4'-Methylpropiophenone: Applications, synthesis and FTIR

General description

4-Methylpropiophenone is a chemical reagent with an aromatic ketone that is propiophenone bearing a methyl group at C-4. It serves as pharmaceutical and synthesis material intermediate, and it is also used in electrocarboxylation reactions. The molecule of 4'-Methylpropiophenone contains a polar carbonyl (C=O) bond and a non polar benzene ring, and the entire molecule is relatively polar, but also has a certain degree of non polarity. Therefore, it can be soluble in both non-polar and polar solvents. The molecules of 4'-Methylpropiophenone contain longer alkyl chains and benzene rings, and there are certain van der Waals forces and hydrogen bonding forces between the molecules. These forces result in relatively high melting and boiling points of 4'-Methylpropiophenone. 4'-Methylpropiophenone is a chemical reagent used for electrocarboxylation reactions. It is an intermediate of the drug Naomanin and can be used as an organic synthesis intermediate and a pharmaceutical intermediate. It is mainly used in laboratory research, development processes and chemical production processes. Its appearance is as follows:

Figure 1 Appearance of 4'-Methylpropiophenone

Applications

Aromatic ketones such as acetophenone, propiophenone and their derivatives have great analytical and pharmaceutical applications. Substituted propiophenones, for example 4'-Methylpropiophenone, has tremendous pharmaceutical applications. 4'-Methylpropiophenoneis used as an antibacterial agent [1]. It is also used as a photo radical polymerization initiator to provide a cross linkable silyl group terminated vinyl polymer [2].

Synthesis

To a 0.5-2 mL process vial sodium p-tolylsulfinate (89.0 mg, 0.50 mmol, 1 equiv.), Pd(O2CCF3)2 (13.3 mg, 0.04 mmol, 0.08 equiv.), ligand (0.06 mmol, 0.12 equiv.), H2O (700 μL), THF (700 μL) and MeCN (131 μL, 2.50 mmol, 5 equiv.) were added. Trifluoroacetic acid (382 μL, 5.00 mmol, 10 equiv.) was added to the reaction mixture and the vial was instantly capped under air. The clear, yellow to orange solution was then heated using microwave irradiation at 100 °C for 1 h. The cold reaction mixture was diluted with 6 mL 2 M NaOH solution and extracted with dichloromethane (3 × 10 mL). The combined organic phases were washed with 2 M HCl (3 x 10 mL) and dried over MgSO4. After evaporation of the solvent the crude product was purified by silica column chromatography (pentane:dichloromethane) to provide the pure isolated product 3a. 4'-Methylpropiophenone as colourless liquid, yield 91%. 1H NMR (400 MHz, CDCl3) δ = 7.88 - 7.84 (m, 2H), 7.26 - 7.23 (m, 2H), 2.97 (q, 3JHH = 7.3 Hz, 2H), 2.40 (s, 3H), 1.21 (t, 3JHH = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ = 200.5, 143.5, 134.4, 129.2, 128.1, 31.6, 21.6, 8.3. [3]

FTIR

For the compound 4'-Methylpropiophenone, the FTIR band observed at 3048 cm-1 and FT-Raman band at 3068 cm-1 have been assigned to CAH stretching vibration. In general the aromatic CAH stretching vibrations calculated theoretically are in good agreement with the experimentally reported values for disubstituted benzene in the region 3200–2900 cm-1. The title molecule 4'-Methylpropiophenone has both out of plane and in-plane aromatic CAH bending vibrations. The CAH in-plane and out-of-plane bending vibrations generally lie in the region 1300–1000 cm-1 and 1000–675 cm-1, respectively. The very strong and strong bands observed at 964 and 842 cm-1 in the FT-IR spectrum and the medium strong band observed at 816 cm-1 in the FT-Raman are assigned to CAH out-of-plane bend- ing vibration for MPP. The theoretically computed wavenumber for this mode falls within the range at 965, 843 and 815 cm-1 (mode Nos. 40, 42 and 43) by B3LYP/6-311++G(d,p) method. The compound under consideration 4'-Methylpropiophenone possesses the two CH3 group in the side substitution chain and phenyl ring. For the assignments of CH3 group frequencies one can expect that nine fundamentals can be associated to each CH3 group. The FT-IR band observed at 2952 cm-1 has been assigned to CH3 symmetric stretching vibration. The C=O stretching vibration in 4'-Methylpropiophenone has a main contribution in the mode, with B3LYP/6-311++G(d,p) predicted frequency at 1694cm-1.

References

[1]Ponnurengam Malliappan Sivakumar, Gayathri Sheshayan, Mukesh Doble, Chem. Bio. Drug Des. 72 (4) (2008) 303–313.

[2]Nakagawa, Ogawa, Tamai, EP 1 923 431 A1, App no: 06797534.2. 2008.

[3]Behrends et al. Microwave-Assisted Palladium(II)-Catalyzed Synthesis of Aryl Ketones from Aryl Sulfinates and Direct ESI-MS Studies Thereof. ACS Catalysis (2011), 1(11), 1455-1459.