Sciencemadness Discussion Board - Boxwood odor

Boxwood odor

moonfisher - 12-3-2016 at 18:00

You know the smell of boxwood in the summer sun? Its an interesting odor. Turns out its made of 4-methyl-4-mercaptopentan-2-one and 3-mercaptohexyl acetate.

4-methyl-4-mercaptopentan-2-one
Uhhh...
3-mercaptohexyl acetate- seems easy enough: 3-mercaptohexanol and acetic acid esterification. Just how to make 3-mercaptohexanol? Sodium hydrosulfate on 3-hexanol a la https://en.wikipedia.org/wiki/Thiol#Preparation?

Didnt find anything bout extractions, so is there a way these can be easily synthesized? Aren't mercaptans THE stinkers? (I also have little experience in org chem...)

It might be a fun project.

Sources:
https://books.google.com/books?id=1KeJCS0in_IC&pg=PT98&a...

https://books.google.com/books?id=EaLysIpGTK0C&pg=PA221&...

Magpie - 12-3-2016 at 18:55

I like the smell of boxwood in the summer. When I see a hedge of boxwood I know I will enjoy walking along side of it.

When I landscaped my front yard a few years back I planted 5 boxwood under my front window in hopes of growing a hedge. But they are struggling and one died. I'm not sure what is wrong. Maybe there's not enough sulfur in my soil.

hyfalcon - 13-3-2016 at 04:01

I think you're on the right track. Most foundations have bits of mortar in the ground. This causes the soil to go alkali. Sulfur would be a good cure, so would cottonseed meal.

CuReUS - 13-3-2016 at 06:09

Quote: Originally posted by moonfisher

3-mercaptohexyl acetate- seems easy enough: 3-mercaptohexanol and acetic acid esterification

S is more nucleophilic than O,so it will get acetylated predominantly.

Quote:

so is there a way these can be easily synthesized?

here's my way

1.synthesis of gamma-butyrolactone from THF
http://pubs.acs.org/doi/abs/10.1021/op980028j

2.reaction of gamma-butyrolactone with ethylMgBr to give 6-hydroxyhexan-3-one
https://www.thieme-connect.com/products/ejournals/abstract/1...

3.acetylation of 6-hydrohexan-3-one using any acetylating agent

4.conversion of ketone to thiol via the thioketal to get the target compound
http://www.orgsyn.org/demo.aspx?prep=cv7p0124

[Edited on 13-3-2016 by CuReUS]

clearly_not_atara - 13-3-2016 at 09:18

From levulinic acid:

1. cycloenolization with acetic anhydride/H2SO4 to 5-methyl-2-furanone.

2. alpha-dimethylation with Li(iPr)2N/Me2CO3 to the 3,3-dimethyl-(1)

3. Hydrolysis to 2,2-dimethyl-5-oxohexanoic acid

4. Precipitation of the silver salt with AgNO3 and bromodecarboxylation to 4-methyl-4-bromo-2-pentanone

5. Na2S2O3 followed by TsOH/H2O and extraction of 4-mercapto-4-methyl-2-pentanone with np solvent

Also generally thioesters are formed kinetically but esters are preferred thermodynamically due to stronger charge delocalization. Under the right conditions you'll get the O-acetyl thiol.

[Edited on 13-3-2016 by clearly_not_atara]

moonfisher - 13-3-2016 at 15:19

Quote: Originally posted by Magpie

I like the smell of boxwood in the summer. When I see a hedge of boxwood I know I will enjoy walking along side of it.

When I landscaped my front yard a few years back I planted 5 boxwood under my front window in hopes of growing a hedge. But they are struggling and one died. I'm not sure what is wrong. Maybe there's not enough sulfur in my soil.

Thankfully I am a "plant nerd"! What side of the building are they growing on? How close to the foundation? What's the texture of the soil? And how is your climate like?

moonfisher - 13-3-2016 at 15:24

Quote: Originally posted by CuReUS

Quote: Originally posted by moonfisher

3-mercaptohexyl acetate- seems easy enough: 3-mercaptohexanol and acetic acid esterification

S is more nucleophilic than O,so it will get acetylated predominantly.

Quote:

so is there a way these can be easily synthesized?

here's my way

Oops! thats the kind of mistake I didnt want to make; although acetylization at that location would be interesting. Thanks for the references.

Step 2 looks tricker. Grignards are cool, but a pain in the ass.

Magpie - 13-3-2016 at 15:33

Quote: Originally posted by moonfisher

Thankfully I am a "plant nerd"! What side of the building are they growing on? How close to the foundation? What's the texture of the soil? And how is your climate like?

West, 12 inches, sandy, desert. Sprinklers water these bushes everyday from about April 1 to Oct 1.

moonfisher - 13-3-2016 at 15:34

Quote: Originally posted by clearly_not_atara

From levulinic acid:

1. cycloenolization with acetic anhydride/H2SO4 to 5-methyl-2-furanone.

2. alpha-dimethylation with Li(iPr)2N/Me2CO3 to the 3,3-dimethyl-(1)

3. Hydrolysis to 2,2-dimethyl-5-oxohexanoic acid

4. Precipitation of the silver salt with AgNO3 and bromodecarboxylation to 4-methyl-4-bromo-2-pentanone

5. Na2S2O3 followed by TsOH/H2O and extraction of 4-mercapto-4-methyl-2-pentanone with np solvent

Also generally thioesters are formed kinetically but esters are preferred thermodynamically due to stronger charge delocalization. Under the right conditions you'll get the O-acetyl thiol.

[Edited on 13-3-2016 by clearly_not_atara]

Thanks! Never would have came up with that myself. Li(iPr)2N sounds like fun

Bert - 14-3-2016 at 03:50

Quote: Originally posted by Magpie

Quote: Originally posted by moonfisher

Thankfully I am a "plant nerd"! What side of the building are they growing on? How close to the foundation? What's the texture of the soil? And how is your climate like?

West, 12 inches, sandy, desert. Sprinklers water these bushes everyday from about April 1 to Oct 1.

What side of the building, how many hours of direct sun light a day to.they get?

Your soil was likely alkaline to start, much of the USA's dessert Southwest is.

Lime from the fresh cement compounds the alkalinity, and hard sprinkler water may well be adding yet more alkalinity due to build up of soluble carbonates. Try a good shot of ammonium sulfate worked into the soil around one of the the plants, cover an area 2X as wide as the drip line of the shrub... if that works, you could add granite dust or Sulfur, along with organic material such as old pine needles worked into the top layer of soil for a long term solution to the high pH issue.

Another big plant nerd here!

[Edited on 14-3-2016 by Bert]

CuReUS - 14-3-2016 at 05:33

Quote: Originally posted by CuReUS

4.conversion of ketone to thiol via the thioketal to get the target compound
http://www.orgsyn.org/demo.aspx?prep=cv7p0124

nobody read this reference carefully ,or they would have pointed out the horrible blunder that I made

in that case, another method has to be adopted to convert the ketone to thiol.Unfortunately I could find any good methods. If anyone knows of a better method please post it here .If a good method is not found,the only thing that can be done is to reduce the ketone to alcohol using NaBH₄ and then do atara's 5th step- Na2S2O3 followed by TsOH/H2O to get the mercaptan.(hoping that the TsOH/H₂O step does not hydrolyse the ester )
The method I found is this
http://www.google.co.in/patents/US2402613

Quote:

Example VII One hundred grams of levulinic acid, 60 grams of sulfur, and 15 grams of cobalt sulfide catalyst prepared as described under Example I are reacted with hydrogen at 1000 to 2000 lbs/sq. in. pressure and a temperature of 150 to 175 C. in a small autoclave. After six hours the absorption of hydrogen has ceased. The products of the reaction are then subjected to fractional distillation after removal of the catalyst by filtration. This material consists principally of the lactone of 4-mercaptovaleric acid formed by cyclization of the 4-mercaptovaleric acid.

also I am sorry to say,but due to a mistake in nomenclature,my synthesis gives 4-mercaptohexyl acetate instead of 3-mercaptohexylacetate

so instead of using 6-hydroxyhexan-3-one,1-hydroxyhexan-3-one has to be used .That is made by reaction of 4-hydroxybutan-2-one with iodoethane
http://www.chemsink.com/reaction/1758390/.
After that the reaction is the same.I will come up with a route to 4-hydroxybutan-2-one later

Quote:

Also generally thioesters are formed kinetically but esters are preferred thermodynamically due to stronger charge delocalization. Under the right conditions you'll get the O-acetyl thiol.

atara I have told you before also ,please provide references .What do you mean by "right conditions" ?

moonfisher ,I also realised that making the compound itself is not enough,you also have to make the correct enantiomer.Since its a natural product,If you don't have the right enantiomer,you won't get the desired smell

[Edited on 14-3-2016 by CuReUS]

moonfisher - 14-3-2016 at 12:46

Quote: Originally posted by Bert

Quote: Originally posted by Magpie

Quote: Originally posted by moonfisher

Thankfully I am a "plant nerd"! What side of the building are they growing on? How close to the foundation? What's the texture of the soil? And how is your climate like?

West, 12 inches, sandy, desert. Sprinklers water these bushes everyday from about April 1 to Oct 1.

Yes! We can nerd together!

Bert is right- the quick-draining sand doesnt help either: the local soil is clay, and they grow like weeds. I am in the wet, temperate NYC region. Even here, exposure to hot afternoon sun puts stress on them. Copious amounts of organic matter is needed- nutrient retention by the soil and absorption by the plant can very substantially with pH, and something to filter the light a little bit, it you are at a high elevation and farther south. It would also save on water costs.

moonfisher - 14-3-2016 at 12:51

Quote: Originally posted by CuReUS

4.conversion of ketone to thiol via the thioketal to get the target compound
http://www.orgsyn.org/demo.aspx?prep=cv7p0124

nobody read this reference carefully ,or they would have pointed out the horrible blunder that I made

Quote:

also I am sorry to say,but due to a mistake in nomenclature,my synthesis gives 4-mercaptohexyl acetate instead of 3-mercaptohexylacetate

Quote:

Also generally thioesters are formed kinetically but esters are preferred thermodynamically due to stronger charge delocalization. Under the right conditions you'll get the O-acetyl thiol.

[Edited on 14-3-2016 by CuReUS]

Thanks for pointing out your errors- it would have taken me MUCH longer, if at all to find them (org chem is not my forte). The entiomer problem is a big issue- no source cites which one is the boxwood one! It will be a learning experience!

These reactions look quite interesting actually. "hoping that the TsOH/H₂O step does not hydrolyse the ester" That was something I did notice a bit later on.

Quote:

eacted with hydrogen at 1000 to 2000 lbs/sq. in. pressure and a temperature of 150 to 175 C

heh...

Magpie - 14-3-2016 at 14:30

Quote: Originally posted by Bert

Quote: Originally posted by moonfisher

The plants are on the West side of the building. They get probably 6hrs/day direct sunlight.

I scraped up some soil from the surface, added some distilled water, and measured the pH. It's neutral to slightly acid.

I bought a 20lb bag of ammonium sulfate for $10. I'll be adding that to the soil around the plants.

Thanks to both of you for your advice.

Dr.Bob - 14-3-2016 at 17:21

I can send you a box of nice red clay from NC if you want more moisture retention and some nice acidic dirt... It also makes nice bricks.

As is often the case, natural product extraction is likely much more practical than total synthesis, although even better might be to move the desired genes into another organism and just express them there. That seems to be the new way to make stuff.

CuReUS - 15-3-2016 at 05:58

I have come up with some routes to make 4-hydroxybutan-2-one

1. from 2-methyloxetane: reaction of this with fenton' reagent should open up the ring,followed by a selective oxidation of the secondary OH over the primary OH to give 4-hydroxybutan-2-one.

2. by aldol addition: from acetone and HCHO.I found a method to make b-hydroxyketones but they don't use HCHO.
https://www.thieme-connect.com/products/ejournals/abstract/1...

or you could convert acetone to its lithium enolate using LDA and then react with HCHO to get 4-hydroxybutan-2-one

you can also see this for more examples
http://www.organic-chemistry.org/namedreactions/aldol-additi...

Quote: Originally posted by moonfisher

eacted with hydrogen at 1000 to 2000 lbs/sq. in. pressure and a temperature of 150 to 175 C
heh...

these conditions are possible in an autoclave

moonfisher,I have spent a considerable time and effort to come up with these reactions and I am sure atara has too. So please try them out atleast on a small scale while you wait for your plants to grow

[Edited on 15-3-2016 by CuReUS]

moonfisher - 15-3-2016 at 14:24

CuReUS,

Don't worry! Ill do it! (eventually

)
Im planning to make the hydroxybutanone this weekend, starting to write the background for the writeup.
Then, the ethyl iodide- ChemPlayer made a vid with aluminium foil, so I will do that one. Is it lachrymatory? The MSDS I found said it is irritating to eyes and skin, do not inhale fumes but nothing specific.

[Edited on 15-3-2016 by moonfisher]

CuReUS - 16-3-2016 at 05:56

Quote: Originally posted by moonfisher

Im planning to make the hydroxybutanone this weekend, starting to write the background for the writeup.

thaaaaank yoou

Quote:

Then, the ethyl iodide- ChemPlayer made a vid with aluminium foil, so I will do that one. Is it lachrymatory?

not as far as I know.
which method will you use to make the hydroxybutanone ? If you are going to use the LDA method,I have an idea .First react the lithium enolate of acetone with ethyl iodide to get 2-pentanone .Then make the lithium enolate again and react that with HCHO to get 1-hydroxyhexan-3-one.
The reason is that if you make the hydroxybutanone first,then do the ethyl iodide reaction,some LDA will get wasted reacting with the OH instead of forming the enolate with the ketone.
you could also make 2-pentanone using grignard reaction between n-propylMgBr and acetonitrile.
di isopropylamine is found in a herbicide called roundup. reacting that with BuLi in dry THF gives LDA.
http://www.sciencemadness.org/talk/viewthread.php?tid=28429

[Edited on 16-3-2016 by CuReUS]

moonfisher - 17-3-2016 at 16:40

Quote: Originally posted by CuReUS

Quote: Originally posted by moonfisher

Im planning to make the hydroxybutanone this weekend, starting to write the background for the writeup.

thaaaaank yoou

Quote:

Then, the ethyl iodide- ChemPlayer made a vid with aluminium foil, so I will do that one. Is it lachrymatory?

I won't be working with organolithium just yet. I can try it in a school lab after Easter, but not at home! I'd stick with the Grignard.
I'm looking at the aldol method. I do want to try the LDA. (I knew the RoundUp would come in useful lol.)

chemrox - 17-3-2016 at 18:50

A very fruitful thread here. Going back to boxwood: thanks for the information. I had no idea a mercaptan could be involved in a pleasant odor. I love smelly compounds and make them from time to time just for fun. Why we're here right? Anyway, wouldn't getting to the boxwood smells involve some really unpleasant odors in your lab and neighborhood? You might be less welcome than a meth lab.

CuReUS - 18-3-2016 at 02:50

Quote: Originally posted by moonfisher

I won't be working with organolithium just yet. I can try it in a school lab after Easter, but not at home! I'd stick with the Grignard.
I'm looking at the aldol method. I do want to try the LDA.

I am a little confused. by organolithium you mean BuLi ,right ? but you need to use it to make LDA. Otherwise you have to buy LDA.
what grignard are you talking about ?

Quote: Originally posted by chemrox

wouldn't getting to the boxwood smells involve some really unpleasant odors in your lab and neighborhood? You might be less welcome than a meth lab.

That's why I am trying to introduce the SH group in the last step.

moonfisher - 18-3-2016 at 03:18

Quote: Originally posted by CuReUS

Quote: Originally posted by moonfisher

I won't be working with organolithium just yet. I can try it in a school lab after Easter, but not at home! I'd stick with the Grignard.
I'm looking at the aldol method. I do want to try the LDA.

I am a little confused. by organolithium you mean BuLi ,right ? but you need to use it to make LDA. Otherwise you have to buy LDA.
what grignard are you talking about ?

Quote: Originally posted by chemrox

wouldn't getting to the boxwood smells involve some really unpleasant odors in your lab and neighborhood? You might be less welcome than a meth lab.

That's why I am trying to introduce the SH group in the last step.

The Grignard is propylMgBr, and the organs lithium is BuLi. Sorry for my sloppy nomenclature.

Looking at the schemes, these mercaptans aren't that stinky. One has a bitter, grapefruit odor, while the other has something between cat urine and pine. Although it is a little crowded where I live, there is also largeish stretches of swamp, if worse comes to worse!

CuReUS - 19-3-2016 at 03:21

after a lot of searching,I have finally found a method to convert the ketone to thiol via reduction of the thione
thioketones(thiones) can be made in 3 ways:
1. the classical H₂S/HCl method
https://books.google.co.in/books?id=0F3FIRgWwhQC&pg=PA18...

http://orgsyn.org/demo.aspx?prep=CV4P0927

2.phosphorus pentasulfide method
http://pubs.rsc.org/en/content/articlelanding/1993/cs/cs9932...
according to this paper,ketones can be selectively converted to thioketones in the presence of esters.This paper also talks about the H₂S/HCl method and also gives reference for the reduction of thiones to thiols using NaBH₄.
But in another paper it is given that P₂S₁₀ reacts with esters
http://pubs.acs.org/doi/abs/10.1021/cr900243d

another reference for pentasulphide- Gattermann, ibid. 28, 2877 (1895)

3.ethyl thioacetate method
couldn't find the paper,try to find it - Mitra, J. Indian Chem. Soc. 9, 637 (1932) [C. A. 27, 3922 (1933)].

a paper on the synthesis of di-tertbutyl ketone gives another reference for the classical method. but its a book,so I couldn't find it - https://www.jstage.jst.go.jp/article/bcsj1926/48/8/48_8_2403...

thioketones can also be reduced using sodium ethoxide ( pg 4/5 or pg 3721) https://www.jstage.jst.go.jp/article/bcsj1926/48/12/48_12_37...
but it can't be done in our compound because a transesterification reaction can occur

moonfisher - 20-3-2016 at 13:28

Thanks again! More to read.

clearly_not_atara - 21-3-2016 at 12:45

http://en.wikipedia.org/wiki/Diacetone_alcohol

You're going through quite a few steps to make something that can be had in one step from acetone.

chemrox - 21-3-2016 at 16:00

Good chemists taste their products whether they do it by licking their fingers is a matter of personal preference. I don't really mean that for everything.. only medicinal products..I think a few chemists have died from carelessness with nitrile gloves and weird transition metal salts. One step from acetone to make which intermediate? thioacetone?

I might be a little "devoted" today..sorry.. long cold rainy day and I can't find the keys to my storage area...my GPS and tile spade are in there and I have three wetlands to delineate this week. Environmental consulting to support organic chemistry fun.

[Edited on 22-3-2016 by chemrox]

CuReUS - 23-3-2016 at 05:14

Quote:

One step from acetone to make which intermediate? thioacetone?

very clever reaction atara.I am impressed

moonfisher ,another idea came to my mind which might avoid the use of LDA
why not react n-propylMgBr with acrylonitrile to get the unsaturated ketone and then add acetic acid across the double bond using michael reaction to directly get the acetylated OH .Then you can convert the ketone to a thione and then a thiol

Quote:

Grignard reagents react with acrylonitrile by 1,2-addition and, after hydrolysis, give a,b-unsaturated ketones

http://reag.paperplane.io/00000035.htm#18

addition of acetic acid to alkenes - https://books.google.co.in/books?id=mMgvCgAAQBAJ&pg=PA38...

[Edited on 23-3-2016 by CuReUS]

clearly_not_atara - 24-3-2016 at 11:52

IIRC formic acid adds easier than any other; I don't have the paper offhand but it's something like an autoclave at 120C. For acetic acid it's more like 200 C and 50 atmospheres or something.

On the other hand, benzyl mercaptan adds to alkenes quite easily at room temperature. It's not as odorous as the short-chain thiols but it does stink. TiO2 is an active photocatalyst:

http://pubs.rsc.org/en/content/articlehtml/2015/cc/c4cc09987...

[Edited on 24-3-2016 by clearly_not_atara]

CuReUS - 25-3-2016 at 02:38

I was thinking about removing a few more steps and one of the ways that can be done is doing a one pot reaction from the ketone to the thiol,similar to a reductive amination.
the first reducing agent that came to my mind was NaBH₃CN, but it cannot be used here because it will react with HCl( from the HCl+H₂S method) to liberate HCN.
sodium triacetoxyborohydride could be used,but I have read that it is unstable.

atara,are you sure about that ? because according to the google book I linked - "the addition of acetic acid to alkenes in acetic acid at reflux is quite general"
also,won't HCOOH decompose at 120'C ?

Quote:

On the other hand, benzyl mercaptan adds to alkenes quite easily at room temperature

forgive me for asking this,but how is this related to our problem ?

clearly_not_atara - 25-3-2016 at 09:28

I can't read your citation but I initially misread your post and thought you were using acetic acid to add the thiol in the keto-thiol. Anyway, I tried to look at the book you linked but Google won't let me see it. I found this:

http://pubs.rsc.org/en/content/articlelanding/1981/c3/c39810...

which seems to sort of confirm my suspicions; a specialized montmorillonite catalyst at >100 C probably wouldn't be useful if all you needed was reflux.

But more importantly, the normal conjugate addition to alkenes gives the Markovnikov product, but we want the anti-Markovnikov product. Therefore you would need to do hydroboration followed by reaction with acetic acid, or HBr/AiBN in a dry solvent.

CuReUS - 26-3-2016 at 01:10

the book which talks about the addition of acetic acid to alkene is - de klein,W.J in "organic syntheses by oxidation with metal compounds",1986, chapter 4. Please try the google book link again,using a different browser maybe ?
good find on the montmorillonite method. IIRC,this clay catalyst is not as rare as it sounds,and was used by meth cooks in the synthesis of b-nitrostyrene from styrene.

Quote:

But more importantly, the normal conjugate addition to alkenes gives the Markovnikov product

atara,with all due respect,I kindly ask you to read up on conjugate addition again

Quote:

A nucleophile reacts with a α,β-unsaturated carbonyl compound in the β position

https://en.wikipedia.org/wiki/Nucleophilic_conjugate_additio...

[Edited on 26-3-2016 by CuReUS]

zero - 9-1-2024 at 12:12

Not sure why no one looked at the literature for this compound, it is well known to be one of the most potent odorants and there is a lot of research on it.

Incidents:
A freezer was painted with paint thinner that had trace mesityl oxide impurity (0.5%) and caused all meat to smell/taste like cat piss by reacting with trace H2S in the meat. [1]

Mesityl oxide produced in a factory caused a bakery 20 miles away to make cat piss cakes by absorbing into the cooling cakes and reacting with sulfur compounds (from the eggs?). [1]

Wilmington, North Carolina smells like cat piss so bad that residents can barely breathe, even indoors. Fortron makes polyphenylene sulfide. Acetone is used as a solvent and contains trace mesityl oxide. This reacts with the sulfur compounds producing the odor. [2]

Odor:
In low concentration it is the odor of boxwood or cat piss. In high concentrations it smells ketone like [3]. The odor threshold is reported between 1-10 ppt. [2]

Synthesis:
Mesityl oxide can be reacted with H2S in a basic alcohol solution to produce 4-MMP.

The simplest procedures are from [3] and more recently [4].
Translated procedure from [4] below:

Quote:

To a 4-L round bottom flask place 490 g of mesityl oxide, 1 1/2 L of 96-proof ethanol and 5 g of solid KOH. Cool the reaction vessel to -15C and introduce H2S while stirring. After 5 hrs. the reaction is completed.

The work-up is carried out according to the instructions of F. ARNDT: The contents of the flask are poured into water, acidified with hydrochloric acid, extracted with ether and the ether solution is extracted with 2n NaOH. The B-mercaptoketone I is removed from the ether solution with 2n NaOH. After separation of the alkaline solution, the mercaptoketone is freed with HCl, separated, dried with Na2SO4 and distilled. I cannot be completely extracted from the ether solution with sodium hydroxide. The workup of the ether solution yields considerable amounts of I in addition to bis-diacetone sulfide from 82-83C. The total yield is 277 g (60% of the total, calculated on reacted mesityl oxide).

Discussion:
I have not attempted yet but do have the reagents to, seems fun like thioacetone. Will try a microscale experiment. At least not water sensitive like my other experiments. Hopefully will finally have a success. I have attached the relevant part of [3] for reference since it was difficult to locate.

[1] https://doi.org/10.1080/10408399109527534
[2] https://www.wwaytv3.com/fortron-confirms-plans-to-address-pl...
[3] F. Arndt (http://dspace.bcu-iasi.ro/handle/123456789/43983?show=full)
[4] https://doi.org/10.1002/jlac.19576100102

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