# Normal Modes, Molecular Orbitals and Thermochemical Analyses of 2,4 and 3,4 Dichloro Substituted Phenyl-N-(1,3-thiazol-2-yl)acetamides: DFT Study and FTIR Spectra

Authors: Ambrish K. Srivastava; Anoop K. Pandey; B. Narayana; B. K. Sarojini; Prakash S. Nayak; Neeraj Misra
Journal: Journal of Theoretical Chemistry
 (2014)

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## Abstract

A detailed spectroscopic analysis of  two dichloro substituted phenyl-N-(1,3-thiazol-2-yl)acetamides at 2,4 and 3,4 positions of the phenyl ring has been carried out by using B3LYP method with 6-31+G(d, p) basis set within density functional scheme. The scaled theoretical wave numbers are in perfect agreement with the experimental values and the vibrational modes are interpreted in terms of potential energy distribution (PED). The internal coordinates are optimized repeatedly to maximize the PED contributions. The molecular HOMO-LUMO surfaces, their respective energy gaps, and MESP surfaces have also been drawn to explain the chemical activity of both molecules. Various thermodynamic parameters are presented at the same level of theory.


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## Body

## 1. Introduction

Acetamide constitutes a distinguished class of biologically active molecules having an amide bond same as that between amino acids in proteins. Amides are also popular for their coordinating ability and which enable them to be used as ligands [1]. In general, a large number of natural products and drugs comprises of heterocyclic moieties containing nitrogen and sulphur atoms [2, 3] and interesting biological activities have been found to be associated specially with thiazole derivatives [4, 5]. In continuation to our previous studies on vibrational dynamics of biomolecules [6, 7], we intend here to report a detailed analysis of vibrational modes of molecules consisting of thiazole ring with acetamide ligand. More recently, such molecules have been shown to possess anti-HIV activities with suitable substitutions [8].We present density functional based theoretical studies on two molecules, namely, 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide and 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide. The two molecules differ only in the position of two chlorines substituted on the phenyl ring. This provides us an opportunity to analyse the effect of position of substitution on vibrational properties. Keeping it in mind, we offer a complete assignment of all normal modes of vibration. The calculated vibrational spectra are compared with the observed ones. The chemical reactivity of molecules is also explained with the help of molecular orbital analysis. The thermochemistry of molecules is discussed by calculating various thermodynamical parameters.


## 2. Computational Method and FTIR Spectra

All the computations were carried out with Gaussian 09 program [9] and Chem3D Ultra 8.0 program [10] was used for a visual presentation of the graphics. The geometries of both molecules were optimized using a hybrid type B3LYP exchange-correlation functional with 6-31+G(d, p) basis set in the framework of DFT. The present computational scheme is very popular and extensively employed in the biomolecular studies due to reliability of its results as compared to experimental data [11]. Vibrational analyses of molecules were performed at the same level of theory. The normal mode frequencies were scaled by equation, ν
scaled
=
22.1
+
0.9543
ν
calculated as recommended by many studies [12–14] in order to make comparison with the observed wavenumbers.To perform experimental FTIR spectroscopy, the title compounds were purchased from Sigma Aldrich with a purity of 98% and used as such without further purification for spectroscopic processing. The FTIR spectra were recorded by using Shimadzu-Model Prestige 21 spectrometer in the region 400–4000 cm−1 with samples in KBr pellet. The FTIR spectra of title molecules are shown in Figure 1.Figure 1
FTIR spectra of (a) 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide and (b) 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide recorded with samples in KBr pallet.


## 3. Results and Discussions

### 3.1.  Crystal Structure and Molecular Geometry

We have already reported X-ray crystallographic studies on these compounds [15, 16]. All these compounds belong to triclinic P
1
- space group. In crystal phase, molecules are linked by pairs of N–H⋯N hydrogen bonds. There is also a weak C–H⋯O interaction in case of 2,4 substitution.The crystallographic parameters were used to model initial structure for the process of geometry optimization. The optimized geometries of both molecules are displayed in Figure2. The mean plane of dichlorophenyl ring is almost perpendicular to that of thiazole ring in both molecules thus forming a sofa shaped structure. The angular changes in hexagonal ring geometry have also been proven to be a sensitive indicator of the interaction between the substituent and the ring [17]. The structural changes in the carbon skeleton involve changes in the bond distances as well as bond angles. They are most pronounced at the place of substitution and depend on the electronegativity as well as on the σ/π, donor/acceptor character of the substituent. All bond-lengths and bond angles are nearly same in both molecules except those in phenyl ring attached with chlorine atoms at different positions. For instance, C–Cl, bond-length 1.752–1.756 Å in 2,4 substituted molecule is reduced to 1.744-1.745 Å for 3,4 substitution.Optimized geometries of (a) 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide and (b) 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide corresponding to the global minima calculated at B3LYP/6-31+G(d, p) level.
(a)
(b)In Figure3, we have shown a linear correlation between DFT calculated and X-ray experimental bond-lengths for title molecules. Note that C–H bond-lengths are not included here. A correlation coefficient (R
2) of greater than 0.99 in both molecules supports the fact that DFT can efficiently reproduce the experimental geometry.Correlation between X-ray experimental and DFT calculated bond-lengths for (a) 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide and (b) 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide.
(a)
(b)


### 3.2. Normal Mode Analysis

The calculated IR and observed FTIR spectra of both molecules are shown in Figure4 for comparison in the wavenumber range of 1800–400 cm−1. The calculated wavenumbers are scaled by using the equation mentioned earlier. All the vibrational modes were properly assigned on the basis of the potential energy distribution (PED). Tables 1 and 2 list calculated frequencies (unscaled as well as scaled), FTIR observed frequencies, IR intensities, and assignments of all normal modes for title molecules. Both molecules contain two ring system, a phenyl ring (R1) and a thiazole ring (R2) connected by acetamide fragment (–NHCOCH2–). For the clarity of discussions, we classified their vibrations into three broad categories.Table 1
Normal mode assignments of 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide at B3LYP/6-31+G (d,p) level.
S.number
Unscaled freq. (cm−1)
Scaled freq. (cm−1)
FTIR freq. (intensity) (cm−1)
IR intensity (a.u.)
Mode of vibration(%PED)
Direction of polarization
1
3600
3458
3199 (s)
79
ν(N17–18H) (
100
)
Along N–H plane
2
3272
3145
1
ν(C–H)R2 (
99
)
Along R1
3
3243
3117
1
ν(C–H)R2 (
99
)
Along R2
4
3234
3108
8
ν
as(22H–19C–25C–21H) (
89
)
Per R2
5
3226
3101
1
ν(C–H)R1 (
99
)
Along R2
6
3188
3064
3055 (w)
5
ν(C–H)R1 (
98
)
Along to 3C–6C
7
3121
3001
1
ν
as(22H–19C–25C–21H) (
89
)
Along R2
8
3068
2950
7
ν(13H–12C–14H) (
91
)
Along R2
9
1748
1690
1691 (s)
273
ν(15C–16O) (
83
)
Opposite to C–O
10
1632
1580
42
ν(C–C)R1 (
59
)
Along R2
11
1599
1548
1544 (m)
16
ν(C–C)R1 (
65
) + β(C–H)R1(
14
)
Along 6C–9H
12
1581
1531
420
ν(20C–24N) (
55
) + β(17N–18H) (
21
)
Along R1
13
1524
1477
109
ν(19C–25C) (
54
) + β(17N–18H) (
12
) + β(C–H)R2 (
15
)
Per R2
14
1506
1459
84
β(C–H)R1 (
74
)
Along R2
15
1473
1428
6
Scissoring (13H–12C–14H(
55
)) + ν(20C–24N) (
40
)
Along R2
16
1461
1416
38
Scissoring (13H–12C–14H)(
72
) + β(17N–18H) (
15
)
Per R2
17
1416
1373
1346 (m)
15
ν(C–C)R1 (
30
) + β(C–H)R1 (
27
)
Along R2
18
1348
1308
61
β(C–H)R1 (
86
)
Along 19C–22H
19
1339
1300
1300 (vw)
1
Rocking (13H–12C–14H)(
39
) + β(C–H)R2 (
42
)
Along R2
20
1330
1291
3
Rocking (13H–12C–14H)(
30
) + ν(C–C)R2 (
54
)
Along R1
21
1304
1267
107
ν(20C–24N) (
45
) + β(17N–18H) (
15
)
Per R2
22
1291
1254
1230 (w)
3
β(C–H)R1 (
76
)
Along R2
23
1227
1193
64
β(C–H)R1 (
54
)+ β(17N–18H) (
32
)
Along R2
24
1224
1190
3
β(C–H)R1 (
71
)
Per R2
25
1205
1172
31
Twist (13H–12C–14H) +β(C–H)R2 and R1
Per R2
26
1178
1146
30
β(19C–22H) (
65
) + β(17N–18H) (
15
)
Along R2
27
1163
1132
4
β(1C–7H–6C–9H) (
65
)
Per R2
28
1119
1090
1103 (m)
50
β(3C–8H) (
43
) + β(6C–9H) (
32
)
Along R2
29
1088
1060
10
Scissoring (21H–25C–19C–22H)(
56
)
Along R2
30
1066
1039
28
Breathing R2
Per R1
31
976
954
960 (w)
7
Twist (13H–12C–14H) +S(16O–15C–17H)
Along R1
32
967
945
1
Twist (1C–7H–6C–9H)
Along R2
33
936
915
9
Rocking (13H–12C–14H)(
45
)
Along R2
34
898
879
3
Twist (21C–25H–19C–22H)
Per R2
35
885
867
866 (w)
11
γ(3C–8H) (
49
)
36
882
864
7
Breathing R2
Along R1
37
871
853
43
Breathing R1
In between R1 and R2
38
834
818
823 (m)
18
γ(1C–7H) (
44
) + γ(6C–9H) (
11
)
Along R1
39
786
772
771 (w)
7
γ(1C–7H) + γ(6C–9H) + β(R1)
Along C–O
40
758
746
43
β(R2)
41
723
712
11
Ring R2 twist
Per R2
42
717
706
698 (m)
43
γ(21C–25H) (
38
) + γ(19C–22H) (
12
)
Along R2
43
693
683
2
Ring R2 twist
Along R1
44
677
668
2
T(13H–12C–14H)
45
648
641
2
γ(C–H)R1 (
54
)
Directed CH2
46
628
621
36
γ(C–H)R1 + γR2 + rocking (13H–12C–14H)
Per R2
47
623
617
7
Twist R2 + rocking (13H–12C–14H)
Along R2
48
579
575
15
γ(7C–1H) (
43
)+ γ(3C–8H) (
39
) + γ(2C–11Cl) (
11
)
Along 2C–11Cl
49
564
560
4
Rocking (13H–12C–14H)(
23
) + γ(19C–22H) (
35
) + γ(17N–18H) (
21
)
Along R1
50
524
522
16
R2 breathing + R1 twist
Per R2
51
510
509
14
γ(17C–18H) + γ(ring R2)
(Along Cl) R1
52
486
486
8
Ring R2 twist +γ(17C–18H) + γ(23C–25C–20C)
53
452
453
3
γ(3C–8H) (
35
) + γ(6C–9H) (
22
) + R(13H–12C–14H) (
31
)
Along 17N–18H
54
437
439
3
Rocking (13H–12C–14H(
29
)) + γ(3C–8H) (
35
) + γ(5C–9H) (
12
)
Per R2
55
398
402
3
β(R1ring)
Per 17N–18H
56
357
363
1
β(C–C)R2 (
23
) + β(15C–16O) (
34
)
Along R2
57
321
328
1
γ(C–C)R2 (
26
) + rocking (13H–12C–14H) (
17
)
Along CH2
58
298
307
1
γ(23C–21H) + γ(28C–17H) + rocking (13H–12C–14H)
Along R1
59
286
295
6
γ(ring R2)
Per R2
60
267
277
4
β(11C–2Cl) (
18
) + β(4C–10Cl) (
13
) + rocking (13H–12C–14H) (
21
)
Along R2
61
201
214
1
β(11C–2Cl) (
11
) + β(4C–10Cl) (
27
) + β(1C–7H) (
23
)
Along R2
62
174
188
1
τ(ring R1 and R2)
Per R2
63
137
153
6
γ(ring R1)
Per R2
64
105
122
1
γ(ring R2)
Per R1
65
96
114
1
γ(ring R2)
Along R2
66
77
96
4
τ(13H–12C–14H)
Per R2
67
32
53
1
Rings R1 and R2 twist jointly
Along R1
68
23
44
1
Rings R1 and R2 twist jointly
Along 4C–10Cl
69
19
40
1
Rings R1 and R2 twist jointly
Along R2
ν: stretching; ν
s: symmetric stretching; ν
as: asymmetric stretching; β
: in-plane-bending; γ: out-of-plane bending; ω: wagging; τ: torsion, S: scissoring; vs: very strong; s: strong; m: medium; w: weak; vw: very weak.Table 2
Normal mode assignments of 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide at B3LYP/6-31+G(d, p) level.
S.number
Unscaled Freq. (cm−1)
Scaled freq. (cm−1)
FTIR freq. (intensity) (cm−1)
IR intensity (a.u.)
Mode of vibration (%PED)
Direction of polarization
1
3598
3456
3197 (s)
97
ν(15N–16H) (
100
)
Along 15N–16H plane
2
3271
3144
1
ν(23C–19H) (
44
) +  ν(17C–20H) (
45
)
Along 2C–9Cl
3
3234
3108
8
ν(23C–19H) (
99
)
Along 6C–8H
4
3220
3095
1
ν(1C–7H) +  ν(6C–8H)
Along 2C–Cl
5
3204
3080
1
ν(9C–23H) (
99
)
Along R2
6
3191
3067
3034 (w)
4
ν(6C–8H) (
48
) +  ν(1C–7H) (
55
)
Along 3C–6C
7
3106
2986
1
ν
as(12H–110C–11H) (
89
)
Along R2
8
3065
2947
8
ν(12H–10C–11H) (
91
)
Along R1
9
1743
1685
1689 (vs)
289
ν(15C–16O) (
83
)
Along 13C–14O
10
1636
1583
1589 (w)
5
ν(C–C)R1 (
59
)
Along R2
11
1600
1549
13
ν(C-C)R1 (
65
) + β(C–H)R1 (
14
)
Along 5C–H
12
1582
1532
1527 (vs)
461
ν(18C–22N) (
55
) + β(15N–16H) (
21
)
Per R1
13
1524
1476
104
ν(C–C)R2 (
54
) + β(15N–16H) (
12
) + β(17C–20H) (
15
)
Per R2
14
1506
1459
1462 (s)
74
β(C–H)R2 (
74
) + ν(C–C)R2 (
21
)
Along R2
15
1476
1431
3
Scissoring (13H–12C–14H(
55
)) +  ν(C-N)R2 (
40
)
Along R2
16
1461
1416
38
Scissoring (13H–12C–14H)(
72
) + β(17N–18H) (
15
)
Along 4C–5C
17
1425
1382
41
ν(C–C)R1 (
30
) + β(C–H)R1 (
27
)
Along13C–15N
18
1349
1310
59
β(C–H)R1 (
46
) + ν(C–C)R1 (
30
)
Along R2
19
1331
1292
1294 (w)
9
Rocking (13H–12C–14H)(
39
) + β(C–H)R1 (
42
)
Along R1
20
1328
1289
1
Rocking (13H–12C–14H)(
39
) + ν(C–C)R1 (
32
)
Per R1
21
1304
1267
107
β(15C–16H) (
26
) + ν(C–C)R1 (
54
)
Per R1
22
1285
1248
1228 (w)
3
β(C–H)R1 (
76
)
Along R2
23
1228
1194
15
β(17C–20H) (
19
) + rocking (11H–10C–12H) (
22
) + β(C–H)R1 (
26
)
Making 5C–10C with an angle 45°
24
1222
1188
3
β(17C–20H) (
19
)+ β(15N–16H) (
22
) + β(4C–24H)R1 (
26
)
Per R2
25
1204
1171
2
Twist (11H–10C–12H) +β(6C–8H)
Per R1
26
1180
1148
35
β(17C–18H)R (
65
) + β
(17N–18H) (
15
)
Along R2
27
1168
1137
3
β(1C–7H) (
65
) + β(6C–8H) (
14
)
Plane containing 13C and per to plane of R1
28
1148
1118
50
β(C–C)R1 (
43
) + β(C–H)R1 (
32
)
Along 15N–16H
29
1089
1061
10
β(17C–20H) (
43
) + β(23C–10H) (
32
)
Along R2
30
1043
1017
35
β(C–H)R1 (
28
) + β(C–C)R1
Per R1
31
977
955
7
Twist (13H–12C–14H) + scissoring (16O–15C–17H)
Along R1
32
970
948
1
Twist (7C–1H-6C–8H)(
59
)
Along R2
33
943
922
12
Rocking (13H–12C–14H)(
45
) + γ(4C–24H) (
29
)
Along R2
34
909
890
11
γ(C–H) (
23
) + γ(C–C) (
49
)
Per R2
35
898
879
3
γ(C–H)R2 (
49
)
Per R2
36
891
872
10
Breathing R1+γ(4C–24H)
Along 6C–5H
37
881
863
7
Breathing R2
Along 15N–10H
38
840
824
815 (m)
17
γ(6C–8H) (
44
) + γ(1C–7H) (
11
)
Along R1
39
781
767
763 (m)
23
γ(6C–8H) + β(ring R1)
Along C–O
40
737
725
729 (w)
8
γ(C–C)R1 (
44
) + γ(C–H)R1 (
11
)
41
719
708
43
γ(23C–14H) (
32
) + γ(17C–20H) (
53
)
Per R2
42
708
698
11
γ(C–C) (
38
) + rocking (11–10C–12H) (
12
)
Along R2
43
699
689
3
γ(C–H) (
23
) + γ(C–C) (
49
)
Along 13–14O
44
681
672
10
τ(13H–12C–14H)
45
652
644
17
γ(C–S–C)R2 (
54
)
Directed CH2
46
634
627
27
γ(15C–16H)R2 + γR2 + rocking (11H–10C–12H)
Per R2
47
624
618
17
γ(C–S–C)R2 (
43
) + γ(C–H)R2 (
39
)
Along R2
48
598
593
580 (w)
9
Twist R1 + Rocking (13H–12C–14H)
Per R2
49
566
562
5
γ(R2) + γ(15N–16H)
Along R1
50
526
524
21
R1 breathing + R2 twist
Per R2
51
510
509
14
γ(17C–18H) + ring R2 out-of-plane bending
Along R1
52
483
483
6
γ(CCC)R1+ γ(C–Cl)R1
Along 13C–10O
53
460
461
1
Ring R1 twist
Along 5C–4C
54
448
450
4
γ(CCC)R1 (
34
) + γ(1C−7H) (
54
)
Plane containing 16H
55
386
391
1
τ(ring R1)
Along 5C–4C
56
356
362
1
β(C–C)R1 (
23
) + β(15N–16H) (
34
)
Along R2
57
319
327
3
γ(C–C)R1 (
26
) + β(13C–14) (
25
)
Along CH2
58
295
304
1
γ(ring R2)
Along 4C–24H
59
288
297
3
γ(CCC)R1 + γ(C–H)R1
Along 18C–15N
60
243
254
1
τ(11H–10C–12H)
Along R2
61
199
212
1
β(C–Cl)R1 (
11
) + β(1C–7H) (
23
)
Along R1
62
183
197
2
τ(ring R1)
Per R2
63
135
151
5
τ(CCC) + γ(CH)R1
Per R2
64
105
122
1
τ(ring R1)
Per R2
65
94
112
0
τ(ring R2)
Per R1
66
76
95
6
τ(11H–10C–12H) + γ(13C–14H)
Along R2
67
33
54
1
τ(ring R1)
Per R2
68
16
37
1
γ(R1)
Along R1
69
12
34
1
Rings R1 and R2 twist jointly
Along 4C–10Cl
ν: stretching; ν
s: symmetric stretching; ν
as: asymmetric stretching; β: in-plane-bending; γ: out-of-plane bending; ω:  wagging; τ: torsion, S: scissoring; vs: very strong; s: strong; m: medium; w: weak; vw: very weak.Calculated IR and observed FTIR spectra of (a) 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide and (b) 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide for comparison in the frequency range of 1800 cm−1–400 cm−1.
(a)
(b)


#### 3.2.1. Phenyl Ring (R1) Vibrations

The phenyl ring vibrations contain the C–H stretching modes in the region 3100–3000 cm−1, which is the characteristic region for the identification of C–H stretching vibrational modes [18]. In this region, the bands are not much affected by the nature of the substituents. The scaled C–H modes are found between 3096–3060 cm−1 which are observed at 3055 cm−1 for 2,4 substituted molecule polarized along 3C–6C and at 3034 cm−1 for 3,4 substitution. These modes are purely stretching having PED greater than 90%. Most of the C–H stretching modes are found to be weak due to charge transfer from hydrogen to carbon atom. Other C–H modes coming from bending (in-plane and out-of-plane), breathing and twisting of ring are found in the region below 1500 cm−1 having medium to weak intensities.The C–C ring stretching vibrations are expected within the region 1650–1200 cm−1 [19]. Most of these ring modes are affected by the substitution to aromatic ring. Scaled frequencies for C–C stretching modes at B3LYP/6-31+G(d, p) are 1580 cm−1, 1548 cm−1, and 1477 cm−1 for 2,4 and 1583 cm−1, 1549 cm−1, and 1476 cm−1 for 3,4 substitution on the ring. Some other C–C modes associated with bending, twisting and breathing vibrations are also found to lie in lower frequency region as well as overlapped with other modes. Most of C–C modes are comparatively stronger than C–H modes.


#### 3.2.2. Thiazol Ring (R2) Vibrations

The vibrations of thiazole ring associated with C–H stretching are calculated in between 3145–2950 cm−1 for title molecules which are essentially independent on the substitutions in the phenyl ring. These values are in agreement with observed bands in thiazoles and its derivatives [20]. The most intense bands corresponding to C–N stretching in thiazole are calculated at 1532-1531 cm−1. These vibrational modes are found to be coupled with N–H stretching and polarized along phenyl ring. The same bands are observed at 1544 cm−1–1527 cm−1 in the FTIR spectra. Other weak modes of thiazole ring vibration associated with breathing and twisting of rings are calculated below 1500 cm−1 and those specially associated with S atom are found near 600 cm−1.


#### 3.2.3. Fragment (–NHCOCH2–) Vibrations

Amides show somewhat strong and broad band in the range between 3500 cm−1 and 3100 cm−1 for N–H stretch as well as a stronger band between 1700 cm−1 and 1650 cm−1 for C=O stretching [21]. Carbonyl absorptions are very sensitive and both the carbon and the oxygen atoms move during the vibration having nearly equal amplitude. The scaled values, 3458 cm−1–3456 cm−1 for N–H stretch and 1690 cm−1–1685 cm−1 for C=O stretch agree with literature values. In FTIR spectra, the corresponding band for C=O stretching are observed at 1691 cm−1–1689 cm−1 while N-stretching frequencies are lowered to 3199 cm−1–3197 cm−1. The differences between calculated and observed N–H stretch band are attributed to the presence of intermolecular H-bond in condensed phase which are absent in the isolated state of molecules.In acetamide fragment, the stretching of methylene (–CH2) group and bending (scissoring and rocking) always occur in 3000 cm−1–2850 cm−1 and below 1500 cm−1, respectively [20]. These vibrations are more common and so are not much of significance. The stretching mode polarized along to ring R2 corresponding to –CH2 is calculated at 2950 cm−1 for 2,4 substitution and 2947 cm−1 for 3,4 substituted molecule.


### 3.3. Molecular Orbital Analysis

The highest occupied molecular orbital (HOMO) represents ability to donate an electron while lowest unoccupied molecular orbital (LUMO) denotes ability to accept it. The HOMO-LUMO plots for title molecules are shown in Figure5. Evidently, the HOMOs of both molecules are located on the thiazole ring including amide fragment while the LUMOs are contributed mainly by phenyl ring system. The transition from HOMO → LUMO in these molecules indicates charge transfer to phenyl ring. The energy difference (E
gap
⁡) between HOMO and LUMO describes the chemical reactivity of molecule. The smaller E
gap
⁡, 4.89 eV in 2,4 substituted molecule as compared to 4.94 eV in 3,4 substitution may suggest that former is chemically more reactive than the latter one. The chlorine atoms attached to adjacent carbons on phenyl ring for 3,4 substituted molecule make it less reactive.HOMO-LUMO and MESP plots for (a) 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide and (b) 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide.
(a)
(b)Figure5 also plots the molecular electrostatic potential (MESP) surface for title molecules. The MESP, a map of electrostatic potential on uniform electron density, is used to visualize charge or electron density distribution within the molecule. The importance of MESP lies in the fact that it simultaneously displays molecular size, shape as well as positive, negative, and neutral electrostatic potential regions in terms of colour grading. In present context, colour code varies between positive region for red and negative for blue regions with an isovalue of 1.00000 eV. Evidently, the electronegative region lies in the vicinity of carbonyl group of amide fragment. On the basis of MESP plot, it can be asserted that an electrophile will be attracted towards the negative region of amide fragment in both molecules.


### 3.4. Thermochemical Analysis

Thermochemical properties of molecules are dominated by molecular vibrations as electronic contribution becomes negligible due to absence of free electrons, especially at the room temperature. Various thermal parameters for title molecules are calculated and reported in Table3. These parameters are related to one another via standard thermodynamic relations and can be useful for the estimation of chemical reaction paths. Zero point energy (ZPE) is also given. Thermal energy of 3,4 substituted molecule is slightly higher than that with 2,4 substitution while heat capacity is smaller. The entropy values are closely related to the geometry of molecules. The substitution of chlorines at 3,4 position of ring leads to an increase in entropy value as compared to 2,4 substitution. The increase in thermal energy and entropy values may indicate the enhancement in molecular vibrations due to steric repulsion generated with chlorine atoms substituted at two consecutive (3,4) positions of the phenyl ring.Table 3
Total energy and various thermodynamic parameters for title molecules calculated at B3LYP/6-31+G(d,p) level.
Parameters
2-(2,4-Dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide
2-(3,4-Dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide
Electronic energy (Hartree)
−1927.348
−1927.345
ZPE (kcal/mol)
108.137
108.118
Thermal energy (kcal/mol)
117.690
117.696
Thermal enthalpy (kcal/mol)
118.281
118.287
Thermal free energy (kcal/mol)
79.187
78.675
Constant volume heat capacity (cal/mol-K)
56.509
56.438
Entropy (cal/mol-K)
131.123
132.861


## 3.1.  Crystal Structure and Molecular Geometry

We have already reported X-ray crystallographic studies on these compounds [15, 16]. All these compounds belong to triclinic P
1
- space group. In crystal phase, molecules are linked by pairs of N–H⋯N hydrogen bonds. There is also a weak C–H⋯O interaction in case of 2,4 substitution.The crystallographic parameters were used to model initial structure for the process of geometry optimization. The optimized geometries of both molecules are displayed in Figure2. The mean plane of dichlorophenyl ring is almost perpendicular to that of thiazole ring in both molecules thus forming a sofa shaped structure. The angular changes in hexagonal ring geometry have also been proven to be a sensitive indicator of the interaction between the substituent and the ring [17]. The structural changes in the carbon skeleton involve changes in the bond distances as well as bond angles. They are most pronounced at the place of substitution and depend on the electronegativity as well as on the σ/π, donor/acceptor character of the substituent. All bond-lengths and bond angles are nearly same in both molecules except those in phenyl ring attached with chlorine atoms at different positions. For instance, C–Cl, bond-length 1.752–1.756 Å in 2,4 substituted molecule is reduced to 1.744-1.745 Å for 3,4 substitution.Optimized geometries of (a) 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide and (b) 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide corresponding to the global minima calculated at B3LYP/6-31+G(d, p) level.
(a)
(b)In Figure3, we have shown a linear correlation between DFT calculated and X-ray experimental bond-lengths for title molecules. Note that C–H bond-lengths are not included here. A correlation coefficient (R
2) of greater than 0.99 in both molecules supports the fact that DFT can efficiently reproduce the experimental geometry.Correlation between X-ray experimental and DFT calculated bond-lengths for (a) 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide and (b) 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide.
(a)
(b)


## 3.2. Normal Mode Analysis

The calculated IR and observed FTIR spectra of both molecules are shown in Figure4 for comparison in the wavenumber range of 1800–400 cm−1. The calculated wavenumbers are scaled by using the equation mentioned earlier. All the vibrational modes were properly assigned on the basis of the potential energy distribution (PED). Tables 1 and 2 list calculated frequencies (unscaled as well as scaled), FTIR observed frequencies, IR intensities, and assignments of all normal modes for title molecules. Both molecules contain two ring system, a phenyl ring (R1) and a thiazole ring (R2) connected by acetamide fragment (–NHCOCH2–). For the clarity of discussions, we classified their vibrations into three broad categories.Table 1
Normal mode assignments of 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide at B3LYP/6-31+G (d,p) level.
S.number
Unscaled freq. (cm−1)
Scaled freq. (cm−1)
FTIR freq. (intensity) (cm−1)
IR intensity (a.u.)
Mode of vibration(%PED)
Direction of polarization
1
3600
3458
3199 (s)
79
ν(N17–18H) (
100
)
Along N–H plane
2
3272
3145
1
ν(C–H)R2 (
99
)
Along R1
3
3243
3117
1
ν(C–H)R2 (
99
)
Along R2
4
3234
3108
8
ν
as(22H–19C–25C–21H) (
89
)
Per R2
5
3226
3101
1
ν(C–H)R1 (
99
)
Along R2
6
3188
3064
3055 (w)
5
ν(C–H)R1 (
98
)
Along to 3C–6C
7
3121
3001
1
ν
as(22H–19C–25C–21H) (
89
)
Along R2
8
3068
2950
7
ν(13H–12C–14H) (
91
)
Along R2
9
1748
1690
1691 (s)
273
ν(15C–16O) (
83
)
Opposite to C–O
10
1632
1580
42
ν(C–C)R1 (
59
)
Along R2
11
1599
1548
1544 (m)
16
ν(C–C)R1 (
65
) + β(C–H)R1(
14
)
Along 6C–9H
12
1581
1531
420
ν(20C–24N) (
55
) + β(17N–18H) (
21
)
Along R1
13
1524
1477
109
ν(19C–25C) (
54
) + β(17N–18H) (
12
) + β(C–H)R2 (
15
)
Per R2
14
1506
1459
84
β(C–H)R1 (
74
)
Along R2
15
1473
1428
6
Scissoring (13H–12C–14H(
55
)) + ν(20C–24N) (
40
)
Along R2
16
1461
1416
38
Scissoring (13H–12C–14H)(
72
) + β(17N–18H) (
15
)
Per R2
17
1416
1373
1346 (m)
15
ν(C–C)R1 (
30
) + β(C–H)R1 (
27
)
Along R2
18
1348
1308
61
β(C–H)R1 (
86
)
Along 19C–22H
19
1339
1300
1300 (vw)
1
Rocking (13H–12C–14H)(
39
) + β(C–H)R2 (
42
)
Along R2
20
1330
1291
3
Rocking (13H–12C–14H)(
30
) + ν(C–C)R2 (
54
)
Along R1
21
1304
1267
107
ν(20C–24N) (
45
) + β(17N–18H) (
15
)
Per R2
22
1291
1254
1230 (w)
3
β(C–H)R1 (
76
)
Along R2
23
1227
1193
64
β(C–H)R1 (
54
)+ β(17N–18H) (
32
)
Along R2
24
1224
1190
3
β(C–H)R1 (
71
)
Per R2
25
1205
1172
31
Twist (13H–12C–14H) +β(C–H)R2 and R1
Per R2
26
1178
1146
30
β(19C–22H) (
65
) + β(17N–18H) (
15
)
Along R2
27
1163
1132
4
β(1C–7H–6C–9H) (
65
)
Per R2
28
1119
1090
1103 (m)
50
β(3C–8H) (
43
) + β(6C–9H) (
32
)
Along R2
29
1088
1060
10
Scissoring (21H–25C–19C–22H)(
56
)
Along R2
30
1066
1039
28
Breathing R2
Per R1
31
976
954
960 (w)
7
Twist (13H–12C–14H) +S(16O–15C–17H)
Along R1
32
967
945
1
Twist (1C–7H–6C–9H)
Along R2
33
936
915
9
Rocking (13H–12C–14H)(
45
)
Along R2
34
898
879
3
Twist (21C–25H–19C–22H)
Per R2
35
885
867
866 (w)
11
γ(3C–8H) (
49
)
36
882
864
7
Breathing R2
Along R1
37
871
853
43
Breathing R1
In between R1 and R2
38
834
818
823 (m)
18
γ(1C–7H) (
44
) + γ(6C–9H) (
11
)
Along R1
39
786
772
771 (w)
7
γ(1C–7H) + γ(6C–9H) + β(R1)
Along C–O
40
758
746
43
β(R2)
41
723
712
11
Ring R2 twist
Per R2
42
717
706
698 (m)
43
γ(21C–25H) (
38
) + γ(19C–22H) (
12
)
Along R2
43
693
683
2
Ring R2 twist
Along R1
44
677
668
2
T(13H–12C–14H)
45
648
641
2
γ(C–H)R1 (
54
)
Directed CH2
46
628
621
36
γ(C–H)R1 + γR2 + rocking (13H–12C–14H)
Per R2
47
623
617
7
Twist R2 + rocking (13H–12C–14H)
Along R2
48
579
575
15
γ(7C–1H) (
43
)+ γ(3C–8H) (
39
) + γ(2C–11Cl) (
11
)
Along 2C–11Cl
49
564
560
4
Rocking (13H–12C–14H)(
23
) + γ(19C–22H) (
35
) + γ(17N–18H) (
21
)
Along R1
50
524
522
16
R2 breathing + R1 twist
Per R2
51
510
509
14
γ(17C–18H) + γ(ring R2)
(Along Cl) R1
52
486
486
8
Ring R2 twist +γ(17C–18H) + γ(23C–25C–20C)
53
452
453
3
γ(3C–8H) (
35
) + γ(6C–9H) (
22
) + R(13H–12C–14H) (
31
)
Along 17N–18H
54
437
439
3
Rocking (13H–12C–14H(
29
)) + γ(3C–8H) (
35
) + γ(5C–9H) (
12
)
Per R2
55
398
402
3
β(R1ring)
Per 17N–18H
56
357
363
1
β(C–C)R2 (
23
) + β(15C–16O) (
34
)
Along R2
57
321
328
1
γ(C–C)R2 (
26
) + rocking (13H–12C–14H) (
17
)
Along CH2
58
298
307
1
γ(23C–21H) + γ(28C–17H) + rocking (13H–12C–14H)
Along R1
59
286
295
6
γ(ring R2)
Per R2
60
267
277
4
β(11C–2Cl) (
18
) + β(4C–10Cl) (
13
) + rocking (13H–12C–14H) (
21
)
Along R2
61
201
214
1
β(11C–2Cl) (
11
) + β(4C–10Cl) (
27
) + β(1C–7H) (
23
)
Along R2
62
174
188
1
τ(ring R1 and R2)
Per R2
63
137
153
6
γ(ring R1)
Per R2
64
105
122
1
γ(ring R2)
Per R1
65
96
114
1
γ(ring R2)
Along R2
66
77
96
4
τ(13H–12C–14H)
Per R2
67
32
53
1
Rings R1 and R2 twist jointly
Along R1
68
23
44
1
Rings R1 and R2 twist jointly
Along 4C–10Cl
69
19
40
1
Rings R1 and R2 twist jointly
Along R2
ν: stretching; ν
s: symmetric stretching; ν
as: asymmetric stretching; β
: in-plane-bending; γ: out-of-plane bending; ω: wagging; τ: torsion, S: scissoring; vs: very strong; s: strong; m: medium; w: weak; vw: very weak.Table 2
Normal mode assignments of 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide at B3LYP/6-31+G(d, p) level.
S.number
Unscaled Freq. (cm−1)
Scaled freq. (cm−1)
FTIR freq. (intensity) (cm−1)
IR intensity (a.u.)
Mode of vibration (%PED)
Direction of polarization
1
3598
3456
3197 (s)
97
ν(15N–16H) (
100
)
Along 15N–16H plane
2
3271
3144
1
ν(23C–19H) (
44
) +  ν(17C–20H) (
45
)
Along 2C–9Cl
3
3234
3108
8
ν(23C–19H) (
99
)
Along 6C–8H
4
3220
3095
1
ν(1C–7H) +  ν(6C–8H)
Along 2C–Cl
5
3204
3080
1
ν(9C–23H) (
99
)
Along R2
6
3191
3067
3034 (w)
4
ν(6C–8H) (
48
) +  ν(1C–7H) (
55
)
Along 3C–6C
7
3106
2986
1
ν
as(12H–110C–11H) (
89
)
Along R2
8
3065
2947
8
ν(12H–10C–11H) (
91
)
Along R1
9
1743
1685
1689 (vs)
289
ν(15C–16O) (
83
)
Along 13C–14O
10
1636
1583
1589 (w)
5
ν(C–C)R1 (
59
)
Along R2
11
1600
1549
13
ν(C-C)R1 (
65
) + β(C–H)R1 (
14
)
Along 5C–H
12
1582
1532
1527 (vs)
461
ν(18C–22N) (
55
) + β(15N–16H) (
21
)
Per R1
13
1524
1476
104
ν(C–C)R2 (
54
) + β(15N–16H) (
12
) + β(17C–20H) (
15
)
Per R2
14
1506
1459
1462 (s)
74
β(C–H)R2 (
74
) + ν(C–C)R2 (
21
)
Along R2
15
1476
1431
3
Scissoring (13H–12C–14H(
55
)) +  ν(C-N)R2 (
40
)
Along R2
16
1461
1416
38
Scissoring (13H–12C–14H)(
72
) + β(17N–18H) (
15
)
Along 4C–5C
17
1425
1382
41
ν(C–C)R1 (
30
) + β(C–H)R1 (
27
)
Along13C–15N
18
1349
1310
59
β(C–H)R1 (
46
) + ν(C–C)R1 (
30
)
Along R2
19
1331
1292
1294 (w)
9
Rocking (13H–12C–14H)(
39
) + β(C–H)R1 (
42
)
Along R1
20
1328
1289
1
Rocking (13H–12C–14H)(
39
) + ν(C–C)R1 (
32
)
Per R1
21
1304
1267
107
β(15C–16H) (
26
) + ν(C–C)R1 (
54
)
Per R1
22
1285
1248
1228 (w)
3
β(C–H)R1 (
76
)
Along R2
23
1228
1194
15
β(17C–20H) (
19
) + rocking (11H–10C–12H) (
22
) + β(C–H)R1 (
26
)
Making 5C–10C with an angle 45°
24
1222
1188
3
β(17C–20H) (
19
)+ β(15N–16H) (
22
) + β(4C–24H)R1 (
26
)
Per R2
25
1204
1171
2
Twist (11H–10C–12H) +β(6C–8H)
Per R1
26
1180
1148
35
β(17C–18H)R (
65
) + β
(17N–18H) (
15
)
Along R2
27
1168
1137
3
β(1C–7H) (
65
) + β(6C–8H) (
14
)
Plane containing 13C and per to plane of R1
28
1148
1118
50
β(C–C)R1 (
43
) + β(C–H)R1 (
32
)
Along 15N–16H
29
1089
1061
10
β(17C–20H) (
43
) + β(23C–10H) (
32
)
Along R2
30
1043
1017
35
β(C–H)R1 (
28
) + β(C–C)R1
Per R1
31
977
955
7
Twist (13H–12C–14H) + scissoring (16O–15C–17H)
Along R1
32
970
948
1
Twist (7C–1H-6C–8H)(
59
)
Along R2
33
943
922
12
Rocking (13H–12C–14H)(
45
) + γ(4C–24H) (
29
)
Along R2
34
909
890
11
γ(C–H) (
23
) + γ(C–C) (
49
)
Per R2
35
898
879
3
γ(C–H)R2 (
49
)
Per R2
36
891
872
10
Breathing R1+γ(4C–24H)
Along 6C–5H
37
881
863
7
Breathing R2
Along 15N–10H
38
840
824
815 (m)
17
γ(6C–8H) (
44
) + γ(1C–7H) (
11
)
Along R1
39
781
767
763 (m)
23
γ(6C–8H) + β(ring R1)
Along C–O
40
737
725
729 (w)
8
γ(C–C)R1 (
44
) + γ(C–H)R1 (
11
)
41
719
708
43
γ(23C–14H) (
32
) + γ(17C–20H) (
53
)
Per R2
42
708
698
11
γ(C–C) (
38
) + rocking (11–10C–12H) (
12
)
Along R2
43
699
689
3
γ(C–H) (
23
) + γ(C–C) (
49
)
Along 13–14O
44
681
672
10
τ(13H–12C–14H)
45
652
644
17
γ(C–S–C)R2 (
54
)
Directed CH2
46
634
627
27
γ(15C–16H)R2 + γR2 + rocking (11H–10C–12H)
Per R2
47
624
618
17
γ(C–S–C)R2 (
43
) + γ(C–H)R2 (
39
)
Along R2
48
598
593
580 (w)
9
Twist R1 + Rocking (13H–12C–14H)
Per R2
49
566
562
5
γ(R2) + γ(15N–16H)
Along R1
50
526
524
21
R1 breathing + R2 twist
Per R2
51
510
509
14
γ(17C–18H) + ring R2 out-of-plane bending
Along R1
52
483
483
6
γ(CCC)R1+ γ(C–Cl)R1
Along 13C–10O
53
460
461
1
Ring R1 twist
Along 5C–4C
54
448
450
4
γ(CCC)R1 (
34
) + γ(1C−7H) (
54
)
Plane containing 16H
55
386
391
1
τ(ring R1)
Along 5C–4C
56
356
362
1
β(C–C)R1 (
23
) + β(15N–16H) (
34
)
Along R2
57
319
327
3
γ(C–C)R1 (
26
) + β(13C–14) (
25
)
Along CH2
58
295
304
1
γ(ring R2)
Along 4C–24H
59
288
297
3
γ(CCC)R1 + γ(C–H)R1
Along 18C–15N
60
243
254
1
τ(11H–10C–12H)
Along R2
61
199
212
1
β(C–Cl)R1 (
11
) + β(1C–7H) (
23
)
Along R1
62
183
197
2
τ(ring R1)
Per R2
63
135
151
5
τ(CCC) + γ(CH)R1
Per R2
64
105
122
1
τ(ring R1)
Per R2
65
94
112
0
τ(ring R2)
Per R1
66
76
95
6
τ(11H–10C–12H) + γ(13C–14H)
Along R2
67
33
54
1
τ(ring R1)
Per R2
68
16
37
1
γ(R1)
Along R1
69
12
34
1
Rings R1 and R2 twist jointly
Along 4C–10Cl
ν: stretching; ν
s: symmetric stretching; ν
as: asymmetric stretching; β: in-plane-bending; γ: out-of-plane bending; ω:  wagging; τ: torsion, S: scissoring; vs: very strong; s: strong; m: medium; w: weak; vw: very weak.Calculated IR and observed FTIR spectra of (a) 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide and (b) 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide for comparison in the frequency range of 1800 cm−1–400 cm−1.
(a)
(b)


### 3.2.1. Phenyl Ring (R1) Vibrations

The phenyl ring vibrations contain the C–H stretching modes in the region 3100–3000 cm−1, which is the characteristic region for the identification of C–H stretching vibrational modes [18]. In this region, the bands are not much affected by the nature of the substituents. The scaled C–H modes are found between 3096–3060 cm−1 which are observed at 3055 cm−1 for 2,4 substituted molecule polarized along 3C–6C and at 3034 cm−1 for 3,4 substitution. These modes are purely stretching having PED greater than 90%. Most of the C–H stretching modes are found to be weak due to charge transfer from hydrogen to carbon atom. Other C–H modes coming from bending (in-plane and out-of-plane), breathing and twisting of ring are found in the region below 1500 cm−1 having medium to weak intensities.The C–C ring stretching vibrations are expected within the region 1650–1200 cm−1 [19]. Most of these ring modes are affected by the substitution to aromatic ring. Scaled frequencies for C–C stretching modes at B3LYP/6-31+G(d, p) are 1580 cm−1, 1548 cm−1, and 1477 cm−1 for 2,4 and 1583 cm−1, 1549 cm−1, and 1476 cm−1 for 3,4 substitution on the ring. Some other C–C modes associated with bending, twisting and breathing vibrations are also found to lie in lower frequency region as well as overlapped with other modes. Most of C–C modes are comparatively stronger than C–H modes.


### 3.2.2. Thiazol Ring (R2) Vibrations

The vibrations of thiazole ring associated with C–H stretching are calculated in between 3145–2950 cm−1 for title molecules which are essentially independent on the substitutions in the phenyl ring. These values are in agreement with observed bands in thiazoles and its derivatives [20]. The most intense bands corresponding to C–N stretching in thiazole are calculated at 1532-1531 cm−1. These vibrational modes are found to be coupled with N–H stretching and polarized along phenyl ring. The same bands are observed at 1544 cm−1–1527 cm−1 in the FTIR spectra. Other weak modes of thiazole ring vibration associated with breathing and twisting of rings are calculated below 1500 cm−1 and those specially associated with S atom are found near 600 cm−1.


### 3.2.3. Fragment (–NHCOCH2–) Vibrations

Amides show somewhat strong and broad band in the range between 3500 cm−1 and 3100 cm−1 for N–H stretch as well as a stronger band between 1700 cm−1 and 1650 cm−1 for C=O stretching [21]. Carbonyl absorptions are very sensitive and both the carbon and the oxygen atoms move during the vibration having nearly equal amplitude. The scaled values, 3458 cm−1–3456 cm−1 for N–H stretch and 1690 cm−1–1685 cm−1 for C=O stretch agree with literature values. In FTIR spectra, the corresponding band for C=O stretching are observed at 1691 cm−1–1689 cm−1 while N-stretching frequencies are lowered to 3199 cm−1–3197 cm−1. The differences between calculated and observed N–H stretch band are attributed to the presence of intermolecular H-bond in condensed phase which are absent in the isolated state of molecules.In acetamide fragment, the stretching of methylene (–CH2) group and bending (scissoring and rocking) always occur in 3000 cm−1–2850 cm−1 and below 1500 cm−1, respectively [20]. These vibrations are more common and so are not much of significance. The stretching mode polarized along to ring R2 corresponding to –CH2 is calculated at 2950 cm−1 for 2,4 substitution and 2947 cm−1 for 3,4 substituted molecule.


## 3.2.1. Phenyl Ring (R1) Vibrations

The phenyl ring vibrations contain the C–H stretching modes in the region 3100–3000 cm−1, which is the characteristic region for the identification of C–H stretching vibrational modes [18]. In this region, the bands are not much affected by the nature of the substituents. The scaled C–H modes are found between 3096–3060 cm−1 which are observed at 3055 cm−1 for 2,4 substituted molecule polarized along 3C–6C and at 3034 cm−1 for 3,4 substitution. These modes are purely stretching having PED greater than 90%. Most of the C–H stretching modes are found to be weak due to charge transfer from hydrogen to carbon atom. Other C–H modes coming from bending (in-plane and out-of-plane), breathing and twisting of ring are found in the region below 1500 cm−1 having medium to weak intensities.The C–C ring stretching vibrations are expected within the region 1650–1200 cm−1 [19]. Most of these ring modes are affected by the substitution to aromatic ring. Scaled frequencies for C–C stretching modes at B3LYP/6-31+G(d, p) are 1580 cm−1, 1548 cm−1, and 1477 cm−1 for 2,4 and 1583 cm−1, 1549 cm−1, and 1476 cm−1 for 3,4 substitution on the ring. Some other C–C modes associated with bending, twisting and breathing vibrations are also found to lie in lower frequency region as well as overlapped with other modes. Most of C–C modes are comparatively stronger than C–H modes.


## 3.2.2. Thiazol Ring (R2) Vibrations

The vibrations of thiazole ring associated with C–H stretching are calculated in between 3145–2950 cm−1 for title molecules which are essentially independent on the substitutions in the phenyl ring. These values are in agreement with observed bands in thiazoles and its derivatives [20]. The most intense bands corresponding to C–N stretching in thiazole are calculated at 1532-1531 cm−1. These vibrational modes are found to be coupled with N–H stretching and polarized along phenyl ring. The same bands are observed at 1544 cm−1–1527 cm−1 in the FTIR spectra. Other weak modes of thiazole ring vibration associated with breathing and twisting of rings are calculated below 1500 cm−1 and those specially associated with S atom are found near 600 cm−1.


## 3.2.3. Fragment (–NHCOCH2–) Vibrations

Amides show somewhat strong and broad band in the range between 3500 cm−1 and 3100 cm−1 for N–H stretch as well as a stronger band between 1700 cm−1 and 1650 cm−1 for C=O stretching [21]. Carbonyl absorptions are very sensitive and both the carbon and the oxygen atoms move during the vibration having nearly equal amplitude. The scaled values, 3458 cm−1–3456 cm−1 for N–H stretch and 1690 cm−1–1685 cm−1 for C=O stretch agree with literature values. In FTIR spectra, the corresponding band for C=O stretching are observed at 1691 cm−1–1689 cm−1 while N-stretching frequencies are lowered to 3199 cm−1–3197 cm−1. The differences between calculated and observed N–H stretch band are attributed to the presence of intermolecular H-bond in condensed phase which are absent in the isolated state of molecules.In acetamide fragment, the stretching of methylene (–CH2) group and bending (scissoring and rocking) always occur in 3000 cm−1–2850 cm−1 and below 1500 cm−1, respectively [20]. These vibrations are more common and so are not much of significance. The stretching mode polarized along to ring R2 corresponding to –CH2 is calculated at 2950 cm−1 for 2,4 substitution and 2947 cm−1 for 3,4 substituted molecule.


## 3.3. Molecular Orbital Analysis

The highest occupied molecular orbital (HOMO) represents ability to donate an electron while lowest unoccupied molecular orbital (LUMO) denotes ability to accept it. The HOMO-LUMO plots for title molecules are shown in Figure5. Evidently, the HOMOs of both molecules are located on the thiazole ring including amide fragment while the LUMOs are contributed mainly by phenyl ring system. The transition from HOMO → LUMO in these molecules indicates charge transfer to phenyl ring. The energy difference (E
gap
⁡) between HOMO and LUMO describes the chemical reactivity of molecule. The smaller E
gap
⁡, 4.89 eV in 2,4 substituted molecule as compared to 4.94 eV in 3,4 substitution may suggest that former is chemically more reactive than the latter one. The chlorine atoms attached to adjacent carbons on phenyl ring for 3,4 substituted molecule make it less reactive.HOMO-LUMO and MESP plots for (a) 2-(2,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide and (b) 2-(3,4-dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide.
(a)
(b)Figure5 also plots the molecular electrostatic potential (MESP) surface for title molecules. The MESP, a map of electrostatic potential on uniform electron density, is used to visualize charge or electron density distribution within the molecule. The importance of MESP lies in the fact that it simultaneously displays molecular size, shape as well as positive, negative, and neutral electrostatic potential regions in terms of colour grading. In present context, colour code varies between positive region for red and negative for blue regions with an isovalue of 1.00000 eV. Evidently, the electronegative region lies in the vicinity of carbonyl group of amide fragment. On the basis of MESP plot, it can be asserted that an electrophile will be attracted towards the negative region of amide fragment in both molecules.


## 3.4. Thermochemical Analysis

Thermochemical properties of molecules are dominated by molecular vibrations as electronic contribution becomes negligible due to absence of free electrons, especially at the room temperature. Various thermal parameters for title molecules are calculated and reported in Table3. These parameters are related to one another via standard thermodynamic relations and can be useful for the estimation of chemical reaction paths. Zero point energy (ZPE) is also given. Thermal energy of 3,4 substituted molecule is slightly higher than that with 2,4 substitution while heat capacity is smaller. The entropy values are closely related to the geometry of molecules. The substitution of chlorines at 3,4 position of ring leads to an increase in entropy value as compared to 2,4 substitution. The increase in thermal energy and entropy values may indicate the enhancement in molecular vibrations due to steric repulsion generated with chlorine atoms substituted at two consecutive (3,4) positions of the phenyl ring.Table 3
Total energy and various thermodynamic parameters for title molecules calculated at B3LYP/6-31+G(d,p) level.
Parameters
2-(2,4-Dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide
2-(3,4-Dichlorophenyl)-N-(1,3-thiazol-2-yl)acetamide
Electronic energy (Hartree)
−1927.348
−1927.345
ZPE (kcal/mol)
108.137
108.118
Thermal energy (kcal/mol)
117.690
117.696
Thermal enthalpy (kcal/mol)
118.281
118.287
Thermal free energy (kcal/mol)
79.187
78.675
Constant volume heat capacity (cal/mol-K)
56.509
56.438
Entropy (cal/mol-K)
131.123
132.861


## 4. Conclusions

We have performed a theoretical density functional calculations on dichloro substituted phenyl-N-(1,3-thiazol-2-yl)acetamides at 2,4 and 3,4 positions of the phenyl ring. The calculated structural parameter shows a good correlation with corresponding experimental data showing the validity of calculations. We have presented complete vibrational mode assignments using same computational scheme. Normal modes are discussed in detail and compared with those observed by FTIR spectroscopy. The chemical reactivity of molecules is discussed by HOMO-LUMO as well as MESP analysis thus exploring the effect of substituent positions. Calculated various thermodynamic parameters are very useful in determining chemical reaction paths.



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*Source: 125841-2014-01-29.xml*