Sciencemadness Discussion Board

Sandmeyer reaction questions

Vitus_Verdegast - 9-4-2006 at 08:43

Looking at :
http://www.organic-chemistry.org/namedreactions/sandmeyer-re...

They state that Sandmeyer-type reactions with thiols, water and potassium iodide don't require catalysis. Yet I was unable to find much references describing the reaction with thiols.

I wonder if anyone has something to offer on that topic?

Also the same question goes for the reaction with formaldoxime, which gives an arylaldehyde.

I have this review, but it lacks information concerning the above:
Hodgson, H. H. Chem. Rev. (1947) 40, 251-277
It is mostly a review about different kind of catalysts used to prepare halobenzenes. They mention cyanobenzene only once.

Thanks in advance :)

solo - 9-4-2006 at 16:24

I found this paper in which they use the said reactions and had some options......solo
--------------------------------------------------------------------------------------------------
2,4-Diamino-5-chloroquinazolinAe nalogues of Trimetrexate and Piritrexim:
Synthesis and Antifolate Activity

Andre Rosowsky,*?t Clara E. Mota,? Joel E. Wright,? and Sherry F. Queenerz
J. Med. Chem. 1994,37, 4522-4528

http://rapidshare.de/files/17616460/Analogues_of_Trimetrexat...

Excerp.....Sandmeyer-type reaction using KCN and CuSO4 as described in the classical paper by Davoll and Johnson(36) was found to give erratic yields. Therefore, we developed a modified process, based on recent work in a different context by Hynes and ~o-workersI.n~ ~th is modification, treatment of the diazotized solution of 19 with CuCVKCN instead of CuSOfiCN allowed 18 to be reliably obtained in '70% yield.

Ref: (36) Davoll, C. J.; Johnson, A. M. Quinazoline analogues of folic acid.
J. Chem. SOC1.9 70, 997-1002.

[Edited on 10-4-2006 by solo]

leu - 9-4-2006 at 17:58

The preparation of iodobenzene in Vogel's is illustrative of a reaction of a diazonium salt with potassium iodide in water :) Sidgewick states that cobalt or iron thiocyanate salts give better yields than the cuprous salts in the Sandmeyer reaction when introducing the thiocyanate radical :D

caribou - 9-4-2006 at 23:01

Perhaps this can be of some help:

James D. Baleja
The Facile Conversion of Aromatic Amines to Arylmethylsulfides with Methylthiocopper
Synthetic Communications, 14(3), 215-218 (1984)
https://www.synthetikal.com/hiveboard/novel/000473295.html

Vitus_Verdegast - 14-4-2006 at 07:18

Thank you all very much!

I will do my own input here too but am pressed for time for the moment.

What would be most interesting is to find examples of the introduction of -SCN, -alkylthio and -CHO groups. Maybe even -OCN?

Sandmeyer - 14-4-2006 at 08:02

Formylation gives low yiled:

http://www.orgsyn.org/orgsyn/prep.asp?rxntypeid=84&prep=...

thiocyanate:

Improved Procedure to Aryl Thiocyanates: A New Synthetic Application of Dry Arenediazonium o-Benzenedisulfonimides

Margherita Barbero*, Iacopo Degani, Nicola Diulgheroff, Stefano Dughera, Rita Fochi
*Dip.to di Chimicia Generale ed Organica Applicata dell'Università, C.so M. D'Azeglio 48, 10125 Torino, Italy; E-mail: fochi@ch.unito.it

Aryl thiocyanates 3 (22 examples) were easily prepared by reaction of dry arenediazonium o-benzenedisulfonimides 1 and sodium thiocyanate (2) in anhydrous acetonitrile at room temperature (20-25 °C) in the presence of copper powder (Procedure A) and at 50 °C or room temperature without the metal catalyst (Procedure B). The yields were from very good to excellent in Procedure A (average yield = 83%), and from modest to excellent in Procedure B (average yield = 63%). In comparison with the thiocyanodediazoniation carried out under traditional Sandmeyer-type conditions, the yields of 3 were higher and the isothiocyanate isomers were formed only in traces. Moreover, the results obtained in the absence of copper confirm the role of the anion of salts 1 as an electron transfer agent.

Barbero, Margherita; Degani, Iacopo; Diulgheroff, Nicola; Dughera, Stefano; Fochi, Rita; Synthesis; 4; 2001; 585 - 590.

Full paper: http://rapidshare.de/files/17996204/s-2001-12362.pdf.html

[...]The most traditional route for obtaining aryl thiocyanates 3 is that of diazotized primary aromatic amine reactions with metal thiocyanates in aqueous solution, mostly under Sandmeyer-type conditions. The yields, quite often unsatisfactory, the concomitant formation of various by-products, including the aryl isothiocyanate isomers [...]

I suppose it has interesting references on traditional Sandmeyer method. But wouldn't it be better to do Ullmann instead? Shortest still would be via direct thiocyanation (NH4SCN/Br2), there are many refs on this reaction, see the Org. Lett paper in the post below. there is also a nice paper on this in wanted refs thread which I requested a year ago or so. Shulgin has also done this: http://www.erowid.org/library/books_online/pihkal/pihkal155....

Using chlorine instead of bromine would give a more electrophilic species which could be used on less activated substrates in electrophilic arom. subst.

This paper describes the traditional Sandmeyer:

Synthesis and Properties of 5-(Substituted) Mercaptotetrazoles
EUGENE LIEBER, TAKASHI ENKOJI
J. Org. Chem.; 1961; 26(11); 4472-4479.

Full paper: http://rapidshare.de/files/18022203/Synthesis_and_Properties...

I haven't seen a direct way to introduce -OCN - you'll likely need to go via diazonium -> phenol(ate) --cyanogen halide--> Ar-OCN, probably not worth the hassle.

[Edited on 14-4-2006 by Sandmeyer]

[Edited on 14-4-2006 by Sandmeyer]

Sandmeyer - 14-4-2006 at 13:06

Ar-SCN --> Ar-SH

With dithionite:

4-iodo-phenyl thiocyanate -alcoholoc potassium hydrosulfite-> 4-iodo-thiophenol

Challenger; Collins; J. Chem. Soc.; 125; 1924; 1379.


4-chloro-2,5-dimethyl-phenyl thiocyanate --Na2S2O4--> 4-chloro-2,5-dimethyl-thiophenol
Patent; I. G. Farbenind.; DE495879.


1-(4-Thiocyanophenyl)pyrrolidine --Na2S*9H2O,NaOH/EtOH/4h--> 4-pyrrolidin-1-yl-benzenethiol
Yield 89%
Kmonicek, Vojtech; Svatek, Emil; Holubek, Jiri; Protiva, Miroslav; Collect. Czech. Chem. Commun.; 51; 4; 1986; 937-947.

With NaBH4:

2-methyl-4-octyloxy-1-thiocyanato-benzene -NaBH4/EtOH-> 2-methyl-4-octyloxy-benzenethiol

Okamoto, Hiroaki; Wu, Jianwei; Morita, Yuki; Takenaka, Shunsuke; BCSJA8; Bull. Chem. Soc. Jpn.; 75; 1; 2002; 175 - 180.

(2-tert-butoxycarbonylamino-5-tert-butyl-4-thiocyanato-phenyl)-carbamic acid tert-butyl ester -NaSH/NaBH4/MeOH-> (2-tert-butoxycarbonylamino-5-tert-butyl-4-mercapto-phenyl)-carbamic acid tert-butyl ester

Prasad, J. V. N. Vara; Org. Lett.; 2; 8; 2000; 1069 - 1072.

Fullpaper: http://rapidshare.de/files/18023556/Synthesis_of_Heterocycli...

With NaOH:


2-thiocyanato-benzaldehyde -NaOH-> 2-mercapto-benzaldehyde

Yield 70 %

Marini, Peter J.; Murray, Keith S.; West, Bruce O.; J. Chem. Soc. Dalton Trans.; 1983; 143-152.

[Edited on 14-4-2006 by Sandmeyer]