β-nitrostyrene

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Structural formula
Structural formula of β-nitrostyrene
trans -β-nitrostyrene
General
Surname β-nitrostyrene
other names
  • trans -β-nitrostyrene
  • trans -1-nitro-2-phenylethene
  • ( E ) - (2-nitrovinyl) benzene
  • β-nitrostyrene
Molecular formula C 8 H 7 NO 2
Brief description

light yellow to yellow crystalline powder or prismatic crystals

External identifiers / databases
CAS number
  • 102-96-5 (unspecified stereochemistry)
  • 5153-67-3 ( E- shape)
  • 15241-23-3 ( Z- shape)
EC number 203-066-0
ECHA InfoCard 100,002,788
PubChem 5284459
ChemSpider 4447524
Wikidata Q15633930
properties
Molar mass 149.15 g mol −1
Physical state

firmly

Melting point

55-58 ° C at 1.013 hPa

boiling point

250-260 ° C

solubility

practically insoluble in water, soluble in ethanol and acetone , very soluble in diethyl ether , chloroform and carbon disulfide

safety instructions
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 315-319-335
P: 302 + 352-304 + 340-305 + 351 + 338
Toxicological data

33 mg kg −1 ( LD Lo ,  mouse ,  ip )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

β-nitrostyrene is an aromatic nitro alkene , which mainly in the trans conformation is present and by a Henry reaction of benzaldehyde and nitromethane is easily accessible. As an α, β-unsaturated nitro compound , β-nitrostyrene is a suitable acceptor for enantioselective Michael additions to Michael donors, such as. B. aldehydes or ketones . β-Nitrostyrene is used in synthesis variants of the γ-aminobutyric acid derivatives baclofen and phenibut and as a precursor for phenethylamine and its derivatives.

Occurrence and representation

As early as 1839, when he distilled liquid Storax resin with concentrated nitric acid, Eduard Simon received an “essential oil” that smelled strongly of cinnamon and solidified in “splendid prisms”, which he called nitrostyrene.

August Wilhelm von Hofmann described and confirmed the substance obtained according to E. Simon's instructions as nitrostyrene.

The first targeted synthesis of β-nitrostyrene was reported in 1883 with the reaction of benzaldehyde with nitromethane in the presence of zinc chloride (acid catalysis).

Johannes Thiele presented β-nitrostyrene for the first time in 1899 in a nitroaldol condensation, later named the Henry reaction , by basic catalysis using potassium methoxide in "excellent yield" as yellowish prisms.

Henry reaction to β-nitrostyrene

The nitro alcohol formed as an intermediate in the reaction of benzaldehyde with nitromethane dehydrates spontaneously with formation of the α, β-unsaturated nitroalkene.

With amylamine as the catalyst, Emil Knoevenagel obtained β-nitrostyrene in 75% yield.

A laboratory procedure that is simple in terms of preparation and using sodium hydroxide solution as a catalyst indicates a yield of 80 to 83%.

The use of methylamine or ammonium acetate in acetic acid as a catalyst has no advantages over alkali hydroxides or alcoholates.

The nitroaldol reaction in the ionic liquid 2- (hydroxyethyl) ammonium format gives small batches of β-nitrostyrene in 90% yield.

Nitration of styrene with nitrogen monoxide NO in 1,2-dichloroethane EDC and dehydration of the nitroalcohol that is formed at the same time by heating with acidic aluminum oxide gives very small batches (1 mmolar) β-nitrostyrene in 95% yield.

Nitration of styrene to β-nitrostyrene

properties

β-Nitrostyrene is a yellow crystalline substance that crystallizes from ethanol in rhombic prisms when it cools and dissolves in many organic solvents. The compound "smells extremely like Zimm" and has "a sweet but extremely burning taste and a tear-irritating odor". The vapors from hot β-nitrostyrene solutions are extremely irritating to the nose and eyes; the skin of the face is particularly sensitive to the solid substance.

Applications

Hydrogenation to β-phenylethylamine

The complete hydrogenation of β-nitrostyrene with hydrogen on a palladium contact gives β-phenylethylamine in 84% yield, compared to 88% in the reduction with borane - tetrahydrofuran complex,

Hydrogenation of β-nitrostyrene

While hydrogenation with lithium aluminum hydride leads to phenylethylamine in only 60% yield, the parent compound is more pharmacologically effective, especially psychotropic phenylethylamines .

Diels-Alder reactions

As an activated alkene and dienophile , β-nitrostyrene reacts with dienes , e.g. B. 1,3-butadiene or 1,3-diphenylisobenzofuran in a Diels-Alder reaction with high yields to the corresponding adducts.

Diels-Alder reactions with β-nitrostyrene

With cyclopentadiene a phenyl-2-nitro norbornene is formed in 85% yield .

Diels-Alder reaction of β-nitrostyrene with cyclopentadiene

Michael reactions

As an α, β-unsaturated nitro compound, β-nitrostyrene is an excellent acceptor in Michael additions. Β-Nitrostyrene reacts with Meldrum's acid in the presence of hydrotalcite in 95% yield to form the Michael addition product,

Reaction of β-nitrostyrene with Meldrum's acid

which when heated in ethanol with elimination of acetone and CO 2 in 85% yield 3-phenyl-4-nitrobutyric acid ethyl ester - a γ-nitrobutyric acid compound - forms. The nitrobutyric acid ester is converted into 4-phenylpyrrolidin-2-one (82%) with sodium borohydride in the presence of nickel (II) chloride hexahydrate, which is converted into the γ-aminobutyric acid (GABA) derivative 4-amino-3 with 6M hydrochloric acid -phenylbutyric acid (as hydrochloride ) phenibut is cleaved.

Synthesis of phenibut

The same reaction sequence with 4-chloro-β-nitrostyrene as the starting compound gives the γ-aminobutyric acid derivative baclofen , which is effective as a muscle relaxant .

When using chiral catalysts, such as. B. quinine - alkaloids , prolinol derivatives or thiourea can with aldehydes - even with the weak nucleophile acetaldehyde

Enantioselective addition to β-nitrostyrene

- and 1,3-dicarbonyl compounds - also with the sterically hindered dipivaloylmethane - Michael addition products can be represented in practically quantitative yield and enantiomeric excesses of up to 99%.

Reaction of β-nitrostyrene with malonic ester

Baylis-Hillman reaction

The Baylis-Hillman reaction is suitable for base-catalyzed CC linkage between aldehydes (or electrophiles) and activated alkenes in the presence of bases, such as. B. DABCO , with highly functionalized products such. B. α-substituted allyl alcohols arise. In the presence of diarylthioureas and the base DMAP , the aldehyde ethyl glyoxylate reacts with β-nitrostyrene in high yields to form 2-hydroxy-3-nitro-4-arylbut-3-enoates.

Baylis-Hillman reaction with β-nitrostyrene

Barton-Zard reaction

The Barton-Zard reaction named after Derek HR Barton , in which β-nitrostyrene (derivatives) with alkyl isocyanoacetates or tosylmethyl isocyanide TosMIC in the presence of a strong base, such as. B. react n -Butyllithium , produces substituted pyrroles. From β-nitrostyrene is formed with the isocyanide TosMIC and ethyl chloroformate the polymer-fixed in the presence of Super Base PS-BEMP, the 4-nitro-3-phenyl-1 H -pyrrole-2-ethyl carboxylate in 76% yield.

Barton-Zard reaction with β-nitrostyrene

3,4-Diarylpyrroles are of interest as starting compounds for aryl-substituted porphyrins and can be prepared in a modest yield (approx. 50%) by reducing β-nitrostyrene with titanium (III) chloride in aqueous 1,4-dioxane , but prepared very easily become.

Formation of 3,4-diphenylpyrrole by reduction of β-nitrostyrene

Further pyrrole syntheses using β-nitrostyrene (derivatives) are described.

Active ingredients based on β-nitrostyrene

Addition products of dithiocarbamates to β-nitrostyrene were synthesized and tested for their effectiveness against bacteria and fungi.

Dithiocarbamate addition to β-nitrostyrene

β-Nitrostyrene and its halogen- or methyl-substituted derivatives were examined for antibacterial properties, as they show high reactivity in the Michael addition towards thiols from cysteine-rich enzymes. However, β-nitrostyrene itself is not very active.

In the presence of traces of sodium methoxide, β-nitrostyrenes and two equivalents of dimethylformamide dimethylacetal in DMF form 1,3,5-triphenylbenzenes in moderate yields (up to 40%) .

annotation

Β-nitrostyrene is sometimes incorrectly stated as a precursor for the dye indigo . However, Ludwig Gattermann mistakenly suspected 2-nitrostyrene as an intermediate stage with β-nitrostyrene.

Review article

  • Conjugated nitroalkenes as intermediates
  • Syntheses with conjugated nitroalkenes
  • Advances in the Synthesis of Conjugated Nitroalkenes

Individual evidence

  1. ↑ Entry on trans-β-nitrostyrene at TCI Europe, accessed on October 25, 2017.
  2. ↑ a b c E. Simon: About the liquid Storax (Styrax liquidus) . In: Liebigs Ann. Chem. Band 31 , no. 3 , 1839, pp. 265-277 , doi : 10.1002 / jlac.18390310306 .
  3. ↑ a b J. Thiele: Condensation of nitromethane with aromatic aldehydes . In: Ber. German Chem. Ges. Volume 32 , no. 1 , 1899, p. 1293-1295 , doi : 10.1002 / cber.189903201209 .
  4. ↑ a b Data sheet trans-β-Nitrostyrene 99% from Sigma-Aldrich , accessed on October 25, 2017 ( PDF ).
  5. ↑ a b Data sheet trans-beta-Nitrostyrene, 98% from AlfaAesar, accessed on October 25, 2017 ( PDF )(JavaScript required) .
  6. ^ William M. Haynes: CRC Handbook of Chemistry and Physics, 91st Edition . CRC Press, Boca Raton, FL, USA 2010, ISBN 978-1-4398-2077-3 , pp. 3-396 .
  7. ↑ a b Data sheet β-nitrostyrene for synthesis (PDF) from Merck , accessed on October 25, 2017.
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  39. ^ N. Milhazes et al .: β-Nitrostyrene derivatives as potential antibacterial agents: A structure-property-activity relationship study . In: Bioorg. Med. Chem. Band 14 , no. 12 , 2006, p. 4078-4088 , doi : 10.1016 / j.bmc.2006.02.006 .
  40. ↑ TY Kim, HS Kim, KY Lee, JN Kim: N, N -dimethylformamide dimethylacetal (DMF-DMA) catalyzed formation of 1,3,5-trisubstituted benzene derivatives from α, β- unsaturated nitro compounds . In: Bull. Korean Chem. Soc. tape 20 , no. 11 , 1999, p. 1255-1256 ( easechem.com [PDF]). N, N -Dimethylformamide dimethylacetal (DMF-DMA) catalyzed formation of 1,3,5-trisubstituted benzene derivatives from α, β-unsaturated nitro compounds ( Memento of the original from October 26, 2017 in the Internet Archive ) Info: The archive link became automatic used and not yet tested. Please check the original and archive link according to the instructions and then remove this notice.  @1@ 2Template: Webachiv / IABot / pdf.easechem.com
  41. ↑ L. Gattermann, Laboratory Methods of Organic Chemistry , pp. 371-372, The Macmillan Co., New York, 1937.
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