Sunday, March 3, 2013

Blog Syn #003A - Secret Ingredient

(Disclaimer: The following experiments do not constitute rigorous peer review, but rather illustrate typical yields obtained and observations gleaned by trained synthetic chemists attempting to reproduce literature procedures. We've taken efforts to stay close to the original procedure, using similar glassware, equipment, and reagents wherever possible. Images have been cropped and scaled to fit in the allotted space, but have not been digitally altered otherwise.)

It's been a wild month since our post concerning IBX-promoted benzylic oxidation. This piece provoked energetic discussion, evidenced by >200 comments (and counting!) between Blog Syn, two Pipeline posts, and Rich Apodaca's insightful discussion at Depth First

Before we wrap up this topic, we at Blog Syn first wish to thank Prof. Phil Baran, Dr. Tamsyn Montagnon, and Dr. Yong-Li Zhong (the original authors) for engaging us honestly and professionally, and helping uncover some of the hidden factors that make this reaction work.

I think we now know the most important one: water.

After reading Tamsyn and Phil's submissions to #003, we were puzzled: what was so different about our reaction conditions? Everyone was following the same procedure  [Santagostino, J. Org. Chem199964(12), 4537] to make their IBX...right?

Well, not really. No one's published the actual NMR spectrum for IBX in quite some time. Neither this paper, nor Kirsch OL 2006, nor JOC 1999[1], nor Tet. Lett. 1994 (which the JOC refers back to) do much more than provide a list of peaks. This next image shows the NMR spectra provided by Phil, Tamsyn, and by an anonymous commenter online at Blog Syn. Note the rather large water peak at 3.4 ppm (possibly from some pre-opened d6-DMSO?)

Next, I made some fresh IBX strictly following the JOC 1999 paper, which includes two acetone washes to dry the IBX. The small bump at 8.4 ppm, which we had believed to be an impurity, might actually be the OH proton of non-solvated IBX. Note that, as I titrate in additional H2O  the bump disappears, the aromatics shift and coalesce, and the 'signature' water peak grows in at 3.4 ppm! 
After discussion with the Blog Syn crew and the authors, we propose "hydrated IBX" may be the active species for the oxidation:

                         

Co-author Yong-Li suggested some 18O-labeled experiments to determine water's role in the reaction. Sadly, we're not equipped for this type of chemistry, but if any readers are, please feel free to report your findings!

Rxn, 20 h, w/H2O
Now the fun part: "hydrated IBX" performs the oxidation! 

Here's a (straight-baseline) TLC; runs "A" and "B" have varying [H2O] in the solvent, which does seem to accelerate the reaction (right). Prof. Nicolaou had remarked on this trend in the Details of ACIEE 2002, 993 (see p. 996) noting that enone dehydrogenation yields decreased when solvent was pre-dried over 4A sieves.

Using "wet" DMSO and fluorobenzene (5:1), and heating to 95 deg C in a foil-coated, fully-submerged screwtop vial, I'm now able to convert 2-methylnaphthalene to naphthaldehyde in 52% yield (brsm). My colleagues have also observed increased conversion of toluene and 4-bromotoluene, but neither go to completion by the published time points.

So, what should we recommend? It seems clear that several critical details are missing from the original Supporting Info. How much have we deviated from the initial conditions?

Based on the information above, and the results in our hands over multiple runs, we will change our recommendation to Reproducible with optimization

We look forward to future communication with all authors involved, and hope that this interchange inspires chemists to have another look at IBX-promoted oxidation reactions...just add water!

[1] We should point out that JOC 1999 does include KF titration values, but the low water % detected does not rule out sufficient hydration of some IBX. Note also that the elemental analysis values deviate enough to include trace water.

140 comments:

  1. Nice work! This kind of problem solving is what I enjoy most in chemistry.

    ReplyDelete
  2. http://www.youtube.com/watch?v=Rwda_u3Y0QQ

    Should be a useful resource for anyone having trouble with these conditions in future. Like an online post-doc...

    ReplyDelete
  3. Well, now you're in trouble. That's important enough that it should be a peer-reviewed publication (esp. with some mechanistic data).

    Who's going to be first author? And more importantly, can SeeArrOh submit the dog as his bio picture?

    ReplyDelete
    Replies
    1. I look forward to ongoing mechanistic studies. Woof!

      Delete
    2. By the way, do peer-review journals explicitly prohibit anonymous submissions?

      Delete
    3. A very good question, Alex. Maybe I'll ask around...

      Delete
  4. Cool. Not surprising, in retrospect, when you think about the structure of the Dess-Martin periodinane.

    ReplyDelete
    Replies
    1. Our thoughts exactly. Plus, assuming it's fully neutral, it *should* have improved solubility. It also helps to explain several of the other side products in the reaction, such as oxygenation para to phenols.

      Delete
  5. Although I am not competent enough on the field to fully appreciate the work done I can identify a great work and communication for the benefit of science. Please continue your work. It is very much appreciated.

    ReplyDelete
  6. Although I am typically a lurker, this discussion reminded me of a paper from Stu Schreiber (JOC 1994, 59, 7549) on the acceleration of the Dess-Martin oxidation by water. I have been using this procedure for years and it never lets me down; DMP oxidations in minutes! I make my own DMP and take good care of it, and by applying their procedures, I never have problems. According to Stu, perhaps you should be acknowledging Dess and Martin themselves in your manuscript?!? BTW: keep up the good work, this is important stuff.

    ReplyDelete
    Replies
    1. Thanks for your comment. We are indeed aware of Schreiber's JOC 1994 paper. In fact, I've often mused about the first line of his Experimental: "Reactions were performed during dry Cambridge winter months...30% relative humidity."

      However, as pertains to IBX, I've never seen our proposed "hydrate" structure (3 OH bound to I) in the synthetic literature (SciFinder, Reaxys, Google). If you are aware of such a study, please let us know!

      Delete
    2. So I do not know of a study myself, but I think the logic fits that your proposal is reasonable. Isn't DMP just the acetylated version of IBX that renders it soluble in a more broad range of organic solvents? I guess I never felt like these oxidants were that different. We are talking about the same oxidation states regardless.

      Delete
    3. Comparison of reagent reactivity based on oxidation state alone is a slippery slope. An organometallic chemist might tell you that reduction potential (mV), associative / dissociative mechanisms, solvation, open coordination sites, ligand sphere, pKa, and a whole host of other variables differentiate any one reagent from another.

      For example: Pd(OAc)2 and Pd(OPiv)2 are in the same oxidation states and have similar counterions. However, their participation in C-H activation chemistry is markedly different.

      Delete
    4. Agreed on the organometallic end of life, but I have yet to see someone reconcile the reactivity of IBX based on a mechanism (SET, etc.) unique to that species vs. DMP.

      Delete
  7. This reminds me of old Sharpless protocol for catalytic selenium dioxide terpene allylic methyl group oxidation, with tBuOOH 4-5 eqivs, 5mol% of SeO2 and few% of salicylic acid as a co-catalyst. I have been playing with the reaction conditions about 15 years ago and found out that 1) salicylic acid gets eventually chewed up and the reaction slows down from then on 2) about 2 mol% of water helped the reaction go faster (over 5;2 ratio the reaction was actually inhibited with water). My boss suggested that SeO2 needed to be depolymerized into monomeric species but more water will deactivate the electrophile. I then tried unsubstituted tetrazole in place of salicylic acid as a oxidation-resistant co-catalyst and it worked even better and water had no accelerating affect on this system. (We never got around to publish this little study)
    So perhaps you could try few mol% of tetrazole or 5-methyltetrazole as a supernucleophilic co-catalyst for IBX oxidation run in anhydrous DMSO. Unsubst tetrazole is hard to buy these days but you could ask nucleotide chemists, they usually have some around.

    ReplyDelete
  8. I know IBX has a lousy solubility in everything apart from DMSO, but what's it like in DMF? I've got an ampoule of DMF-d7 (-61 °C m. pt) and a scheduled low temperature NMR session next week if someone wants to FedEx me a sample... You might be able to see the dynamic behavior freeze out and should see two species.

    ReplyDelete
    Replies
    1. IBX is soluble in DMF up to 25-30 mg/ml = ~0.1 M: Mendeleev Communications, 2008, 18(6), 309-311.

      Delete
  9. amazing work guys (and girls?) love the blog looking forward to the next reaction :)

    ReplyDelete
  10. I hate to be an epic downer, but people need to ask themselves why members of a blog had to invest time figuring out why they could NOT reproduce a reaction found in the literature. I'm not blaming the bloggers at all. I'm blaming the authors of the paper.

    I mean look at us. We are celebrating the fact that we got a little more than HALF of the reported yield described in the JACS paper. Even Phil couldn't get the reported 90%. I would give Phil et al a pass if the yield was 5 or 10% below the reported one, but we're talking a 25-38% difference. That is HUGE and we're calling that optimized!

    Granted, this isn't as egregious as that "Oxidation of Benzhydrol to Benzophenone with NaH" paper, but omissions like these result in the loss of hundreds of work-hours. During my PhD, I had attempted to perform the ketone to enone oxidation with IBX/MPO, and I got absolutely no reaction. Ever since then, I read any Nicolaou paper with extreme caution and skepticism.

    I commend the bloggers for examining this reaction. Too bad we won't see any corrigendum to the JACS paper (and for the whole Nicolaou IBX publication series) anytime soon.

    ReplyDelete
    Replies
    1. Hi Anon2:46 - Want to discuss this with me directly? Shoot an email over to seearroh_AT_gmail.com

      Delete
    2. It's because they exaggerated the yields in the paper. They lied. Just like all these frauds who put >98% yield after column chromatography. But the incentive to lie is pretty easy. Better yield, better ee, better DR = better paper. If you run a reaction get a 60% yield, why not put 80%? No one will ever know, no one will ever be able to prove you lied, and it makes you look like a better chemist! The shameless self promotion of PI's, the obsession with impact factor, and quantity over quality is killing science.

      In a perfect world, the reviewers of such work, should:

      1. Not know the names of the authors on a paper
      2. Repeat parts of the experiment to determine the quality of science

      If lets say Phil gets 90% yield on a reaction, and four other chemists who try the reaction get 30-70%. Sure, Phil may be a better a chemist, but if something can be reproduced by the average chemist, it isn't very useful is it.

      Delete
    3. While yield inflation and "best yield" reporting are certainly problematic, and apparently quite widespread, this level of criticism is highly unfair.

      1) The grad students on the original projects probably did the reactions dozens or even hundreds of times. Any chemist knows if you do the same chemistry even 10 times, by the last reaction your yield will be much better. This applies to PB's chosen grad student as well as the blog posters.

      2) In response to: "If lets say Phil gets 90% yield on a reaction, and four other chemists who try the reaction get 30-70%. Sure, Phil may be a better a chemist, but if something can be reproduced by the average chemist, it isn't very useful is it."

      This is utterly and completely false. Many "difficult" procedures are useful and worthwhile. A few that come to mind (of different difficulty, for different reasons) are Rieke magnesium preparations, ATRP, direct (hetero)arylation, or some of the more esoteric DIBAL reductions. It's nice to know just how difficult, but sometimes (usually?) the authors are the best at it, and therefore not the best judges of the so called difficulty for an "average chemist" - whatever that is.

      The problem here is not the reaction, or the chemists, or even the paper. Perhaps the SI could have been better, but it also seems clear the original authors did not fully understand the reaction (and still don't)...like so many reactions. But, they understood it better than everyone else, and got it to work, and are still helping to iron out the details...years later. It's hard to ask for too much else.

      Also, thanks to the Blog Syn crew for all of this. It is a valuable service to the chemical community.

      --
      Troggy

      Delete
    4. @SeeArrOh Thanks for the offer, but I would like to remain, well, anonymous.

      Anon1:24's message may have been rather blunt, but he's not completely incorrect. I'm less inclined to believe that this problem is systemic. Not knowing the author of a paper I'm refereeing would be great because I could simply filibuster the paper and take the work....jk. Number 2 is a better idea and Organic Syntheses has been doing that very thing for decades now. However, dissemination of research would slow down to a crawl.

      @Troggy It's completely fine if the authors don't completely understand the reaction, but if it leads to unreliable yields, then they should examine it before publishing.


      Ah the good old days of chemistry. I absolutely LOVE repeating procedures described between the late 1800s to about 1989, especially in German publications like Liebigs Annalen, Chem Ber., and old school Angewandte, because I always got the yield they reported, down to the milligram for both the main product and any side product(s).

      Delete
  11. Given the sheer number of groups that have used IBX and IBX/mpo for enone synthesis I think you should question your own technique there. There are at least 50 independent groups that have used it.

    ReplyDelete
    Replies
    1. Do you see any enone? ArMe to ArCHO is a very different transformation, one with which people struggled in the case of IBX... Not to question your judgement, I think you should at least read the post before writing a snotty comment

      Delete
    2. He was referring to a commenter above that mentioned they could not make an enone from a ketone with IBX/mpo... Maybe you should heed your own advice and read comments before making a snarky reply.

      Delete
  12. Milkshake I was responding to the above anonymous post regarding enone synthesis - not the whole blog syn entry.

    ReplyDelete
  13. Nice one. Is the hydrate less explosive?

    ReplyDelete
  14. I'm sure that you guys have a flood of chemists wanting to tackle the next big reaction. If not, please let me know how I can help.

    ReplyDelete
  15. I think this is a great idea and want to thank you guys for doing something that you really shouldn't have to do. It would be one thing if you just said "the reaction didn't work" and left it at that, but you guys are actually shedding light on the nuances of the reaction and what is needed to make it work.

    That said, I agree with PSB that there should be a private discussion with the author before anything goes public. I understand that a discussion shouldn't be necessary, that everything necessary for the reaction to work should already be in the SI, but I think it respectful to give the author a shot at making things right BEFORE the failed reaction goes public.

    This has the added benefit of accelerating discovery of the issues hindering the reaction. If Phil hadn't had it run successfully in his lab with data on the reagents supplied, it probably would have taken much longer to figure out water was the issue.

    ReplyDelete
  16. If you have time to spare - it would be incredibly useful to have those NMR spectra uploaded in slightly larger resolution.

    ReplyDelete
    Replies
    1. Hey, Anon: Email me at seearroh_AT_gmail, and I can send you any enhanced copies you'd like.

      Delete
  17. This effort is really great, we def need a bigger spotlight on reproducibility in synthesis. Yesterday as a member of GWIS (in the US), I got to meet 5 amazing Indian women scientists as part of an International Visitor Leadership program sponsored by the State Department. They shared a funding opportunity in India that may be of interest conceptually.

    Essentially it's a grant program through CSIR (Indian version of NIH as I understand it) where anyone can submit a proposal, generally highly creative with high risk of failure. This is targeted for people who may be in remote areas or for some reason has had to step away from research. If selected, they will receive funding to carry out the research in the nearest R&D research center/university that has a collaboration with CSIR.

    So the bigger picture of what I'm getting at is the suggestion that an agency with sufficient funds (govt or even ACS) with a vested interest in reproducing work could fund individuals (part-time?) to carry out these reactions at participating labs with existing infrastructure.

    And yes, it is a bit pie in the sky, but no harm in thinking big..

    ReplyDelete
  18. Congrats excellent blog!.Thank you! I also enjoy the comment section is so richful, but I also like making and publishing posts. It is fun for me to comment back to people.


    Greetings from Venezuela!!!!

    Perfumes mas Vendidos

    ReplyDelete
  19. Its a valuable content shared,would like to know more about it.

    Benzophenone

    ReplyDelete
  20. this was good thanks. i will like to add that you can Buy U-47700 online | Buy U-47700 powder | online U-47700 shop-Bathsaltforsale.com
    Buy U-47700 powder online from bathsaltforsale.com and other research chemical products
    Buy Research Chemicals online at the best possible prices. We are a research chemical vendor from usa and and we also supply research chemicals in europe, Asia and mostly areas with legislation.From us you could buy U-47700 powder online,5-methylethylone,4-cec crystals,carfentanil,a-pvp crystals,mdpv,synthacaine research chemical and much more.Visit our website http://www.bathsaltforsale.com/en/745-buy-u-47700-powder-online.html to order research chemical, cannabinoids, stimulants and other related products at the best possible prices. We also to provide legal bath salts at lowered cost
    Follow our U-47700 powder tutorial video on Youtube

    ReplyDelete
  21. Buy u-47700 | Buy u-47700 powder | Buy u-47700 research chemical | Buy u-47700 online - Bathsaltforsale.com


    Buy u-47700 | Buy u-47700 powder from www.bathsaltforsale.com and other research chemical products
    Buy u-47700 online at low cost. You can also buy u-47700 powder or crystal form. We supply research chemicals and bath salts in usa and and we also supply research chemicals in europe, Asia and most areas with legislation.From us you could buy U-47700 research chemical online,5-methylethylone,4-cec crystals,carfentanil,a-pvp crystals,mdpv,synthacaine research chemical and much more.Visit our website http://www.bathsaltforsale.com/en/745-buy-u-47700-powder-online.html to order u-47700, cannabinoids, stimulants and other related products at low cost. We also to provide legal bath salts at lowered cost


    Follow our Buy U-47700 powder tutorial video on Youtube

    ReplyDelete
  22. What a great nice and educative blog
    You may also be searching Buy research chemicals-furanyl-fentanyl online

    Contact US

    Phone:- 4013083901

    Email:- info.standarddrugs@usa.com

    Wickr Id:- drubybay1010

    Website :-https://standardpharme.com/

    ReplyDelete
  23. It's a great work as this can be helpful for anyone in trouble with chemicals. To get info about a range of chemicals used by workers in many researches visit at:- https://buyresearchchemicalsusa.biz/

    ReplyDelete
  24. Some genuinely choice posts on this web site I really impressed with your writing skills you used to write wonderful I have found some Best Escorts Service in Islamabad and new Models Profiles Karachi Escorts for Articles and i will come back for more articles. https://islamabadescorts69.tumblr.com/
    Lahore Escorts
    Karachi Escorts
    Islamabad Escorts
    Escorts in Islamabad
    Escorts in Karachi
    Escorts in Lahore

    ReplyDelete
  25. Thank you for sharing this informative content. DMSO

    ReplyDelete
  26. I got married 2 years ago and it just seemed that there was no excitement in my sex life. My dysfunction to perform to the best of my abilities in bed made it harder for my wife and me to have a good time during sex. And i was having the feelings that she may decide to get a divorce one day. I knew something had to be done in order to improve my sex life and to save my marriage because my marriage was already falling apart, so when i was on my Facebook page i came across a story of how Dr JOHN helped him enlarged his penis to 7ins better.so i Immediately copied the Email address of the Dr and explained to him my problem,he gave me some simply instruction which i must follow and i did easily and my friends Today, i am the happiest man on Earth, All Thanks to Dr JOHN for saving my marriage and making me a real man today.You can as well reach the Dr below for help on your problem, for he has the solution to all...
    Email: DRJOHNTEMPLE@GMAIL.COM WHATSAPP NUMBER +2347064927420

    ReplyDelete
  27. I think this is one of the most significant information for me.
    And i’m glad reading your article. But should remark on some general things, the web site style is perfect, the articles is really great : D. Good job…
    holiday palace
    red dragon
    pussy888
    918kiss

    ReplyDelete
  28. "
    "
    Girls Whatsapp Groups 8290260868 "Only Girls"
    "
    "

    ReplyDelete
  29. Nice Lines.
    I really like your knowledge about medicines.
    Buy nembutal online

    ReplyDelete
  30. Sometime it becomes very hard to find a well written and well established bog which give you correct and useful information. However, I found this blog and got some relevant information which are really helpful for me. Jb escort girl service

    ReplyDelete
  31. I read your post and it is really good , keep writing more
    Buy Weed Seeds Online
    Buy A-796,260 Online
    Buy Phenethylamine Psychedelics online
    Buy DMT Dimethyltryptamine Online
    Buy 5-methoxy DALT online
    Cannabis Oil For Sale
    Buy enzodiazepines online you can as well text/whatsapp +1(646)883-3072 , Telegram: primenature or email:primepharma0@gmail.com for more details.

    Buy Fentanyl powder Online
    Buy TH-PVP Powder Online
    Order Oxycodone Morphine Online
    Buy A-PVP Online
    Buy Crystal Meth Online
    Buy Acetyl Fentanyl Powder Online
    Buy Carfentanil Online
    Buy 4-MMC Online
    BUY AMPHETAMINE ONLINE
    CBD Isolate Powder 99%+
    Buy Ephedra Powder Online

    ReplyDelete
  32. Buy Fentanyl Online now available on chemicalsmarket. We believe in being an honest fair company Buy best product’s in chemical market. Buy U-47700 Online

    See More:- http://chemicalsmarket.org/

    ReplyDelete
  33. Don´t fail to see the light. we are aware that there are lots of people on social media pretending to be agent of Illuminati brotherhood. Be careful, not everyone you see online here is real. This organisation is for PEACE, WEALTH, POWER and FAME. The organisation requires no blood sacrifice If interested, kindly Whatsapp: +1(315)3161521

    ReplyDelete
  34. GRAB THIS LIFE CHANGING OPPORTUNITY TODAY
    Make a right and positive choice for this chance of opportunity for you today to be among the 5 lucky persons that the great USA Illuminati wants to admit and makes wealthy, famous, rich, be entitled to million dollars and above all given maximum protection against anything harmful to human existence .
    if interested to join whatsapp: +1(315)3161521

    ReplyDelete
  35. Chem Dawg Oil Cartridge

    CHEM DAWG VAPE PEN CARTRIDGE is sustainably grown cannabis that’s been cleanly extracted using a supercritical CO2 method

    See More:- https://www.snowboarderstrains.com/product/chem-dawg-oil-cartridge/

    ReplyDelete
  36. Hello viewers are here to share my testimony on how I joined the brotherhood of illuminati. 3weeks back when I wanted to join the brotherhood I was fraud and scammed by the fake people using the website until I met a friend here called MR Scott ..who helped me to become a member of the great brotherhood of illuminati . today I can boost of  money .If you are interested and you need the help of my helper CALL or WHAT'S APP hima on: +1(315)316-1521
    thank u as u make up your mind to join may god Baphomet bless you....

    ReplyDelete
  37. This comment has been removed by the author.

    ReplyDelete
  38. This comment has been removed by the author.

    ReplyDelete
  39. This comment has been removed by the author.

    ReplyDelete
  40. https://blog-syn.blogspot.com/2013/03/blog-syn-003a-secret-ingredient.html
    https://bookmarking2123.blogspot.com/2019/11/a4-copier-paper-wholesale.html
    https://bookmarking2123.blogspot.com/2019/11/a4-copy-paper-manufacturers-in-thailand.html
    https://civilwarrx.blogspot.com/2015/11/mercury-and-water-two-civil-war.html
    https://bradyurology.blogspot.com/2014/02/alternative-medications-to-prevent.html
    https://brophysolicitorsimmigration.blogspot.com/2012/08/new-2-year-extension-for-students.html
    https://brunosblogm.blogspot.com/2019/10/new-testimony-further-links-indian.html
    https://build-its.blogspot.com/2011/04/how-to-fit-your-pc-in-power-mac-g5-case.html
    https://buyieltstoeflpteonline.blogspot.com/2020/02/buy-toeflpte-certificate-online-canada.html
    https://buytoeflcelpipptecertifcateonline.blogspot.com/2019/10/apply-for-celpippteielts-without-exam.html

    ReplyDelete
  41. This comment has been removed by the author.

    ReplyDelete
  42. Priyatakur is one of the hot and Independent Escorts in bangalore who offer the best escort service.
    She is a sex bomb and once you visit our site you can check her pictures. She is sexy, bold and beautiful as well.
    She has a sexy approach which you will never forget. Once you check our gallery you will be stunned.
    She belongs from high profile status and she just loves to enjoy her life with customers.
    As you will hire an independent escort service so you will never feel unknown. With her you will always feel homely.
    whitefield escorts ##
    Escorts in Electronic City ##
    MG Road call girls ##
    Russian escorts bangalore##

    ReplyDelete


  43. Buy top quality handguns, rifles, shortguns and other firearms and have them shipped discreetly to your address.
    We do same day shipment, and tracking information is provided as soon as shipment is made.
    All products come with manual and most of them are still in box but not all are brand new.
    These are not stolen and there’s a sales document issued for each.
    We also ship to an FFL for those who prefer it that way.
    Please feel free to visit our website https://www.legitarmsdealer.com/
    smith-wesson-mp-shield https://www.buycounterfeitbills.com/
    https://medicalpillsonline.com https://allbengalkittens.com/
    https://www.legitarmsdealer.com/ http://goldenretrievers.company.com/ https://www.parottdise.com
    https://capuchinmonkey.company.com/ capuchin-monkeys-for-adoption
    buy-african-grey-parrots
    golden-retriever-for-sale

    ReplyDelete
  44. https://buydacweedonline.com/product-tag/russian-pound-cake-strain/
    https://buydacweedonline.com/shop/delta-8-thc-online-for-sale/
    https://buydacweedonline.com/
    https://buydacweedonline.com/shop/glo-extracts-for-sale/
    https://buydacweedonline.com/product-tag/super-silver-haze-x-apple-juice/
    https://buydacweedonline.com/shop/moon-rock-strain/
    https://buydacweedonline.com/shop/buy-yang-krt-carts/
    https://buydacweedonline.com/shop/supreme-carts-for-sale-online/
    https://buydacweedonline.com/shop/london-pound-cake/
    https://buydacweedonline.com/shop/ice-capz-online-for-sale/

    ReplyDelete
  45. Thanks for sharing the best and informative article.

    ReplyDelete
  46. This is my very first time that I am visiting here and I’m truly pleasurable to see everything at one place. Your writing was good in every way. 4-aco-dmt.

    ReplyDelete
  47. Hi there,

    Thank you so much for the post you do and also I like your post, Are you looking for Buy Sleeping Pills Online in the whole UAE? We are providing Abortion Pills in Qatar, Where I can Buy Abortion Pills in Qatar, Abortion Pills For Sale in Riyadh, Ru 486 Cytotec in Riyadh, Buy Abortion Kit Online in Riyadh ,Buy Abortion Kit Online 2021 in Riyadh, Buy Abortion Kit Online in Qatar, Cytotec 200 Mcg kikolo Online, Abortion Pills For Sale in Bahrain, Ru 486 Cytotec in Bahrain, Buy, Abortion Kit Online in Bahrain, Abortion Pills in Bahrain, Cytotec 200 Mcg in Bahrain, Abortion Pills For Sale in Jeddah, Ru 486 Cytotec in Jeddah, Buy Abortion Kit Online in Jeddah City, Ru 486 Cytotec in Riffa, Where I Can Buy Abortion Pills In RIffa, Buy Abortion Kit Online In RIffa, Abortion Pills in Dubai, Cytotec 200 Mcg in Riffa,Cytotec 200 Mcg in ,Misoprostol in Dubai pharmacy, Abortion pills for sale in Dubai, Where I can buy Abortion pills in Dubai, Abortion Pills price in Dubai, Abortion Pills in UAE for sale, Abortion pills for sale in Ajman, Where I can buy Abortion pills in Sharjah, Buy Miferpristone and Misoprostel online UAE, Cytotec price in Dubai, Abortion pills Cytotec available in Dubai, Buy Abortion pills in Dubai, Cytotec price in Dubai, Abortion pills in Dubai, Mifegest kit in UAE with the well price and our services are very fast.

    Click here for title="Restoril - Online Plan Pharmacist"/>MORE DETAILS......

    CONTACT US
    Phone :+1 (443) 718-9645
    Email: support@healthsbiopharma.com



    ReplyDelete
  48. If you are looking to ORDER-WHOLESALE-LIVE RESIN | BUY-WHOLESALE-LIVE RESIN-ONLINE

    ORDER-DELTA 8 THC DISTILLATE | BUY-DELTA 8-WHOLESALE-PRICE-ONLINE

    Buy-Bulk-CBC-Isolate-Powder | ORDER-CBC-CRYSTALS-ONLINE

    For more infor please contact the following.....

    CALL/TEXT/WHATSAPP >>>>>>>>>
    +1(424) 235 3914

    EMAIL >>>>>>>>> support@420labextracts.com

    ReplyDelete
  49. HOW THE ILLUMINATI BROTHERHOOD HELPED ME BECOME SUCCESSFUL IN LIFE, BEING POOR OR SUCCESSFUL IN LIFE IS A CHOICE, IF YOU ARE BOLD TO TAKE THE STEPS YOU WILL BE SUCCESSFUL IN LIFE AND ENJOY WITH YOUR GENERATIONS



    How i become successful in life, I am so grateful today is because of the illuminati brotherhood. the Illuminati brotherhood continues to change my life day by day, hails to the illuminati brotherhood, i was deeply strangled up by poverty and i had no body to help me, and also i search for help from different corners but to no available, i have worked so hard to make it in life, i have done so many things in life, just to make it and live a happy life with my family, i do not know what to do next i was just thinking about my life, i see people around me getting rich but to me, i get poor everyday of my life, i start to think of what to do next just to get rich and live a good life, one day i think of going for research in google, and i say how many people giving testimony on how the illuminati brotherhood helped then to get rich and famous, so i think of joining the illuminati brother so that i can also get rich and be famous in life, because i have go through pains in life, so i make up my mind and decide to join the illuminati brotherhood, to my own believe i see my life changed for when i followed the process of joining the illuminati, the good news is that when i join the illuminati i was given amount of $2,000,000.00 USD to start a new life, i am so proud of myself and i am a great man today, because of the illuminati brotherhood, the mission of the illuminati brotherhood is to wipe away suffering and hardship away from everyone life. so if you are a business man/woman, an artist, a pastor, a working class, student and you want wealth,fame,protection,long life, prosperity just name it, the illuminati brotherhood is ready to help you achieve your dreams, if you live in America it is free to join the illuminati brotherhood, you have to email: churchofinitiationcenter@gmail.com WhatsApp call or text +16616664507 on how to join the illuminati brotherhood, join and see changes in your life.

    ReplyDelete
  50. Shop our selection of 1000mg disposable carts for sale delta 8 thc cartrdiges today!

    ReplyDelete
  51. This is an excellent post about Cannatonic Strain. Your work is greatly appreciated. Please keep it up.

    ReplyDelete
  52. Am short of words for the amazing profit you helped me earn in just a week with binary options strategy am so sorry I doubted at the beginning, I invested $200 and earn $2,500 in just one week, and kept on investing more, today I am financially successful, you can contact him via Email: (andersoncarlassettrade@gmail.com) whatsapp(+1(252)285-2093) I advice you shouldn't hesitate He's great.

    ReplyDelete
  53. Nice. Your Blog is quite impressive. You put valuable content and i got a lots of information. Cheap Weed

    ReplyDelete
  54. Thanks for sharing. Your blog is more informative. This is very nice article and very good information. We really enjoy your blog & content.

    ReplyDelete
  55. Thank you for posting this article.

    We at CarDotCheck propose a free VIN check so that you can get all the facts and information on the chassi of the car before going into the future.

    ReplyDelete
  56. Unique & best blog post i have ever seen in the internet. Buy fleshlight Online
    anal fleshlight

    ReplyDelete
  57. all the services you want are available at body massage in hyderabad, all the hot massage girl therapists here are quite capable of serving you to your heart's content, so don't think anything come fast and enjoy yourself

    ReplyDelete
  58. Massage can be adapted to suit various fitness levels, ages, and physical abilities. visit body to body massage centres near me

    ReplyDelete
  59. massage in chennai employ various healthcare professionals, including therapist, our therapists are expert of various spa so come and enjoy with our therapists, our therapists are provide best skin glow to your body with massage

    ReplyDelete
  60. pg slot co login สามารถทำได้ผ่านช่องทางต่างๆ ดัง1. เว็บไซต์ของ PG Slot: ท่านสามารถเข้าสู่ระบบผ่านเว็บไซต์ของ PG Slot ได้โดยตรง โดยสามารถสมัครสมาชิกได้ฟรี

    ReplyDelete
  61. looking for a non stop female to male spa near me 24 hours in bangalore with afforadable prices and mind blowing therapist.

    ReplyDelete
  62. we provide certified and experienced female therapist, they are talented for give all type of massage to you, so come and enjoy with our therapists

    ReplyDelete
  63. Nice blog post! keep posting just like as content. we are a Pharmacy Dropshipper. we ship medications around the world in bulk volume at best rate. kindly visit our website www.overseasdropshipper.com

    ReplyDelete
  64. For companies and marketers hoping to take advantage of the enormous potential that social media platforms provide in the Indian market, an smm panel india is an invaluable tool.

    ReplyDelete
  65. Spa services by our skilled beauticians are capable of pampering your skin in many ways with this you can enjoy different dates with them, all type of massage girl therapists are available at spa in hyderabad center

    ReplyDelete
  66. Terminate unplanned pregnancy upto 11 weeks of gestation. Buy Abortion Pills online USA at cheap price from our store.

    ReplyDelete
  67. I want to share with you my testimony of how I joined this great organization of the NEW WORLD ORDER, really I was so poor in my life that I was almost close to death, i tried many times to join but all was in vain, whereupon I was facing fake people who were claiming to be agents . They ate my money without helping me out there. I totally lost hope but because i was interested and focused on my dream, I continued trying there I meet another person who told me he will help me out still i didn't trust him at all because of the first pain i passed through, he still also asked me to send him money there i got scared but with time he sent me his membership id card,trust in him little and i accepted to send him money, but what amazed me is that immediately after sending him money for initiation items, i got initiated within 2hour onlines and i receive my $1,000,000 directly to my account there i trusted him more and he is the only agent i trust because he helped me seriously. So my friend, if you want to join contact him through whatsapp +2348180828544.

    ReplyDelete
  68. Cool and that i have a keen proposal: How Much Home Renovation Can I Afford home bathroom remodel

    ReplyDelete