Y. B. Chavan College of Pharmacy Problems solving skill in Spectroscopy Dr. K. G. Baheti Y. B. Chavan College of Pharmacy Aurangabad

Data of spectroscopic problems: Example Look at Molecular weight, Molecular formula and % of elements Look at UV data Look at the IR absorption bands >1500 cm-1 (Functional Groups) Look at the NMR to determine (No. & types of proton(s)) Draw some possible structures and see if they "work" with the IR, NMR and unsaturation. Molecular Formula % C, %H, %O or %N UV IR NMR Mass

1. Calculate the total number of rings plus double bonds(Double bond equivalent)DBE): For the molecular formula:  CxHyNzOn Rings + double bonds = x - (1/2)y + (1/2)z + 1 Example: Calculate the double bond eq. for C6H6 Ring + Double bond Equivalent: 6-1/2*3+0+1 = 4 This formula consist of four double bond or one ring +3 double bond Calculate the double bond eq. for C4H8O3 Ring + Double bond Equivalent: 4-1/2*8+0+1 = 1 This formula contain one ring or one double bond.

Calculate the double bond eq. for C3H8O2 Ring + Double bond Equivalent: 3-1/2*8+0+1 = 0 This formula contain one ring or one double bond Calculate the double bond eq. for C12H12N2 Ring + Double bond Equivalent: 12-1/2*12+1/2*2+1 = 8 This formula contain two rings + six double bonds OR One ring + seven double bonds.

If the molecular formula contain halogens, then while calculating the DBE each halogen may be considered as a hydrogen and it should be added to hydrogen. Example: C10H7Br Ring + Double bond Equivalent: 10-1/2*8+0+1 = 7 This formula contain two rings + Five double bonds OR One ring + six double bonds

Determination of C, H and other elements: Examples: Given: Mol weight= 72 C 66.66%, H11.1% and O 22.3%. Ans: Total % of element = 66.66+11.1+22.3 = 100% Formula No. of carbon = 72* 66.66/ 100 * 12 = 3.99 ~ 4 No. of Hydrogen = 72* 11.1/ 100 * 1 = 7.99 ~ 8 No. of Oxygen = 72* 22.3/ 100 * 16 = 1.0035 ~ 1

Structural formulas of hundreds of Organic compounds (drugs)have been reported, based upon sound experimental evidence from spectroscopic experiments. Thus spectroscopy helps in structural determination. Structure of atoms and molecules comes from studying their interaction with light (electromagnetic radiation). Different regions of the electromagnetic spectrum provide different kinds of information as a result of interactions.

NMR Data interpretation H ppm Multi-plicity No of H Interpretation Probable structure 5.60 d 1H 6.60 t 7.38-7.60 m 5H 9.27 0.99 6H 1.73 nonet 3.35 2H 4.21 Broad (s) C9H8O C4H10O

C4H7O2Cl C4H9ON H ppm Multi-plicity No of H Interpretation Probable structure 0.92 t 3H 1.95 quintet 2H 2.9 1H 12.7 S, Broad 0.95 1.60 sextet 2.1 6.6, 7.2 S C4H7O2Cl C4H9ON

Sample molecules are ionized by ionization method. Mass Spectrometry: Sample molecules are ionized by ionization method. The m/z ratio of these ions is measured accurately by electrostatic acceleration and magnetic field perturbation, providing a precise molecular weight. Ion fragmentation patterns may be related to the structure of the molecular ion. m/Z Relative abundance M+ Base Peak Mass Spectrum

Look at Mass Data/ Spectra Molecular ion peak – Molecular weight/ even/odd-nitrogen rule Isotopic peak – Isotopes of atoms present in comp. Fragmentation pattern - Diff. types of fragments of comp. 3-Phenyl-2-propenal C9H8O MW = 132.16

n-Methylbenzylamine C8H11N MW = 121.18

2-Butenoic acid C4H6O2 MW = 86.09 Mass: 323

Problems Fragments: C=O, COOH, CH2, CH2 CH3 Structure/Ans: Mol wt.: 116 UV: 283nm, max 22 IR(Cm-1) 3000-2500(b), 1715(s), 1342(w) NMR  ppm: 2.15, s, 3H 2.6, t, 2H 2.30, t, 2H 11.2, s, 1H Fragments: C=O, COOH, CH2, CH2 CH3 Structure/Ans: Data Discussion Inference UV: 283nm,  max 22 Low intensity at 283nm C=O may present IR(Cm-1) 3000-2500(b), 1715(s), 1342(w) Broad peak of OH, H-bonding Carbonyl str. COOH NMR  ppm: 2.15, s, 3H 2.6, t, 2H 2.30, t, 2H 11.2, s, 1H Singlet indicate no neighboring H t, 2 neighboring H, deshilded,-CH2 t-neighboring proton, -CH2 Singlet, OH -CH3 -CH2- -OH

Problems Mol Formula: C9H10O2 UV: 274nm, max 2050 IR(Cm-1) 3031v, 2941w, 1725s,1608, 1504w, 1060s, NMR  ppm: 2.35, s, 3H 3.8,s, 3H 7.2-7.8,dd,4H Fragments: CH3, CH3 attached to COO, COO, C6H4(Ar) Structure/Ans: Data Discussion Inference Mol Formula: C9H10O2 CxHyNzOn DBE= x - (1/2)y + (1/2)z + 1 DBE=5 5 DBE present. May be one aromatic ring UV: 274nm,  max 2050 Med intensity, Aromatic with acid or ester group IR(Cm-1) 3031v, 2941w, 1725s,1608, 1504w, 1060s Ar. Str, Alkyl str, str., Ester str, Ar C=C str, C-O str. Aromatic, CH3, C=O in ester NMR  ppm: 2.35, s, 3H 3.8,s, 3H 7.2-7.8,dd,4H S indicate no neighboring H S indicate no neighboring H,Deshilded Ar. H, Substitution at 1, 4 position -CH3 -CH3 attached with CO Ar. ring with 1, 4 sub.

Problems Mol Wt: 191 %C 56.50, %H 2.60 %N 7.30 IR(Cm-1) 3000-2500(b), 2225(m), 1715(s), 1605, 1518(S), 1344(s), 900-700(s) NMR  ppm: 11.3, s, 1H 7.3-7.9, m, 4H Fragments: COOH, NO2, CC, C6H4 Structure/Ans: Data Discussion Inference Mol Wt: 191 %C 56.50, %H 2.60 %N 7.30 % O = 100-56.5 + 2.6 + 7.3 = 33.6 Number of (C 9, H 5, N 1, O 4) CxHyNzOn DBE= x - (1/2)y + (1/2)z + 1 DBE=8 8 DBE present May be one aromatic ring and highly unsaturated IR(Cm-1) 3000-2500(b), 2225(m), 1715(s), 1605, 1518(S), 1344(s), 900-700(s) -OH str, H-bonded, CN/CC str, C=O of COOH str, C=C Ar str, NO2 Str, O-disubstitution in benzene COOH, CN/CC, NO2 NMR  ppm: 11.3 s, 1H 7.3, t,1H 7.5, d, 1H 7.7, t, 1H 7.9,d,1H S indicate no neighboring H, highly dedshided Aromatic H -COOH Benzene ring

Problems Mol Wt: 158, UV: 225nm, max 50 hexane IR(Cm-1) 2977-2857(m), 1828(s), 1757(m), 1457(m) NMR  ppm: 2.7, septet, 6.4 square 1.2, d, 37.2, square Fragments: Two set CH(CH3)2 , CO-O-CO Structure/Ans: Data Discussion Inference UV: 225nm,  max 50 Low intensity at 225nm Does not give much information IR(Cm-1) 3077-2857(m), 1828(s), 1757(m), 1457(m) C-H str, 1828(s) and 1757(m) characteristic of anhydride, C-C str, CH3, CO-O-CO, NMR  ppm: 2.7, septet, 6.4 sq. 1.2, d, 37.2, square Septet indicate six neighboring H, one H (two sets) 37.2/6.4=5.816H, d, neighboring 1H CH(CH3)2 two set (CH3)2 two set

1.3, t, 3H, CH3 3.4, s, 2H, CH2 4.3, q, 2H, CH2 (attached to Comp. with mol. formula C5H7NO2 gave following spectra analyze the spectra and propose the structure. 2260cm-1- CN 1747 cm-1 ester Str at 1200 confirm C-O and hence ester 1.3, t, 3H, CH3 3.4, s, 2H, CH2 4.3, q, 2H, CH2 (attached to electronegative O2, shifted to downfield)

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