isothiocyanate

Image:Isothiocyanate group.svg

In organic chemistry, isothiocyanate is a functional group as found in compounds with the formula {{chem2|R\sN\dC\dS}}. Isothiocyanates are the more common isomers of thiocyanates, which have the formula {{chem2|R\sS\sC\tN}}.

Occurrence

Many isothiocyanates from plants are produced by enzymatic conversion of metabolites called glucosinolates. A prominent natural isothiocyanate is allyl isothiocyanate, also known as mustard oils.

Cruciferous vegetables, such as bok choy, broccoli, cabbage, cauliflower, kale, and others, are rich sources of glucosinolate precursors of isothiocyanates.{{cite web |title=Isothiocyanates |url=https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/isothiocyanates |publisher=Micronutrient Information Center, Linus Pauling Institute, Oregon State University |access-date=14 April 2019|date=1 April 2017}}

Structure

The {{chem2|N\dC}} and {{chem2|C\dS}} distances are 117 and 158 pm.{{cite journal |doi=10.1016/j.chemphys.2008.10.024|title=Structure and polarized IR spectra of 4-isothiocyanatophenyl 4-heptylbenzoate (7TPB)|year=2008|last1=Majewska|first1=Paulina|last2=Rospenk|first2=Maria|last3=Czarnik-Matusewicz|first3=Bogusława|last4=Kochel|first4=Andrzej|last5=Sobczyk|first5=Lucjan|last6=Dąbrowski|first6=Roman|journal=Chemical Physics|volume=354|issue=1–3|pages=186–195|bibcode=2008CP....354..186M}} By contrast, in methyl thiocyanate, {{chem2|N\tC}} and {{chem2|C\sS}} distances are 116 and 176 pm.

Typical bond angles for {{chem2|C\sN\dC}} in aryl isothiocyanates are near 165°. Again, the thiocyanate isomers are quite different with {{chem2|C\sS\sC}} angle near 100°.{{cite journal |doi=10.1016/S0040-4020(99)00386-5 |title=The chemistry of thiocyanic esters |date=1999 |last1=Erian |first1=Ayman W. |last2=Sherif |first2=Sherif M. |journal=Tetrahedron |volume=55 |issue=26 |pages=7957–8024 }} In both isomers the {{chem2|SCN}} angle approaches 180°.

Synthesis

Allyl thiocyanate isomerizes to the isothiocyanate:{{cite journal |doi=10.1021/ed048p81 |title=The Preparation and Isomerization of Allyl Thiocyanate. An Organic Chemistry Experiment |date=1971 |last1=Emergon |first1=David W. |journal=Journal of Chemical Education |volume=48 |issue=1 |page=81 |bibcode=1971JChEd..48...81E }}

:{{chem2|CH2\dCHCH2SCN -> CH2\dCHCH2NCS}}

Isothiocyanates can be prepared by treating organic dithiocarbamate salts with lead nitrate or tosyl chloride.{{OrgSynth | author = Dains FB | author2 = Brewster RQ | author3 = Olander CP | title = Phenyl Isothiocyanate | year = 1926 | volume = 6 | pages = 72 | doi = 10.15227/orgsyn.006.0072}}{{cite journal | last1 = Wong | first1 = R | last2 = Dolman | first2 = SJ | title = Isothiocyanates from tosyl chloride mediated decomposition of in situ generated dithiocarbamic acid salts | journal = The Journal of Organic Chemistry | year = 2007 | volume = 72 | issue = 10 | pages = 3969–3971 | pmid = 17444687 | doi = 10.1021/jo070246n}}

:File:Synthesis phenylisothiocyanate 1.svg

Isothiocyanates may also be accessed by the fragmentation reactions of 1,4,2-oxathiazoles.{{ cite journal | last1 = O'Reilly | first1 = RJ | last2 = Radom | first2 = L | title = Ab initio investigation of the fragmentation of 5,5-diamino-substituted 1,4,2-oxathiazoles | journal = Organic Letters | year = 2009 | volume = 11 | issue = 6 | pages = 1325–1328 | pmid = 19245242 | doi = 10.1021/ol900109b }} This methodology has been applied to a polymer-supported synthesis of isothiocyanates.{{ cite journal | last1 = Burkett | first1 = BA | last2 = Kane-Barber | first2 = JM | last3 = O'Reilly | first3 = RJ | last4 = Shi | first4 = L | title = Polymer-supported thiobenzophenone : a self-indicating traceless 'catch and release' linker for the synthesis of isothiocyanates | journal = Tetrahedron Letters | year = 2007 | volume = 48 | issue = 31 | pages = 5355–5358 | doi = 10.1016/j.tetlet.2007.06.025 }}

Reactions

Isothiocyanates are weak electrophiles, susceptible to hydrolysis. In general, nucleophiles attack at carbon:

Image:ThiazolidineSynthesis.gif enolate with phenyl isothiocyanate. In this one-pot synthesis{{cite journal | author1 = Ortega-Alfaro, M. C. | author2 = López-Cortés, J. G. | author3 = Sánchez, H. R. | author4 = Toscano, R. A. | author5 = Carrillo, G. P. | author6 = Álvarez-Toledano, C. | title = Improved approaches in the synthesis of new 2-(1, 3-thiazolidin-2Z-ylidene)acetophenones | journal = Arkivoc | year = 2005 | volume = 2005 | issue = 6 | pages = 356–365 | doi = 10.3998/ark.5550190.0006.631 | doi-access = free | hdl = 2027/spo.5550190.0006.631 | hdl-access = free }} the ultimate reaction product is a Thiazolidine. This reaction is stereoselective with the formation of the Z-isomer only.]]

Electrochemical reduction gives thioformamides.{{cite book|title=The Chemistry of Cyanates and Their Thio Derivatives|volume=Part 1|editor-first=Saul|editor-last=Patai|year=1977|publisher=Wiley|location=Chichester|lccn=75-6913|isbn=0-471-99477-4|chapter=The electrochemistry of cyanates and related compounds|first1=Ole|last1=Hammerich|first2=Vernon D.|last2=Parke}}{{rp|340}}

Flavor research

Isothiocyanates occur widely in nature and are of interest in food science and medical research. Vegetable foods with characteristic flavors due to isothiocyanates include bok choy, broccoli, cabbage, cauliflower, kale, wasabi, horseradish, mustard, radish, Brussels sprouts, watercress, papaya seeds, nasturtiums, and capers. These species generate isothiocyanates in different proportions, and so have different, but recognizably related, flavors. They are all members of the order Brassicales, which is characterized by the production of glucosinolates, and of the enzyme myrosinase, which acts on glucosinolates to release isothiocyanates.