A New Method for the Synthesis of Aliphatic Nitro Compounds<sup>1,2</sup>

Kornblum, Nathan; Larson, H. O.; Blackwood, Robert K.; Mooberry, David D.; Oliveto, Eugene P.; Graham, Galen E.

doi:10.1021/ja01588a059

Cited by 143 publications

(74 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To a solution of 4-chlorobenzaldehyde (1.2 g, 8.5 mmol) and 2-methyl-l-nitropropane 4 (2.57 g, 25.5 mmol) [12] in dry THF (4.5 mL) was added 1,1,3,3-tetramethylguanidine (289 µl, 2.5 mmol) by syringe. The resulting yellow-orange solution was stirred at room temperature for 72 h. The solution was then concentrated in vacuo to a yellow oil and directly flash-chromatographed on silica gel (hexanes/ethyl acetate, 4:1) to afford 1.24 g (61%, 91% corrected for recovered 4-chlorobenzaldehyde) of nitroalcohol 5 as a colorless oil.…”

Section: Threo-and Erythro-1-(4-chlorophenyl)-2-nitro-3-methylpropanomentioning

confidence: 99%

“…This report addresses a novel preparation of racemic 2 which utilizes the nitroaldol (Henry) reaction [10] and the classical aminopinacol rearrangement [11] as the key steps. Our synthesis of (±)-2 (Scheme 2) commences with the reaction of 2-methyl-1-nitropropane 4, freshly-prepared by the method of Kornblum [12], and 4-chlorobenzaldehyde thereby furnishing nitroalcohol 5. The nitroaldol reaction required extended reaction times despite the usage of bases/reaction systems such as potassium fluoride/DMF, triethylamine/THF, sodium methoxide/methanol or the silyl nitronate of 4 [13].…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Rearrangement Route to Fenvaleric Acid

Luzzio¹,

Fitch²

2000

J. prakt. Chem.

View full text Add to dashboard Cite

Esfenvalerate, (S,S)-α-cyano-3-phenoxybenzyl-2-(4-chlorophenyl)-3-methylbutyrate (1), one of the most widely-used pesticides in the synthetic pyrethrin analog class, holds a prominent place in the agrochemical world [1]. Designated by Several trade names such as Sumicidin ® , Sumi-alpha ® , Asana XL ® , Pydrin ® and fenvalerate ® [2], esfenvalerate is a broad-spectrum insecticide which exhibits limited mammalian toxicity and adequate stability in the environment [3]. Esfenvalerate has two chiral centers, thus allowing for the preparation of four possible stereoisomers, with the (S,S)-stereoisomer having the highest insecticidal activity [4]. Several routes have yielded racemic and stereochemically pure 1, both in isotopically-labeled and unlabeled form. A simple retrosynthetic analysis, formally an ester cleavage, transforms 1 to 2-(4-chlorophenyl)-3-methylbutyric acid (fenvaleric acid) (2) and (α-cyano-3-phenoxybenzyl alcohol (3). (Scheme 1). Therefore, the majority of previous routes for the preparation of 1 resides in the synthesis of fenvaleric acid (2). Examples of previously-reported syntheses of 2 include alkylation of 4-chlorophenylacetonitrile with isopropyl halides [5] followed by hydrolysis and optical resolution [6], rhodium-catalyzed asymmetric hydroformylation reactions of 2-methyl-1-(4-chlorophenyl)propene followed by oxidation [7], asymmetric reduction of 3-methyl-2-chlorophenyl-2-butenoic acid [8] and asymmetic alkylation of 4-chlorophenylacetic acid with a chiral auxiliary [9]. Our interest Abstract. (±)-Fenvaleric acid 2, the key intermediate for the preparation of the pesticide esfenvalerate 1, was prepared by a novel sequence which first involves the Henry reaction of 2-methyl-1-nitropropane and 4-chlorobenzaldehyde. The nitroaldol reaction provided nitroalcohol 5 which was then rein an alternative laboratory-scale synthesis of (±)-2 emerges from the standpoint of evaluating potential prepa-rative routes for isotopic labeling as well as probing the utility of the Henry reaction in preparing small molecules of commercial interest. This report addresses a novel preparation of racemic 2 which utilizes the nitroaldol (Henry) reaction [10] and the classical aminopinacol rearrangement [11] as the key steps. Our synthesis of (±)-2 (Scheme 2) commences with the reaction of 2-methyl-1-nitropropane 4, freshly-prepared by the method of Kornblum [12], and 4-chlorobenzaldehyde thereby furnishing nitroalcohol 5. The nitroaldol reaction required extended reaction times despite the usage of bases/reaction systems such as potassium fluoride/DMF, triethylamine/THF, sodium methoxide/methanol or the silyl nitronate of 4 [13]. Finally, the reaction of nitroalkane 4 and 4-chlorobenzaldehyde in the presence of a catalytic amount of 1,1,3,3-tetraduced to the corresponding aminoalcohol 6. Submission of 6 to an aminopinacol rearrangement promoted by nitrous acid deamination then afforded aldehyde 8 through a 1,2-aryl shift. The product fenvaleric aldehyde 8 was then converted to the title compound 2 by a modified Jone...

show abstract

Section: Threo-and Erythro-1-(4-chlorophenyl)-2-nitro-3-methylpropanomentioning

confidence: 99%

mentioning

confidence: 99%

A Rearrangement Route to Fenvaleric Acid

Luzzio¹,

Fitch²

2000

J. prakt. Chem.

View full text Add to dashboard Cite

show abstract

“…Kornblum et al (1956) for 'synthesizing nitroalkanes by reacted with sodium nitrite in Nfl-dimethyl formamide (DMF).…”

Section: Preparation Of 5hexenylmercuric Bromidementioning

confidence: 99%

Organic tanks safety program FY96 waste aging studies

Camaioni¹,

Samuels²,

Linehan³

et al. 1996

View full text Add to dashboard Cite

“…This transformation proved troublesome, since the application of published procedures for the transformation of halides into nitroalkanes [12,13] to the reaction between sodium nitrite and benzyl bromide, used as a model, did not lead to the expected phenylnitromethane but to benzyl nitrite as the only product. This problem could be overcome by addition of urea to the reaction mixture in order to increase the solubility of sodium nitrite in the dimethylformamide used as solvent [14], and under the new conditions (-20 °C, urea, DMF) the model reaction gave phenylnitromethane in 80% yield. This result was further improved by the use of benzyl iodide as the substrate, which led to the desired nitro derivative in 99% yield after 5 h at -20 °C.…”

Section: Resultsmentioning

confidence: 99%

Convenient Synthesis of Highly Functionalized, 3,4-Disubstituted Indole Building Blocks

Miranda¹,

López‐Alvarado²,

Avendaño³

et al. 2007

TOOCJ

View full text Add to dashboard Cite

Several 3,4-disubstituted indole building blocks were synthesized, containing a one-carbon functional group at C-4 and a three-carbon chain bearing at least one functional group. A C-4 functionalized indole derivative was prepared by application of the Leimgruber-Batcho reaction. Several three-carbon chains were subsequently installed at the indole C-3 position. In the first strategy employed, a Mannich reaction was followed by the creation of a C-C bond by phosphine-induced generation of a 3-methyleneindolenine species, which was trapped by diethyl malonate. Alternatively, a Vilsmeier formylation at C-3 was followed by Knoevenagel or Wittig reactions or by treatment with ethyl diazoacetate in the presence of a Lewis acid. Direct introduction of the three-carbon chain at C-3 using a Lewis acid-catalyzed Michael reaction was also achieved. Further functionalization of the benzylic position attached to C-4 by attachment of a nitro group was carried out, but preparation of a tricyclic welwistatin fragment by intramolecular nitroalkane acylation or intramolecular Henry reactions was not possible.

show abstract

A New Method for the Synthesis of Aliphatic Nitro Compounds^1,2

Cited by 143 publications

References 0 publications

A Rearrangement Route to Fenvaleric Acid

A Rearrangement Route to Fenvaleric Acid

Organic tanks safety program FY96 waste aging studies

Convenient Synthesis of Highly Functionalized, 3,4-Disubstituted Indole Building Blocks

Contact Info

Product

Resources

About

A New Method for the Synthesis of Aliphatic Nitro Compounds1,2

Cited by 143 publications

References 0 publications

A Rearrangement Route to Fenvaleric Acid

A Rearrangement Route to Fenvaleric Acid

Organic tanks safety program FY96 waste aging studies

Convenient Synthesis of Highly Functionalized, 3,4-Disubstituted Indole Building Blocks

Contact Info

Product

Resources

About

A New Method for the Synthesis of Aliphatic Nitro Compounds^1,2