p-nitroacetanilide

Essential chemical intermediates in dye manufacture are nitroanilines. In this experiment series, p-nitroaniline is synthesized by a multi-step sequence as shown in Figure 1. This compound is used to synthesize the azo dye Para Red.

In order to prepare p- nitroaniline from acetophenone, by chemical reactions, one functional group on monosubstituted benzene is transformed into another and then an electrophilic aromatic substitution reaction is done to obtain the target compound. The various compounds prepared will be characterised by ¹H NMR spectroscopy.

As shown in Equation 1, the first step for synthesizing p-nitroaniline is preparing acetophenone oxime from acetophenone. Oximes are highly crystalline featuring a carbon-nitrogen double bond with an OH group on the nitrogen atom. They are extensively used for the protection, purification and characterization of carbonyl compounds in synthetic organic chemistry. Oximes are versatile building blocks used to synthesize nitrogen containing compounds.

Figure 1. p-nitroaniline

Equation 1. Synthesis of acetophenone oxime.

Safety

Ethanol is flammable and must be handled with care. Acetophenone, sodium acetate trihydrate and acetophenone oxime are irritable to the skin, eyes and respiratory system.

Hydroxylamine hydrochloride is corrosive, avoid all contact and handle with care. Deuterochloroform is toxic and handle with care.

Synthesis of Acetophenone Oxime

Procedure

To a solution of 30mL water and 10mL ethanol solution in a 100mL round bottom flask,

acetophenone (3.75mL), hydrated sodium acetate crystals (7.50g) and hydroxylamine hydrochloride (3.75g) are added.

The mixture is heated by stirring on a hot water bath for 10min as shown in Figure 2. On the top of the solution, colorless oil drops should form. The mixture is cooled for 30min in an ice bath during which oil solidification must take place. If required, crystallization is induced by scratching the flask sides with a glass rod. The white solid is collected by filtration, washed with cold water and dried in the air. The crude product is recrystallized from boiling water ensuring that all oil droplets dissolved. The purified product is then filtered and dried and yield is recorded as shown in Figure 3.

Figure 2. Experimental setup for the synthesis of acetophenone oxime

Figure 3. Purified acetophenone oxime

Figure 4 shows the ¹H NMR spectrum of acetophenone, a singlet (3H) at 2.60ppm, corresponding to the methyl group at position 1. The five aromatic protons at positions 4, 5 and 6 resonate as a multiplet between 7.39-8.09ppm.

Figure 4. ¹H NMR spectrum of acetophenone, CDCI₃

Figure 5 shows the ¹H NMR spectrum of acetophenone oxime wherein a singlet (3H) is seen at 2.36ppm, corresponding to the methyl group at position 1.

In the range 7.30 to 7.84ppm, the five aromatic protons are positions 4, 5 and 6 resonate as a broad multiplet. At 9.31ppm, the exchangeable NOH proton is observed as a broad singlet with a low peak integration value.

Figure 5. ¹H NMR spectrum of acetophenone oxime, CDCI₃

The next step in p-nitroaniline synthesis is preparing acetanilide from acetophenone oxime as shown in Equation 2.

Equation 2. Synthesis of acetanilide.

Synthesis of Acetanilide: the Beckmann Rearrangement

Procedure

3mL concentrated sulfuric acid is placed in a boiling tube and heated in a hot water bath until the temperature of the acid reaches around 90 °C. Acetophenone oxime (3g) is added in small portions with stirring over a period of 20 min. For a further 15min the reaction mixture is stirred. The cool mixture is poured to crushed ice to precipitate the title compound. The solid is collected by filtration and washed with cold water. The crude product is recrystallized from 50mL water and yield is recorded.

The ¹H NMR spectrum of acetanilide (Figure 6) shows a singlet (3H) at 2.14ppm, corresponding to the methyl group at position 1. The five aromatic protons at positions 4, 5 and 6 resonate as a broad multiplet between 7.02-7.65ppm. As seen in the peak integration The signal for the exchangeable NH proton may also be overlapping with the multiplet as suggested by the peak integration value.

Figure 6. ¹H NMR spectrum of acetanilide, CDCl3

The third step in synthesizing p-nitroaniline is nitration of acetanilide using a mixture of concentrated sulfuric and nitric acids to obtain nitroacetanilide (Equation 3). The main colorless product, p-nitroacetanilide, is almost insoluble in ethanol and filtering out is possible, while the yellow ortho isomer remains in the filtrate.

Equation 3. Synthesis of p-nitroacetanilide

Nitration of acetanilide

Procedure

1.5mL of glacial acetic acid is placed in a boiling tube and 1.5g of acetanilide is added. The mixture is stirred and 3mL of concentrated sulfuric acid is added. The hot reaction mixture is cooled in an ice/salt bath till there is a temperature drop to 0.5 °C.

Slowly, 0.6mL of fuming nitric acid is added ensuring the temperature does not rise above 20 °C. After adding, the reaction mixture is brought to room temperature and allowed to stand for 20 min. The mixture is poured onto ice and maintained for another 20min. The crude yellow solid is collected by filtration, washed with water and dried in the air. From the minimum amount of hot ethanol, p-nitroacetanilide is recrytsallized as a cream-coloured crystalline solid (Figure 7). Dry in the air and record your yield.

Scheme 3. Synthesis of p-nitroacetanilide.

Figure 7. (a)-(b). Crude and recrystallised p-nitroacetanilide.

The ¹H NMR spectrum of acetanilide (Figure 8) shows a singlet (3H) at 2.05ppm, corresponding to the methyl group at position 1. The five aromatic protons at positions 4, 5 and 6 resonate as a broad multiplet between 6.97-7.74ppm. The exchangeable NH proton is also observed in DMSO-d6 at 9.91ppm as a broad singlet.

Figure 8. ¹H NMR spectrum of acetanilide, DMSO-d6

p-nitroacetanilide’s ¹H NMR spectrum (Figure 9) shows a singlet (3H) at 2.10ppm, corresponding to the methyl group at position 1. The four aromatic protons at positions 4 and 5 appear as a second order AA'BB' system, with two multiplets centred at 7.77 and 8.21ppm. The exchangeable NH proton is observed at 10.52ppm as a broad singlet.

Figure 9. ¹H NMR spectrum of p-nitroacetanilide, DMSO- cf6.

The hydrolysis of p- nitroacetanilide under acidic conditions is the final step in the synthesis ofp-nitroaniline (Equation 4).

Hydrolysis of p-nitroacetaniline

Procedure

A 25mL round bottom flask is charged with a solution of concentrated sulfuric acid (4mL) and water (3mL). p-nitroacetanilide (0.7g) is added and heated the reaction mixture gently under reflux for 20min. The hot mixture is poured into cold water (20mL), and the pH of the solution is adjusted with sodium hydroxide solution (2M, approximately 120mL) until alkaline and a yellow precipitate is obtained. Cool the mixture in an ice bath. The crude yellow solid is collected by filtration , washed thoroughly with water and dried in the air. It is recrystallized from 1:1 ethanol/water mixture to obtain bright yellow crystals of the title compound.

Equation 4. Synthesis of p-nitroacetanilide.

The ¹H NMR spectrum of p-nitroacetanilide (Figure 10) shows two doublets at 6.59 and 7.95ppm, corresponding to the four aromatic protons at positions 2 and 3 respectively. The signal for the exchangeable NH2 protons is overlapping with the doublet at 6.59ppm, as indicated by the 2:1 peak integration values.

Figure 10. ¹H NMR spectrum of p-nitroanilide, DMSO-d6.

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Synthesis of poly[(pyrrole-2,5-diyl)-co-(4-hydroxylbenzylidene)] catalysed by Maghnite– H+

Larbi B, Hachemaoui A, Ahmed Y, Abdelghani B, Karime C, Mohamed B. Synthesis of poly[(pyrrole-2,5-diyl)-co-(4-hydroxylbenzylidene)] catalysed by Maghnite– H+. Orient J Chem 2013;29(4)

Larbi B, Hachemaoui A, Ahmed Y, Abdelghani B, Karime C, Mohamed B. Synthesis of poly[(pyrrole-2,5-diyl)-co-(4-hydroxylbenzylidene)] catalysed by Maghnite– H+. Orient J Chem 2013;29(4). Available from: http://www.orientjchem.org/?p=1146

http://www.orientjchem.org/vol29no4/synthesis-of-polypyrrole-25-diyl-co-4-hydroxylbenzylidene-catalysed-by-maghnite-h/

Most of the PPHB were found to be soluble in organic solvents such as tetrahydrofuran (THF), CH2C12, N,N-dimethylformamide (DMF), and sulfolane. Although polymers have highly conjugated chains due to the high degree of dehydrogenation, they were very soluble in organic solvents such as THF, giving grey solutions of high concentrations. The very good solubility of polymers in spite of their high degree of π-conjugation is due largely to the bulky side groups (Φ) at the methane carbon =C (Φ) link and also to the low molecular weight to some extent.

The UV-Vis absorption was recorded with an OPTIZEN 2120 spectrometer. Figure 2 shows the optical absorption spectra of polymers PPHB in CH2Cl2 solution. The colours of the polymer solution were brown or almost black. The absorption spectra in Figure 2 shows the band in the range of (300–350) nm assigned to the π-π* transition of the aromatic heterocycles since it corresponds to the same band as its precursor, and the band in the range of (400–430) nm is assigned to the π-π* transition.

Figure 2: Spectre UV-visible de PPHB (in CH2Cl2). Click here to View figure

The 1H-NMR spectra of PPHB were obtained to further investigate and confirm the proposed structure. Figure 3 shows the 1H-NMR spectrum of PPHB in DMSO, The resonance at 10.45 ppm is assigned to the proton resonance of hydroxyl group in the benzene ring. The resonance at 9.14 ppm is assigned to the proton resonance of hydrogen in pyrrole .we observe a new proton resonance of 6.64–6.93 ppm was observed, indicating the formation of the quinoid rings in the polymer backbone, x and y are impurities. The polymers so obtained are readily soluble in common organic solvents, such as chloroform, dichloromethane, THF.

Figure 3. 1H-NMR spectrum (300 MHz) of PPHB in DMSO  Click here to View figure

Figure 4 shows the FT-IR absorption spectra of PPHB. A distinct peak at 772 cm_1 of PPHB is due to the Cb–H the out-of plan vibration, characteristic of α-linkage in pyrrole ring. The peak at 1685 cm-1 of Fig. 4 is assigned to the C=C and the stretching vibration of aromatic in phenylene , this assignments is based on the FT-IR spectrum of pyrrole. The broad band at 3303 cm_1 is N–H stretching vibration of pyrrole ring and O–H vibration of hydroxyl on benzene ring in the side chain.

Figure 4.FT-IR spectrum of PPHB  Click here to View figure

Figures 5 show the TGA curves of PPHB obtained in a helium atmosphere at a heating rate of 100 0C/min. This polymer show bad thermal stability. For example, the intrinsic PPHB has an onset of thermal decomposition of 100 0 C attributed to OH, the second at 114 0C is assigned to carbon bridge, so the PPHB is little stable at high temperature.

Figure 5. TGA spectra of PPHB Click here to View figure

Conclusions

Maghnite–H+, proton exchanged montmorillonite clay is an effective initiator for the copolymerization of 4-hydroxybenzaldehyde with pyrrole.

A novel polymer, poly[(pyrrole-2,5-diyl)-co-(4-hydroxybenzylidene)], which has a π-conjugated chain was synthesized by using Maghnite–H+ as catalyse. The resultant polymer showed good solubility in common organic solvents and good film formability. Such results may serve primarily to illustrate a new strategy to increase the solubility of  low band gap polymers through the arrangement of different aromatic heterocycles in conjugated polymer backbones.

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The Diels-Alder-Reaction with inverse-Electron-Demand, a very efficient versatile Click-Reaction Concept for proper Ligation of variable molecular Partners

1H-NMR-Spectrum of the 9 in D6-DMSO. The structure illustrates the shift calculation for protons of the compound with ChemDraw Ultra 2004. (Numbers indicate the predicted shift of the signals in ppm; quality of estimation is indicated in colour: blue = good, red = rough)






This open question for the synthesis of tetrazine-based dienes in aqueous solution is answered below. The possibility of the synthesis of tetrazines functionalized with aryl compounds is attractive and could be successful. As illustrated in schema/table 3 the synthesis worked via the following educts: 2-cyanopyrimidine 6 and 4-cyanobenzoic acid 7 react with 80% aqueous hydrazine 8 to the intermediate 3,6-diaryl-1,2-dihydro-1,2,4,5-tetrazine 9 in 40 to 50 % yield. The oxidation to the corresponding 1, 4-diaryl-1,2,4,5-tetrazine is next reaction step followed by the conversion to the acid chloride with thionyl dichloride which in turn was reacted with the Boc-mono-protected 1,3-propylenediamine to the propyleneamine substituted acid amide 10. After deprotection with TFA the amino group was transferred with the acid chloride derivative of the TMZ 11 to the TMZ-diaryl-tetrazine 12 a diene compound poised for the DARinv. The corresponding NMR H spectra are shown in the figures 2-5.

The Diels-Alder-Reaction with inverse-Electron-Demand, a very efficient versatile Click-Reaction Concept for proper Ligation of variable molecular Partners Wiessler M, Waldeck W, Kliem C, Pipkorn R, Braun K - Int J Med Sci (2009)

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 Variable-temperature NMR spectroscopy is probably the most convenient and sensitive technique to monitor changes in molecular structure in solution. Rearrangements that are rapid on the NMR time-scale exhibit simplified spectra, whereby non-equivalent nuclear environments yield time-averaged resonances. At lower temperatures, when the rate of exchange is sufficiently reduced, these degeneracies are split and the underlying “static” molecular symmetry, as seen by X-ray crystallography, becomes apparent. Frequently, however, such rearrangement processes are hidden, even when they become slow on the NMR time-scale, because the molecular point group remains unchanged. Judicious symmetry breaking, such as by substitution of a molecular fragment by a similar, but not identical moiety, or by the incorporation of potentially diastereotopic (chemically non-equivalent) nuclei, allows the elucidation of the kinetics and energetics of such processes. Examples are chosen that include a wide range of rotations, migrations and other rearrangements in organic, inorganic and organometallic chemistry.

Symmetry Breaking in NMR Spectroscopy: The Elucidation of Hidden Molecular Rearrangement Processes

Symmetry 2014, 6(3), 622-654; doi:10.3390/sym6030622

http://www.mdpi.com/2073-8994/6/3/622

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Anthracene-resorcin[4]arene-based capsules: Synthesis and photoswitchable features

Herein we present the synthesis and the photochemical behavior of several new hemicarcerands containing anthracene units as photoactive species. By means of NMR investigations of compounds 9 and 11 the dimerization mode was revealed as a 9,10-9′,10′-dimerization, classically known from anthracene. Nevertheless only compound 11 could be converted to the opened form upon irradiation with 300 nm. Reopening of compounds 9 and 10could not be achieved so far either by heating or by irradiation.

Anthracene-resorcin[4]arene-based capsules: Synthesis and photoswitchable features

http://pubs.rsc.org/en/content/articlelanding/2011/ob/c1ob06030a#!divAbstract

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Conformational control of anticancer activity: the application of arene-linked dinuclear ruthenium(II) organometallics†

Fig. 3 ¹H NMR spectra of 4a (top) and 5a (bottom) (D₂O, 400 MHz, 298 K, 10 mM).
Resonances are identified with coloured circles: linker phenyl – red, Ru arene – blue, CH – green, PTA – orange, CH₂ – black and CH₃ – purple.

Scheme 1 Synthesis and numbering scheme of the mononuclear oxalato-complex 2a,  dinuclear oxalato-complexes 3a–6a and chlorido-analogues 2b–6b. /////////////////http://pubs.rsc.org/en/content/articlehtml/2014/sc/c4sc00116h/////////////// DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE Join me on Linkedin Join me on Facebook FACEBOOK Join me on twitter      Join me on google plus Googleplus  amcrasto@gmail.com