₂Cl₂/H₂O 1:1 8 100

Br₂/H₂O₂ c 1:0.7:1 hexane/H₂O 1:1 0 0

HBr/H₂O₂ 1:2:2 CH₂Cl₂/H₂O 1:2 87 93

^a Based on the converted 2-nitrotoluene. ^b 36% aqueous H₂O₂. ^c 2- and 3-Bromohexanes are formed.

Table 15. Bromination of alkylbenzenes substrate

(S) brominating agent S:Br:H₂O₂ solvent conversion (%) yields (%)^a

toluene Br₂/H₂O₂ 1:0.7:1 CH₂Cl₂/H₂O 1:1 93 94

toluene^b Br₂/H₂O₂ 1:1:1 CH₂Cl₂/H₂O 1:1 100 70

toluene NaBr/H₂O₂/H₂SO₄ (1) 1:2:2 CH₂Cl₂/H₂O 1:1 96 92

ethylbenzene Br₂/H₂O₂ 1:0.7:0.5 CH₂Cl₂/H₂O 1:1 87 92

ethylbenzene NaBr/H₂O₂/H₂SO₄ (1) 1:2:2 CH₂Cl₂/H₂O 1:1 91 94

ethylbenzene Br₂/H₂O₂ 1:2:1.5 CH₂Cl₂/H₂O 1:1 93 89

cumene^c Br₂/H₂O₂ 1:0.7:0.5 CH₂Cl₂/H₂O 1:1 60 5

p-CN-toluene Br₂ 1:1:0 CH₂Cl₂ traces traces

p-CN-toluene Br₂/H₂O₂ 1:1:1 CH₂Cl₂/H₂O 5:1 100 95

o-CN-toluene Br₂/H₂O₂ 1:1:1 CH₂Cl₂/H₂O 5:1 97 98

o-Cl-toluene Br₂/H₂O₂ 1:1:1 CH₂Cl₂/H₂O 1:1 100 94

p-Cl-toluene Br₂/H₂O₂ 1:1:1 CH₂Cl₂/H₂O 1:1 100 93

p-Me-benzoic acid Br₂/H₂O₂ 1:1:1 CH₂Cl₂/H₂O 1:1 100 87

Et-p-Me-benzoate Br₂/H₂O₂ 1:1:1 CH₂Cl₂/H₂O 1:1 100 91

p-NO₂-toluene Br₂ 1:1:0 CH₂Cl₂ 21 100

p-NO₂-toluene^d Br₂/H₂O₂ 1:1:1 CH₂Cl₂ 100 88

p-NO₂-ethylbenzene^d Br₂/H₂O₂ 1:1:1 CH₂Cl₂ 98 86

2-NO₂-4-MeO-toluene Br₂/H₂O₂ 1:1:1 CH₂Cl₂/H₂O 1:2 85 98

^a Based on the converted alkylbenzene. ^b 28% of PhCHBr₂ is formed. ^c alpha-Methylstyrene and alpha-methyl-beta-bromostyrenes are the main reaction products. ^d 36% aqueous H₂O₂ has been utilised.

_{fear fear hate hate}

moo
(Hive Bee)
11-01-03 09:22
No 468080
      Another one
(Rated as: excellent)

High atomic yield bromine-less benzylic bromination
Mestres, Ramon; Palenzuela, Jesus
Green Chemistry 4(4), 314-316 (2002)

Abstract
A two-phase mixture (sodium bromide, aqueous hydrogen peroxide/carbon tetrachloride or chloroform) under visible light provides a simple and convenient system for benzylic bromination of toluenes. A high atomic yield for bromine atoms is attained. Substitution of the chlorinated solvents by other more environmentally benign organic solvents has been attempted and good results are obtained for methyl pivalate.

_{fear fear hate hate}

Rhodium
(Chief Bee)
11-01-03 15:33
No 468126
User Picture       THF to GBL in 75% yield in 4h using H2O2/Br2

This caught my eye:

Oxidation of Tetrahydrofuran (THF) to gamma-Butyrolactone

Ten millimoles of THF and 4 mmol of Br2 were refluxed for 1 h in a mixture of 5 mL of CH2Cl2 and 5 mL of water. Four millimoles of H2O2 was added, and the mixture was refluxed for 1 h; an additional 4 mmol of H2O2 was added, and the mixture was refluxed for 2 h.

After four hours they achieve 92% conversion and 81% yield, meaning that THF can be converted to GBL in 75% overall yield using hydrogen peroxide with catalytic bromine (which can be made in situ from any bromide salt)...

Who is going to be the first to scale this up to a usable environmentally friendly OTC GBL production procedure?

WeakEndChemist
(Stranger)
11-20-03 05:30
No 471887
      Understanding this interaction

Trying desperately not to be referred to a n00b who should have use tfse, I have searched a bit in reference to what exactly is catalytic bromine. Obviously it's formed from a bromine salt, and I've found that NaBr is fairly easy to purchase. Being that it's called Br2 i'm assuming it's elemental bromide... however, i always figured that it's damned hard to break a salt into elemental parts because of the strong ionic bond in them. So figuring this out on my own has been a horrific failure. I won't lie and say i know enough about chemistry, so please pity the fool.

Thanks

Sure, I'll try some... Is it dangerous?

moo
(Hive Bee)
11-20-03 05:51
No 471889
      Understanding this reaction

Trying desperately not to be referred to a n00b who should have use tfse

It would be much better to study chemistry as there are a lot of free resources, try it.

Being that it's called Br2 i'm assuming it's elemental bromide... however, i always figured that it's damned hard to break a salt into elemental parts because of the strong ionic bond in them.

It is elemental bromine, not bromide. The hydrogen peroxide is used to oxidise the bromide ions to elemental bromine, which then goes on and oxidises whatever it is used to oxidise thusly being reduced back to bromide ions, which are then available for reacting again in the same manner. That is why it is called catalytic bromine, it isn't used up in the reaction but hydrogen peroxide is.

If you want to understand these reactions you must at least read the article, I didn't include the PDF for nothing. If you do not understand what they say... well, then I guess you'll just have to study chemistry as there is no other way to be able to understand chemistry. It is much fun in the end. smile

_{fear fear hate hate}

Chromic
(Synaptic Self-Mutilator)
11-20-03 06:00
No 471892
      Not me

My problem was that the THF that one can get from pipe cement contains acetone. If you try and form Br2 and react it with "mostly pure" THF, you will get bromoacetone. The bromoacetone formed left me crying. It's highly irritating shit to deal with, even in small qty's. Post 363729 (Chromic: "bromoacetone", Chemistry Discourse)

I'd absolutely love to see someone work on this who has access to reagent grade thf... (well, I do, but I have to go thru a chem supplier--and THF isn't really watched, so, perhaps I'm just complaining)

Rhodium
(Chief Bee)
11-20-03 07:29
No 471906
User Picture       removing acetone from THF

Can't you remove the acetone from the THF by washing with bisulfite, or if everything else fails, reduce the acetone to IPA and then distill the THF/IPA mixture from KOH or Mg/I₂ (which should trap the IPA as its alkoxide)?

Chromic
(Synaptic Self-Mutilator)
11-21-03 09:23
No 472204
      Washed with bisulfite

Yeah, I did wash with bisulfite. That didn't remove all of it... perhaps other suggestions you mentioned would have worked. Ideally I should get some pure THF to do this sort of experimentation with.

Chromic
(Synaptic Self-Mutilator)
11-27-03 19:09
No 473493
      Some more questions

Moo, in the Deno paper that you dug up, J. Am. Chem. Soc.; 1967; 89(14); 3550-3554, mentioned in Post 308130 (moo: "THF oxidations", Novel Discourse) I noticed that they use 4x equivilants of Br2 and conduct this experiment cold and in the dark.

If I've got this right, the paper mentioned in this post uses 1.2 eq Br2 (.4eq added as Br2 and .8eq generated catalytically as in H2O2 + 2 Br- + 2 H+ -> Br2 + 2 H2O) and conducts it at reflux with no mention of protecting from light. This is just strange. 1.2eq versus 4eq? They also change the solvent system from just water (as in the Deno paper) to a mix of DCM and water. Can anyone think of any reasons for changing the conditions so much?!?

Of course, there's also the great Tetrahedron; 2000 56; 1905-1910 ref as well that uses bromate... they talk about over-oxidizing the THF and forming small amounts of succinic acid... although they do isolate most of the product, 75% yield, thru atmospheric distillation.

Also, can you guys see anywhere if the 75% yield in this paper is an isolatable yield, or is it a GCMS yield? (like the GABA->GHB/GBL is a 100% yield by GCMS--but of that only 75% can be isolated) They just say that "the mixture was analyzed"--which doesn't say much.

P.S. why is there three bromine/THF refs and one H2O2/THF refs on the hive and no one but me as reported results on them? Am I just unaware of other people working on these routes?

moo
(Hive Bee)
11-28-03 02:34
No 473540
      THF / GBL / Br2 / H2O2
(Rated as: excellent)

Moo, in the Deno paper that you dug up, J. Am. Chem. Soc.; 1967; 89(14); 3550-3554, mentioned in moo: "THF oxidations" (Novel Discourse) I noticed that they use 4x equivilants of Br2 and conduct this experiment cold and in the dark.

In that ref they tried the ratios of THF:Br₂ 1:5, 4:1 and about 5:1. The focus of the article was on studying the kinetics and mechanism of this reaction, so I guess they weren't so interested in seeing if the reaction works with stoichiometric ratios of the reactants. In that post I say that they did the reaction in dark to avoid free-radical bromination -- this is a claim I must take back not only because of the article posted in this thread, but because of the following quote from the Deno article:
It was evident from qualitative observations that irradiation, even by simple sunlamps, greatly increased the rate of disappearance of Br₂. Where the irradiated reaction gives the same products as the dark reaction, it would presumably be preferable from a synthetic viewpoint. However, in the one case investigated with care, benzyl isopropyl ether, the irradiated reaction gave different products. In retrospect we regret that we did not examine the light-catalyzed reaction more extensively.

It might be that this reaction can proceed both by ionic and free-radical mechanisms but evidently it doesn't matter in practice.

If I've got this right, the paper mentioned in this post uses 1.2 eq Br2 (.4eq added as Br2 and .8eq generated catalytically as in H2O2 + 2 Br- + 2 H+ -> Br2 + 2 H2O) and conducts it at reflux with no mention of protecting from light. This is just strange. 1.2eq versus 4eq? They also change the solvent system from just water (as in the Deno paper) to a mix of DCM and water. Can anyone think of any reasons for changing the conditions so much?!?

In the table 13 they say "Conversion based on oxidant", so not all THF gets oxidised in that example. The other example of an ether oxidation uses 2 equivalents of hydrogen peroxide in addition to 0.1 equivalents of elemental bromine.

Why the two-phase system? That is one of the key features of their article, the fact that the two-phase system affects certain reactions positively and eliminates unwanted side reactions, so they go on and try the same system with other substrates. In other refs DCM is not needed at all. It could be that this reaction is not so fickle and various reaction conditions can lead to good results.

Also, can you guys see anywhere if the 75% yield in this paper is an isolatable yield, or is it a GCMS yield? (like the GABA->GHB/GBL is a 100% yield by GCMS--but of that only 75% can be isolated) They just say that "the mixture was analyzed"--which doesn't say much

The 73% yield is the isolated yield, GC says 80%. https://www.rhodium.ws/pdf/thf2gbl.pdf

P.S. why is there three bromine/THF refs and one H2O2/THF refs on the hive and no one but me as reported results on them? Am I just unaware of other people working on these routes?

I think there have been mentions of the H₂O₂/Fe(II) method being horribly messy but no actual results. It might be that as the doses of GHB are so high that a good GBL method is characterised by good volume efficiency, and there is no simple worked-out volume-optimised method, nobody has wanted to start messing with the scary peroxide-forming THF and the possibility of failure. By the way, there are five Br/THF refs, two of them mentioned in Post 381459 (moo: "THF -> GBL patents etc.", Methods Discourse). It is possible to use chlorine too. Maybe a possibility for a H₂O₂/HCl method? Or an electrolytic cell with NaCl as the electrolyte with sulfuric or hydrochloric acid added so that the pH is 1 as recommended (Post 243610 (foxy2: "Re: Easy Oxidation of THF to GBL", Novel Discourse))?

I still haven't found out if lead oxide (PbO₂ aka lead peroxide in older literature) is suitable for an anode in oxidation of halogen ions. Both graphite and platinum are used for this purpose.

_{fear fear hate hate}

Chromic
(Synaptic Self-Mutilator)
11-29-03 09:56
No 473746
      Uhm

Also, can you guys see anywhere if the 75% yield in this paper is an isolatable yield, or is it a GCMS yield?

Moo, I meant for the paper in this thread. Not for the bromate ref on Rhodium.

I'm pretty sure I'll attempt this chemistry if I have enough time. I'd be aiming towards more like 100ml THF, small amount NaBr (10g?), small amount of acid, (perhaps a small amount of DCM, ie 100ml) then slowly adding like ~150g 35% H2O2 (ie about 1.2eq and keeping at reflux if done in DCM). The volumes in that case would be much more reasonable. Thoughts? The theory would be around 100ml of GBL, hopefully one could recover half that. Those volumes would be quite competitive with GBL produced via GABA diazotiation.

moo
(Hive Bee)
11-30-03 09:21
No 473862
      Oh, of course! :-D I think it is a GC/MS ...

Oh, of course! laugh I think it is a GC/MS yield, as it seems the yields for the other reactions are always analyzed that way and never isolated.

_{fear fear hate hate}

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