Sciencemadness Discussion Board - Thiourea Dioxide --> better than borohydride?

Thiourea Dioxide --> better than borohydride?

Pages: 1 2

manimal - 6-2-2009 at 20:09

Here's an article that I also posted on wetdreams about reducing stuff (ketones) with TUD. Since this compound has been used in the past to reduce nitro groups, and is otherwise mainly unexplored, one wonders what other interesting things can be reduced.

Reduction of Organic Compounds with TUD I: Reduction of Ketones to Secondary Alcohols

Tet. Letters, Vol. 13, Issue 5, 1972, pp. 343-346

Attachment: sdarticle.pdf (166kB)
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Ebao-lu - 7-2-2009 at 04:07

You mean the reductuve amination of ketones? Possibly, it would work. As well as with nitroalkene reduction to amines..
Very interesting reagent, indeed (never heared about it).

[Edited on 7-2-2009 by Ebao-lu]

sparkgap - 7-2-2009 at 04:42

So I thought I should be mentioning this patent and the patents that reference formamidine sulfinic acid (which is thiourea dioxide's fancy name) listed...

sparky (~_~)

Formula409 - 7-2-2009 at 20:51

Quote:

Originally posted by Ebao-lu
You mean the reductuve amination of ketones? Possibly, it would work. As well as with nitroalkene reduction to amines..
Very interesting reagent, indeed (never heared about it).

[Edited on 7-2-2009 by Ebao-lu]

How would this be done? Would the imine be formed, isolated and then reduced with the thiourea dioxide?

Formula409.

manimal - 8-2-2009 at 00:03

Well, seeing as imines are stable in basic solutions I would stick to the conditions described in the paper.

IIRC sodium dithionite can also reduce ketones, but yields are poor unless a cosolvent of diethylformamide is used. Here, the authors simply used aqueous ethanol and got excellent yields (100% yield of diphenylcarbinol from benzophenone).

UnintentionalChaos - 8-2-2009 at 01:46

Ah! Thiourea dioxide (Thiox, aminoiminomethanesulfinic acid, formamidine sulfinic acid) is highly OTC, as it is available for use with dyes. One of the more popular uses is to reduce indigo dye to a soluble form before dipping the cloth in. Upon air exposure, the "leucoindigo" reoxidizes to the insoluble blue form within the fibers of the cloth. If reduction is anything like with indigo, the reaction is sluggish.

I wonder if this reaction can be modified to promote the dimerized side products. This would essentially be a pinacol coupling, but without the need for multiple equivalents of metallic magnesium and mercury salts or any of the other expensive or nasty things usually used for pinacol couplings.

[Edited on 2-8-09 by UnintentionalChaos]

Siddy - 8-2-2009 at 03:43

That reference stats it is effective for aromatic nitro, azo etc, but not aliphatic nitro - any reference for that? Nitromethane > Methylamine?

Ebao-lu - 8-2-2009 at 09:16

no refference- only proposal. Methylamine can be prepared from urotropine, or if it is not avaliable, from ammonia+formaldehyde

[Edited on 8-2-2009 by Ebao-lu]

[Edited on 8-2-2009 by Ebao-lu]

Vogelzang - 8-2-2009 at 11:25

More interesting patents:

US 5350425 Method of reducing vat dyes and the process of dyeing fabrics therein
column 1 lines 49+
Typically, sodium dithionite has been employed to reduce the dyes to
their leuco form, as is shown U.S. Pat. No. 3,798,172. Sodium dithionite
decomposes rapidly in the presence or absence of air; therefore, large, excess
quantities of this compound are used to reduce all of the dye and to maintain
the dye in is soluble leuco form. Regrettably, the use of sodium dithionite
raises ecological concerns.
column 1 lines 64+
Another reducing agent that has received some attention is
thiourea dioxide in an alkaline solution. However, thiourea dioxide is a
strong reducing agent, and therefore tends to over reduce the vat dye. When
reducing indigo overreduction is readily apparent by the smell of fecal
material which is present when indole (the overreduction product) is in the
reaction.
indigo -> leucoindigo using Al, NaOH & H2O column 7, several examples columns 8 and 9

US 2872482 Process of making thiourea dioxide
Column 1
Thiourea dioxide has heretofore been prepared by the oxidation of thiourea by the use of hydrogen peroxide.

US 2150921 Manufacture of imino-amino-methane-sulphinic acid
oxidation of thiourea by the use of hydrogen peroxide

US 2164930 Process for reducing vat dyestuffs
use of thiourea dioxide for reducing vat dyes

http://www.pat2pdf.org

Nicodem - 9-2-2009 at 00:41

Quote:

Originally posted by UnintentionalChaos
I wonder if this reaction can be modified to promote the dimerized side products. This would essentially be a pinacol coupling, but without the need for multiple equivalents of metallic magnesium and mercury salts or any of the other expensive or nasty things usually used for pinacol couplings.

Pinacol coupling requires one electron donor reducents since it goes via a SET mechanism. Thiourea dioxide is a two electron donor.

UnintentionalChaos - 12-2-2009 at 19:49

Quote:

Originally posted by Nicodem

Quote:

Pinacol coupling requires one electron donor reducents since it goes via a SET mechanism. Thiourea dioxide is a two electron donor.

I was merely mentioning page 344 of the original paper, which suggests SET as a possible mechanism to explain the formation of (9,9'-bifluorenone)-9,9'-diol when the molar ratio of thiourea dioxide to NaOH to fluorenone was 1:1:1. I suspect it works very well in this case since the proposed intermediate radical is in the benzylic position of two phenyl rings simultaneously. Perhaps this side reaction could be promoted and extended to other phenyl carbonyl compounds and alpha-beta unsaturated carbonyls.

Nicodem - 13-2-2009 at 01:25

You are correct, they even detected the anion radical with ESR. This is thus not such a simple reduction as it appears at the first glance. I doubt the reaction can be made selective for the pinacol coupling even for such cases where the anion radical intermediate is exceptionally stabilized simply because it will always react faster with the reducent rather than encountering another radical anion (a problem which is obviated in the reactions with metals where the coupling happens on the metal surface). However, a SET mechanism of reduction using thiourea dioxide opens other more promising possibilities, especially for radical cyclisations, and I'm surprised nobody made any further research since 1972 when that study was published.

manimal - 14-2-2009 at 00:32

Literature from Scifinder:

Thiourea dioxide as a reducing agent.
Gore, P. H. Acton Tech. Coll., London,
Chemistry & Industry (London, United Kingdom) (1954), 1355. CODEN: CHINAG ISSN: 0009-3068. Journal language unavailable. CAN 49:68864 AN 1955:68864 CAPLUS Abstract

A preliminary survey shows that +H2N:C(NH2)SO2- (I) is a powerful reducing agent, capable of reducing aromatic nitro, azoxy, azo, and hydrazo compds. to amines, quinones
to hydroquinones, and a no. of dyes to their leuco derivs., in excellent yields.
Reduction is carried out by adding I in 1 portion to H2O, pyridine, or HCONMe2 (or mixts. of these) in the presence of excess NH4OH, or caustic alkali and warming the mixt. to 70° on a H2O bath with occasional shaking.

Synthesis of 2-aminomorphine and 2-aminocodeine. Reduction of aromatic nitro groups with formamidinesulfinic acid.
Chatterjie, Nithiananda; Minar, Arlene; Clarke, Donald D.
New York State Inst. Basic Res. Mental Retard., Staten Island, NY, USA.
Synthetic Communications (1979), 9(7), 647-57. CODEN: SYNCAV ISSN: 0039-7911. Journal written in English. CAN 92:42180 AN 1980:42180 CAPLUS
Abstract

2-Aminomorphine (I, R = H, R1 = H2N) and 2-aminocodeine (I, R = Me, R1 = H2N) were prepd. in yields of 60 and 81%, resp., by redn. of I (R1 = NO2) with formamidinesulfonic acid. 2-H2NC6H4CO2H, 3-H2NC6H4OH, and 4-H2NC6H4Me were similarly prepd. in yields of 85, 90, and 56%, resp., by redn. of the corresponding nitro compds.

Reduction of organic compounds with thiourea dioxide. II. Reduction of aromatic nitro compounds and syntheses of hydrazo compounds.
Nakagawa, Kunio; Mineo, Satoshi; Kawamura, Satoko; Minami, Kyoji. Fac. Pharm. Sci., Tokushima Bunri Univ., Tokushima, Japan. Yakugaku Zasshi (1977), 97(11), 1253-6.
CODEN: YKKZAJ ISSN: 0031-6903. Journal written in Japanese. CAN 88:190270 AN 1978:190270 CAPLUS
Abstract

Thiourea dioxide, readily obtained by treating thiourea with H2O2, reduced nitro compds. to the corresponding arom. amines. Redn. of PhNO2 to PhNH2 in an alk. soln. showed that PhNHNHPh was formed from nitroso-, azo- and azoxybenzene in good yield. Substituted hydrazobenzenes were formed from the corresponding azobenzenes.

Indexing -- Section 25-6 (Noncondensed Aromatic Compounds) Section cross-reference(s): 23

Reduction of organic compounds with thiourea dioxide.
Gu, Shang-Xiang; Yao, Ka-Ling; Hou, Zi-Jie; Wu, Ji-Gui. Dep. Chem., Lanzhou Univ., Lanzhou, Peop. Rep. China.
Youji Huaxue (1998), 18(2), 157-161.
CODEN: YCHHDX ISSN: 0253-2786. Journal written
in Chinese. CAN 128:321229 AN 1998:290865 CAPLUS
Abstract

Org. compds. contg. nitro, carbonyl, or double bond can be reduced with thiourea dioxide in good yield using an aq. ethanolic soln. in the presence of sodium hydroxide.

Nicodem - 16-2-2009 at 00:20

Thanks for your search. To bad the reference that looks most interesting is published in Chinese. There are many other references for reductions with thiourea dioxide, but most of them are about azo to hydrazo, N-oxides to amines, heterocyclic N-oxides to heterocycles, nitrile N-oxides to nitriles, nitroaromatics to anilines, nitrosoamines to hydrazines, disulfides to thiols (also diselenides and ditellurides), etc.
There is almost nothing about ketones to alcohols (one example is in Bioorganic & Medicinal Chemistry, 14 (2006) 7051-7061).
An interesting reaction where thiourea dioxide is not used as a reducent is its reaction with amino acids to yield guanidino acids (Synthesis (2000) 1656-1658).
The weirdest use is to deoxygenate 2,3-epoxyketones to the coresponding enones (Tetrahedron Letters, 38 (1997) 745-748). I did not even knew this was possible with any reagent.

About its properties:

Quote:

Application of aminoiminomethanesulfinic acid as an antioxidant.
Knopp, Christian.
Scientia Pharmaceutica, 51 (1983), 51, 283-90.

Abstract: Aminoiminomethanesulfinic acid (I) [1758-73-2] has no antioxidant properties at pH <7. I reduces iodine to iodide at room temp. in alk. soln. and on heating at acidic pH values. KMnO4 reacts with I to form MnO2 and cyanamide [420-04-2]; the latter is also formed in the reaction of I with acidic H2O2. I is not oxidized or hydrolyzed at pH 1-6 in O-satd. H2O; at alk. pH values, cyanamide is formed together with an unidentified compd. I is hydrolyzed by heating at pH 3.65 1% soln. without O to form formamidine [463-52-5], sulfide, and sulfite. At room temp., I forms guanidine [113-00-8] in the presence of NH3. With benzylamine [100-46-9] at pH 8, I forms benzylguanidine [2211-57-6], and with piperidine [110-89-4], it forms piperidinecarboxamidine [4705-39-9]. The mechanisms of the reaction are discussed. The use of I as an antioxidant in pharmaceuticals appears problematical.

It has quite nice and useful uses for being such an easily available reagent from photochemicals suppliers.

Formula409 - 16-2-2009 at 00:25

Nicodem, you didn't happen to see any refs for reductions of imines did you?

Formula409.

Nicodem - 16-2-2009 at 00:36

There were a couple of references where N-oxides of imines were reduced to a mixture of secondary amine and imine, but nothing about the reduction of imines or enamines themselves. Maybe there is more on Beilstein, but I don't have the time at the moment.

Baphomet - 16-2-2009 at 03:31

This is a good find, since reducing agents are one of the harder reagents for garage chemists to acquire (in this chemist's experience anyway

)

Perhaps it would be possible to produce it through the action of sodium percarbonate on thiourea?

If anyone has the full text for "Reduction of organic compounds with thiourea dioxide" I can translate it for you.

Formula409 - 16-2-2009 at 03:41

Quote:

Originally posted by Baphomet
This is a good find, since reducing agents are one of the harder reagents for garage chemists to acquire (in this chemist's experience anyway

I've made a request in the references section for all the above articles. I will U2U you when it becomes available.

On that note, here is Synthesis of 2-aminomorphine and 2-aminocodeine. Reduction of aromatic nitro groups with formamidinesulfinic acid., thanks tapira1!
http://www.sciencemadness.org/talk/viewthread.php?action=att...

Formula409.

[Edited on 16-2-2009 by Formula409]

Baphomet - 16-2-2009 at 03:49

Thanks Formula.

Here is an outline for preparation of the compound using H2O2:

Preparation of formamidinesulfinic acid

116 g of 30 % hydrogen peroxide weight out in a beaker on
accurate technical balance. Pour the hydrogen peroxide into a
1000 ml beaker and dilute it with 600 ml of distilled water. Place
the beaker into a large vessel (e.g. enameled pot) and encase it
with a mixture of gently grinded ice and sodium chloride. Place the
glass stirrer powered with electric motor into the liquid and under
continuing mixing allow the solution to cool down to 5 °C. Then,
during two hours, under the continuing intensive mixing, add with
spoon small doses of 38 g gently pulverized thiourea. The
temperature during this process should be between 5 and 20 °C.
Refresh the coolant if necessary. When all amount of thiourea is
added continue with cooling of the mixture with ice and sodium
chloride for next 1 hour. Then cool down all mixture close to
freezing point. Filter the separated formamidinesulfinic acid
preferably with small glass frit. Wash obtained product with small
quantity of icy water and then with small portion of methanol.
Washed acid is dried up in vacuum desiccator upon anhydrous
calcium chloride.

from
http://www.orglist.net/archive/2001/att-0115/00-part

Nicodem - 16-2-2009 at 04:45

Quote:

Originally posted by Baphomet
Perhaps it would be possible to produce it through the action of sodium percarbonate on thiourea?

Thiourea dioxide is available as photo developing reagent. It does not need to be bought from chemical suppliers. You can simply order it from an online shop.

Quote:

If anyone has the full text for "Reduction of organic compounds with thiourea dioxide" I can translate it for you.

The access to Yakugaku Zasshi is free for everyone. Pay attention not to use the Reference section for requesting freely available papers as it only causes confusion.
Reduction of Organic Compounds with Thiourea Dioxide. II. Reduction of Aromatic Nitro Compounds and Syntheses of Hydrazo Compounds

manimal - 16-2-2009 at 13:10

Quote:

Originally posted by UnintentionalChaos

I wonder if this reaction can be modified to promote the dimerized side products. This would essentially be a pinacol coupling, but without the need for multiple equivalents of metallic magnesium and mercury salts or any of the other expensive or nasty things usually used for pinacol couplings.

Have you seen European Journal of Organic Chemistry - Volume 2002, Issue 19 , Pages 3326 - 3335, from this thread?.

TiCl3+NaOH reduces aromaticketones to the dimers in good yields.

Baphomet - 16-2-2009 at 18:25

Quote:

Originally posted by Nicodem
Thiourea dioxide is available as photo developing reagent. It does not need to be bought from chemical suppliers. You can simply order it from an online shop.

Thanks but online there only appears to be wholesalers selling 50kg drums. I will keep looking.

Quote:

The access to Yakugaku Zasshi is free for everyone. Pay attention not to use the Reference section for requesting freely available papers as it only causes confusion.

Thanks for the link. However it is the wrong article, I cannot read Japanese..

Baphomet - 16-2-2009 at 18:50

Ah ok, I see that it goes under the trade name of 'Thiox'

UnintentionalChaos - 16-2-2009 at 21:47

Quote:

TiCl3+NaOH reduces aromaticketones to the dimers in good yields.

I take it that this is a spin off of the McMurry Reaction. The problem is 1: the TiCl3 is used in quite some excess, and TiCl3 is not happy to sit on your shelf. It's typically made in-situ with TiCl4 and magnesium, just like samarium iodide.

You should look for thiox at places that sell supplies for the home dyer. Places that sell indigo powder usually carry it, and it is also sometimes labelled as color remover (although this may be mixed with sodium carbonate. check before you buy it).

[Edited on 2-17-09 by UnintentionalChaos]

497 - 17-2-2009 at 02:00

So am I right in thinking that this stuff can reduce both a double bond and a nitro group? Like maybe a nitrostyrene to phenethylamine in one step? That would be lovely.

Baphomet - 17-2-2009 at 02:45

Quote:

Originally posted by 497
So am I right in thinking that this stuff can reduce both a double bond and a nitro group? Like maybe a nitrostyrene to phenethylamine in one step? That would be lovely.

Certainly seems that way (pictures in the second paper

). In the first paper (ketone to alcohol) the authors make the point that extra reductant should be added, and in several small increments to obtain maximum yield.

I'm wondering if it is strong enough to produce gold nanoparticles? A small test is in order

manimal - 18-2-2009 at 23:29

Quote:

Originally posted by Baphomet
If anyone has the full text for "Reduction of organic compounds with thiourea dioxide" I can translate it for you.

Here is the link to the Chinese article in Youji Huaxue (Chinese Journal of Organic Chemistry). http://www.cqvip.com/qk/93463X/199802/2933582.html.

I don't know if you have to pay them for access or not. I tried registering, but it rejected every email address I typed in. I can't understand what they're asking for because it's all Chinese to me.

Baphomet - 19-2-2009 at 00:15

I managed to register. It forces you to have a 'strong' password and select the correct occupation & category. The article only costs 2RMB and I'd happily pay this small sum but it requires payment through a mainland China mobile phone, which I don't have! Sorry..

solo - 19-2-2009 at 21:13

Study on reduction of organic compounds with thiourea dioxide #157
GU SHANGXIANG, YAO KALING, HOU ZIJIE and WU JIGU
Chinese Journal of Organic Chemistry 1998, 18 (2): 157-161

Abstract
Reported alcohol in alkaline aqueous solution containing thiourea dioxide nitro, carbonyl and olefinic bond to restore the role of organic compounds to study these reaction conditions, reaction products and reaction mechanism.

NOte: this study is in Chinese ....so I hope someone can translate for you and then maybe you should post it her later.....solo

Attachment: Study on reduction of organic compounds with thiourea dioxide .pdf (308kB)
This file has been downloaded 1461 times

Formula409 - 19-2-2009 at 21:47

Thank you solo. I have U2U'd Baphomet.

497 - 19-2-2009 at 21:57

Have a look at this. US Patent 4610802, it talks about adding small amounts of hydrides to greatly increase thiourea dioxide's reducing power at lower pHs.

What it interesting, is it gives measured redox potentials of (fairly dilute) thiourea solutions at various pHs with and without other additives. For example its redox potential at pH 13 is -750mV while NaBH4 is no higher than -390mV over the whole pH range, although it's concentration is much lower (does concentration make a difference?)

How much does this tell about TDO's reducing power? Can you get an idea of what something will and won't reduce by looking at its redox potential?

[Edited on 19-2-2009 by 497]

Nicodem - 20-2-2009 at 00:13

Quote:

Originally posted by 497
For example its redox potential at pH 13 is -750mV while NaBH4 is no higher than -390mV over the whole pH range, although it's concentration is much lower (does concentration make a difference?)

How much does this tell about TDO's reducing power? Can you get an idea of what something will and won't reduce by looking at its redox potential?

The redox potential of a reagent (against a standard electrode) can only tell the equilibrium constant of a redox reaction of this reagent with a substrate when the redox potential of this substrate (against the standard electrode) is known. However, it can not tell if the reaction does indeed occurs.
In ionic reactions, reactions on electrodes, or metal/ions reaction this information is important, because these reactions generally do indeed occur when the redox difference allows (ions easily transfer electrons from one to the other or get them from metal surfaces). However, in organic chemistry this information is of little value since the route a reaction will take is not only depending on the thermodynamic allowance (redox potential) but also on the kinetics (determined by activation energy for each mechanistic possibility). And this second condition is what is most important for predicting a reaction outcome in organic reactions. That's why studying the mechanisms and the reaction transition states is the most important thing in organic chemistry if a student is to become a synthetic organic chemist.

Baphomet - 20-2-2009 at 19:01

Here is the first page. Anything I'm not sure about has been left verbatim so that nothing is lost in translation. For example, 'attracting the base' is the literal translation which I guess means basic conditions are required..

Code:


The role of sulfur dioxide in the reduction of organic compounds.

Gu Shang Xiang, Yao Ka-Ling, Wu Ji-You

Department of Chemistry, Lanzhou University, Lanzhou 730000


Abstract:
A study of reaction conditions, reaction products and reaction mechanism for the action of sulfur dioxide containing nitro, attracting base and the olefinic bond of organic compounds

Keywords: sulfur dioxide, reduction, organic

Sulfur dioxide is a very good new reducing agent; in the textile, printing and dyeing, chemical and metallurgical industries and has a wide range of other applications.
Under alkaline conditions a sulfoxylate species can be released, with a high reduction potential, to restore a long time, to a certain extent stabilized after the reduction potential, etc., so in recent years it has been used in organic synthesis.
In this paper, that the reducing agent, containing nitro, attracts the base and the olefinic bond of the compounds to restore the role of research, discussed the reaction conditions 
The impact of the reduction product and its reaction mechanism was discussed. The method is simple and easy to control with facile conditions, and a low chance of explosion. 
By ketone reduction for alcohol and nitro compounds reduced to amines, it is able to obtain a high yield.
The method described here is comparible to other synthetic methods. At the same time, it can replace traditional methods for the reduction of olefins and catalytic hydrogenation reaction of olefins under more moderate temperature and pressure conditions.

497 - 20-2-2009 at 19:51

Sulfur dioxide, not thiourea dioxide? I'm confused.

Still, it looks interesting, can't wait to see more.

solo - 20-2-2009 at 20:00

Topic Information

What is thiourea dioxide?

Thiourea dioxide is also called formamidine-sulfinic acid or aminoiminomethanesulfinic acid and is often abbreviated as TDO or TUD. Thiourea dioxide is a powdered stable compound, which dissolves in water and decomposes gradually to exhibit a reducing action. But, this reaction is slow, and particularly in an acidic to weakly alkaline region. Thiourea dioxide is stable and its reducing action is weak. Usually, thiourea dioxide dissolves in water and produces sulfoxylic acid through formamidine-sulfinic acid. This reaction is promoted by the application of heat or in the presence of an alkali, and a strong reducing action is thereby exhibited. TDO is useful as a reducing agent ; it reduces vat dyes, ketones to alcools and hydrocarbons and conjugated unsaturated acids to the corresponding saturated acids. It is an excellent antioxidant in the stabilization of percholorethylene. It is mainly used in dyeing and paper making industry stead of using sodium hydrosulphite, organic synthesis in synthetic fibre industry, additive of polymerzation, stabilizer for polythene sensitizer of photographical emulsion.

Physical and Chemical Properties

Other Name: Formamidine sulfinic acid, Amino imino methanesulfinic acid

Appearance and Odor: White crystal powder, odorless

Formula: CH4N2SO2

Molecular weight: 108.12

Melting Point: 126℃

PH: 4(1% Solution)

CAS No.: 1758-73-2 or 4189-44-0

UN No.: 3341

Dangerous Goods Class: 4.2

Specification:

Purity: 99.%Min

Thiourea: 0.10%Max

Moisture:0.05%Max

Iron(Fe):10ppm Max

Sulphate: 0.17%Max

Packing:

500kg or 1000kg jumbo bags.

50kg fiber drums.

25kg or 50kg woven bags.

25kg kraft compound plastic bags or upon customers' demands.

Storage:

Storage in dry clean, well- ventilated condition, the warehouse temperature under 30℃ . Keep away from moisture and raining.

[Edited on 20-2-2009 by solo]

manimal - 20-2-2009 at 20:16

Am I right in ascertaining from the pictures that it can reduce benzylic ketones all the way to the hydrocarbon?

I sort of got a rough translation after installing the right fonts and copying and pasting into google translate.

Nicodem - 23-2-2009 at 00:16

Baphomet, for the beginning it would be enough if you could only translate the tittles and substrate/product columns in Table 4, with the pertaining experimental. The rest currently does not seem particularly interesting.

Baphomet - 24-2-2009 at 04:38

Happy to help:

Code:



Reactant      Product        Reactant:TUD:NaOH  Hours Temp    Yield   BP (lit. BP)
Cyclohexene   Cyclohexane    1:2:8              8     58.0    58.0    81 (80.7)
Cyclopentene  Cyclopentane   1:2:8              6     39.0    39.0    49 (49.3)
1-Hexene      Hexane         1:2:8              6     55.6    55.6    68 (69)
1-Heptene     1-Heptane      1:2:8              6     54.0    54.0    98 (98.4)
1-Octene      1-Octane       1:2:8              6     46.5    46.6    124 (125.6)


1.4
Regarding Benzophenone reduction, Diphenyl methanol production rates were 14.1% and 19.3%
(Other conditions identical to table 3, and the medium alkaline as well).

When in an alkaline medium the production rate is 98.7%. This results in TUD having a
solubility dependent upon the medium in which it is used. In alkaline solution other
tautomers may be formed easily and subsequently broken down into highly reductive
SO2(-2) species:

(diagram)

Thus, TUD only has a strong reducing ability in alkaline medium.

[Edited on 24-2-2009 by Baphomet]

Bolt - 24-2-2009 at 10:07

The reactants and products are the same! =/

Nicodem - 24-2-2009 at 10:29

Bolt: No they are not. You misread.

Baphomet, thanks a lot, but could you please also take care also of the part of the discussion talking about this reduction of olefins as well as the experimental.
I guess "production rates" would be "yields"? Also the rest is a bit hard to understand. Is that a direct machine translation output or do you correct/interpret it as well? It would be nice if you could interpret it in such a way as to make it more coherent. But thanks for your effort nevertheless.

Baphomet - 25-2-2009 at 00:32

Quote:

Baphomet, thanks a lot, but could you please also take care also of the part of the discussion talking about this reduction of olefins as well as the experimental.

Sure, which page / paragraph do you want?

Quote:

I guess "production rates" would be "yields"?

Yes, it says "product rates were respectively 14.1% and 19.3%" so they mean yield.

Quote:

Also the rest is a bit hard to understand. Is that a direct machine translation output or do you correct/interpret it as well?

It's just my personal reading of it. The text may seem a little clumsy because I have tried to leave it as a literal translation and simply correct the grammar. Unfortunately it is not the perfect language for scientific communication.

Nicodem - 25-2-2009 at 02:04

I would have to be able to read and understand Chinese to tell you which page or paragraph. Surely there must be a discussion where they interpret the results shown in Table 4? This reduction of non-conjugated alkanes is so exceptional that they must have devoted some explanatory text to it. It would also be their duty to provide a hypothesis of the mechanism, even if they did no experimental work to prove it. In short, I'm interested in anything in there connected with their experiments on the reduction of alkenes, including the experimental part.

It is very exceptional that such a simple (nonmetalic) reducent reduces simple olefins and this would be the most accessible reagent for amateurs to be used in such a reaction.

I understand that Chinese, a language having a totally context based meaning, is very hard to translate, particularly for scientific texts, and I appreciate every effort you make.

manimal - 25-2-2009 at 07:19

Here's a cleaned-up machine translation using a combination of google and altavista, and cross checking between the two. I think it's fairly accurate.

Quote:

Olefin reduction to the alkanes is more difficult, and requires a highly alkaline solution(Table 4).

Some Alkenes have a great tendendency to polymerize, such as cyclopentene. At a temperature higher than 60C a viscous, polymer like substance forms. Therefore, the reaction can only take place at a lower temperature, and the corresponding yield is lower.

In the TD reduction of cyclohexene, EPR study has found that this reaction system proceeds through H+ radicals, the measured g = 2.004. Note that the reduction by TD of the olefin proceeds through the course of free radicals.

...

1.64g(.02mol) cyclohexene (homemade) is added to 5ml 95% ethanol. The molar proportions of olefin:TD:NaOH is 1:2:8. Under stirring at 80C, a solution of TD and NaOH in 30ml water is added over the course of 1h. Stirring is continued for another 5h. At that time, a sample is taken for EPR measurement. The reaction is allowed to continue for another 2 hr, then the mixture is cooled and extracted with ether. The extraction is fractionated and the 80.5-81C fraction is collected, a clear colorless liquid (cyclohexane). For other reaction conditions see table. Product b.p. is basically consistent with literature values.

Nicodem - 25-2-2009 at 23:51

Thanks, that is exactly what I wanted. I'm glad they made an ESR experiment that confirmed the radical pathway. Very strange that nobody noticed the potential of thiourea dioxide for radical reactions, particularly radical anion cyclisations. With the current price of sammarium(II) iodide, any alternative would be more than welcome (and SmI2 does not even work on alkenes!).

Ebao-lu - 26-2-2009 at 01:32

I guess the reaction with carbonyl compounds is not obligatory having a radical pathway. TUD is a 2e reductant, and 1 molecule of TUD can reduce 1 molecule of carbonyl compound directly. And in case of cyclopentene, it is realy amazing. What is the yield in the cyclohexene procedure(:sorry, did not notice it in the table above

?

[Edited on 26-2-2009 by Ebao-lu]

Formula409 - 26-2-2009 at 01:59

Quote:

Originally posted by Ebao-lu
I guess the reaction with carbonyl compounds is not obligatory having a radical pathway. TUD is a 2e reductant, and 1 molecule of TUD can reduce 1 molecule of carbonyl compound directly. And in case of cyclopentene, it is realy amazing. What is the yield in the cyclohexene procedure?

Reactant Product Reactant:TUD:NaOH Hours Temp Yield BP (lit. BP)
Cyclohexene Cyclohexane 1:2:8 8 58.0 58.0 81 (80.7)

Nicodem - 26-2-2009 at 02:36

Quote:

Originally posted by Ebao-lu
I guess the reaction with carbonyl compounds is not obligatory having a radical pathway.

Indeed, it is not obligatory, but it seems a common case. Now there are already two papers (this Chinese one and the old Tetrahedron) experimentally confirming a SET mechanism. Single electron transfers are not so rare in sulfur chemistry, there are several other cases known (like during the oxidation of mercaptans or, after all, even the radical reaction of sulfur with alkanes at high temperatures trough homolysis of S-S bonds).

Ebao-lu - 26-2-2009 at 03:20

Yes, well, it must be SET then (if mentioned in papers). I imagined a mechanism, with attacking of carbonyl by sulfinic O-, then attack of OH- at sulfur atom, and then rearrangement of the product in a 6-membered intermediate state, but realised it is also SET with anion-radical formation that i believed first to be an alcohol.
I wonder how, i wonder why cyclohexene does not polymerise if the reaction is having a free-radical mechanism? Thats probably because it immediately reacts with another TUD molecule, or the same +5 sulfur atom.

ps: above supposed mechanism does not explain the cyclohexene reduction, because there can not be any imaginable cyclohexene+ TUD conjugate, so there should some another mechanism.
Also, if it is so strong reductant, why it can't reduce carbonic acid derivatives? I guess, that is only due to all carboxyl synthones ere easily hydrolysed to COO- with base, and TUD is having also a negative charge, so they are electrostatically repulsing. But if we amend this, hope it will work? Maybe it is possible to use some metal ions to get the anions closer (like Cu2+, Fe2+). By the way, can TUD reduce these metals to 0 state? It will also be promising, getting nanoparticles of metals that can also be used as reducing agents

[Edited on 26-2-2009 by Ebao-lu]

Ebao-lu - 26-2-2009 at 08:39

Quote:

When in an alkaline medium the production rate is 98.7%. This results in TUD having a

solubility dependent upon the medium in which it is used. In alkaline solution other

tautomers may be formed easily and subsequently broken down into highly reductive

SO2(-2) species:

What are those "tautomers" mentioned above? Do they want to say, SO2(2-) is the core reducing agent, or it is only proposal? What is the mechanism supposed in tetrahedron?

manimal - 5-6-2009 at 14:17

Quote: Originally posted by Nicodem

There were a couple of references where N-oxides of imines were reduced to a mixture of secondary amine and imine, but nothing about the reduction of imines or enamines themselves.

I would be interested in seeing those references.

Siddy - 22-8-2009 at 01:21

What are the thoughts on thiourea dioxide working on aliphatic nitro's to amines?

Barium - 22-8-2009 at 11:11

I doubt it will reduce a aliphatic nitro group all the way to the amine. But hey, try it! Add a couple of equivilents to a milliliter of nitromethane and see if there is a reaction. Let us know the results.

Siddy - 24-8-2009 at 18:31

Yeah, its a shame thioure dioxide has no common sources.

Another idea,

What about coupling thiourea dioxide with ammonium chloride/zinc?

Zinc/Ammonium chloride gets it half way (to hydroxylamine) and then thiourea as hydride source to finish it off? It might be more effective than zinc/ammonium foramte.

eg, R.T. stirring of nitromethane with fresh zinc power, ammonium chloride and thiourea dioxide.

Paddywhacker - 24-8-2009 at 23:08

Thiourea dioxide should be available from the same type of shops that sell raw indigo for dyeing.

Nicodem - 24-8-2009 at 23:20

...as well as specialized shops that sell chemicals for photography developing (for example, one of the most known companies, Silve***int, sells it for £15.00 per 100g). It would be good to actually first check the catalogues of the "common sources" before claiming they do not sell it, particularly since it was already mentioned in this thread earlier that one needs not to acquire it trough chemical sellers.

Ammonium chloride is an acid, therefore you can not use thiourea dioxide for reductions in its presence. Besides, I fail to see the point. Zinc in the presence of HCl reduces nitroaromatics and nitroaliphatics all the way to amines.

Magpie - 11-5-2010 at 22:28

In searching for an OTC source of sodium dithionite (SD) I found that the hobbyist dye suppliers have replaced it with thiourea dioxide (TUD). This seems due to the fact that SD cannot be shipped by air, as it is hazard class 4.2 (spontaneously combustible). TUD is also classed 4.2 but still seems to be readily available. Go figure. The dye people say TUD is 5 times as potent as sodium dithionite. This may be another reason it is replacing SD. I couldn't find an OTC source of pure SD.

I'm having a difficult time learning just how TUD works. It has the formula (NH2)(NH)C(S)O(OH), and is aka aminoiminomethanesulfinic acid. In alkaline aqueous conditions with some heating it breaks down to urea and sulfoxylic acid (H2SO2) by adding one molecule of water, I guess. It seems that this non-isolable sulfoxylic acid, or the sulfoxylic anion, SO2(2-) is the specie that actually does the reducing, ie:

SO2(2-) ----> SO2 + 2e- .........(I theorize)

If anyone can verify or correct my assumptions about TUD please do so.

Edit: Looking further it seems that the actual reductant and products of the reduction are dependant on the nature of the oxidant and the reaction conditions. This I think is true of all reaction scenarios, redox or otherwise.

[Edited on 12-5-2010 by Magpie]

[Edited on 12-5-2010 by Magpie]

Magpie - 19-5-2010 at 18:34

In searching the OTC market for sodium dithionite I found RIT Dye's "White-Wash." The package lable says it contains sodium hydrosulfite and anhydrous sodium carbonate.

A Dutch paper, kindly posted by ayush, provided an assay method using redox titrimetry. 0.1N potassium ferricyanide is used as the oxidant; methylene blue is used as indicator. The titration flask must be kept flushed with an inert gas to prevent the air oxidation of dithionite which oxidizes with extreme ease. I used argon, which being heavier than air, worked well.

It still is a tricky assay, and I ran it several times before I was satisfied. For paper I used a 3" square of one ply of toilet paper. The result was 86% sodium dithonite dihydrate.

dithionite titration.jpg - 102kB

[Edited on 20-5-2010 by Magpie]

Thiourea dioxide synth

mnick12 - 25-5-2010 at 20:26

I found this thread interesting, and thought that I would have a go at thiourea dioxide they way the did in the article posted. Everything was the same except I did it at 1/10th the scale. The reaction was easy to do but I ended up with 1.81gr of dry product from the 3.8g of thiourea. So my question is do I have to dilute the H2O2 so much, or can I leave it at 30% and save my product from being carried away in the finished solution?

Also has anyone here conducted any experiments reducing compounds with thiourea dioxide? If not I am open for any ideas.
Oh and I may post a few pics on thiourea dioxide synth sometime soon if anyone is interested.

Formula409 - 26-5-2010 at 05:21

Quote: Originally posted by mnick12

I found this thread interesting, and thought that I would have a go at thiourea dioxide they way the did in the article posted. Everything was the same except I did it at 1/10th the scale. The reaction was easy to do but I ended up with 1.81gr of dry product from the 3.8g of thiourea. So my question is do I have to dilute the H2O2 so much, or can I leave it at 30% and save my product from being carried away in the finished solution?

Also has anyone here conducted any experiments reducing compounds with thiourea dioxide? If not I am open for any ideas.
Oh and I may post a few pics on thiourea dioxide synth sometime soon if anyone is interested.

Thanks for giving it a go! I used approx 50% H2O2 in the synth with the amounts changed to give the same stoichiometry and I got pretty low yields too (30-40%). Maybe the patent is just trying to sound better than it actually is? I also tried with the H2O2 diluted to 30% but got identical yields.

For trying reductions, camphor seems to be a great choice as the reactions are already documented and it is available OTC pure and reasonably priced!

Formula409

Nicodem - 26-5-2010 at 13:56

Quote: Originally posted by mnick12

Also has anyone here conducted any experiments reducing compounds with thiourea dioxide? If not I am open for any ideas.

I would suggest an attempt at reducing vanillin. I suspect that under properly basic conditions it would get reduced all the way to 4-hydroxy-3-methoxytoluene (trough the quionone methide intermediate). Even though I have some strong suspicions about the paper linked bellow of being just one of those numerous typical fictional stories,* I would nevertheless try using their experimental in such an attempt (obviously with a double amount of thiourea dioxide for vanillin), it's a typical procedure anyway:

ARKIVOC, 2009, 141-145.

* There are plenty of papers claiming this reagents reduces nitroaromatics to anilines under similar conditions. Besides, my BS detector goes wild in such cases due to the unfortunate frequency of fictional papers coming from India&Iran&Co. combined with certain weird things of which maybe the weirdest one is the oxygen content measured with an elemental analysis! Besides, the products are known compounds and they don't even give melting points and back them up with references. Another improper thing is in that they did not include any references for the nitroaromatics being reduced with thiourea dioxide. I'm sorry to say this, but whoever was the peer reviewer for this paper truly did a very lousy job.

mnick12 - 26-5-2010 at 15:01

I like both of your ideas,but I have a few comments.
Formula you said that camphor is OTC, I know it is used in some soaps and things like that, but is it available as a pure material?
So camphor would be reduced to Borneol?

Nicodem,
I like the idea of reducing vanillin, but I do not have access to it in a pure form. Though I may be able to get some ethylvanillin, but it will be few weeks before I can get it shipped. Oh one more thing the paper you kindly shared mentioned the reduction of nitroketones and nitroaldehydes, but do you know if TUD is capable of reducing carboxylic acids?
Thanks.

Nicodem - 5-6-2010 at 02:16

Quote: Originally posted by mnick12

Oh one more thing the paper you kindly shared mentioned the reduction of nitroketones and nitroaldehydes, but do you know if TUD is capable of reducing carboxylic acids?

No, it can not reduce carboxylic acids.
Another paper from the same authors as above is in the attachment (DOI: 10.1080/00397910802026220). This time I leave it to the reader to judge whether it is science or science fiction. Note they claim p-hydroxybenzaldehyde reduces to p-hydroxybenzyl alcohol using 1 equivalent of thiourea dioxide. It would be interesting to test this on vanillin (or "ethyl vanillin"). If would also be interesting to test the reduction of vanillin using double amounts of thiourea dioxide and NaOH, without EtOH cosolvent (a cosolvent is not needed as vanillin dissolves well in aqueous NaOH) and longer reflux.

Attachment: Novel Chemoselective Reduction of Aldehydes in the Presence of Other Carbonyl Moieties with Thiourea Dioxide.pdf (151kB)
This file has been downloaded 3323 times

Formula409 - 7-6-2010 at 23:28

Quote: Originally posted by mnick12

I like both of your ideas,but I have a few comments.
Formula you said that camphor is OTC, I know it is used in some soaps and things like that, but is it available as a pure material?
So camphor would be reduced to Borneol?

Have a look at mothballs - depending where you are from they should contain fairly pure camphor. There are also p-dichlorobenzene ones, but in Australia they don't sell them at all.

Hope this helps!

Formula409.

DJF90 - 8-6-2010 at 11:02

Some mothballs are Naphthalene...

[Edited on 8-6-2010 by DJF90]

Paddywhacker - 8-6-2010 at 14:30

Quote: Originally posted by mnick12

See this photo, but don't let the manji freak you out.

camphor.jpg - 57kB

Magpie - 8-6-2010 at 14:37

Quote: Originally posted by DJF90

Some mothballs are Naphthalene...

[Edited on 8-6-2010 by DJF90]

Yes, I have some Enoz "old fashioned" moth balls, which claim to be 99.95% napthalene. I've never used them for any higher purpose, however.

https://www.wegmans.com/webapp/wcs/stores/servlet/ProductDis...

roductDisplay

[Edited on 8-6-2010 by Magpie]

Lambda-Eyde - 8-6-2010 at 15:00

Paddywhacker: I like the swastika.

not_important - 8-6-2010 at 15:49

In SE Asia and nearby countries camphor is somewhat common, in the rest of the world you'll find naphthalene or p-dichlorobenzene.

Indians immigrating to western countries not infrequently discover that their auspicious and even holy symbol has quite different means in their new country.

JohnWW - 9-6-2010 at 01:45

Quote: Originally posted by Lambda-Eyde

Paddywhacker: I like the swastika.

Were the Nazis into producing their own camphor as part of their war effort? I doubt it, although camphor trees are found in the parts of southeastern China, Taiwan, and Indochina that were occupied by the Japanese for many years until the end of the war in the Pacific.

densest - 9-6-2010 at 12:01

I've seen synthetic camphor in 1-ounce packages in pharmacies (chemists' shops) in the US. It's also available mail order - there may be an extra fee for airtight packaging! Natural camphor is harder to find and much more expensive.

not_important - 9-6-2010 at 18:21

Quote: Originally posted by JohnWW

Were the Nazis into producing their own camphor as part of their war effort?...

sigh - the swastika, both deosil and widdershins, have been used for thousands of years throughout the world. It generally has connotations of good luck, auspicious circumstances, and even holyness. The Wikipedia article is fairly accurate, I'd suggest reading it.

Sedit - 9-6-2010 at 19:41

I concure with N_I. The swastika is a symbol of good luck and good fortune. People that associate it with Nazi know very little about the most important symbol in the history of the earth. It is the ONLY symbol that spanded every continent even when they where not suppose to have contact with each other. Those who dispise it need to learn more about it and see that it could rewrite history as we know it if more study was done. The nazis didn't chose that symbol by chance alone and like it or not Goodluck and prosperity did have a habit of following them around....

peach - 12-6-2010 at 05:51

I'm going to make some assumptions about why you might be interested in these reductions and camphor.

Firstly, the type of material you're after for "those reactions" is called dark camphor, and it's not sold due to it being carcinogenic. If you want camphor for something more legal, you can buy refined bottles of it for not a lot of money.

There also other methods for producing "those amines" that don't involve amalgams or borohydrides. I have read first hand accounts from people running these methods and yielding the amines they're after. But they're "those types" of people and the posts are on "those forums".

[Edited on 12-6-2010 by peach]

mnick12 - 12-6-2010 at 11:56

Well I found a source of Vanillin so I will order some of that to reduce with TUD . Though I need to look around for camphor.

When the vanillin arrives I will attempt to reduce it using TUD, and I will go ahead and post my results. I may post pictures if anyone wants. But it may take a bit for the Vanillin to arrive.

organometallic - 12-6-2010 at 17:16

mrnick12: I would appreciate photos. This will produce the dihydroxybenzaldehyde, correct?

mnick12 - 12-6-2010 at 17:55

No I dont think so remember vanillin is already an aldehyde take a look on wiki http://en.wikipedia.org/wiki/Vanillin. The fully reduced vanillin would be 2-methoxy-4-methylphenol. But that could be converted into an aldehyde a number of ways if you really wanted to.

DJF90 - 12-6-2010 at 22:51

Actually you're not gonna get rid of that oxygen so easily so it'll really be 2-methoxy-4-methylbenzyl alcohol.

organometallic - 13-6-2010 at 00:01

Sorry if I'm wrong but surely it'll be 3-methoxy-4-hydroxy benzyl alcohol?
quoting nicodem: 'Note they claim p-hydroxybenzaldehyde reduces to p-hydroxybenzyl alcohol using 1 equivalent of thiourea dioxide.' sorry if im wasting your time though i just dont see how it would convert the hydroxy to a methyl group, that involves adding a carbon somehow...

DJF90 - 13-6-2010 at 00:26

I was correcting the product that mnick12 gave. I failed to notice that he had misnamed the product from vanillin. However you yourself suggested the dihydroxyaldehyde would be obtained. That ain't gonna happen either. Need a strong lewis acid to do that.

[Edited on 13-6-2010 by DJF90]

organometallic - 14-6-2010 at 11:02

O.K noted, so it won't convert the phenolic -OH to a methyl then as well :]
How likely is is that TUD could be used to hydrogenate the double bond on a nitrostyrene, or maybe convert say phenyl-2-nitropropene to phenyl-2-nitropropane, or all the way to amphetamine?
What about the corresponding nitrostyrene for 2c-b or mescaline?

It occured to me, do the other ring substituents on the nitrostyrenes derived from 2,5-dimethoxybenzaldehyde and 3,4,5-trimethoxybenzalehyde contribute any electron density to the double bond in the nitrostyrene, making it harder to hydrogenate that for straight benzaldehyde?

[Edited on 14-6-2010 by organometallic]

Lambda-Eyde - 14-6-2010 at 11:31

Is this really a forum where it is allowed to openly discuss the synthesis of amphetamines? I thought this was a forum for people who embrace chemistry as a hobby.

Oh, and please spare me for the libertarian crap and the excuse that "it's allowed as long as it is scientific".

DJF90 - 14-6-2010 at 12:58

It's fucking ridiculous isn't it...

Barium - 14-6-2010 at 14:08

Organometallic, TUD won't hydrogenate anything, but it can reduce various functionalities. Learn the difference between reduction and hydrogenation/hydrogenolysis. Wery few things will selectively attack the double bond in a beta-nitrostyrene and I strongly doubt TUD is one of those. It might very well reduce a nitrostyrene to the oxime though.

zed - 14-6-2010 at 15:28

Likewise, the direct reduction of Nitro-Propenyl Benzenes to Amines, is quite difficult.

LiAlH4 can achieve that objective, and very few other things. Just figure that all reagents that are inexpensive, easy to obtain, and safe to handle......Will fail.

Perhaps you would benefit from a few days of pouring through the archives. Just read through string after string, of vaguely related material. There is a lot of very exotic information on Science Madness, but much of it....is tucked away in odd places.
---------------------------------------------------------
Methinks the lady doth protest too much!

peach - 19-6-2010 at 18:13

Quote:

amphetamine?
What about the corresponding nitrostyrene for 2c-b or mescaline?

I appreciate where you're coming from, but going that far with naming specific drugs as targets is a bad plan on this forum.

Quote: Originally posted by DJF90

It's fucking ridiculous isn't it...

Saying that, two stickied topics are preparing benzaldehyde and acetic anhydride.

Quote:

LiAlH4 can achieve that objective, and very few other things.

That's the hinky dinky stuff someone was selling kilos of on here whilst not collecting any information from his buyers. Silly boy.

[Edited on 21-6-2010 by peach]

manimal - 30-7-2010 at 23:52

Quote: Originally posted by Nicodem

* There are plenty of papers claiming this reagents reduces nitroaromatics to anilines under similar conditions. Besides, my BS detector goes wild in such cases due to the unfortunate frequency of fictional papers coming from India&Iran&Co. combined with certain weird things of which maybe the weirdest one is the oxygen content measured with an elemental analysis! Besides, the products are known compounds and they don't even give melting points and back them up with references. Another improper thing is in that they did not include any references for the nitroaromatics being reduced with thiourea dioxide. I'm sorry to say this, but whoever was the peer reviewer for this paper truly did a very lousy job.

Checkout this article that states that 60% of Chinese PhD candidates admit to plagiarism and bribery: http://www.csmonitor.com/2006/0516/p01s03-woap.html

turd - 31-7-2010 at 01:07

Quote: Originally posted by zed

Likewise, the direct reduction of Nitro-Propenyl Benzenes to Amines, is quite difficult.

LiAlH4 can achieve that objective, and very few other things. Just figure that all reagents that are inexpensive, easy to obtain, and safe to handle......Will fail.

???
http://www.erowid.org/archive/rhodium/chemistry/nitrostyrene...
Needless to say, small scale rocks.

mnick12 - 28-8-2010 at 22:53

Well I got some vanillin a while ago, and if I have the time tomorrow I will make some more TUD and try reducing some vanillin. If I do not have enough time I will finish it up later in the week.

Stay tuned.

UnintentionalChaos - 15-7-2011 at 12:57

Hey look, someone (me) actually used TUD for something! I reduced 3-nitrophthalhydrazide to luminol, which is a reduction of an aromatic nitro group. So, not the most impressive demo of reducing power, but it's something:

http://youtu.be/-PGtoZEZnzc

Reduction at 3:34
Glowing stuff at 19:33

AndersHoveland - 16-7-2011 at 23:55

NaBH4 supposedly can reduce picric acid to 1,3,5-trinitropentane.
M. Adam and T. Severin, Chem. Ber. Volume 96, p448. (1963)
The reaction is also mentioned in another paper, which mentions both microbial reduction and reduction with borohydride:
http://aem.asm.org/cgi/reprint/58/9/2933.pdf

Do you think thiourea dioxide is too strong of a reducing agent for the reaction?

[Edited on 17-7-2011 by AndersHoveland]

Magpie - 21-3-2013 at 19:05

I would like to be able to reduce ketones/aldehydes but have no NaBH4. I've been wondering if thiourea dioxide would be capable of reducing cyclohexanone. Based on the following excerpt it looks like it may be possible. What do you think?

excerpt from a University of Warwick PhD thesis, February 2008 by James Frederick Shuan-Liang
Reduction of 4-tert-Butylcyclohexanone with Thiourea dioxide

Experimental
"4-tert-butylcyclohexanone (463 mg, 3 mmol) was added to a solution of the thiourea dioxide and sodium hydroxide in ethanol (6ml) and water (4 ml) and heated to 78 ºC under a nitrogen atmosphere for 4 h. The reaction mixture was cooled to RT and acidified with 2 M hydrochloric acid. The white suspension was partitioned over diethyl ether, filtered and separated. The aqueous layer was extracted with diethyl ether and all organic media combined, dried (sodium sulfate), filtered and concentrated to an off-white solid. Purification was achieved via flash chromatography (silica, 20 g) with n-pentane and 10–25% diethyl ether/n-pentane to afford the cis and the trans-diastereoisomers of 4-tert-butylcyclohexanol as a white wool.

•Thiourea dioxide(648 mg, 2 equiv.) and sodium hydroxide (480 mg, 4 equiv.) gave the alcohol (211 mg, 45%, 3:97cis:trans)."

[Edited on 22-3-2013 by Magpie]

paw_20 - 22-3-2013 at 06:54

I don't see why it wouldn't reduce cyclohexanone Magpie that t-butyl group shouldn't make a difference in the 4 position

Magpie - 26-3-2013 at 17:28

I am attempting to reduce 10mL of cyclohexanone to cyclohexanol with thiourea dioxide. The reaction is being conducted at reflux (~78°C) in ethanol with some water and NaOH added. Reaction time so far is 2 hours and may continue for another 2 hours.

Thiourea dioxide is also known as aminomethane sulfinic acid.

(-NH2)(=NH)C-S(=O)(-OH)

There was a great deal of white solids formed early from a clear charge. There does not seem to be any gases generated as I have it contained with a balloon filled with argon.

Does anyone know what are the likely by-products?

I really don't want to make a separation using diethyl ether. Perhaps dichloromethane can be used instead?

[Edited on 27-3-2013 by Magpie]

[Edited on 27-3-2013 by Magpie]

Nicodem - 27-3-2013 at 07:44

Quote: Originally posted by Magpie

Does anyone know what are the likely by-products?

All byproducts from the reagents are washed away by water or diluted brine (urea, higher sulfates, etc.) so you don't have to worry about it.

Depending on how much cosolvent you used, you could just dilute with 10 ml of about 10% brine, wash the crude product with saturated brine, dry over Na₂SO₄ and distill. You can use some dichloromethane to reduce the mechanical losses, but I would not bother using it for an extraction as it really isn't necessary. If you used a relatively large amount of ethanol, it might be best to first remove it by carefully rotavaping or distilling it off directly from the reaction mixture (don't exaggerate so you don't loose the product as well).

Due to the miniscale you are using, any of this might not be reasonable, if all you need is to check if the reaction works or not. But essentially you only need to get about a mL of a distillate for a bp determination and check the yields at a larger scale experiment where the mechanical losses will be less notable. You will also be able to fractionate and thus obtain a purer product at a larger scale. A problem you might encounter will be the uncertainty of the identification due to the close bp of cyclohexanol and cyclohexanone, especially if you get a mixture of the two due to incomplete conversion. If you have 2,4-dinitrophenylhydrazine, you might check for the presence of cyclohexanone by derivatization and TLC.

Magpie - 27-3-2013 at 08:12

Thanks Nicodem for your comments. I apologize for not providing a more complete description of my procedure. Here's the details:

So far what I have done is to scale this reaction up by a factor of 32.1 based on the information in the Shuan-Liang thesis referenced above.

So, just for a charge of 10mL of cyclohexanone the following were added: 95% ethanol, 193mL; H2O, 129mL; NaOH, 15.4g; TUD, 20.8g. After 4 hours at reflux I turned off the heat and left it overnight. That's where I am right now.

The thesis then says to acidify with 2M HCl, which I have calculated may be up to as much as 193mL. The next step is to "partition" with ether, filter both phases, extract the aqueous with more ether, combine the ethers, dry them with Na2SO4, then concentrate to an off-white solid. This solid is then purified by flash chromatography.

I won't be doing the flash chromatography. But the rest of this procedure seems reasonable and doable by me. I just don't like preparing and handling ether. But I will do what is necessary. My goal is to get as much yield as possible. Without doing any calculations the theoretical yield should be ~10g I would think.

Nicodem - 27-3-2013 at 09:03

Quote: Originally posted by Magpie

So far what I have done is to scale this reaction up by a factor of 32.1 based on the information in the Shuan-Liang thesis referenced above.

So, just for a charge of 10mL of cyclohexanone the following were added: 95% ethanol, 193mL; H2O, 129mL; NaOH, 15.4g; TUD, 20.8g. After 4 hours at reflux I turned off the heat and left it overnight. That's where I am right now.

You shouldn't scale-up a 3 mmol reaction by factoring up like that for a few reasons. Firstly, at 3 mmol it is the tendency of all organic synthetic chemists to use a much more diluted reaction mixture from what would be considered optimal (by the rule of thumb one initially uses 10 mL of a solvent for each gram of the substrate if the scale of the not-yet-optimized reaction is more than about 20 mmol). Secondly, your substrate requires much less cosolvent as its logP is significantly lower than that of 4-t-butylcyclohexanone. Ideally, for something like cyclohexanone, you could check the reaction in the absence of a cosolvent. Less ideally, the kinetics would be too slow in the absence of a cosolvent, but a minimum of 1 : 6 : 2 ratio of cyclohexanone vs. ethanol vs. NaOH(aq) volumes should give you a biphasic or even monophasic mixture with excellent partitioning enabling for good reaction kinetics and easy work up. The ratio could be potentially lowered to 1 : 3 : 1 by reducing the excess of thiourea dioxide and NaOH. Thirdly, when setting up reactions it is always good to consider how will the amount of solvents and reagents influence the work up.

To get back on the work up of this specific reaction mixture, I suggest you to concentrate to a volume of about 150-170 mL by distilling off the ethanol using a short Vigreux or another simple column to prevent loosing the relatively small amount of the product with steam/ethanol. Then saturate with NaCl and extract with about 20 mL dichloromethane, wash the extract with 50 mL water, remove the solvent and make a short path distillation to remove the nonvolatiles. This should give you a crude product that can be tested for its bp. Due to the short path distillation, it could remain contaminated with some residual ethanol which can give you a false negative from the bp determination.

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I won't be doing the flash chromatography.

It is not really feasible for something as volatile as cyclohexanol anyway.

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I just don't like preparing and handling ether. But I will do what is necessary.

You don't need to. Dichloromethane will do just fine and if you remove most of the ethanol and use NaCl like I suggested, you wont need to do multiple extractions either. Considering the logP of cyclohexanol, one extraction will be enough (actually, the cyclohexanol should already oil out upon saturation with NaCl).

Also, the neutralization with HCl in the original procedure is obsolete and an optimized reaction would probably not necessitate for a triple excess of thiourea dioxide and NaOH. It is possible that a 50% excess works just well. And Na2CO3 or K2CO3 instead of NaOH might also perform equally well or better.

Edit: Reconsidered a few things.

[Edited on 27/3/2013 by Nicodem]

Magpie - 27-3-2013 at 09:24

Thanks for the insight and rule-of-thumb for regular scale reactions. Before setting up the reaction I did think about scaling back on the solvent/co-solvent. But after the reaction proceeded for not very long a great deal of white solids appeared. In fact so much, that bumping became an issue. I shut down twice to first add boiling stones then to add a magnetic stir bar. Bumping was mitigated but never went away.

Should I go a head and acidify with the 2M HCl before proceeding?

Edit: I see your reconsiderations. Thanks.

[Edited on 27-3-2013 by Magpie]

Magpie - 27-3-2013 at 09:42

Would it be best to heat the batch up to try to liquify it and then try to filter out all those solids before proceeding?

Or, perhaps it would be best to start over rather than possibly wasting dichloromethane on the extraction. I have 9mL of cyclohexanone left and plenty of the other reagents.

Magpie - 27-3-2013 at 11:47

Here is a picture of the post reaction mix. It doesn't look as solids-laden as I had imagined. So will proceed per your recommendations, Nicodem. That's a 1000mL RBF, BTW.

post reaction for cyclohexanol.JPG - 95kB

[Edited on 27-3-2013 by Magpie]

Magpie - 27-3-2013 at 18:06

Here's a summary of today's work, with pictures of the reaction product workup for cyclohexanol from alkaline (pH=8.5) aqueous ethanol (60% alcohol).

The reaction product was first filtered to remove the white solids: about 20g by eye (see picture below). The yellow tinged transparent filtrate was then distilled using a jury-rigged short path column, also shown below. There is about 3" of loose ss scrub pad in the column. The final picture shows the results of the distillation. Note that a thin layer of oil can be seen floating on the pot residue. Tomorrow this residue will be saturated with NaCl then extracted with dichloromethane per Nicodem's guidance.

The products have a strange sulfurous smell. Sometimes a trace of H2S is present, but mostly it is like smelling SO2. Most of this odor left when the filter cake was removed from the lab.
============================

Edit: Today I realized what the by-products smell like: urine. This makes sense considering the composition of TUD.

solids removal on 15cm Buchner.JPG - 82kB

short path distillation column.JPG - 104kB

distillation results for cyclohexanol.JPG - 101kB

[Edited on 28-3-2013 by Magpie]

[Edited on 28-3-2013 by Magpie]

[Edited on 28-3-2013 by Magpie]

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