Author Topic: 2C-SCN and Thiocyanation  (Read 1381 times)

0 Members and 1 Guest are viewing this topic.

imp

  • Guest
2C-SCN and Thiocyanation
« on: October 24, 2003, 12:22:00 AM »
This thread is devoted to the synthesis of 2C-SCN, or 2,5-Dimethoxy-4-thiocyanatophenethylamine, and DOSCN, or 2,5-Dimethoxy-4-thiocyanatoamphetamine.

Several years ago a very, very, very respectable bee here at The Hive attempted the synthesis of 2C-SCN through the pseudohalogenation of 2C-H with thiocyanogen, (SCN)2. Two experiments were performed, one using Br2/KSCN and the other Br2/Pb(SCN2) (the thiocyanogen being formed by the action of bromine on thiocyanate). Each reaction failed unfortunately. SWIM can think of two reasons for the failure...

i. Thiocyanogen requires extremely anhydrous conditions to form properly.
ii. More likely, thiocyanogen is just a very weak agent, having a reactivity between that of bromine and iodine.

So, a new effective thiocyanation reagent is badly needed so that we may analyze these very intriguing new compounds. Now, SWIM will provide three possible procedures for the successful thiocyanation of 2C-H. The first will work almost indefinitely, the second has a good chance, and the third is just an idea. Let's begin.


Copper(I)-Mediated Thiocyanation of Nonactivated Aryl Iodides
--------------------------------------------------------------
ref: Synth. Comm., 26(18), 3413-3419 (1996)

Abstract: Various aryl thiocyanates were easily prepared in acceptable yields by heating aryl iodides with cuprate complex K[Cu(SCN)2] in DMF.

Unlike alkyl halides, aryl halides are generally too inactive toward thiocyanate anion to afford aryl thiocyanates. Early workers made some attempt to use copper salts for overcoming this difficulty. In most cases, however, the major product was not the expected aryl thiocyanates but their descendants. To our knowledge, the work by Clark and coworkers was the only successful case, where charcoal-supported CuSCN was found to be effective for the thiocyanation of nonactivated haloarenes. However, it is not free from some drawbacks such as the use of large excess of reagent and tedious effort necessary for preparing the supported copper salt. In this paper, we wish to report that the thiocyanation of nonactivated iodoarenes can be effected with ease using cuprate complex K[Cu(SCN)2] as the thiocyanating agent in a dipolar aprotic solvent.

...we found that thiocyanatodurene could be obtained by the heterogeneous interaction between iododurene and CuSCN in hot DMF. However, the yield of thiocyanatodurene was low because of the concurrent formation of considerable amounts of nitrile and disulfide. In order to enhance the solubility and improve nucleophilicity of CuSCN, one equiv KSCN was added to the reaction system to generate the cuprate complex K[Cu(SCN)2]. By this modification, the formation of nitrile was considerably depressed and the yield of thiocyanatodurene rose up to 57%. Under these conditions, the thiocyanation proceeded in homogeneous phase.

The effect of CuSCN/KSCN ratio was also investigated; addition of an equimolar amount of KSCN improved the yield of thiocyanatodurene considerably, but further addition affected only slightly and a large excess of KSCN was found to work adversely, lowering the yield. Among various dipolar aprotic solvents examined, DMF was the solvent of choice. Attempted reaction in HMPA resulted in the formation of nitriles and disulfides. Compared with KSCN, other thiocyanates such as NaSCN, Ba(SCN)2.2H2O and NH4SCN gave no better results.

General Procedure:

Copper(I) thiocyanate and potassium thiocyanate were used after drying in vacuo for 6 h. All solvents were used after distillation.

Under an argon atmosphere, a mixture of iododurene (0.52 g, 2.0 mmol), CuSCN (0.24 g, 2.0 mmol), KSCN (0.19 g, 2.0 mmol) and DMF (5 mL) was heated with stirring in an oil bath and maintained at 140 C for 12 h. The reaction mixture gradually turned brown. After cooling, the mixture was diluted with benzene (10 mL) and water (10 mL), and then filtered through a Celite bed. Aqueous phase was extracted with benzene (10 mL x 2) and the combined organic phase was washed with water, dried over Na2SO4, and concentrated. The resulting orange-colored oil was chromatographed on silica gel (hexane as eluent) to afford thiocyanate (57%).

2-Acetylaminophenyl Thiocyanate : 40% yield

4-Methoxyphenyl Thiocyanate : 34% yield

4-Methylphenyl Thiocyanate : 52% yield

(Now of course 2C-I will require amine protection through its acetyl or phthalimide)



Thiocyanation of Aryl Ethers using Thiocyanogen Chloride (Cl.SCN)
------------------------------------------------------------------
ref: J. Chem. Soc. 1960, 318

Reactions between metal thiocyanates and halogens are discussed. A rapid reaction in acetic acid between lead thiocyanate (1 mol.) and chlorine (2 mol.) gives a solution of thiocyanogen chloride, which is converted into thiocyanogen if more lead thiocyanate is added. Thiocyanogen chloride solutions were also obtained from potassium thiocyanate and chlorine in acetic acid... Aryl ethers and anilides, which are unreactive towards thiocyanogen, give thiocyanato-derivatives in high yield when treated with thiocyanogen chloride in acetic acid : PhX + Cl.SCN ---> p-C6H4X.SCN + HCl.

We were particularly interested in using thiocyanogen chloride in acetic acid. It was expected that this solvent, as in the case of nuclear aromatic halogenation, would be a better medium for nuclear aromatic thiocyanation than the carbon tetrachloride which we had previously used... The nature of the solvent affects the ease with which the reaction occurs. For example, whereas it was quantitative in acetic acid, under similar conditions of time and temperature (15 min.; 20 C) it occurred to the extent of 93% in chloroform and 35% in carbon tetrachloride.

...the solutions thus prepared are suitable for nuclear thiocyanation of numerous aromatic compounds which are unaffected by thiocyanogen.


Preparation of Thiocyanogen Chloride from Potassium Thiocyanate in Acetic Acid. - "AnalaR" acetic acid was dried by refluxing it for 4 hr. with 5% acetic anhydride; the dried acid was used without removal of the anhydride for all the experiments described in this paper. Dry chlorine was passed into this solvent to give a ~0.4N-solution. Finely ground "AnalaR" potassium thiocyanate was dried over phosphoric oxide for 1 week in a vacuum and was added to 500 ml. of the acetic acid/chlorine solution, in 1:1 molecular ratio, and the mixture was stirred for 15 min. at 20 C. An exothermic reaction was apparent (4 C rise) during the first 3 min. The titre of the resulting thiocyanogen chloride solution was 94% of that of the chlorine solution. Addition of cyclohexene (1 mol.) resulted in a rapid reaction, giving 1-chloro-2-thiocyanatocyclohexane (78%).

(Note: The paper says that when adding lead thiocyanate to the greenish-yellow chlorine solution, the colour changes to the orange-yellow of the thiocyanogen chloride. SWIM assumes the same colour change should occur when using KSCN.) Any thoughts on using bromine instead of chlorine?



Thiocyanation using KSCN/Oxone
-------------------------------

This is just an idea SWIM had when reading some oxone mediated halogenation reactions. How about it? SWIM is not familiar with the pseudohalogenic properties of the SCN anion, so this is really just a wild guess. Oxone is really a quite new reagent popping its head up everywhere in synthetic journals, so there's no wonder this path hasn't been explored yet.

Mix some KSCN in MeOH with your 2C-H freebase, then add some oxone and see what transpires. It is very much worth a try. If KI/oxone can iodinate 2C-H, then surely KSCN/oxone can thiocyanate it. 


Any ideas?

Kinetic

  • Guest
Thiocyanation
« Reply #1 on: October 24, 2003, 06:35:00 AM »
And I quote:

Monobrominate, you say. What about thiocyanate? - just add in soln 1.2 eqv of
KSCN and then dropping bromine. This will be very fun product. BTW, the
rodano-derivative can be reduced to Shulgin's dream - bare thio group :)


Courtesy of Assholium - posted here originally, and archived at

https://www.thevespiary.org/rhodium/Rhodium/chemistry/2cb-new.txt



Can't get much simpler than that 8)


imp

  • Guest
That doesn't work for 2C-H
« Reply #2 on: October 24, 2003, 07:22:00 AM »
Ummmm, perhaps you didn't read what SWIM wrote above. But that method doesn't work with 2C-H - that's the whole point of this thread. A bee here at The Hive tried it twice with no success, because thiocyanogen is too weak of a thiocyanation reagent to effect the aromatic nucleus.

Also, SWIM thinks Assholium is full of shit (as his name might have implied). There's no way that 2C-SCN-2EtO would be as psychedelic as he claimed. Here is this original thread...

Post 108811

(dormouse: "Thiocyanation of 2C-H  -Rhodium", Novel Discourse)

Vitus_Verdegast

  • Guest
I wouldn't conclude to that so soon..
« Reply #3 on: October 24, 2003, 08:15:00 AM »
There's no way that 2C-SCN-2EtO would be as psychedelic as he claimed.

Based on what? There is always the possibility of exemption on a general rule, esp. with an unexplored substituent like -SCN on the ring.

Well, before we jump in conclusions, I've seen that Assholium was around recently, perhaps he would like to comment on this?

BTW I'm glad you bring this topic back up, the possibilities of unexplored pseudohalogenide substituents has been fascinating me for a while.


Assholium

  • Guest
clear, please
« Reply #4 on: October 24, 2003, 09:56:00 AM »
Also, SWIM thinks Assholium is full of shit (as his name might have implied).

 - it's direct offence, right?

imp

  • Guest
Jumping to Conclusions
« Reply #5 on: October 24, 2003, 12:17:00 PM »
Okay, Vitus is correct, SWIM did jump to conclusion... sorry Assholium (although you do have an amusing username). But SWIM still does not believe that you formed the thiocyanate compound, maybe something else happened? SWIM doubts that you remember the exact reaction, as it was a very long time ago. But if you remember any details, could you please post them? Obviously, you must have done the thiocyanation using the acetate salt, correct?

Rhodium, are you around?? Your thoughts would be very useful here (if you know what SWIM means  ;) ).

Anyway, just got back from the library with A BUNCH of useful papers detailing thiocyanation... it is going to take some time to type up however.

SWIM is going to solve this problem no matter what, really don't care if no one else is interested in it. Expect to hear a bioassay in the future!

note: the word "future" may mean a couple of years... ;)

imp

  • Guest
Cupric Thiocyanate anyone?
« Reply #6 on: October 24, 2003, 01:37:00 PM »
ref: Ber., 67, 944 (1934)

Cupric thiocyanate, the use of which may be considered still another modification of this general procedure, shows promise of being very effective. It releases thiocyanogen merely by the dissociation of the cupric to cuprous salt.

2Cu(SCN)2 ---> 2CuSCN + (SCN)2

Cupric thiocyanate, prepared in advance, or a paste of copper sulfate and sodium thiocyanate is equivalent proportions is added to a solution of the compound in methanol or acetic acid, and the mixture is warmed to 35-80 C until the black cupric thiocyanate has changed completely to the white cuprous thiocyanate. The product is isolated by dilution with water, followed by extraction with ether.

Cupric thiocyanate is prepared by treating an aqueous solution of copper sulfate with an equivalent amount of aqueous sodium thiocyanate. The precipitate is filtered and washed with ethanol and ether.

A solution of 3.6 g. (0.025 mole) of alpha-naphthol in 30 cc. acetic acid is warmed gently with 19 g. (0.105 mole) of cupric thiocyanate until decoloration of the copper salt is complete. The solution is filtered and diluted with water. An oil separates but soon crystallizes. Yield 3.6 g. (72%) of 4-thiocyano-1-naphthol.

imp

  • Guest
More...
« Reply #7 on: October 24, 2003, 01:41:00 PM »
ref: Org. React., vol 3., pp 240 - 265 (1946)

The direct replacement of a hydrogen atom by a thiocyano group through the use of thiocyanogen, (SCN)2, is commonly termed thiocyanation. This replacement reaction is limited practically to aromatic amines and phenols, although a few particularly reactive aromatic hydrocarbons can be thiocyanated.

The reagent is used in synthesis in essentially the same way as the halogens, with the exception that certain precautions must be observed owing to the instability of thiocyanogen. Thiocyanogen is a liquid which on cooling forms a colorless, crystalline solid melting between -3 and -2 C. At room temperature is polymerizes rapidly to a reddish orange, amorphous mass of indefinite composition known as pseudo- or para-thiocyanogen. Although relatively stable in inert, dry solvents, thiocyanogen may polymerize in solution, expecially under the catalytic influence of heat, light, moisture, or oxygen. Thiocyanogen is readily hydrolyzed to produce thiocyanic acid and hypothiocyanous acid.

(SCN)2 + H2O ---> HSCN + HOSCN

The latter is unstable and is converted into hydrocyanic acid and sulfuric acid, both of which occur as end products of the overall hydrolysis.

The extreme sensitivity of thiocyanogen toward hydrolysis and polymerization probably accounts for the long interval between its formulation by .... when thiocyanogen is employed in chemical reactions, it is prepared in solution and more commonly is produced in situ.

Thiocyanogen is often classified as a pseudohalogen because of its resemblance to halogens in its chemical behavior. It attacks even noble metals like gold and mercury; it reacts with nitric oxide, aqueous hydrogen sulfide, hydrazoic acid, ammonia, and hydrochloric acid. It is released from metal thiocyanates by the action of chlorine, bromine, and other oxidizing agents (imp: ahhhm, oxone perhaps?). Halogen-thiocyanogen combinations are formed with chlorine and with iodine. Thiocyanogen is similar to iodine in its chemical reactivity but is slightly less electronegative.

Thiocyanogen reacts with aromatic compounds that are highly susceptible to substitution with the introduction of a thiocyano group. Reactions reported thus far are mainly with phenols of the benzene and naphthalene series and with primary, secondary, or tertiary amines of the benzene, naphthalene, and anthracene series. Apparently the presence of other substituents, such as nitro, chloro, bromo, alkoxy, carboxyl, or carbethoxy groups, does not interfere with the reaction provided that an active position is still available; however, the presence of a sulfonic acid group may prevent the reaction, since it is reported that p-amino- and p-hydroxy-benzenesulfonic acids do not undergo thiocyanation.

The thiocyano group is introduced into aromatic amines with rapidity; it enters a free para position if available, otherwise an ortho position. For example, aniline is converted into 4-thiocyanoaniline (97% yield), o-toluidine into 4-thiocyano-o-toluidine (80% yield) and anthranilic acid into 5-thiocyanoanthranilic acid (80% yield). Acetylation of the amino group prevents thiocyanation.

The reaction of phenols with thiocyanogen has not been studied so extensively as that of amines. Phenol is converted to 4-thiocyanophenol in 69% yield, o-cresol into 4-thiocyano-o-cresol in 90% yield, thymol into 4-thiocyanothymol in 95% yield, and alpha-naphthol into 4-thiocyano-1-naphthol in 83% yield. The point of attack is again the para position if free; ortho substitution occurs when this position is blocked, as in the reaction of p-cresol and beta-naphthol (100% yield). The effect of a substituent other than an alkyl group in the position ortho to the hydroxyl group has been examines to only a limited exten; the yiled of the thiocyano product is lowered in the case of an alkoxyl (guaiacol, 21% yield), hydroxyl (pyrocatechol, 48% yield, and resorcinol, 60% yield).

Aromatic hydrocarbons of the benzene and naphthalene series do not undergo thiocyanation, but certain hydrocarbons with several condensed benzene rings do... Anthracene, benzpyrene, benzanthracene.

Miscellaneous Reactions

2RNH2 + (SCN)2 ---> RNHSCN + RNH3SCN
2R2NH + (SCN)2 ---> R2NSCN + R2NH2SCN
C2H5SH + (SCN)2 ---> C2H5SSCN + HSCN

The reagent is prepared by the action of an oxidizing agent upon thiocyanic acid or a metal thiocyanate. The oxidation of thiocyanic acid in an organic solvent is accomplished by means of such reagents as lead tetracetate, lead peroxide, or manganese dioxide, but the yield is so low that the preparation from metal thiocyanates is much to be preferred. Lead thiocyanate reacts rapidly and quantitatively with bromine to form thiocyanogen and lead bromide, which is removed readily by filtration.

Solvents that have been used with thiocyanogen include benzene, bromobenzene, carbon tetrachloride, chloroform, ether, ethylene bromide, carbon disulfide, pet. ether, methyl acetate, nitromethane, and anhydrous formic and acetic acids. At low temperatures such solvents as saturated solutions of alkali thiocyanates in methanol or acetone can be used. The yield in the thiocyanation of amines is 20-30% higher when the reaction is carried out in a neutral medium like methanol rather than in acetic acid. Ether is usually not satisfactory because the solvent is attacked and because some of the amine is precipitated as the thiocyanate. On the other hand, thiocyanation of phenols appears to give better yield in acetic acid solution than in neutral solvents.

Moisture must be excluded form thiocyanation solution in order to prevent hydrolysis. Another troublesome side reaction, particularly in concentrated solutions, is polymerization, which is induced by light, heat, and the presence of hydrolysis products. Polymerization is reported to be dependent upon the dielectic constant of the solvent. imp: Acetic acid is best by far


Lead thiocyanate, used advantageously in the formation of thiocyanogen, is prepared from lead nitrate and sodium thiocyanate. To an ice-cold solution of 45 g. lead nitrate in 100 cc. of water is added a cold solution of 25 g. sodium thiocyanate in 100 cc. of water. Lead thiocyanate precipitates as a fine, white powder. It is collected on a filter, washed free of nitrates with ice water, and then dried in vacuum over P2O5 in the dark. The product should remain perfectly white.
One part by weigh (in grams) of lead thiocyanate is suspended in 5 to 10 pars by volume (cc) of the desired solvent. The solution is cooled to 5-10 C, and a small portion of 10% bromine in the same solvent is added. The mixture is shaken vigorously until the color due to the bromine disappears. The process of addition and shaking is repeated until the calculated amount of bromine has been used. The suspended solids are allowed to settle, the thiocyanogen solution is decanted, and the residual solids are washed by decantation with small portions of the solvent.
Decoloration of the bromine solution by lead thiocyanate is usually immediate. As heat is evolved by the reaction, the flask must be cooled regularly during the preparation to maintain the low temperature necessary to stablize thiocyanogen. At the end of the reaction lead thiocyanate should remain in about 10% excess imp: if we choose to use thiocyanogen bromide, we will need to use equimolar amounts of Br2 and Pb(SCN)2. Solutions of pure thiocyanogen are water-clear and colorless.
Since the reaction between bromine and lead thiocyanate is quantitative, the amount of thiocyanogen present can be taken as equivalent to the amount of bromine added to the solution provided the reagent is used immediately.


Well, SWIM thinks this offers much useful information. The thiocyanogen chloride and the oxone/KSCN ideas in the first post on this thread are sounding better and better by the second. SWIM also has a paper detailing the preparation of thiocyanogen bromide (bromine is easier to handle than chlorine). This will come soon.

imp

  • Guest
Mwwwhahaha, oh yes....
« Reply #8 on: October 27, 2003, 11:08:00 AM »
More proof the oxone method may just work....

ref: Syn. Comm., 31(19), 3041-3045 (2001)

A Facile Synthesis of Aryl Thiocyanates using Sodium Perborate
-------------------------------------------------------------

Thiocyanation of arenes is an important synthetic strategy for preparation of aryl thiocyanates which provides attractive routes to many type of heterocyclic compounds having marked physiological activity. Consequently, a variety of methods for the thiocyanation of arenes have been reported... CuSO4/metal thiocyanate (SWIM posted previously), Br2, Pb(OAc)4, MnO2...

Sodium perborate is an inexpensive, easily available, safe and easy to handle oxidant. Sodium perborate has been used for a variety of oxidation reactions. Recently we have prepared 1,2-benzisoxazole, N,N-diacylhydrazines and halogenated aromatic compounds using sodium perborate. As an extension of our work on sodium perborate, we explored the possibility of thiocyanation of arenes using sodium perborate and ammonium thiocyanate. Substituted aromatic and some heterocyclic compounds when treated with ammonium thiocyanate and sodium perborate in glacial acetic acid (SWIM KNEW IT!!) at r.t. gave the corresponding thiocyanato compounds. The reaction worked well giving good to excellent yields of the product.

It is observed that deactivated rings i.e. nitrobenzene and non-activated rings i.e. benzene do not undergo thiocyanation reaction even after 1 h at room temperature. Whereas, activated and active hetero aromatic rings undergoes thiocyanation reaction smoothly. It is interesting to note that aniline undergoes thiocyanation without affecting the amino group, possibly thiocyanogen (SCN)2 is instantly formed in situ. Therefore aniline undergoes thiocyanation without oxidation under the experimental condition used.

Experimental:
-------------
A solution of SPB (0.31 g, 2 mmol) and NH4SCN (0.08 g, 1.2 mmol) in glacial acetic acid (20 mL) was stirred at r.t. Immediately substituted aromatic compound (1 mmol) was added and the resulting mixture was stirred at room temperature for 15 min. The completion of the reaction was confirmed by TLC. After completion of reaction, water (50 mL) was added and the product was extracted by CH2Cl2 (3 X 25 mL). The organic layer washed with H2O (2 X 20 mL), dried (Na2SO4), and concentrated under reduced pressure to get the product. It was purified by s.c.c. on silica gel (60-120) using CHCl3: pet. ether (60-80) as an eluent.

In conclusion, we have developed a facile, easy, and inexpensive route to synthesis of aryl thiocyanates mediated by sodium perborate. The present procedures appear attractive due to its experimental simplicity and generally high yields of product.

Now here is what SWIM suggests. A thiocyanogen halide is known to be a more effective reagent in thiocyanation reactions. So, mix the SPB with NH4SCN in GAA and add an equimolar amount of NaX (X = -Cl, -Br, -I) to generate the thiocyanogen halide from the plain thiocyanogen. Now add the aromatic! SWIM thinks it's a good idea to try. Oxone has to work in place of SPB, it would just add the most perfect final touch.

BTW: Aren't people curious about 2C-SCN/DOSCN? It's a new compound that may easily bee made from 2C-H and have very potent properties, if the report with the 2-EtO homologue was correct. Go to the library people!


Oh Antoncho, SWIM will have a synthesis of 5-nitrovanillin ---> 5-diazovanillin for you in a bit! Yes, SWIM actually found several papers finally!

Vitus_Verdegast

  • Guest
Excellente !!!
« Reply #9 on: October 27, 2003, 12:14:00 PM »

BTW: Aren't people curious about 2C-SCN/DOSCN? It's a new compound that may easily bee made from 2C-H and have very potent properties, if the report with the 2-EtO homologue was correct. Go to the library people!


Actually SWIM is very enthusiast!! Asap as some new 2C-H and ammonium thiocyanate arrives (and he finally moves his lazy ass and starts to make some TLC plates), he will try your proposed scheme using perborate.


I was also thinking 4-Br-2,5-DMBA --> 4-SCN-2,5-DMBA, but I doubt that the latter would survive the final nitroalkene reduction (please correct me if I'm wrong, I hope I am  ;) )


Rhodium

  • Guest
2C-H is not as activated as their substrates
« Reply #10 on: October 27, 2003, 02:10:00 PM »
I must unfortunately interject some scepticism here, as they manage to thiocyanate phenol, indole, anilines and styrene, while there is no reaction at all with benzene and nitrobenzene.

Even though 2C-H is more activated than benzene, it is still far from being as activated as the substrated listed above, so I belive it is below 50% chance that this reaction works successfully to make 2C-SCN. I have read an article claiming that a Lewis acid like Al(SCN)3 is required to thiocyanate phenol ethers with (SCN)2... I'll get back with more info.

imp

  • Guest
Let's think this through
« Reply #11 on: October 27, 2003, 03:41:00 PM »
SWIM also has some skepticism, but it's mixed. Who would have thought that NaI/oxone could effect iodination on 2C-H?? Why shouldn't it be possible with a SCN if the right solvent is used? Rhodium, your understanding of chemistry is far beyond SWIM's, but do you understand why SWIM can't help but become somewhat optimistic?

Although SWIM admits enthusiasm is reserved about using (SCN)2 to effect thiocyanation, SWIM is VERY EXCITED about using SCN.Cl or SCN.Br. Very many aromatics, including aryl ethers, that are not effected by (SCN)2 are much more reactive towards SCN.Cl and will be thiocyanated successfully... JCS, pp. 318 (1960)


The thiocyanation of mononuclear aromatic compounds with thiocyanogen is normally restricted to amines and phenols, though it may be applied even to benzene if carried out in the presence of Friedel-Crafts catalysts, which presumably polarize the S-S bond of thiocyanogen. Similarly, the polar character of the S-Cl bond in thiocyanogen chloride makes this a more powerful reagent than thiocyanogen for such electrophilic substitutions. As with halogenations, the rate of these thiocyanations is affected by the polarity of the solvent.

PhX + Cl.SCN --> p-C6H4X.SCN + HCl: (X = )NMe2 > OH > OMe > NHBz > NHAc > OPh > NMeAc

This is identical with the order of reactivities of these benzene derivatives in nuclear substitutions by molecular halogen in acetic acid.




Interesting, no? SWIM has much more references to give, it will take some time though (including thiocyanation of the very unreactive benzene). Rhodium, SWIM thinks the Al(SCN)3 article was viewed over (was it in Acta Chem. Scand.?)

Now that we know a cheap oxidizing agent like sodium perborate can be used to generate both (SCN)2 and a halogen, we can make the reaction more 'user friendly' and elegant by generating both simultaneously to create the more reactive thiocyanogen halide.

Vitus, SWIM is very glad to see your enthusiasm! SWIM is confident we will develop a procedure, but we must tread our path slowly and under well-informed premises. The more information we gather, the more random articles we retrieve, the more ideas we come up with and are able to support, then the more knowledge we gain and the chances of success will increase.

(sorry for all the blabbering ... SWIM had a good day in the library.  :P )

Edit: Almost forgot your question Vitus! No, SWIM thinks you have to do the thiocyanation at the end - although you might be able to form the free thiol (-SH) for the 2C-T-X's. Rhodium knows much better.
Also, has anyone ever considered (OCN)2 or straight cyanogen? SWIM has a small one line reference to its existence. (Ugghh! - why can't SWIM ever be satisfied? Always has to want more and more and ...)


Rhodium

  • Guest
Thiocyanogen Halides better than Thiocyanogen
« Reply #12 on: October 27, 2003, 05:16:00 PM »
has anyone ever considered (OCN)2 or straight cyanogen?

Cyanogen is the name for (CN)2 so (OCN)2 is oxycyanogen (c.f. thiocyanogen). I could find no references for either (OCN)2 or BrOCN in the literature other than theoretical discussions, so they are probably less stable than a tweeker at a DEA conference  ;)

Now that we know a cheap oxidizing agent like sodium perborate can be used to generate both (SCN)2 and a halogen, we can make the reaction more 'user friendly' and elegant by generating both simultaneously to create the more reactive thiocyanogen halide.

I'm sorry, I actually missed that suggestion you wrote above in red - BrSCN has much greater chance of success than (SCN)2.

BTW, Here are a few references on Thiocyanogen Iodide:

Preparation
J.Chem.Soc.; 1960; 604,606.
9.Congr.Soc.Pharm.Clermont-Ferrand 1957 S.203,205.
C.R.Hebd.Seances Acad.Sci.Ser.C; 282; 1976; 345.
Ann.Chim.(Paris); 6; 13; 1961; 481,509.

Use
Tetrahedron Lett.; 1978; 4991-4994. DOI:

10.1016/S0040-4039(01)85790-7


C.R.Hebd.Seances Acad.Sci.; 251; 1960; 1027.
Bull.Soc.Chim.Fr.; 1964; 2569.
J.Prakt.Chem.; 311; 1969; 238.
J.Prakt.Chem.; 323; 1; 1981; 89-92.
Bull.Chem.Soc.Jpn.; 56; 8; 1983; 2458-2462.

Kinetic

  • Guest
Another rude interjection
« Reply #13 on: October 28, 2003, 03:12:00 AM »
Although unlike my original post, this one isn't sponsored by GBLTM

Still, it was meant to imply the in-situ formation of BrSCN may occur, on adding bromine to the solution of KSCN. Surely bromine is a strong enough oxidising agent for this to occur?

On the subject of 2C-OCN, if one somehow had a free OH group at the 4-position, a way to prepare 2C-OCN could by the different route of adding plain cyanogen bromide to the phenol, as in

Organic Syntheses, CV 7, 435

(http://www.orgsyn.org/orgsyn/default.asp?formgroup=base_form_group&dataaction=db&dbname=orgsyn). As Rhodium so eloquently put it, a roundabout way seems to be necessary to introduce the OCN group. The discussion in the article hints at the reasons behind this; hardly surprisingly, the aryl cyanates have activated cyano groups. Maybe someone could comment on the potential side-effects of putting this into one's body...

Edit: Aha! Now I see.. Please ignore the second paragraph of this post (after reading the threads

Post 190955

(Antoncho: "CH3-C6H5SO2*CH3O - an OTC methylating agent?", Chemistry Discourse)
and

Post 108811

(dormouse: "Thiocyanation of 2C-H  -Rhodium", Novel Discourse)
). Still, Rhodium did say in the first thread that

The literature does not clearly answer if 2 KSCN + Br2 produces KBr + BrSCN or 2KBr + (SCN)2, so the active thiocyanation agent may either be BrSCN or (SCN)2


- So at least my misunderstanding was in good company. ;)