A series of 2, 4, 5-trisubstituted oxazole: Synthesis, characterization and DFT modelling

Article abstract of DOI:10.1016/j.molstruc.2016.02.033

A new series of 2,4,5-trisubstituted oxazole were synthesized with good yields using simple methodology. All the compounds were thoroughly characterized by IR, NMR (¹H and ¹³C) and mass spectrometry and structures of 2-(4-butyloxyphenyl)-4,5-dimethyloxazole (5b) and 4,5-dimethyl-2-(4-(octyloxy)phenyl)oxazole(5e) were unambiguously determined by X-ray crystallography. Evidently, the crystal structures of these compounds showed C-HaN and C-HaO intermolecular interactions. The electronic structures of these compounds were also studied by DFT at B3LYP/6-311G ++ level of theory.

Full text of DOI:10.1016/j.molstruc.2016.02.033

Journal of Molecular Structure 1114 (2016) 181e188
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
A series of 2, 4, 5-trisubstituted oxazole: Synthesis, characterization
and DFT modelling
Vinay S. Kadam, Saminaparwin G. Shaikh, Arun L. Patel*
Department of Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara-390 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A new series of 2,4,5-trisubstituted oxazole were synthesized with good yields using simple method-
ology. All the compounds were thoroughly characterized by IR, NMR (1H and 13C) and mass spectrometry
and structures of 2-(4-butyloxyphenyl)-4,5-dimethyloxazole (5b) and 4,5-dimethyl-2-(4-(octyloxy)
phenyl)oxazole(5e) were unambiguously determined by X-ray crystallography. Evidently, the crystal
structures of these compounds showed CeH/N and CeH/O intermolecular interactions. The electronic
structures of these compounds were also studied by DFT at B3LYP/6-311G þþ level of theory.
© 2016 Elsevier B.V. All rights reserved.
Received 30 November 2015
Received in revised form
8 February 2016
Accepted 8 February 2016
Available online 11 February 2016
Keywords:
2-(4-alkyloxyphenyl)-4,5-dimethyloxazole
Trisubstituted oxazole
X-ray diffraction
Density functional theory
1. Introduction
antibiotics and antiproliferatives contain oxazole ring systems.
Some very important derivatives of 2,5-diaryloxazoles, such as
Oxazoles have been found as subunits in numerous natural
products [1]. Oxazole is also a valuable precursor in various
biochemical as well as synthetic transformations [2e5].
annuloline (from Loliummultiflorum) [6] and halfordinol (from
Halfordiascleroxyla) [7] have been isolated from plant sources and
have also been prepared in the laboratories. Annuloline was the
first demonstration of the oxazole ring in nature.
Numerous pharmacologically important compounds used as
* Corresponding author.
E-mail address: arunpatel_5376@yahhoo.co.in (A.L. Patel).
http://dx.doi.org/10.1016/j.molstruc.2016.02.033
0022-2860/© 2016 Elsevier B.V. All rights reserved.

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V.S. Kadam et al. / Journal of Molecular Structure 1114 (2016) 181e188
Oxazole ring containing pimprinine (a mold metabolite from
Streptomyces pimprina) acts as antibiotics. Several methods for the
synthesis of pimprinine have been reported [8].
acid in three steps by following the reported procedure [24].
A mixture of 3-chloro-2-butanone (1.17 g, 0.014 mol) and 4-
alkyloxy benzamide (4a-e) (0.028 mol) in glacial acetic acid
(1.5 mL) was stirred at 120 ꢁC under nitrogen atmosphere for 18 h.
The reaction mixture was cooled to room temperature. The reaction
mixture was neutralized by adding saturated solution of K2CO3
(10 mL). The neutralized reaction mixture was extracted with
dichloromethane (3 ꢂ 10 mL). The organic phase was separated,
dried over anhydrous sodium sulfate and concentrated under
reduced pressure. The crude product was purified by column
chromatography on silica gel with ethyl acetate and petroleum
ether (1:20) to afford compound 5aee.
Among the numerous heterocyclic moieties of biological and
2.2.1. 4,5-Dimethyl-2-(4-propoxyphenyl)oxazole (5a)
Yield: 38%. M.p. 59e61 ꢁC. 1H NMR (400 MHz, CDCl3):
d 1.059 (t,
pharmacological interest, the oxazole ring is endowed with various
activities. Oxazole derivatives have shown activity against inflam-
mation [9], diabetes [10], bacterial infection [11], cardiovascular
disease [12], viral [13] and cancer [14e20]. Owing to these facts,
oxazole derivatives have attracted considerable attention in field of
medicinal research, and resulted in development of numerous in-
vestigations on their synthesis and biological activities during the
last decade. However, very little efforts have been paid to the
synthesis of trisubstituted oxazoles.
3H), 1.811e1.863 (q, 2H), 2.152 (s, 3H), 2.304 (s, 3H), 3.968 (t, 2H),
6.931e6.960 (d, 2H, ArH), 7.900e7.933 (d, 2H, ArH). 13C NMR
(100 MHz, CDCl3):
d
(ppm) 10.04, 10.50, 11.27, 22.53, 69.52, 114.53,
854,
120.46, 127.38, 131.42, 142.62, 159.27, 160.42. IR (KBr, cmꢀ1):
n
1170, 1250, 1414, 1500, 1550, 1650, 2990. Mass (EI): (m/z) 232
(M þ þH).
2.2.2. 2-(4-butoxyphenyl)-4,5-dimethyloxazole (5b)
Oxazoles have been synthesized by various methods utilizing
a-
Yield: 40%. M.p. 60e62 ꢁC. 1H NMR (400 MHz, CDCl3):
diazo ketones, -acyloxy ketones and -acylamino ketones as syn-
a
a
d
0.997e0.983 (t, 3H, eCH3), 1.508e1.523 (m, 2H, eCH2),
thetic intermediates. However, preparation of these reactive in-
termediates is not always straightforward because of various
drawbacks involved inthese reactions, suchaslong reaction time, low
yields, and forced reaction conditions [21]. Bredereck and Bangert
showed a relatively simple approach to the synthesis of oxazoles by
1.781e1795 (m, 2H, eCH2), 2.144 (s, 3H, eCH3), 2.29 (s, 3H, eCH3),
3.998e4.009 (t, 2H, eOCH2), 6.933 (d, 2H, ArH), 7.902 (d, 2H, ArH).
13C NMR (100 MHz, CDCl3):
d
(ppm) 10.07, 11.29, 13.86, 19.23, 31.26,
67.76, 114.55, 120.47, 127.40, 131.44, 142.64, 159.29, 160.45. IR (KBr,
cmꢀ1):
n 844, 1151, 1174, 1248, 1384, 1423, 1499, 1532, 1550, 1584,
the reaction of amides with a-hydroxy ketones [22]. We report here
1630, 1640, 2981. Mass (EI): (m/z) 246 (M þ þH).
synthesis of 2-(4-alkyloxyphenyl)-4,5-dimethyloxazole derivatives
and other trisubsituted oxazole derivatives. A simple and practical
synthetic methodology was used to achieve the desired molecules.
These compounds were thoroughly characterized by IR, NMR (1H and
13C), mass spectrometry. The structures of representative compounds
were determined by single crystal X-ray diffraction. Density Func-
tional Theory (DFT) calculations were performed to shed more light
on the electronic structures of these molecules [23].
2.2.3. 2-(4-(hexyloxy)phenyl)-4,5-dimethyloxazole (5c)
Yield: 35%. M.p. 74e75 ꢁC. 1H NMR (400 MHz, CDCl3):
d
0.921e0.938 (t, 3H, eCH3), 1.333e1.368 (m, 4H,-CH2), 1.457e1.493
(m, 2H, eCH2), 1.784e1.820 (m, 2H, eCH2), 2.149 (s, 3H, eCH3),
2.302 (s, 3H, eCH3), 3.977e4.014 (t, 2H, eOCH2), 6.926e6.948 (d,
2H, ArH), 7.897e7.897 (d, 2H, ArH). 13C NMR (100 MHz, CDCl3):
d
(ppm): 10.07, 11.29, 14.05, 22.61, 25.71, 29.17, 31.59, 68.06, 114.53,
120.45, 127.38, 131.43, 142.62, 159.28, 160.43. IR (KBr, cmꢀ1):
n
740,
2. Experimental
842,1028,1179, 1248, 1309, 1422, 1474,1500,1559, 1612,1648, 2976.
Mass (EI): (m/z) 274 (M þ þH).
2.1. Physical measurements
All the chemicals were reagent grade and used as purchased.
Moisture-sensitive reactions were performed under an inert atmo-
sphere of dry nitrogen with dried solvents. Reactions were moni-
tored by TLC analysis using Merck 60 F254aluminium coated plates
and the spots were visualized under UV light. Column chromatog-
raphy was carried out on Silica gel (60e140 mesh). All melting points
were determined using Thiele's tube using paraffin oil and are un-
corrected. IR spectra were recorded in range from 4000 to 400 cmꢀ1
using KBr pellets on a Shimadzu Prestige 21 spectrometer with 4
scan numbers. Mass spectra were recorded on Thermo-Fischer DSQ II
GCMS instrument. NMR spectra were recorded on a Bruker Avance-
III 400 spectrometer in CDCl3. Diffraction data were collected using
2.2.4. 2-(4-(heptyloxy)phenyl)-4,5-dimethyloxazole (5d)
Yield: 35%. M.p. 77e79 ꢁC. 1H NMR (400 MHz, CDCI3):
d 0.911 (t,
3H), 1.300e1.341 (m, 6H), 1.356e1.498 (m, 2H), 1.772e1.843 (m,
2H), 2.306 (s, 3H), 2.308 (s, 3H), 4.00 (t, 2H), 6.928e6.957 (d, 2H,
ArH), 7.899e7.922 (d, 2H, ArH). 13C NMR (100 MHz, CDCl3):
d
(ppm): 10.08, 11.30, 14.10, 22.62, 25.99, 29.07, 29.22, 31.78, 68.09,
114.20, 114.55, 120.47, 127.39, 131.45, 142.63, 159.29, 160.44. IR (KBr,
cmꢀ1):
n 850, 1022, 1170, 1250, 1415, 1505, 1560, 1600, 1650, 2995.
Mass (EI): (m/z) 288 (M þ þH).
2.2.5. 2-(4-(octyloxy)phenyl)-4,5-dimethyloxazole (5e)
Yield: 37%. M.p. 78e79 ꢁC. 1H NMR (400 MHz, CDCl3):
d
0.990
CuK
a
(
l
¼ 1.5418 Å) radiation on an Xcalibur, Eos, Gemini diffrac-
0.997 (t, 3H, eCH3), 1.329e1.372 (m, 8H,-CH2), 1.432e1.494 (m, 2H,
eCH2), 1.789e1.843 (m, 2H, eCH2), 2.154 (s, 3H, eCH3), 2.308 (s, 3H,
eCH3), 3.987e4.020 (t, 2H, eOCH2), 6.930e6.952 (d, 2H, ArH), 7.899
tometer. DFT calculations were performed using Gaussian 09 pro-
gram with B3LYP functional and 6-311G (þþ) basis set.
7.921 (d, 2H, ArH). 13C NMR (100 MHz, CDCl3):
d
(ppm): 10.10, 11.31,
14.13, 22.68, 26.03, 29.22, 29.25, 29.36, 31.82, 68.09, 114.55, 120.47,
127.40, 131.44, 142.64, 159.30, 160.44. IR (KBr, cmꢀ1):
2989, 1649,
2.2. General procedure for the synthesis of 2-(4-alkyloxyphenyl)-
4,5-dimethyloxazole (5aee)
n
1615, 1560, 1503, 1472, 1344, 1307, 1256, 1172, 1019, 847. Mass (EI):
4-Alkyloxybenzamide were synthesized from 4-hydroxy benzoic
(m/z) 302 (M þ þH).

V.S. Kadam et al. / Journal of Molecular Structure 1114 (2016) 181e188
183
Scheme 1. Synthesis of 2-(4-alkyloxyphenyl)-4,5-dimethyloxazole.
Scheme 2. Synthesis of 4,5-bis((methylthio)methyl)-2-phenyloxazole.
2.3. General procedure for the synthesis of 4,5-dimethyl-2-
phenyloxazole (7a) and 2-(4-chlorophenyl)-4,5-dimethyloxazole (7b)
reaction mixture was filtered and residue was washed with CCl4.
Combined filtrate was treated with sodium bisulphite and dried over
anhydrous Na2SO4. Solvent was removed under reduced pressure
and crude product was further purified by column chromatography
(silica gel, pet ether). White solid compound (5.061 g) was obtained.
A mixture of 3-chloro-2-butanone (1.17 g, 0.014 mol) and ben-
zamide (6a and 6b) (0.028 mol) in glacial acetic acid (1.5 mL) was
stirred at 120 ꢁC under nitrogen atmosphere for 18 h. The reaction
mixture was cooled to room temperature. The reaction mixture was
neutralized by adding saturated solution of K2CO3 (10 mL). The
neutralized reaction mixture was extracted with dichloromethane
(3 ꢂ 10 mL). The organic phase was separated, dried over anhydrous
sodium sulfate and concentrated under reduced pressure. The crude
product was purified by column chromatography on silica gel with
ethyl acetate and petroleum ether (1:20) to afford compound 5.
Yield: 98%. M.p. 126e128 ꢁC. 1H NMR (400 MHz, CDCI3):
d
4.474
(s, 2H), 4.628 (s, 2H), 7.465e7.521 (m, 3H, ArH), 8.060e8.092 (m, 2H,
ArH). 13C NMR (100 MHz, CDCl3):
(ppm): 25.2, 29.2, 114.53, 120.45,
3015, 1601,
d
127.33, 131.41, 142.68, 159.11, 160.46. IR (KBr, cmꢀ1):
n
1509, 1468, 1440, 1209, 768, 699. Mass (EI): (m/z) 330.5(M þ þH).
2.5. Synthesis of 4,5-bis((methylthio)methyl)-2-phenyloxazole (9a)
In a 100 ml round bottom flask,1.13 g of sodium hydrosulfide was
added in 50 mL methanol and stirred at room temperature. Then
5.061 g of 4,5-bis(bromomethyl)-2-phenyloxazole was added in one
portion to it andreaction mixture was refluxed for 8 h under nitrogen
atmosphere. Dark reddish colored reaction mixture was obtained.
Excess solvent was removed under reduced pressure and crude
product was purified by column chromatography (silica gel, pet
ether-ethyl acetate, 6:1) to obtain 1.94 g of yellow solid compound.
2.3.1. 4,5-Dimethyl-2-phenyloxazole (7a)
Yield: 44%. M.p. 49e50 ꢁC (lit., 50e52 ꢁC) [25]. 1H NMR
(400 MHz, CDCI3):
d 2.2 (s, 3H) 2.4 (s, 3H), 7.43e7.45 (m, 3H, ArH)
7.98e8.03 (m, 2H, ArH). Mass (EI): (m/z) 173 (M þ þH).
2.3.2. 2-(4-chlorophenyl)-4,5-dimethyloxazole (7b)
Yield: 52%. M.p. 121e123 ꢁC (lit., 122e124 ꢁC) [26]. 1H NMR
Yield: 48%. M.p. 84e86 ꢁC. 1H NMR (400 MHz, CDCl3):
d 3.442 (s,
(400 MHz, CDCI3):
d
2.168 (s, 3H), 2.326 (s, 3H), 7.400e7.428 (m, 2H,
(ppm):
ArH), 7.911e7.933 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3):
d
3H), 3.482 (s, 3H), 4.496 (s, 2H), 4.587 (s, 2H), 7.457e7.473 (m, 3H,
ArH), 8.075e8.099 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3):
10.12,11.28,126.31,127.08,132.13,135.64,143.74,158.21. IR (KBr, cmꢀ1):
n
3021, 2950,1611,1502,1450, 856, 790. Mass (EI): (m/z) 208 (M þ þH).
2.4. Synthesis of 4,5-bis(bromomethyl)-2-phenyloxazole (8a)
2.70 g of 4,5-dimethyl-2-phenyloxazole (7a) was dissolved in
90 mL of dry CCl4. To this solution 5.55 g of NBS was added in one
portion and reaction was stirred at room temperature for 1 h. The
Scheme 3. Synthesis of dimethyl 2-phenyloxazole-4,5-dicarboxylate.

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V.S. Kadam et al. / Journal of Molecular Structure 1114 (2016) 181e188
d
(ppm): 14.5, 29.02, 31.1, 114.53, 120.45, 127.33, 131.41, 142.68,
159.11, 160.46. IR (KBr, cmꢀ1):
n 3050, 2940, 1600, 1500, 1459, 1259,
799, 768. Mass (EI): (m/z) 266 (M þ þH).
2.6. Synthesis of dimethyl 2-phenyloxazole-4,5-dicarboxylate (11)
To the stirred slurry of N-benzoyl glycine 2.0 g in 30 mL of dry
THF, 14.2 g (10eq) of oxalyl dichloride was added dropwise under
N2 atmosphere. After complete addition, mixture was stirred for
overnight. The excess of oxalyl dichloride was removed and reac-
tion mixture was concentrated under low pressure. To this mixture
1.7 mL (1.5 eq) of TEA and 15 mL of dry MeOH was added. This
solution was stirred for 3 h at room temp. The residue was
concentrated under reduced pressure and crude product was pu-
rified by column chromatography (pet ether: Ethyl acetate) to yield
2.4 g as a white solid compound.
Yield: 20%, M.p. 47e48 ꢁC (lit., 45e47 ꢁC) [27]. 1H NMR (400 MHz,
CDCl3):
(t, 1H), 7.930e7.954 (d, 2H). 13C NMR (100 MHz, CDCl3):
53.54, 127.84, 129.09, 131.35, 133.37, 142.03, 162.62, 163.45, 166.46.IR
d
3.949 (s, 3H), 4.037 (s, 3H), 7.551e7.559 (t, 2H), 7.613e7.653
d
(ppm):
Fig. 1. Molecular structure of 2-(4-butyloxyphenyl)-4,5-dimethyloxazole (5b) and 2-
(4-(octyloxy)phenyl)-4,5-dimethyloxazole (5e). Ellipsoids are drawn at the 50% prob-
ability level and H atoms have been omitted for clarity.
(KBr, cmꢀ1):
n 3035, 2957, 1737, 1689, 1608, 1508, 1473, 1435, 1259,
1042, 992, 914, 799, 768, 699, 549. Mass (EI): (m/z) 262 (M þ þH).
Table 1
3. Results and discussion
Values of Torsion angles and Length of short contacts of compound 5b and 5e.
Compounds
Torsion angles
Length of short contacts
3.1. Chemistry
5b
O1C7C1C6 (4.33ꢁ)
N1C7C1C2 (2.07ꢁ)
O1C7C1C6 (2.07ꢁ)
N8C7C1C2 (2.09ꢁ)
O1eH11 2.65 Å
C4eH12a 2.89 Å
O2eH3 2.65 Å
2-(4-Alkyloxyphenyl)-4,5-dimethyloxazole derivatives (5aee)
were synthesized by the procedures shown in Scheme 1 using the
modified Bredereck method [22]. Treatment of 4-hydroxy benzoic
acid with appropriate alkyl halides in presence of alcoholic KOH has
afforded 4-alkoxybenzoic acids (2a-e) in 80e90%. Compounds 4
were obtained in good yield by treatment of compounds 2 with
thionyl chloride at reflux temperature and followed by treatment
with ammonium hydroxide in THF at room temperature.
4,5-Dimethyl-2-phenyloxazole (7a) was synthesized from ben-
zamide by refluxing with 3-chloro-2-butanone in glacial acetic acid
(Scheme 2). Compound 7a was treated with NBS in dry CCl4 for
1 h at room temperature to obtain dibromo derivative 8a, which
was refluxed with NaSH in MeOH for 8 h to obtain 2-(4-
methoxyphenyl)-4,5-bis((methylthio)methyl)oxazole (9a).
Moreover, dimethyl-2-phenyloxazole-4,5-dicarboxylate (11)
was also prepared by treating N-benzoyl glycine (10) with oxa-
lyldichloride in dry THF under N2 atmosphere followed by treat-
ment with methanol in presence of triethyl amine (Scheme 3) [27].
All the synthesized compounds, 5aee, 7a, 9a and 11 were
characterized by their spectral data (IR, Mass and 1H and 13C NMR).
The structures of compound 5b and 5e were elucidated by means of
single-crystal X-ray diffraction study.
5e
N8eH10b 2.55 Å
angles). Compound 2-(4-(octyloxy)phenyl)-4,5-dimethyloxazole
(5e) crystallizes in triclinic system with space group P-1. Similar
to compound 5b, both benzene ring and oxazole ring were almost
co-planar to each other. Table S1 summarize the crystal structure
and refinement data whereas Table S2 and Table S3 summarizes
selected bond lengths and bond angles, respectively.
Interestingly, the incorporation of O-butyl substituent on the
ethereal linkage changes the structural and electronic features of the
molecule that apparently modify the number and nature of non-
covalent interactions (Fig. S1). For instance, the C12eH12a group
associated with the methylene moiety which is indeed in a close
proximity to the ethereal linkage and the centroid of the benzene
ring (Cg), essentially involved in the intermolecular CeH … p, (dis-
tance 2.89 Å) donoreacceptor interactions, arranging the molecules
linearly along c-axis as shown in the following Fig. 2. Whereas, CeH
group of one of the methyl of oxazole is mainly involved in CeH … O
(distance 2.65 Å) weak hydrogen bonding interactions, arranging the
molecules along b-axis in zig-zag networking (Fig. 3).
3.2. Single crystal X-ray diffraction (SCXRD)
The molecular structures for 2-(4-butyloxyphenyl)-4,5-
dimethyloxazole (5b) and 4,5-dimethyl-2-(4-(octyloxy)phenyl)oxa-
zole (5e) were elucidated by SCXRD (Fig. 1). Crystals of both com-
pounds were obtained from slow evaporation of diethyl ether solutions
at room temperature. A suitable crystal was selected and data were
collected at 293ꢁ K using CuK
a
(l
¼ 1.5418 Å) radiation on an Xcalibur,
Eos, Gemini diffractometer. Both structures were solved and refined
using Olex2 [28]. The structure was solved with the Superflip [29]
structure solution program using Charge Flipping and refined with
the ShelXL [30] refinement package using Least Squares minimization.
The compound 2-(4-butyloxyphenyl)-4,5-dimethyloxazole (5b)
crystallizes in monoclinic system with space group P21/c. The
oxazole ring was almost planar to the benzene ring (Table 1 torsion
Fig. 2. Arrangement of molecules through CeH …
axis.
p intermolecular contacts along c-

V.S. Kadam et al. / Journal of Molecular Structure 1114 (2016) 181e188
185
Fig. 3. Arrangement of molecules through CeH … O weak H-bonding intermolecular interactions along b-axis forming a zig-zag networking (a) Capped Sticks and (b) Spacefill
representation of molecular packing.
Fig. 4. A linear arrangement of molecules of compound 5e involving CeH … N interactions forming 1D chain-like structure.
Interestingly, molecules of compound 5e showed a number of
intermolecular CeH … O and CeH … N interactions (Fig. 4). For
instance, the molecule present in the asymmetric unit forms a close
contact with neighboring molecules, arranging the neighboring
molecule in an anti-parallel fashion through CeH … O interactions
involving C3eH3 group of benzene and ethereal oxygen atoms
(Table 1). Principally, the oxazole moiety of the asymmetric molecule is
involved in CeH … N donoreacceptor interaction, arranging the
neighboring molecule parallel along a-axis as shown in Fig. 4. Overall,
the asymmetric molecule forms an aggregate of three molecules
(Fig. S2). In fact, C10eH10b and N8 groups of oxazole moietyare mainly
involved CeH … N (distance 2.55 Å) weak H-bonding interactions and
arranging the molecules linearly along-axis as shown in Fig. 4.
3.3. Computational data
DFT calculations were performed using Gaussian 09 program
[31] with B3LYP functional and 6-311G(þþ) basis set on the series
Fig. 5. Optimized structure of compound 5b and 5e (Vertical and Horizontal view).

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V.S. Kadam et al. / Journal of Molecular Structure 1114 (2016) 181e188
of the reported compounds.
Calculated IR spectra of these series of compounds were
compared with the experimental spectra. We presented intense
vibrational modes in frequency region from 700 to 4000 cmꢀ1
(Table 3). It was concluded that in compound 5e, band 847 cmꢀ1
which corresponds to 867 cmꢀ1 of calculated one was arises due
CeH out of plane deformation of phenyl ring. The 1019 cmꢀ1 band
observed was from CeO stretching (1021 cmꢀ1 calculated). The
calculated frequency 1213 cmꢀ1 occurred from CeH in plane
deformation of phenyl ring which was experimentally found at
1256 cmꢀ1. CeC Skeletal vibrations of phenyl ring found at
It was observed that geometric parameters of the optimized
structures are in good agreement with that from the SCXRD data.
The optimized structures of all oxazole derivatives showed co-
planarity between phenyl and oxazole rings (in compound 5e
dihedral angles for O1C7C1C6 and N1C7C1C2 was 0.47ꢁ and 0.6ꢁ
respectively) which is in congruence with SCXRD data
(Fig. 5)(Table 2). Structure optimization of compound 7b, 9a and
11 showed quite flat geometry expect in 9a were bulky S atoms
causes out-of-plane distortion.
Table 2
Optimized structures of compound 5a, 5c, 5d, 7b, 9a, 11.

V.S. Kadam et al. / Journal of Molecular Structure 1114 (2016) 181e188
187
Table 3
IR spectra values obtained from Experiment and DFT calculations.
Compound Experimental (cmꢀ1
)
DFT calculations (cmꢀ1
)
5e
7b
9a
11
2989, 1649, 1615, 1560, 1503, 1472, 1344, 1307, 1256, 1172, 1019, 847.
3021, 2950, 1611, 1502, 1450, 856 790
3050, 2940, 1600, 1500, 1459, 1259, 799, 768
3013, 2992, 1673, 1648, 1522, 1453, 1254, 1213,1021, 988, 867
3109, 3067, 3016, 1668, 1517, 1437, 1093, 1040, 874, 770
3185, 3042, 1522, 1491, 1283, 1074, 802
3035, 2957, 1737, 1689, 1608, 1508, 1473, 1435, 1259, 1042, 992, 914, 799, 768, 699, 549 3188, 3049, 1697, 1653, 1516, 1377, 1287, 1081, 807
Fig. 6. Electrostatic potential maps of compounds 5b, 7b, 9a and 11.
1472 cmꢀ1 and 1649 cmꢀ1 which was confirmed by 1453 cmꢀ1 and
1648 cmꢀ1 (calculated). Asymmetric CH3 stretching was observed
at 2989 cmꢀ1 corresponds to the calculated at 2991 cmꢀ1. For
compounds 5a, 5b, 5c and 5d similar data was obtained.
4. Conclusion
In summary, a series of 2,4,5-trisubstituted oxazole were pre-
pared and characterized by standard spectroscopic methods and X-
ray crystallography. Notably, the crystal structures of 2-(4-
butyloxyphenyl)-4,5-dimethyloxazole (5b) and 4,5-dimethyl-2-(4-
(octyloxy)phenyl)oxazole (5e) showed significant non-bonding
In compound 7b, CeCl stretching (calculated 770 cmꢀ1
)
observed at 790 cmꢀ1, while CeH out of plane deformation of
phenyl ring (calculated 874 cmꢀ1), CeC Skeletal vibrations of
phenyl ring (calculated 1517 cmꢀ1) and asymmetric CH3 stretching
(calculated 3016 cmꢀ1) were found at 856 cmꢀ1, 1502 cmꢀ1 and
3021 cmꢀ1 respectively. Compound 9a showed CeH out of plane
deformation of phenyl ring (calculated 802 cmꢀ1) and CeH defor-
mation for CH2 group (calculated 1287 cmꢀ1) at 799 cmꢀ1 and
1259 cmꢀ1. The CeC Skeletal vibrations of phenyl ring, and asym-
metric CH3 stretching occurred at 1473 cmꢀ1 and 2957 cmꢀ1. In
compound 11 1737 cmꢀ1 and 1689 cmꢀ1 band corresponds to C]O
stretching of ester group which were at 1653 cmꢀ1 and 1697 cmꢀ1
in theoretical one.
intermolecular interactions such as CeH …
p, CeH/N and
CeH/O interactions, forming a fascinating 1D and 3D molecular
networking, respectively. DFT calculations were preformed on these
molecules and compared with experimental results. DFT calculated
electrostatic potential maps were obtained and effects of different
substitutions on charge distribution pattern were analyzed.
Acknowledgment
ALP acknowledges GUJCOST, Gandhinagar, Gujarat (India) for
the financial support (Project No. GUJCOST/MRP/2014-15/408). One
of the authors, VSK acknowledges DST-PURSE program for
providing fellowship. The authors would like to acknowledge the
DST-PURSE program for funding the single crystal X-ray diffrac-
tometer facility at the Faculty of Science, The Maharaja Sayajirao
University of Baroda, Vadodara, Gujarat (India). The authors would
like to acknowledge Dr S S Zade, Associate Professor, IISER, Kolkata
for DFT calculations.
DFT calculated electrostatic potential maps of these compounds
showed in Fig. 6. Substituents on oxazole ring showed significant
effect on the overall charge distribution pattern. It reveals that in 2-
(4-alkyloxyphenyl)-4, 5-dimethyloxazole derivatives, negative
charge was concentrated over N-atom of oxazole ring and O-atom
of ethereal linkage compared over the rest of molecule. Substitu-
tion of chloro group showed little effects on charge distribution
pattern. In 4,5-bis((methylthio)methyl)-2-phenyloxazole (9a), S-
atoms of thio-ethers showed increased charge density compared to
carbon atoms and thus were able to modify the charge distribution.
In dimethyl 2-phenyloxazole-4, 5-dicarboxylate (11) carbonyl ox-
ygen atoms of ester groups were effectively able to altered the
charge distribution of molecule (Fig. 6).
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.molstruc.2016.02.033.

188
V.S. Kadam et al. / Journal of Molecular Structure 1114 (2016) 181e188
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