Monday, February 18, 2013

Blog Syn #003: Benzylic Oxidation of Arylmethanes by IBX

(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.)

Update 2: 2/27/13 - Added Tamsyn NMR and email
Update 1: 2/25/13 - Added Phil NMR and email

Ref: Nicolaou, K. C.; Montagnon, T.; Baran, P. S.; Zhong, Y. L. J. Am. Chem. Soc. 2002124, 2245–2258.
Supporting Info

Experimenters: Three - B.R.S.M. and coworker (United Kingdom),  See Arr Oh (Somewhere, U.S.A.)

Recommendation: Pending Blog Syn repeat
Initial - Difficult to reproduce - little / no product observed or isolated.
*See below for Phil Baran's response and repeated reaction.



In Blog Syn's third installment, we examine a benzylic oxidation reaction pointed out by Chemjobber commenter Jose. Jose claims “0% conversion for multiple substrates with multiple chemists" using this reaction. The source paper is one of a four-part series penned by K.C. Nicolaou and Phil Baran describing the multitudinous uses of o-iodoxybenzoic acid (IBX) in organic synthesis. With Jose’s comment fully in mind, the Blog Syn Team members See Arr Oh and BRSM put the reaction to the test. 

A day in the library can save you a week in the lab, so let’s examine this paper’s impact using SciFinder: it's been cited 179 times from 2002-2013. Using the “Get Reactions" tool, coupled with SciFinder’s convenient new “Group by Transformation” feature, we identified 54 reactions from the citing articles that can be classified as “Oxidations of Arylmethanes to Aldehydes/Ketones" (the original reaction's designation). Of these 54 reactions, only four (4) use the conditions reported in this paper, and all four of those come from one article:  Binder, J. T.; Kirsch, S. F. Org. Lett. 20068, 2151–2153, which describes IBX as “an excellent reagent for the selective oxidation to generate synthetically useful 5-formylpyrroles.” Kirsch's yields range from 53-79% for relatively complex substrates, not too shabby.

Well, let’s see how things stack up for BRSM and See Arr Oh.


TRIAL 1 / 1a:


Experimenter: BRSM (and friend!)
Scale: 1 mmol (the paper claims 0.1 mmol to 1 mmol, without giving scales for specific entries. Used SI general procedure)
Example: 4-bromotoluene (table 5, entry 6)



Reagents: Aldrich fluorobenzene, 99%, borrowed and used as recieved;  Aldrich 4-bromotoluene, 98%, used as is; ACROS Extra Dry  DMSO, 99.7%  / AcroSeal'd bottle (almost new), IBX prepared according to JOC 1999, 4537, stored in freezer ~6 months. 

Observations:  A 1:1 mixture of DMSO:PhF was used at the suggested concentration of 1.25 M with respect to IBX as starting material wasn't soluble in DMSO. The reaction was carried out in a sealed tube that had been oven-dried for several days at 140 ºC and cooled under argon. IBX was found to be almost completely insoluble in this solvent system even at 90 ºC (Dry-Syn temperature). Stirred for 16 h, causing no apparent change to the white suspension. Worked up as described, except that saturated NaHCO3 solution was substituted for the 5% solution used by the authors. A white solid was recovered (177 mg). TLC after workup (20% ethyl acetate in petrol 40-60)  showed a faint new spot at Rf 0.5 that stained rapidly with KMnO4 dip without heating. 

Analysis: Crude 1H NMR showed trace product, with the balance being made up by starting material with traces of PhF and 2-iodobenzoic acid. As the mass recovery was good (177 mg crude back from 171 mg starting material) and the product aldehyde is not volatile (bp 240 ºC), it must be concluded that the reaction did not occur.



BRSM, crude NMR

Advice: As See Arr Oh and others have observed, the main problem with trying to repeat this work is the lack of an unambiguous Experimental procedure. Reactions were apparently carried out in either DMSO, or 1:2 DMSO:Fluorobenzene according to the paper, but the SI says that the ratio is substrate-dependent and that the reaction is faster if the amount of fluorobenzene is minimised. With such scant detail, it's pretty hard to say how precisely we repeated the reaction. Also, although I'm reasonably sure my IBX was good, I wonder what the authors used. As they don't state otherwise I presume that commercial IBX was used, if their general SI preamble is to be believed. I've never bought IBX, but I imagine it's packed out with lots of stabilisers, which might be important for the reaction. Would be interesting to try again with commercial IBX just to be sure.

Extra Credit: A lab-mate of mine tried a 1 mmol reaction on toluene (table 5, example 1), which was obtained from Fisher Scientific via our communal drying towers, using the same reagents and set-up as above. His tube was in the same Dry-Syn as mine, for the same time, and worked up identically. No colour change was observed and TLC against benzaldehyde seemed to indicate that no product had formed in the reaction before work-up. His crude NMR is a bit different to mine (presumably a lot of toluene was lost during workup and concentration), but still shows a serious lack of aldehydes. 

"Lab friend," toluene, with IBX

TRIAL 2: 


Experimenter: See Arr Oh
Scale: 1.0 mmol
Example: 2-methylnaphthalene (Table 5, Entry 10) 



Reagents: ACROS fluorobenzene, 99%, dried over 4A sieves; ACROS 2-methylnaphthalene, 97%, Alfa DMSO, 99.9% HPLC / ChemSeal bottle, IBX prepared in-house following JOC 1999, 4537, recrystallized, stored in freezer ~6 mos. IBX so prepared was active in enone dehydration reaction (see: Baran, Nicolaou ibid.)

Observations: Combined all reagents in oven-dried pressure tube under N2 stream. White suspension in 1:1 DMSO / fluorobenzene. Heated to 85-90˚C on sand bath. Suspension turns peach-orange, then deep yellow. Heated 19 h. TLC at 19 h shows faint spot at Rf 0.5 (5% MTBE / Hept). Workup: bicarb wash, extract with MTBE 3x, washed with H2O, dried over Na2SO4, concentrated to yellow solid, 220 mg.

Analysis: Crude 1H NMR: <5% product observed. 

SAO, Crude NMR

Advice: Supporting Information indicates a "substrate dependent ratio [of fluorobenzene:DMSO] with fluorobenzene conc. being minimized." My reaction never went completely into solution, despite attempts to sonicate / shake flask. It's possible that a different ratio of solvent may have promoted the reaction, but I'm skeptical.

SAO, Crude solid
SAO, Unreacted mixture


Author Response: Sent over by Prof. Phil Baran, Feb 10, 2013 (highlights mine): 

"...my recollection was that the IBX we made was ALWAYS completely soluble in DMSO at higher temperature (80 degrees I recall), and dissolved in DMSO prior to use in the oxidation reaction.. I always tried to do my reactions in pure DMSO. In addition, we never ordered IBX, it was always made freshly before use, ensuring that it was made with an internal heating temperature of 73 degrees Celsius to get the optimal yield and purity of product.  IBX quality was discerned by 1H NMR in DMSO prior to use. I'd recommend you try these reactions without the fluorobenzene, which was used with certain substrates that were not soluble in pure DMSO at elevated temperature.  


It's unfortunate that the SI was not clear enough for you and your colleagues to repeat it, but I can assure you that this reaction IS reproducible and was done independently by several highly qualified chemists within the Nicolaou laboratory prior to publication.  There might also be value in reproducing one of the substrates reported in one of the other literature examples that use IBX for benzylic oxidation (the 2006 Org. Lett., page 2151 you mention for example). In addition to the papers that use stoichiometric IBX others have found catalytic versions also capable of benzylic oxidation."

[Update(2/25/13) - Tamsyn Montagnon was indadvertently left off the original email chain.]

2/12/13
"It is right to suggest doing these reactions without fluorobenzene - I think a lot of the issue is that simple alkanes are pretty tricky in these reactions, because they aren't soluble in DMSO so you get little micelles floating on the surface and not reacting – ironically, this is a reaction that works better on more complicated substrates that have more functionality to assist in solubilizing them....FB certainly hinders the reaction (again probably a facet of creating almost a two phase reaction mixture)......and IBX is most certainly completely soluble in DMSO at RT, let alone elevated temps, anybody that has ever oxidized an alcohol with IBX knows this - IBA on the other hand is not, it crashes out during IBX oxidations and hinders the work of IBX (probably by being more Lewis acidic and sequestering non-productively substrate - if you add extra equivs of IBX once you have IBA in a reaction (in alcohol oxidations, dehydrogenations, benzylic oxidations whatever) you don't push it to completion you just end up with more IBA crashed out. The fact that they made a "Dess Martin" from their IBX means nothing ...God knows what oxidant you get if you heat up an IBX/IBA mixture in (Ac)2O."


TRIAL 3: 


B.R.S.M. (again) - We decided to re-run the reaction, given Prof. Baran's helpful suggestions.



Based on these comments, I decided that I'd have to remake the IBX fresh to their specifications in order to test the reaction properly. At first, I made IBX using the second procedure in the Oxone JOC paper (i.e. using 3 equiv. Oxone and a more dilute reaction mixture). I repeated the reaction on the scale (5g) and concentration given in the paper. On Phil's suggestion, I also used a thermometer and a great deal of time to ensure that the internal temperature was held at 70-73 degrees C. As promised, this batch contained no 2-iodobenzoic or 2-iodosobenzoic acid, but it did have around 5% of some other impurity I couldn't identify. The prep supposedly delivers 99% analytically pure IBX, so I was a little disappointed.

BRSM's new IBX batch

It's interesting to note at this point that the NMR data for IBX given in the Org. Synth. prep for Dess-Martin seems a little odd; two of the aromatic protons have coupling constants of 14.8 Hz, which seems inexplicably large to me. The chemical shifts given in the Org. Synth. prep do match the literature, but I can't find coupling constants given anywhere else for IBX to compare. Mine are not that large. Strange. Also, all batches of IBX I have analyzed by NMR have a broad peak around 10, which I'd always put down the the OH, but this doesn't seem to be mentioned in the literature. 

**This batch was totally soluble in neat DMSO at RT**

I checked my 2-iodobenzoic acid starting material by NMR - it was pure and free from impurities. I really wanted to make "perfect" IBX to give the benzylic oxidation a fair hearing, so I borrowed some 2-IBA and some Oxone from another group and tried again. I produced another batch, essentially identical to the first one, which is to say, ~95% pure by NMR. My colleague and I re-ran our benzylic oxidations on PhMe and 4-Br-PhMe with this "new" IBX. Based on the authors' recommendations we used neat DMSO. The IBX didn't dissolve immediately, although the literature (Tet. Lett.) says that it can take 10-15 mins stirring to go in. We starting heating straight after adding it and about 10 mins later, at an oil bath temp of 40 degrees C, we obtained clear solutions. 

In the case of PhMe, the results were similar, with perhaps a larger aldehyde peak in the crude NMR, although given the volatility of the toluene we couldn't really measure conversion accurately. Benzaldehyde was also visible by TLC, which it wasn't for the first run. My colleague attempted a column but no aldehyde could be isolated. For the 4-Br-PhMe (which I ran) the results were quite different from last time. The mass recovery was worse - only 100 mg back from 171mg, compared to perfect recovery last time - although the same scale and workup were used. Also, the crude NMR was messier and didn't seem to contain as much unreacted SM. Still apparently <5% aldehyde, though. And the literature boiling point is ~240 degrees, so I doubt I lost it. 


TRIAL 4: 


(Update: 2/21/13) See Arr Oh here again: noting suggestions made by Prof. Baran and various commenters, I re-set a 1.0 mmol reaction, this time in pure DMSO with 0.1 volume of H2O under a lab air environment. I observed the material going mostly into solution (60 degrees), and a lemon-yellow color evolved inside of 2 hours.

Checking the reaction by TLC at 12 hours, however (see Just Like Cooking) did not indicate a much better result than I had obtained previously. Perhaps, as suggested, my IBX is simply too old; commenters' suggestions to re-make a new batch, recrystallize, or test IBX by iodometric titration are all under consideration. 

I have heard that BRSM may be running the reaction with other co-solvents / conditions, so keep those fingers crossed!

*Author Addendum: One week after our initial post, Prof. Phil Baran wrote in with a successfully duplicated reaction and a much more elaborate experimental write-up. Below, I've reproduced his email and pictures in their entirety.


"I write regarding your entry on IBX oxidation of aryl methyl groups which your team found to be irreproducible.  I have subsequently had a student run this reaction under the published conditions and the results, documented with pictures of everything, are below.  I would like to mention that in the future it is very easy for you or any of your readers to contact me directly with any questions – those experiencing trouble could have emailed me anytime. Looking back on those days, well over a decade ago, I remember KC watching Yong-Li (one of the most incredible chemists I've ever worked with) and I do these reactions and us sharing TLC plates with him in our excitement. It was fun to do this reaction again and it brought back nice memories :)

Since your blog is quite new, I think it might be nice if in the future you give the authors a week or so to respond to claims of irreproducibility. After all, the paper has been out for over a decade so would an extra week hurt? You are, I suppose, in search of the truth. And the truth cannot always be realized with "Speed and Aplomb" as your blog advertises.  Incidentally, my colleague Jin-Quan Yu has also reproduced his reaction and sent you all the evidence that it is, in fact, completely reproducible (not "moderately" so as is stated on your website).  

I understand that your blog is meant to be helpful but you should also remember (as Yong-Li, a 10 year Merck Process veteran reminded me the other day) that many reactions have a "window" of reproducibility. In the current case it might be with regards to the quality of the IBX used (your spectrum of "good" IBX does not look very good - see attached for an example of what good IBX looks like) and the actual internal temperature employed.  If you are doing the reaction on something as volatile as toluene or 2-methylnapthalene then you must ensure that the entire flask, vial, or sealed tube is at 80-100 degrees or the SM will simply "hang out" at the the cooler part of the vessel. That's precisely why you and your colleagues saw little or no product because the SM was never actually exposed to the IBX (high or low quality it should have worked to some extent). Seems obvious in retrospect, and thats probably why it wasn't explicitly stated in the SI. That was our mistake.

Over the years my students have run dozens (if not hundreds) of literature reactions that either did not work in their hands or gave significantly lower yields of product than reported – before around 1995 many papers had no SI or procedures to speak of (except maybe JOC). I think all experienced organic chemists have seen this. That's why journals like Org. Syn. and Org. Proc. Res. Dev. exist. General procedures in an SI are mostly general guidelines. In the full paper we did give a number of examples of different conditions and it is up to the chemist to decide on the best ones for a given substrate (as the Kirsch group did in 2006 when they successfully oxidized several complex benzylic substrates at 110 degrees in DMSO with IBX).  

Your blog will remind the community of the importance of documenting even the most minute and subtle details and pictures of reaction setups of new reactions.  General procedures are clearly not always enough and, ideally, a Supporting Information should resemble an Organic Synthesis prep. Our group will certainly keep this in mind in the future and I suspect most of the academic community will too. And again, I am available day or night to anyone (anonymous or not) that has questions about anything I have co-authored.

Thanks for pushing the field in a positive direction.

Best Wishes,

phil

p.s. Tamsyn will also be emailing you again soon (you ignored her first email with suggestions) with her pictures of a reproduced reaction from a different lab.

–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

The following is the procedure, TLC, NMRs (of IBX, 2-methylnapthalene, and product), and reaction setup used for 2-methylnapthalene (the substrate that you obtained "0% yield" on).

To a 1.25M solution of 2-methylnapthalene (distilled, 22 mg) in DMSO/PhF (5:1) was added IBX (NMR spectrum attached) and the reaction was heated to 95 degrees for 24 hours (TLC performed with 9:1 Hexanes:EtOAc). The vial was wrapped in foil and submerged as low as possible in the oil bath to prevent the volatile SM from escaping.  As a control, if the reaction was done with pure DMSO and submerged only halfway, the napthalene refluxed at the top of the vial (confirmed by cooling it and watching the 2-methylnapthalene crystallize) and <10% conversion was observed since the reaction cannot take place if all reactants are not in solution.  After 24 hours the reaction was worked up exactly as described in the SI (using 5% NaHCO3) and extracted with EtOAc. A silica column was run and 16mg of pristine product (65%) was obtained.  I'm certain if this is done on larger scale and/or the solvent ratio is modified slightly a much higher yield can be obtained. This was essentially the first time (aside from the pure DMSO reaction) this student did this reaction and it will be the last."

SM

SM in DMSO-d6
Fluorobenzene

DMSO-d6

All SM before reaction.

IBX in DMSO-d6
Rxn, showing 95 deg C

Close up on oil bath w/vials

TLC

Final product

Final pdt NMR, CDCl3
*See Arr Oh here: We at Blog Syn thank Prof. Baran for his willingness to re-run the reaction, and for sending over visual evidence. Once we have a chance to run it in our hands with the improved conditions, we will reconsider the above recommendation.

Author Addendum II: Dr. Tamsyn Montagnon has also written in with a duplicated reaction. Below, I've reproduced her email and pictures in their entirety:

"You may want to consider the following:

[1] Good IBX really is NOT hard to make. It should be free flowing, crystalline with a definite sparkle. See attached 1H NMR.

[2] There is in your discussion a throw away comment about the 2-methylnaphthalene not being volatile. Have you never showered and then left your hair to dry at room temperature? – water evaporates at RT, just as 2-methylnaphthalene does at 95 ºC. I suggest to you that at the working temperatures of this reaction, the biggest problem may be substrate evaporation (or “hanging out” on the colder parts of the flask as Phil said).

[3] As Phil also said every reaction has a window. I think we can all agree that the window for this reaction is pretty narrow and that what you are seeking in your blog-site work are wide windows, ones that aren’t so sensitive to the many variables in play. This, however, is a more complex discussion than you are making out to be.

[4] We need fluorobenzene to reflux in these reactions and in so-doing wash substrate back into the reaction from the walls of the vessel, but it clearly slows/inhibits the reaction also – so, we need to tune this balance carefully and with patience. Scale will have a big influence on how well this process works.

[5] Likewise, IBX decomposes under the reaction conditions (heating in a DMSO solution) so again we have to balance this with the need for higher temperatures to initiate the reaction when trying to find the best conditions for each substrate.

[6] I also believe the method used in isolation of the products is critical here. The reaction by-products are solids onto which the products stick (these hypervalent iodine compounds are all very oxaphilic Lewis acids). Without care, the layers are hard to separate and material gets lost in amongst the solid residue and poorly separated layers.

Moving on to the test reaction I conducted this week. Unfortunately, I work in a lab with extremely limited resources and therefore I have encountered some problems; the most important being we have no fluorobenzene on site, a lag time of a month on all orders we place for chemicals and very little money for consumables. For these reasons, I had to conduct the reaction with benzene instead of fluorobenzene – as you’ll appreciate I kept the scale small, because I really wasn’t keen on large scale benzene refluxing. It has to be said though that it is rather an important 5 ºC at the given reaction temperatures that we are talking about here (benzene refluxes at 80 ºC and fluorobenzene at 85 ºC), but despite this I obtained significant product (in contrast to your claim of no product). I also used 1-methylnapthalene not 2-methylnapthalene because this is all that we had.

Photos are attached of all relevant reagents/ set up etc.

Otherwise, I carried out the reaction exactly as Phil described in his procedure except that I added the IBX (3 equiv.) in four evenly spaced portions (be careful not to open up a hot reaction and loose all the substrate in the course of these additions though!). Also, with regard to the work up, I prefer to extract with diethyl ether because EtOAc or DCM drag IBX/by-product residues into the organic phase. I also tend to filter through a small pad of celite (after addition of diethyl ether) to remove solids.

I obtained 27 mg, 48 % of the desired aldehyde (1H NMR attached) and recovered 20 mg, 40 % unreacted start material."



Starting materials
1-methylnaphthalene NMR

IBX NMR
Reaction setup

TLC, crude reaction

Pdt NMR, CDCl3
*We at Blog Syn thank Dr. Montagnon for her willingness to duplicate the reaction and for sending over visual evidence. We will incorporate her reaction into our final assessment.

Roundup:


This reaction clearly requires mojo. We observe a fairly substantial difference between the authors’ results and ours; a quick poll around the blogosphere suggests others also have trouble with this reaction. An unclear Supporting Info, a highly-variable reagent, and possible physical phenomena (IBX solubility, temperature control, etc) could potentially explain our experimental results. 

Given Blog Syn’s credo, we must deem this reaction Difficult to reproduce.

Thanks to B.R.S.M. (and friend) for synthetic runs, and for the second round based on Dr. Baran's advice. Readers, have you run this before, successfully? Please discuss your secrets in the Comments section.

217 comments:

  1. I tried this a few times, never got any product over 5%. We tried different people making the IBX, buying IBX, hell I think we even roped in another lab down the hall to see what we were missing.

    My PI just assumed it was b/c I wasn't super awesome like Phil. Oh well, maybe I will forward him this post.

    ReplyDelete
  2. MOAR! I actually learn something about organic chemistry.

    And really consider Kickstarter, or compatible, to cover your costs and get more people involved.

    ReplyDelete
  3. 1) I wonder about the role of water in this reaction. It may be possible that traces of water are necessary... so not so dry DMSO could be better.

    2) About IBX and Nicolaou... I tried once to reproduce the conversion from cheap cycloheptAnone to expensive 2-cyccloheptEnone. According to them (JACS 2002, 2245) is possible to do that step in 88% yield avoiding the cycloheptenDIEN-one. NO WAY. Conversion in each attempt (fresh and good IBX) was low and selectivity poor, so you end up having a tedious mixture of three cycloheptxxxones. When commenting that to my boss, he said "ah, yeah, we tried that in the past and didn't work at all". End-game: Sigma-Aldrich was happy to sell us our desired product.

    3) I must say as well that a colleague of mine could make her desired cyclooctaDIENone from the cyclooctAnone using this method. But she had to "get expertise"... IBX from second method of the JOC, adjusting equivalents.... etc. Presence of iodoso-species in IBX were not good for this reaction.

    ReplyDelete
    Replies
    1. And good to see you here Santi,
      This reaction is weird, but it (under some kind of magic condition) work.

      substitute magic with whatever variable come up in your mind

      Delete
  4. It'd be interesting if someone from Prof. Baran's lab who has done this successfully could post a successful run in the same "open lab book" format you use. Your efforts are interesting, but together with a successful reaction it'd be potentially quite instructive.

    (Obviously it may be that nobody from the Baran lab is reading this or has time, but a guy can hope.)

    ReplyDelete
    Replies
    1. We can hope! I really wanted this one to work; we did the first reactions over a week ago, but waited in order to test out Prof Baran's suggestions before going live. I made two new IBX batches for this post in order to give the reaction a fair trial. These reactions probably do work, but apparently not with the published proceedure. I'd love to know what we're doing wrong!

      Delete
    2. I assure you, they are reading this.

      Delete
  5. It's a relief to see this post. I tried to repeat this IBX oxidation in my grad school a few years ago. I freshly prepared my IBX through both means: KBrO3 and oxone. None gave me significant conversion with toluene as substrate. I ended up changing my synthetic route. My 2 cents: is it possible that some metal contamination in IBX helped the authors getting higher conversion?

    ReplyDelete
    Replies
    1. That's a very interesting question, given the recent surge in "metal-free" reactions that ended up having ppb levels of Cu and Pd in the bicarbonate bases...

      Delete
    2. Unfortunately Prof. Baran's suggestion to try the 2006 Org. Lett paper substrates/methodolgy is useless as that paper doesn't give ANY experimental detail other than a picture of the IBX oxidation w/ reagents, molar equivalents, and temps. The SI in that paper is silent wrt to the reaction other than showing NMR data.

      Delete
    3. Here's the link: http://pubs.acs.org/doi/suppl/10.1021/ol060664z

      Delete
  6. Keep up the great work guys, I think this is an extraordinarily valuable contribution to the chem blogosphere! And who knows, maybe Blog Syn will help authors think a little about the quality of their method sections and SI.

    ReplyDelete
  7. I think it is quite possible that the IBX used in Baran work was made by the old KBrO3 + H2SO4 route and contained bromide/bromate impurities. Br radical is quite a good agent to bring about benzylic bromination and oxidative solvolysis of benzyl bromides in DMSO with heating is a good way of making aldehydes. I would try to re-run the reaction in the presence of a) 20mol% of KBr b) 20 mol% of KBrO3

    by the way, KBrO3 alone is not too shabby for oxidizing benzylic positions as long as you rund the reaction at reflux in water during the day - sunlight is critical for starting the radical chain. Oxidation of undesired enantiomer of chloramphenicol base (to a racemizable aminoketone) with aqueous KBrO3 is done industrially, with floodlight illumination

    ReplyDelete
  8. IBX, prepared by the oxone prep (95% purity has always worked for me), or IBX-MPO is my standard for oxidation of ketones to enones and I have used it successfully multiple times on various substrates, although I never tried benzylic oxidation.
    Tips:
    As mentioned above, it needs water to react...I use wet DMSO. As Phil said, use only enough co-solvent to dissolve your substrate if DMSO won't do it. Also, IBX starts decomposing not much above 90 degrees...I try to keep my reactions at 80 or below. Finally, while milkshake may call me a wimp, the KBrO3 prep makes IBX that is shock sensitive.

    ReplyDelete
    Replies
    1. Anon (and Follower, below): Ah, the Schreiber paper: https://www.broadinstitute.org/chembio/lab_schreiber/pubs/pdffiles/193.pdf

      I don't doubt that water also accelerates the reaction, however, the SI explicitly states: "All reactions were carried out under an argon atmosphere with dry solvents under anhydrous conditions, unless otherwise specified."

      No one would doubt the value of trace O2 in the solvent for these oxidations, either...but, again, this doesn't jive with the SI as written.

      Delete
    2. Entry 3 in Table 5 of the paper shows that the addition of water (100 eq) has no effect on the reaction (same conditions w/ effectively the same yield as anhydrous conditions).

      A large number of chemist-hours have clearly been wasted by the synthetic community trying to reproduce the claims in this paper. I find it interesting that a decade later, there is not a single reported reaction in SciFinder which confirms the claims AND reports synthetic details.........

      Delete
    3. Actually ALL IBX procedures afford shock sensitive materials and should be treated with some degree of caution. I would never heat IBX that wasn't first dissolved in DMSO, and even then I would do it behind a blast shield. The commercial versions of IBX have stabilizers added to improve stability, but I would still be wary of heating IBX on anything but a small scale. It's been a long time since I've worked with IBX, but I seem to recall that you can make 0.2 or 0.3 M DMSO solutions of the stuff if you just stir at room temp for a while (~20-30 min). It's worth the wait.

      When I was a first year grad student in K.C.'s group we submitted an Org. Synth. prep on the room-temperature oxidation of TMS enol ethers to enones using IBX-MPO complex. (Interestingly enough, percent conversion in this reaction depended on solubility of your substrate in DMSO.) Our submission included the Oxone prep of IBX and during safety checking by some process chemists it was found that this "safe" IBX explosively decomposed during bomb calorimetry, taking the instrument with it. I recall that they also observed some shock sensitivity. Rightfully so, they refused to put IBX in their reactors from that point forward and our submission was ultimately rejected on safety grounds.

      I also know of a really bad accident that happened during the preparation of DMP from IBX on a large scale. The reaction violently erupted, shattering the flask and the suspected cause was the heating of undissolved IBX after the chemist's stirrer stopped functioning.

      Delete
  9. further to Santi Barrosso's comment I saw a paper a while back (possibly S.Schreiber?) where they reported a reaction that would only work with one batch of their DMP it turned out to be slightly wet so they ended up adding a minute amount of water and the reaction started working again with whatever batch of stock DMP they had, could be the case here? *speculation*

    ReplyDelete
    Replies
    1. no it is not the case, IBX is not acetylated. I remember that Schreiber group paper - nothing earth-shattering. People have been starting Dess-Martin with a drop of tBuOH much before, and what works even better for activation is a small amount of pyridine. (Pyridine also keeps TES ethers and other highly acid sensitive protecting groups from coming off by DMP)

      Delete
    2. yeah it really wasn't earth shattering! but just popped into my head. Cheers for the tips with the DMP heard of some of those before now I think about it...damn my brain!

      Delete
  10. Unrelated to this post, but I (and other chemists more technically talented than me) have had trouble reproducing the synthesis of O-(2,4-Dinitrophenyl)hydroxylamine as reported in this paper: http://pubs.acs.org/doi/abs/10.1021/jo034456l.

    According to the paper, the product is made is >90% yield and excellent purity upon deprotection with hydrazine. I was never able to reproduce this result after trying about a dozen times using the original procedure and various modifications (source of hydrazine, etc.). I'd love to know if it was just us me being a crappy chemist or if there was something truly wrong with the reaction/procedure.

    This reagent was also used in Kurti's recent paper (http://pubs.acs.org/doi/full/10.1021/ja309637r) on amination of boronic acids (although they have a commercial source for their reagent).

    ReplyDelete
  11. Hot Diggity Dog! I am exceedingly glad to see these results- they are wholly consistent with ours, it's good to know we weren't hacks. If the reaction works, I suspect it is a due to trace impurities in the IBX; good for a follow-up paper if anyone is in the market! The paucity of refs for reactions using those conditions certainly says something....

    ReplyDelete
  12. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678-2720.

    "In the midst of their desperation and hope,
    Yong-Li Zhong and Phil postulated that raising the temperature
    might persuade the lactol to reveal its primary alcohol,
    thus rendering it susceptible to oxidation by DMP. They
    proceeded to design, in complete secrecy (from K.C.N.), an
    experiment in which hydroxylactol 132 was to be heated in
    refluxing benzene with excess DMP! It is fair to say at this
    junction that had they informed me of their intention to heat
    DMP at such temperatures, I would have most likely
    instructed them against this course of action in light of the
    assumption that DMP could possibly be explosive at high
    temperatures. Their plot was, therefore, perfect and they got
    away with it..." "...That was when I (K.C.N.) heard
    about their daring escapades with high-temperature DMP
    oxidations. In retrospect I am, of course, glad that I did not
    interfere with this part of the expedition which brought us
    within striking distance of the ™Minotaur" the CP molecules"

    "Upon increasing the
    reaction temperature to 90 C, remarkably efficient conversion
    to 215 was observed. In fact, this result was initially
    received with considerable skepticism by one us (KCN).
    Could it be that inadequate experimental technique led to this
    bizarre finding or had we discovered another unique reaction?
    And how is it that no one had ever reported such
    reactions with iodine(v )-based reagents or hypervalent iodine
    compounds in general? It was time to consider this issue from
    a more global perspective."

    ReplyDelete
    Replies
    1. Perhaps you didn't pay enough to Charon to get across the river to the land of reactions, that laboratory in the sky, where the yields are always 100% and they are all reproducible.

      Delete
    2. In Ancient Greece there were slaves that worked long hours for their masters. Their role was to please the masters as best they could, some having intentions to be masters one day. Sometimes a didactic intercourse was set up with these slaves but that failed to resolve the issues. Other slaves would then respond, mostly with wild speculations. However like one eyed Cyclopses they failed to root out the issue, as like the masters' slaves they were blinded and did not look at the broader system at work.

      Delete
  13. This is totally outside my expertise, but the fact that something weird is going on with IBX before you even use it seems to be a red flag. Figuring out the explanation might give you the answer and would probably be worth doing in any case. (Could this have anything to do with tautomerism of IBX?)

    ReplyDelete
  14. How lucky I am to come across your website on a reaction which I have been trying to attempt during my work. I have a nitrated benzocycloheptenone which I thought could be a trial to see if I can achieve selective benzylic oxidation (that was the primary aim). After doing the initial reaction with 3 equivalents of IBX, using a small amount of fluorobenzene in DMSO (not dried or anything) at around 88 deg C over two days I landed up with something. After further investigations, we concluded that we had a benzotropone. We also tried this reaction with a phenol group installed on the benocycloheptenone. The reaction seems to give similar results (yet to be fully investigated). The Nicolaou paper also delves in enone formation, so I assume that is what is happening in my substrate rather than benzylic oxidation. Hope my two cents about this reaction helps....Looking forward to hearing from others as it would be really interesting for me if this reaction works either ways...

    ReplyDelete
  15. This is a wonderful blog, thanks for all your work! Are you planning on doing some reactions that you expect to be reproducible or is this blog only for dodgy stuff? I really hope that it's the former; this could show how well written and helpful the supporting information can be!

    ReplyDelete
    Replies
    1. Dear Anon - No, we'd like to expand the blog to include anything reproducible. The Blog Syn mission isn't to chastise or condemn, only to ensure that a prep performed in your lab works just as well in mine.

      If you have any reactions to suggest, please don't hesitate!

      Delete
    2. I would like to see those palladium catalyzed cyanation papers that claim to use DMF as cyanide source being reproduced...

      Delete
  16. I think gippgig is on to something. Inconsistency in the dissolution behavior of the IBX makes me suspicious.

    The Org Syn prep contains a footnote describing the iodometic titration of the reagent to determine its activity. Might be worth checking the activity of your IBX via that method before each reaction to ensure it has not degraded, as Baran did note in his response they used freshly prepared stuff.

    Inconsistent dissolution behavior could also indicate distinct crystal forms of IBX, which may have different solubility properties. Looking at the Org Syn and JOC preps, there's nothing to dismiss the possibility that you don't get different crystal forms of this reagent via the cooling crystallization.

    I worked with with iodosobenzene (PhI=O) for a while and remember that its structure was polymeric as a solid. To get it to do the reaction I needed, I had to add MeOH to break the poolymeric structure and form PhI(OMe)2. Could also be that IBX has some polymeric versus monomeric character that is poorly controlled in the IBX prep, resulting in variable activity in reactions. In those cases addition of water may be critical to controlling solubility or reactivity of the IBX.

    So many variables, so little time. Fun to speculate though.

    ReplyDelete
    Replies
    1. Also, what about titrating your "failed" reactions? Do you actually have active IBX left?

      Delete
  17. Here's a procedure I recently used that worked exactly as advertised: Nakamura, et al. JACS 2012, 134, 19366-19369. Starting material was easy to prepare, ligand was available in 1-2 steps, and I used materials right out of our stockroom without further purification. Products could be very useful for the synthesis of chiral catalysts. The procedure worked just as well on >1g scale as it did on the smaller reported scale.

    ReplyDelete
  18. Can someone post a balance chemical equation?

    ReplyDelete
  19. Maybe we should consider an alternative iodine(V)-based oxidant: Look in Zhdankin et al., JOC 2005, 70, 6484. To make it, all you need to do is (1) take 2-iodobenzoic acid and make the acyl chloride, (2) make the isopropyl ester, (3) stir the ester in a mixture of DCM/concentrated bleach/dry ice and stir overnight. I made (and still have) gram quantities of the oxidant in less than two days. The oxidant has two I-O double bonds, if you were wondering. (I haven't verified how potent or pure the oxidant is aside from NMR, but I did effect the oxygen-atom transfer of iron(II) compounds with this reagent, and it gave a similarly clean result to iodosobenzene.)

    This paper has some interesting insights. One, they can oxidize alcohols to ketones or aldehydes...with a catalyst of TFA, BF3.Et2O, or KBr. (Milkshake's bromine-based oxidant hypothesis above seems intriguing here). Two, they suggest ligand exchange is important; TFA likely generates a trifluoroacetate-iodine(V) reactive species in the catalysis. Three, the solubility of the oxidant is much better than iodosobenzene since it is no longer a polymer, and they have appreciable solubility in chloroform and acetonitrile.

    Anyway, maybe I'll try some of this chemistry with Zhdankin's reagent. (I'm not even an organic chemist, but who cares, trying chemistry outside my project once in a while can be fun.)

    ReplyDelete
  20. A couple thoughts --
    with these 'small' starting materials might it be better to try sealed tube?
    as Baran points out you may be losing the starting material.

    can you use KI starch strips to check oxidant?

    ReplyDelete
    Replies
    1. Just be careful - IBX is explosive at elevated temperatures.

      Delete
  21. Very decent of Prof. Baran to contribute and show us where the problem is. I regularly do a reaction in a sealed vessel and didn't even realise it may need to be fully submerged. Learn something new every day.

    Perhaps in future a photo of the reaction set-up ought to be included to help identify problems like this?

    ReplyDelete
  22. Are you kidding me? That procedure has nothing in common what-so-ever with the original publication. Via what route was the pristine via-NMR IBX made?? Can someone still in a lab run p-bromotoluene (bp= 184 -185 C!)? I have run hundreds of sealed-tube reactions and reflux on the tube walls has always been sufficient....

    That said, I am exceedingly impressed Phil B was so conscientious and forthcoming, and it clearly illustrates his research ethics which in my experience are far, far from the norm. He should be truly and honestly commended for that. I am also exceeding sorry for precipitating what must have been a truly hellish week for that grad student- mea culpa!

    Glad to see that Blog Syn had made a significant addition to the literature, and look forward to more of the same.

    ReplyDelete
    Replies
    1. Chemists greatly pride themselves in their work and admitting faults is tough, but still, redemption can be a bitch and having to do this at all is sad.

      Delete
    2. Hellish week? The reaction is dump and stir. If you follow the above procedure with good IBX it will work. The 2-methylnapthalene doesn't need to be distilled. It can be used straight out of any decent bottle--that stuff is a rock. Same goes for the DMSO and fluorobenzene. I didn't know what to believe so I just ran it myself last night. My colleague also reproduced it with a different bottle of IBX. idk why it didn't work the first time.

      Delete
    3. Dear Anon 9:37 - Perhaps you could send over a write-up and pictures of your successful reactions. I would be glad to have another potential collaborator.

      Delete
  23. 'Pristine' IBX can be made by the published route (J. Org. Chem. 1999, 64, 4537-4538) but-as this blog is a testament to-the real procedure is slightly modified:

    IBX (>99%, 1HNMR, EA)

    2-iodobenzoic acid (5.0 g, 0.20 mol) was added to an aqueous solution of Oxone (37.2 g, 0.061 mol, 3 eq, 200 mL) in a 0.5 L flask. The suspension was set to 70 °C (internal temperature). Care must be taken to keep the internal temperature below 72 °C. The suspension was stirred for 2 hours then removed from the oil bath and cooled slowly to room temperature. Once at room temperature the flask was cooled to 0 °C for 1 hour by an ice bath. The solid formed was filtered, washed four times with 100 mL of ice cold water, then washed two times with 100 mL of acetone. The resulting solid was dried under vacuum to provide IBX.

    Key details: -unlike the paper reports, the reaction is not complete in 1 hour and you should stir for 2-2.5 hours
    -even slightly elevated temperature (75 degrees or so) produces byproducts

    I've scaled that up to 50g with the same purity of IBX obtained on all occasions. IBX made this way was also used by Anon 9:37 and his coworker successfully.

    IBX NMR: http://postimage.org/image/ri2sievv7/

    ReplyDelete
    Replies
    1. Thank you for the input. I'll run mine this way in the future.

      Delete
    2. I can confirm this. Exact same reaction, 20 mmol scale, 71.2 C internal temp. I ran mine for about 5 hours, cooled it to 0 C for 15 min, washed with room temp water and acetone. 78% yield, and that's with some slipping through filter paper, and some getting sucked up by the high-vac (I was in a bit of a hurry ha..)

      Proton NMR: http://s23.postimage.org/dhqcyu1p7/IBX_HNMR.jpg
      Zoomed In: http://s24.postimage.org/at8vunjfp/IBX_HNMR_zoom.jpg

      Delete
    3. Actually, Anon, note that your IBX looks a lot like BRSM's IBX. It's "dry" IBX...see what happens by NMR when you add 1 drop of H2O. (answer: it starts to look like Phil and Tamsyn's).

      I think there's a lot more at work here than we think. Check back here later for our updated assessment.

      Delete
    4. Anon 4:35 here.
      I'll rerun proton with H2O and D2O tomorrow and see how it turns out. I have noticed some differences, namely splitting patterns. I'm also doing a couple runs with 4-bromotoluene per Prof. Baran's comments. Tried these reactions about 5 months ago and failed, so I have somewhat of a vested interest in this. I'll email with data/results/photos.

      Delete
  24. What does the vapor pressure of 2-methylnaphthalene need to be in order to be entirely volatilized 150 degrees below it's boiling point? Does it sublime? Does anyone really have an oil bath deep enough to run a 200 mL reaction like this? Ironically, this may work better on more complex substrates, like Baran's student suggested, both because they're more soluble in DMSO, and they're less likely to vaporize, but most people wouldn't be willing to try because it didn't work in the model system.

    The prep for IBX reminds me a lot of making dibutylboron triflate. You needed a crazy strong vacuum, because you started to see impurities come in at higher distillation temps. That meant a well maintained pump, and using copious amounts of teflon grease and clamps to seal the (massive) apparatus. The good stuff was water white and froze at ~-10C, but most people couldn't get there.

    ReplyDelete
  25. Hello guys,
    Thanks a lot for doing this and bringing attention to the issue of reproducibility.

    I have one suggestion. Given you do not write now posts on a reaction but rather update the existing one, would it be possible to somehow indicate the updated parts? Perhaps, some kind of color variations or nested "update boxes". A label like "version 3, 28/02/13" at the beginning would be also useful.

    ReplyDelete
    Replies
    1. A very fair assessment. I've added an "Update" statement at top, and will figure out some way to differentiate the headings. Thanks!

      Delete
  26. i think phil baran and his lab deserve a large amount of praise for this, as do the folks behind blog-syn (though that should go without saying). it's hard to imagine a more positive outcome than an independent group trying to reproduce notoriously tricky reaction, failing, and then getting detailed notes from the experimentalist that elucidate how to successfully run such a reaction. it was their own "mojo" that got them into this situation in the first place, but this is peer review at its best (better than jacs, obviously).
    as an overarching point while i appreciate the full and non-vitriolic response from baran and his lab, this should be more cautionary than redemptive. get it right the first time. and second time, and third time.
    on a separate note, i agree with baran that the experimentalists should have a reasonable time to respond; for better or worse, blog-syn in its early stages is a tribunal, so should hear the case of the defendant before passing judgement to the internet people.
    please, keep em coming.

    ReplyDelete
    Replies
    1. Aaron - Thanks for the constructive feedback. As the risk of going in circles, I left a comment on Pipeline that bears repeating: for Blog Syn #002 and #003, we reached out to the authors very early in the process. I sent emails to Profs. Yu and Baran on 1/29/13, and their posts went live on 2/12 and 2/18. Is 2-3 weeks "unreasonable?"

      Thanks,
      SAO

      Delete
    2. any chance i can get my last name removed there? autocompleted.

      Delete
  27. Kudos to blog syn et al. That being said, I would like to comment on the idea that the original authors should be able to respond to blog syn before a post goes live. If this is done, I think the original post and the author response should go live together. I do not think blog syn should have to run a method, ask the original group what they think, take pointers, try again, and then make a first post so to speak with pointers from the authors. If this is truly a vetting of important procedures, shouldn't the procedure as written in the SI be tested on its own with amendments added later? I realize that could seem a bit vindictive but it may also globally improve the state of SIs if people know their original procedure can be validated (or not, as the case may be) using the words as written with all amendments noted after the fact. I'm a big fan of testing methods and global improvements in SI.

    ReplyDelete
  28. (Jose, as anonymous):

    Damn nice work! It is ironic that we were *too* rigorous in our trials and therefor pooched the rx.... good to know for the future!

    ReplyDelete
  29. I think Anon 7:57 has a fair point. By publishing the original article (which leads to the idea of irreproducibility), a fair number of people will have that idea stuck in their heads. I feel that it is incomplete at this stage and could be left until the authors respond and you give it another try. While this would require longer times for each post, I feel like there would be less confusion and a complete "story" to each reaction.

    ReplyDelete
    Replies
    1. Dear Anon7:38 - I believe Anon7:57 was actually arguing the counterpoint.

      Again (not to repeat myself overmuch) we have ALWAYS reached out to authors long before we publish a post. Lead time for #001 was only 1 day, but we learned better, and gave Profs. Yu and Baran >2 weeks to respond.

      There's no guarantee that each professor we contact will choose to repeat the reaction in their hands vs. just giving advice, so we publish posts after we've 1) heard back from them, and 2) attempted (once) to "re-do" the reaction.

      Delete
  30. They deposited some gear for summit-push and returned to lower camps. https://www.fiverr.com/sabakhan695

    ReplyDelete
  31. I ma very pleased to find a post on Benzylic Oxidation of Arylmethanes by IBX, since its a post that i haven't been privileged to view before. I find the information quite explicit, very professional and helpful. It would a great thing to keep sharing the same kind of information. With the best Online Sales Development Help, you will surely make your business prosper while facing less or no fierce competition. We are experts that provides the most genuine, quality and professional services.

    ReplyDelete
  32. We are providing best Medication Delivery and Sleep Apnoea Clinic at chemist works. Contact us CHEMISTWORKS BROADWAY, 8am - 10pm, 24*7, t: +61 2 9212 4377.Sleep Apnea Clinic

    ReplyDelete

  33. Hey, Wow all the posts are very informative for the people who visit this site.Good work!We also have a Blog.Please feel free to visit our site. Thank you for sharing.
    how to deposit money into perfect money
    Keep Posting:)

    ReplyDelete
  34. What a great nice and educative blog
    You may also be searching buy research chemicals - black tar heroin-online
    Contact US

    Pnone:- 4013083901

    Email:- info.standarddrugs@usa.com

    Wickr:- drubybay1010

    Website :-https://standardpharme.com/

    ReplyDelete
  35. Love it! Very interesting topics, I hope the incoming comments and suggestion are equally positive. Thank you for sharing this information that is actually helpful. You know you are purchase from Discover Credit Card?

    ReplyDelete
  36. Thanks for share great info. This article is very informative and helpful to me. Thanks
    Indiancallgirlsinmalaysia.com Give u best escorts girls in Kuala Lumpur Malaysia. I' ll give u brilliant escorts in Malaysia, Indian escorts in Malaysia and much more

    ReplyDelete
  37. Buy 5c-akb48 Poland from Chemonly.com a highly reputed store for chemonly.com. at affordable price.

    ReplyDelete
  38. We have all that you may require. Every one of us have the best escorts that you can get in your so don’t hold up and pick your booking with every one of us, as just our Escorts Services in Islamabad is as well as can be expected satisfy what you are really searching for procedures not hold up and join with and figure out how to make your booking with us.
    In the event that territory in Islamabad and paying special mind to escorts In Islamabad, Top Escorts services in Islamabad then you have one decision left that is to lease Islamabad Escorts Services are on high of various Call Girls in Islamabad. Islamabad is that the capital of Islamic Republic of Pakistan in this manner we tend to center that we will give you high Pakistani Model Escorts Services in Islamabad there. We day by day meet with totally unique nationalities people subsequently perceive the style of each person. You can just benefit Islamabad Escorts or Islamabad Call Girls because of square measure. they a great deal of brave and hot and can bunk from there for you, Islamabad escorts can play on the bed with you basically in five-star structures because of thy get their sexual powers a considerable measure of in inn rooms than to individual places. Our Islamabad Vip escorts square measure perfect spotless, amazing and has form sense to show up a ton of sizzling. people who square measure attempting to have fun with Drama player and high incline models in Islamabad haven’t any should stress because we will give you VIPs on premium premise. we have tremendous skill in giving escorts in IslamabadEscorts services Islamabad from various escorts offices.

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

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

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

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

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

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

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

    ReplyDelete
  46. buy alprazolam,ketamine,mdma,crystal meth,fentanyl at shop4herbalincense.com

    Order Fentanyl, Oxycodone , Xanax Bars , Percs , Roxicodone at low cost..With us , you get meds discreet with no prescription. We've worked to create a fast,
    efficient and fair system for order processing. We know you want your order quickly, at the lowest possible cost.Check some of our highly purchased meds;

    We are the best supplier of pain medications and research chemicals .our prices are affordable .
    For more details contact our website through any of the details provided below
    Management

    Visit: shop4herbalincense.com


    Call: +1 (925)-338-9583 (USA/Canada)

    whatsapp: +1 (925)-338-9583

    ReplyDelete
  47. buy alprazolam,ketamine,mdma,crystal meth,fentanyl at https://shop4herbalincense.com

    Order Fentanyl, Oxycodone , Xanax Bars, Buy research chemicals
    Percs , Roxicodone at low cost..With us , you get meds discreet with no prescription. We've worked to create a fast,
    efficient and fair system for order processing. We know you want your order quickly, at the lowest possible cost.Check some of our highly purchased meds;

    We are the best supplier of pain medications and research chemicals .our prices are affordable .
    For more details contact our website through any of the details provided below
    Management

    Visit: https://shop4herbalincense.com


    Call: +1 (925)-338-9583 (USA/Canada)

    whatsapp: +1 (925)-338-9583

    ReplyDelete
  48. Haridwar Escorts administrations with an ideal degree of polished methodology that necessities to keep up a stage for the right qualities. Haridwar is known as our escort administrations. Escort administrations with an abnormal state of accommodation and solace to give administrations, we are constrained to our urban communities in Haridwar. Ewscorts service in Haridwar what they are and what they are great.
    Haridwar Escorts
    Haridwar Escorts
    Haridwar Escorts
    Haridwar Escorts
    Haridwar Escorts
    Haridwar Escorts
    Haridwar Escorts

    ReplyDelete
  49. Every Pathankot get touching females is well offered as well as qualified and seen by partner and cell phone woman profession so they will come across 100 % s to our useful clients by offering their best solutions.
    Follow us:-
    Vip Pathankot Escorts
    Pathankot Escorts Service
    Pathankot Escorts
    Call Girl in Pathankot Escorts Service

    ReplyDelete
  50. Escort agencies in Mcleodganj are plenty but ensure you book via high class escort agency in order to get the best independent escorts in Mcleodganj . Our name fits us perfectly and our many regular clients would second that too. Top Mcleodganj Independent Escorts can be found in an elite escort.
    Follow us:-
    mcleodganj escorts
    Vip Girls In mcleodganj

    Call Girls In mcleodganj

    Escort service In mcleodganj
    Vip Girls In mcleodganj

    ReplyDelete
  51. We can ensure our customers to get the modern, reliable and lovely Call Girls In Goa our office. There are a few escorts who realize that how to manage the clients and give them benefits that are fulfilling. Thusly, individuals all through the city can be guaranteed about getting the arousing administrations out of our Goa Escorts
    Goa Escorts
    Vip Escorts In Goa
    Call Girls In Goa
    Escorts Service In Goa
    Goa no. 1 Escorts Service
    Best Goa Escorts
    Goa Escorts

    ReplyDelete
  52. The town of Development and rishikesh is likewise famous for its biryani rishikesh town has its all records, that is very old city of India and it has its personal dignity individuals .
    Follow us:-
    Vip Call Girls In Rishikesh
    Rishikesh Escorts
    Escorts Service In Rishikesh
    Rishikesh Escorts
    Escorts Service In Rishikesh
    Call Girls In Rishikesh

    ReplyDelete
  53. Once the services stipulations females partner and cell phone woman Dehradun more attention in Dehradun partner and cell phone woman assistance, it should be the first choice category.
    For more information
    Dehradun Escorts
    Hyderabad Escorts
    Escort Service in Rishikesh
    Vip Escorts Service in Mussoorie
    Haridwar Escorts Service

    ReplyDelete
  54. Are U searching a Top Model Escorts in Malaysia Contact to +60182600361 Provide a Best Model Escorts Services in Malaysia.
    Call girl's in Malaysia

    ReplyDelete
  55. You should just call and arrange a meeting with Jaipur escorts. You will be treated with passion and happiness – all respected clients are serving with the most intense regard. This implies you don't require to tension over your disrepute being infected. Note that most young females are autonomous call girls Jaipur.
    Udaipur Escort
    Malviya Nagar Escort

    ReplyDelete
  56. Best VIP Escorts Service in Islamabad & Karachi
    Call Now Mr: Arman 03004111461 and Visit our Sites:

    Islamabad Call girls

    Call girls in Islamabad

    ReplyDelete
  57. There are various types of Chandigarh Call Girls involved with this industry. There are many married women who like to spend quality time with men in order to escape their isolation and loneliness, apart from single women. There are dissatisfied housewives in the community and newly married Call Girls in Chandigarh. Women are looking for companionship because their husbands are living abroad or are not happy with the strength of their husbands. There are a couple of women who leave their homes as soon as their husbands leave them in the house alone to work in their offices.

    ReplyDelete
  58. Welcome to Greater Noida globe of amazing hotties! Greater Noida is your one-stop destination to book high-profile autonomous Greater Noida Escorts Service, providing the finest adult entertainment service for all those seeking enjoyment in this town. We cater to the sensual needs of tourists, professionals, businessmen and industrialists with a carefully selected team of beautiful, stylish and sophisticated beauty. Our escorts are the industry's true gems. They're happy, exuberant, and lively. They have a knack to discover fresh sensual fun limits, and to their highest satisfaction please individuals.

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

    ReplyDelete
  60. The smart and modern people go for the Mcleodganj escorts that are available at our Escorts to fulfill their fantasies in the way they want.
    Follow us:-
    Call Girls In Mcleodganj
    Mcleodganj escorts
    Mcleodganj Escorts Service
    Vip Call Girls In Mcleodganj
    Escort service In Mcleodganj
    Mcleodganj Escorts

    ReplyDelete
  61. Thanks to Author this is finest blog on Benzylic Oxidation of Arylmethanes for me, I have read this blog fully Excellent article and its information I really like this kind of post I also recommended this to circle, currently we are providing our escorts services in Nainital Escorts, Dehradun Escorts and Mussoorie Escorts , if you are intrested kindly visit and have fun.

    ReplyDelete
  62. I've found here a lot of interesting information for the knowledge I need. all that you provide for us, it was very valuable and supportive, you shake for sharing this astonishing post.
    Chandigarh Call Girls |
    Mohali Escorts |
    Zirakpur Escorts |
    Panchkula Escorts |
    Ambala Escorts |

    ReplyDelete
  63. It's craftsmanship to offer mind boggling satisfaction in lovemaking. Our model escorts are able to do such things. Jaipur Escorts Service is the best. Its pre-play session or getting a charge out of intercourse in different positions. Do you have the opportunity to appreciate the provocative image of Jaipur Call Girls models? Yeah, without a doubt, your answer will be. Our escort demonstrates that the most smoking miracles will be offered by Jaipur.
    Udaipur Call Girls
    Malviya Nagar Call Girls

    ReplyDelete
  64. If you want to hire a beautiful college girl, you have to convey this message to us so that we can send these college Dehradun escorts at your service.

    ReplyDelete
  65. If you are not alone and want to spend time, then you can rent the Chandigarh escort service. I believe that there is no better option than this.

    Chandigarh call girls
    Amritsar escort service
    Dehradun escort service
    Jalandhar escort service

    ReplyDelete
  66. I love reading your articles and I shared it with my friends.People also like it and give good feedback. Thank you.
    cheap call girls in chandigarh offers the fantastic call girls services like anal and oral sex with beautiful girls.

    ReplyDelete
  67. Nisha Sharma is an russian escorts with high profile here for your entertainment. call girls provides best escort service @ cheap rates.

    Pune Escorts
    Pune Call Girls
    Goa Call Girls
    Call Girls In Goa

    ReplyDelete
  68. They are always arranged to supply all sort is escorts of ajmer. If you have to get ajmer hot young ladies, you may chase down the web and around then you may see the photographs of the escorts that you suit better
    Follow us:-
    Ajmer Escorts
    Ajmer Escorts service
    Call girls in ajmer
    Vip escorts in ajmer

    Ajmer escorts
    Ajmer escorts service
    Call girls in ajmer
    Vip escorts in ajmer

    ReplyDelete
  69. In any case, most of the spots are not known not in time of the delight go of you, you should take the office of the escorts. These escorts are not like the assistant of you they are the extraordinary and decent master office of you anyway by exciting the gathering people in patna with a decent way.
    Follow us:-
    Patna escorts
    Patna escorts Service
    Call girls in Patna
    Vip escorts in Patna

    ReplyDelete
  70. Sometime few educational blogs become very helpful while getting relevant and new information related to your targeted area. As I found this blog and appreciate the information delivered to my database. Johor Bahru escort model service

    ReplyDelete
  71. Priyanka Bajaj Escort Service in Chandigarh is easy to get Chandigarh Escorts as we have lots of beautiful female Escorts who are ready for pleasure and erotic fun with clients to enjoy and exchange love between them to earn little bit of money for daily life style.
    Follow Us:-
    Chandigarh Escorts
    Chandigarh Escort

    Independent Chandigarh Escorts
    Chandigarh Escort Service

    VIP Call Girls In Chandigarh
    Chandigarh Call Girls

    ReplyDelete
  72. A1 Mcleodganj Escorts to hire Independent Call Girls in Mcleodganj available 24*7. Meet our female Escorts in Mcleodganj to try luxury escorts satisfaction.
    Follow us:-
    Mcleodganj Escorts
    Call Girls In Mcleodganj
    Mcleodganj escorts
    Mcleodganj Escorts Service
    Vip Call Girls In Mcleodganj
    Escort service In Mcleodganj

    ReplyDelete
  73. Book the best high profile Indian, Russian escorts in Dehradun in no time! Call us for photos and videos of sexy call girls in Dehradun on WhatsApp for selection!
    Follow Us:-
    Dehradun Escorts
    Dehradun Escorts
    Dehradun Call Girls
    Independent Dehradun Escorts
    Dehradun Escorts
    Dehradun escorts services
    independent escorts in Dehradun
    Dehradun Escorts Service

    ReplyDelete
  74. Nice blog and nice pictures. This type of work needs so much hard work and engineering skills. Thanks for sharing. I am looking forward to see more posts from you. Islamabad Escorts

    ReplyDelete
  75. 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
  76. Hi, I am really glad I have found this info. Today bloggers publish only about gossip and net stuff and this is actually irritating. A good blog with interesting content, this is what I need. Thanks for making this website, and I will be visiting again. Do you do newsletters by email? Vedic Astrologers

    ReplyDelete
  77. Professionally written blogs are rare to find, however I appreciate all the points mentioned here. I also want to include some other writing skills which everyone must aware of. jb escort

    ReplyDelete
  78. Welcome to the Bangalore accompanies site. The spot for you to find the most restrictive, authentic and able escorts in the city. At the point when you hold one of our Bangalore accompanies, you can depend upon the manner in which that you will dependably be getting the best.
    Follow us:-
    Bangalore escorts
    Bangalore escorts service
    Call girls in Bangalore
    Vip escorts in Bangalore
    Bangalore escorts agency
    Bangalore call girls

    Vip escorts in Bangalore
    Bangalore escorts agency
    Bangalore call girls
    Bangalore escorts
    Bangalore escorts service
    Call girls in Bangalore

    ReplyDelete

  79. We provide:

    100% Real Photos, just Original, no any Fakes!
    Everything private, secret and confidential!
    Just premium friendly Escorts in Lahore and hot in bed services for VIP males
    Exclusive famous porno stars sometimes
    Only TOP, VIP, elite, high class and luxury services.

    call girls in Lahore

    ReplyDelete
  80. Due to my high-class services and beautiful female Escorts, we have emerge as the most winning and capable Escort Service in Zirakpur. Our hot and burning Escorts girls will serve you with the most seductive sex acts, in agreement with your tastes. With the aid of satisfactory sex acts like blowjob, deep throat oral sex with no a condom, handwork, body to body influence, striptease, doggie style, and many more, our escorts are expert sufficient to plea to your sexual preference.
    Mohali Call Girls
    Chandigarh Call Girls

    ReplyDelete
  81. Chandigarh is the area that gets prominent folks alongside organization deligates. Choosing unwinding minutes right now love is every now and again a required. Men and agents living in Chandigarh usually want to get went with a certified high class lady, the person who isn't simply sexual anyway exquisite excellence.
    chandigarh escorts

    call girls in chandigarh

    chandigarh Escort service

    escorts service in chandigarh

    chandigarh call girls

    chandigarh escort service

    ReplyDelete
  82. With Haridwar Escorts you can pick any sort of woman dependent on precisely what your prerequisites are. , in the event that you are a specialist and have no opportunity to fulfill some one of a kind woman we can help.
    Haridwar Escorts
    Call Girls In Haridwar
    Haridwar Escorts
    Haridwar Escorts
    Haridwar Escorts
    Haridwar Escorts
    Haridwar Escorts
    Haridwar Escorts
    Haridwar Escorts

    ReplyDelete
  83. Enjoy the best time with the attractive looking Manali escort
    Are you feeling bored? Is the stress level too high at office? The beautiful Manali escort can change your mood. Just book a date with her today. You will get a relaxed day with the pretty looking escorts. Every man needs some physical pleasure. Due to excessive work load and the pressure from family you miss the chance totally. This will affect your body in a negative way. The Call girls in Manali understand this fact. Thus, they will give you all types of pleasure which your body needs. You can now pack up your bags and reach to a destination unknown. The pretty girls will always be with you. Folks come and go from the city of Manali. But, they hardly experience the beauty of Manali girls. You can now call us to make a meeting.


    Manali escort

    Manali escorts

    Call Girl In Manali

    Call Girls In Manali

    Manali Call Girls

    Manali escort Service



    ReplyDelete
  84. Interesting Article. Hoping that you will continue posting an article having a useful information. Dess Martine

    ReplyDelete
  85. Call Girls in Lahore | Top Escort Girls Pakistan
    https://topescortgirlspakistan.com/

    Top Escort Girls Pakistan purely focuses to turn fantasies into actual realities. Main effort is to fulfill al of your kinky and sexual needs that you get the highest satisfaction of your life. If you are looking for the top best Call Girls in Lahore. No need to worry because you have us. We are one of the bestests in call girls business in Lahore furthermore we are the largest Call Girls Services Agency in Lahore.

    We also provide service in deffierent cities on Pakistan:

    Escorts in Lahore
    Call Girls in Lahore
    Escorts in Rawalpindi
    Call Girls in Rawalpindi
    Escorts in Karachi
    Call Girls in Karachi
    Escorts in Islamabad
    Call Girls in Islamabad

    ReplyDelete
  86. Need to get a serious deal in administration of Greater Noida escorts? If you want some magic at your organization meeting, pick our Escorts in Greater Noida at that point who will take on your secretary's work. All customers want an extremely competent contact to reassure them and simple customers intrigue, as we are probably aware of any company meeting to get.
    Escort in Greater Noida
    call girls in Greater Noida
    escort service in Greater Noida
    Russian escort in Greater Noida

    ReplyDelete
  87. Chandigarh Escorts, A magnificent choice for top independent Chandigarh escorts service. I am here to give you the finest independent escorts in Chandigarh.
    Follow us:-

    Chandigarh Escorts||
    Chandigarh Escorts||
    Chandigarh Escorts||
    Chandigarh Escorts||
    Chandigarh Escorts||
    Chandigarh Escorts||
    Chandigarh Escorts||
    Chandigarh Escorts||
    Chandigarh Escorts||

    ReplyDelete
  88. Hello my name is Miss Leena I am from Lahore I give you best ever Escorts Service in Lahore. I have many more new girls for you in your town (Pakistan) I not avalible only in Lahore I give you Escorts service in Lahore, Karachi Islamabad and Murree. I (Miss Leena) give you 100 scure and safe Sex in Lahore, College and school going girls also give you best service on the bed and off the bed also. I work in Lahore for last 6 years.
    Only I have top calss escorts service.












    hello..! ✅ Good news for you we add some new girls in your Town (Lahore). we also have School and college going girls in Lahore.
    If you search Escorts Girls in Lahore you see my website on this website you found 20 girls in Lahore. Our girls are not typicl call girls in lahore. we also give you service in any hotel in Lahore.
    Escorts in Lahore is the bigest escorts service in Lahore
    Lahore Escorts
    Elite Lahore Escorts
    Call girls in Lahore 💋 ( Miss leena best vip hot sex call girls provider in lahore 💙 _ +92 305 3777077 _ 💙 _ and 🌟 on 🍀 whatsApp num 📞, call now ) 💋

    ReplyDelete
  89. Along with many promotions from the first sign up แทงบอล ออนไลน์ The application process is easy via 5 channels: 1. Line id 2. Call through the webpage number 3. Live Chat

    ReplyDelete
  90. FULL SEX SERVICE IN HOTELS PAKISTANI LAHORE

    Call Girls in Pakistan lahore 🔴


    Vip Hot call girls in lahore {+92-323-3333153 } Anytime Contact Real Percent Neat And Clean Cooperative Full Hot Sex Staff
    Best Vip Pakistan Lahore Call Girls neat and clean Cooperative staff Call girls in Lahore
    I love this Topic I serach this one for many time butt now i see this Lahore Escorts we offer you best Escorts service in Lahore
    Lahore Call girls +92 323 3333153 miss honey provider best vip escorts service in lahore.
    You are sure to have one of the most fabulous Call girls in Pakistan in this modern era. We promised you to provide professional Escort Services in Pakistan as we have well trained and beautiful Escorts in Pakistan.
    Escorts service in pakistani Lahore Lahore Escorts srvice honey moon best happy night Escorts srvice in Lahore Escorts in Lahore is the best key word to search call girls in Lahore
    we serve best and VIP escorts in Islamabad also.
    Vip best real escorts service provider [ Miss honey +92 323-3333153 call now 📞 on WhatsApp number reall personal contact ] full sex call girls in pakistan Lahore islamabad karachi
    Call girls in Lahore
    Call girls in islamabad
    Call girls in karachi
    Call girls in rawalpindi
    Lahore call girls
    Lahore escorts service
    Lahore hot sex models
    Best Call girls in Lahore
    Vip Call girls in Lahore
    Hot Call girls in Lahore
    Sex Call girls in Lahore
    Full sex Call girls in Lahore
    Lahore in hotel service
    Models Call girls Lahore
    top luxury escorts Lahore
    vip luxury Call girls Lahore
    Lahore sex in hotels
    Miss Honey +923233333153 call now ⭐️



    ReplyDelete
  91. What are you saying, man? I realize everyones got their own view, but really? Listen, your blog is neat. I like the energy you put into it, specially with the vids and the pics. But, come on. Theres gotta be a better way to say this, a way that doesnt make it seem like everyone here is stupid!
    Pakistan Urdu News

    ReplyDelete
  92. I will say a kid have you considered you will say which was an engaging remuneration affiliation Mcleodganj Escorts get-togethers you a people say a year earlier will be too charming points of interest call after we go charming preferences again the word engaging is titanic awesome commendable head so we can identified with the wood advantage as well.
    Follow us:-
    Mcleodganj Escorts
    Mcleodganj Escorts Service
    Mcleodganj Call Girls

    Mcleodganj Escorts
    Mcleodganj Escorts Service
    Mcleodganj Call Girls

    Mcleodganj Escorts
    Mcleodganj Escorts Service
    Mcleodganj Call Girls

    Mcleodganj Escorts
    Mcleodganj Escorts Service
    Mcleodganj Call Girls

    ReplyDelete
  93. Hello Friends, I am Sohni, your loving partner who is always ready to give you the pleasure the way you always need.
    Chandigarh Escort |
    Escorts in Chandigarh |
    Chandigarh Call Girls |

    ReplyDelete
  94. Rkescorts welcomes you to a very beautiful gorgeous busty blonde Chandigarh escorts. Book Our Online Call Girls Book sexy Escort Girls in Chandigarh services 24hrs. Visit us today!!

    http://www.rkescorts.com/
    http://www.rkescorts.com/Dehradun-escorts.html
    http://www.rkescorts.com/Manali-escorts.html
    http://www.rkescorts.com/Mussoorie-escorts.html
    http://www.rkescorts.com/Mohali-escorts.html
    http://www.rkescorts.com/Agra-escorts.html
    http://www.rkescorts.com/Panchkula-escorts.html
    http://www.rkescorts.com/Jaipur-escorts.html
    http://www.rkescorts.com/Zirakpur-escorts.html
    http://www.rkescorts.com/call-girls-manali.html

    ReplyDelete
  95. Escorts in Islamabad organization is most likely the best escort models and high class Islamabad Escorts are giving unbelievably Educated, Beautiful, appealing and capable Call Girls in Islamabad which totally satisfy you. We are the principle master association with an unprecedented grouping of noticeable Escorts Services in Islamabad.
    Escorts in Islamabad

    Islamabad Escorts

    Call Girls in Islamabad

    Escorts Services in Islamabad

    ReplyDelete
  96. Hello, Guys Welcome the best vip Lahore girls
    pleases visit our website for
    escorts in Lahore
    call girls Lahore
    Lahore escorts
    call girls in Lahore
    escorts services in Lahore
    Escorts in Pakistan
    Pakistan Escorts
    escort in Lahore
    We have the best escorts service in #Lahore for book your escort call now 03353777077

    ReplyDelete
  97. Our agency has a good collection of individuals who are ready to give you the perfect forms of assistance. There is never a fault being noticed in the nature of services from our darlings. Chandigarh Independent call girls are extremely passionate in guiding men to safety. There is not a fault promise which you are to find out given by our darlings. Being proficient in this mentioned context over the years, they are capable of marking a great impact in the moods of customers. The journey of intimate love with these darlings in arms would turn out to be blissful enough for the clients.


    Chandigarh Escort
    Chandigarh Escort Service
    Chandigarh Escorts
    Zirakpur Escorts
    Mohali Escorts
    Panchkula Escort Service
    Ludhiana Escort Service
    Amritsar Escorts Services
    Jalandhar Escorts

    ReplyDelete
  98. ลักษณะเด่นของ แทงบอล168 ขอดีของ ufa777 รวมทั้ง ufabet.com ปากทางเข้า ยูฟ่าเบท168



    อีกหนึ่งคุณลักษณะเด่นของทางเว็บของพวกเราก็คือ การเล่น บอลสเต็ป อย่างต่ำเริ่ม 2-12 คู่ พนันอย่างต่ำ 10 บาท เหมาะกับผู้เล่นทุนน้อย หรือนักเสี่ยงดวงที่อยากแบบขำๆเล่นแบบชิวๆไม่คิดมากมาย พวกเราก็ให้บริการ แต่ว่าสำหรับผู้เล่นไม้ต้น อยากได้พนันหลักล้าน ทางเว็บไซต์พวกเราก็มีจ่าย เพราะเหตุว่าเว็บไซต์พวกเรา เป็นเว็บไซต์ใหญ่จ่ายจริง ยืนยันการคลัง ไม่มีอันตราย และก็ มั่นคง 100%

    ReplyDelete
  99. If you'd incline toward not getting a visit, a Ludhiana Escorts can be masterminded. This is a selective involvement with which you arrange to take a quick trip and see among our heavenly Ludhiana Escorts. On the off chance that you are scouring with the evaluations of fulfilment centre points pass on across Panchkula and when you happen to keep away from Playmate in contact and outcall Escorts, exceptional for you since you have over the most trusted and expert Elite Ludhiana Escorts office.

    ReplyDelete
  100. We've taken efforts to stay close to the original procedure


    Sexy Casino
    ALLBET Casino

    ReplyDelete
  101. I recently found many useful information in your website especially this blog page.nice informastion. Thanks for sharing . Buy 1 Star Google Reviews

    ReplyDelete
  102. Timing and motive for this post is excellent. Great way to write and post it. Keep it up!.


    Escort services in Mumbai

    ReplyDelete
  103. Going to graduate school was a positive decision for me. I enjoyed the coursework, the presentations, the fellow students, and the professors. And since my company reimbursed 100% of the tuition, the only cost that I had to pay on my own was for books and supplies. Otherwise, I received a free master’s degree. All that I had to invest was my time. Unique Dofollow Backlinks

    ReplyDelete
  104. Attractive section of content. I just stumbled upon your blog and in accession capital to assert that I get in fact enjoyed account your blog posts. Any way I will be subscribing to your augment and even I achievement you access consistently quickly. If you want to dead pixel buddy

    ReplyDelete
  105. Zed Black luxury is a range of 4 fresh fragrances that are charcoal free Incense sticks and are packed in premium packing. The fragrance of Zed Black Luxury will take you to the world of luxury, make your mind calm & peaceful and thus gives you luxurious heavenly like feeling.
    Features of Zed Black Incense Sticks:
    Pleasing Aroma
    Long Lasting fragrance
    Non-toxic
    zed black luxury agarbatti

    ReplyDelete
  106. A sand blasting machine with two hoses of which one hose is connected to the bottom of the handle and the other hose is connected to the lower side of the barrel. It has a repository of loose sand. Some type of container or container is formed by this type. As the gun is fired, the air produces a suction that pulls the sand into the gun. Now sand can be reused by collecting it and placing it back into the reservoir.

    ReplyDelete
  107. Delite Cleaning Services is a professional cleaning company that offers BATHROOM Cleaning services. Our staff are trained, punctual, and efficient. We have extremely high standards and never cut corners as we tackle all the dust, grime, and dust leaving a meticulously perfect finish to homes, offices, and industries that we serve.

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

    ReplyDelete
  109. Murree is a well-liked vacation spot thanks to its picturesque scenery and comfortable year-round climate.
    Villas In Bhurban

    ReplyDelete
  110. Welcome to the 8 Marla bhurban cottages , a place of wealth, sophistication, and spectacular views that will make your stay unforgettable. Each cottage features a big, well-decorated interior with a room and a library, making it suitable for a small family holiday or a romantic weekend.

    ReplyDelete
  111. Great Info!!! Thanks for sharing the information with us.

    ReplyDelete