Free radical 4‐nitrophenylation of thieno[2,3‐<i>b</i>]pyridine. Part 1: General experimental procedure and prediction of isomeric ratios of products

Journal of Heterocyclic Chem

Reed

2001

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A 1:1 geometrically oriented encounter complex between thieno[2,3-b]pyridine (1) and 4-nitrophenyldiazoacetate (2) is proposed to account for the dominant formation (ca. 64%) of the 2-isomer in the mixture of 4-nitrophenyl-1 isomers obtained previously. A mechanism involving one-electron transfer from 1 to 2 plus fragmentation of 2 -• into 4-nitrophenyl free radical, N 2 , and acetate ion is invoked. Formation of other isomers is discussed.It is noted that there is a close correlation between orientational rules plus mechanisms of reaction for numerous free-radical substitutions (S R ) with S N reactions of alkyllithiums on furan, thiophene, Nalkylpyrroles, pyridine, and their condensed aromatic molecules, including 1, as substrates. Also isomeric selectivities for S E , S N , and S R substitutions into 1 were shown to be qualitatively consistent with one another. While S E reactions occur largely at position 3 and then at 2, S N and S R reactions occur either at 2 or 6. Selectivity for positions 4 or 5 is small or zero.

Section: Imentioning

confidence: 99%

“…A Correlaton of Isomeric Selectivities in Electrophilic, Nucleophilic and Free-Radical Substitutions into Thieno[2,3-b]pyridine (1).…”

Section: IVmentioning

confidence: 99%

Free‐radical 4‐nitrophenylation of thieno[2,3‐b]pyridine. Part 3: Consideration of mechanistic and selectivity factors involved in the substitution process

Journal of Heterocyclic Chem

Reed

2001

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“…

…”

mentioning

confidence: 99%

“…In a preceding paper [1] we reported an experimental procedure for the free-radical 4-nitrophenylation of thieno- [2,3-b]pyridine (1) by means of the hypothetical intermediate 4-nitrophenyldiazoacetate (2) under buffered conditions to yield a mixture of monosubstituted 4-nitrophenyl derivatives 3. Processing of this mixture led to two separable solid, crude products, Y (acetone-insoluble, chloroform-soluble, rust-colored) and Z (acetone-soluble, yellow-red sublimate) in yields of 12% and 20%, respectively.…”

mentioning

confidence: 99%

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Free radical 4‐nitrophenylation of thieno[2,3‐b]pyridine. Part 2: Isolation and structural studies of three samples of mono (4‐nitrophenyl) products; relative yields of the five possible isomers

Journal of Heterocyclic Chem

Weakley

Gilbertson

2001

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From the crude mixtures of isomeric 4-nitrophenylthieno [2,3-b]pyridines (3) previously reported [1] were isolated three analytically pure samples, viz. the 2-isomer (yellow needles, mp 258°, 3a), the 6-isomer (red prisms, mp 182°, 3e), and a ternary mixture of the 2-, 3-, and 4-isomers (orange needles, mp 213°, 3a:3b:3c = 1.3:1.0:0.5). The 258°compound was identified as either 3a or 3b by its 1 H nmr spectrum and definitively as the former by its x-ray crystallographic analysis. The isomeric identities of the 182°and 213°s amples were established from their 1 H nmr spectra only. No 5-isomer (3d) was identified. Semi-quantitatively, relative isomeric yields fit the pattern 2-(64%)>>6-(14%)≥3-(12%)>4-(6%)≥5-(≤4%). Crystallographic data for 3a are presented.J. Heterocyclic Chem., 38, 189 (2001).In a preceding paper [1] we reported an experimental procedure for the free-radical 4-nitrophenylation of thieno- [2,3-b]pyridine (1) by means of the hypothetical intermediate 4-nitrophenyldiazoacetate (2) under buffered conditions to yield a mixture of monosubstituted 4-nitrophenyl derivatives 3. Processing of this mixture led to two separable solid, crude products, Y (acetone-insoluble, chloroform-soluble, rust-colored) and Z (acetone-soluble, yellow-red sublimate) in yields of 12% and 20%, respectively. The present paper reports the isolation and identification of two chemically pure isomers and one analytically pure isomeric mixture from those products, as well as a semi-quantitative relationship amongst the yields of the five possible 4-nitrophenylthieno[2,3-b]pyridine isomers 3a-3e.Three variations on column chromatography with silica gel/chloroform were used to effect preliminary fractionations of the components of Y and Z. These fractions were analyzed qualitatively by thin-layer chromatography, with rejection of spots that were visible in ultraviolet light but were colorless in daylight as being non-nitrophenyl-bearing byproducts. Fractions were then subdivided further by thick-layer chromatography on silica gel into single-spot components (or ones which were only slightly contaminated by an impurity) for isolation and weighing. From Y (see Experiment II) was isolated the fast-moving (R f 0.76 with a solvent of chloroform-ethyl acetate, 1:1) 6-(4-nitrophenyl)thieno[2,3-b]pyridine isomer (3e) as red prisms, mp 181-182°, readily identified isomerically by means of its 1 H nmr spectrum (vide infra). Use of a column of activated silica gel for chromatography of part of Z (Experiment I) effected separation of the slower-moving (R f 0.63) 2-(4-nitrophenyl)thieno[2,3-b]-pyridine isomer (3a), obtained as yellow needles, mp 257-258°, easily identifiable from 1 H nmr as bearing its nitrophenyl substituent in the thiophene ring of 1 (singlet for one proton at δ 7.64). Single-crystal x-ray crystallography then established the location of this substituent at position 2 on the parent molecule (vide infra).Another portion of Z was chromatographed on a column of non-activated silica gel (Experiment III) and led to the successive is...

ChemInform Abstract: Free Radical 4‐Nitrophenylation of Thieno[2,3‐b]pyridine. Part 1. General Experimental Procedure and Prediction of Isomeric Ratios of Products.

Miller

2001

ChemInform