CHE532

UV-vis, chemical reactivity, IR.
The most brilliant analysis ever done on a structural puzzle was surely the solution ( 1953 ) of the terramycin problem. It was a problem of great industrial importance, and hence many able chemists had performed an enormous amount of work trying to determine the structure. There seemed to be too much data to resolve the problem, because a significant number of observations, although experimentally correct, were very misleading. Woodward took a large piece of cardboard, wrote on it all the facts and, by thought alone, deduced the correct structure for terramycin.
OH O
OHOH
N
HO
O
OH
NH
2
O

http://pubs.acs.org/paragonplus/submission/joceah/joceah_authguide.pdf
The J. Org. Chem Guidelines require that authors report the data used to characterize (demonstrate purity and establish identity of) the compounds whose preparation they describe. The requirement applies both to new compounds and to known compounds whose isolation or preparation by a new or improved method is being reported.
JOC upholds a high standard for compound characterization to ensure that compounds being added to the chemical literature have been correctly identified and can be synthesized in known yield and purity by the reported preparation, isolation, and purification methods.
For all new compounds, evidence adequate to establish both identity and degree of purity (homogeneity) must be provided.
Purity documentation must be provided for known compounds whose preparation by a new or improved method is reported.

Ensuring that these compound-characterization and computation-reporting requirements are met is one of the responsibilities of editors and reviewers.
The Compound Characterization Checklist, will be provided to reviewers to help them evaluate the overall completeness of the characterization data.
Identity. Evidence for documenting the identity (molecular) of most new compounds should include both NMR data and either HRMS or elemental analysis data.
•
Excludes some polymers / oligomers / biological macromolecules.
HRMS: need sufficiently small estimated uncertainties, to exclude alternative plausible formulas.
elemental analysis: should be within 0.4% of the Calcd values for the proposed formula

Identity
Melting point range
HRMS
IR
UV-Vis
1 H NMR
13 C NMR
● MS
● Optical rotation/ORD/CD
● Enantio/Diastereomer ratio
● X-ray [CIF]
● Heteronuclear NMR
1 H/ 13 C NMR spectrum (95%)
Chromatographic evidence:
•
Quant. GC, HPLC, or electrophoresis
Elemental analysis
Purity

IR, NMR are not as convincing for very large discrete molecules as they are for typical smaller organic molecules.
Biomacromolecules. The structures of biomacromolecules may be established by providing evidence about sequence and mass.
•
Sequences may be inferred from the experimental order of amino acid, saccharide, or nucleotide coupling,
• from known sequences of templates in enzyme-mediated syntheses, or
• through standard sequencing techniques.
•
Typically, sequence information for a discrete polymer/ oligomer/ biopolymer will be accompanied by MS data that establish the molecular weight.

Demonstrating the Purity of New Organic Compounds
Purity (at least 95%). Evidence for documenting compound purity may include one or more of the following:
A standard 1D 1 H NMR spectrum or proton-decoupled
13 C NMR spectrum showing at most trace peaks not attributable to the assigned structure. A copy of a spectrum with a signal-to-noise ratio sufficient to permit seeing peaks with 5% of the intensity of the strongest peak should be included in the supporting information for publication. For new compounds, copies of both 1H and
13C spectra are often required (see ‘ Identity ’ above).
Combustion elemental analytical values for carbon and hydrogen (and nitrogen, if present) agreeing with calculated values within 0.4%.

Demonstrating the Purity of New Organic Compounds
Quantitative gas chromatographic analytical data for distilled or vacuum-transferred samples, or quantitative
HPLC analytical data for materials isolated by column chromatography or separation from a solid support. The stationary phase, solvent (HPLC), detector type, and percentage of total chromatogram integration represented by the product peak should be reported.
For known solid compounds, a narrow melting point range that is in close agreement with a cited literature value.

Demonstrating the Purity of New Organic Compounds
The type of acceptable evidence depends on
• method of preparation
• air and thermal stability
• amount of sample available
• structural complexity
• nature of likely impurities
•
For example: combustion analysis would not be an appropriate choice for the product of an isomerization reaction;
1 H NMR spectra would need to be supplemented with other evidence
• when reasonably likely impurities (including unreacted starting materials) do not have unique resonances or are NMR-silent
•
Example: an inorganic salt.
A narrow melting point range is not sufficient by itself to document the purity of a new compound.

A word to the wise
When doing chemical research:
•
Get spectra sooner instead of later.
•
Cleaning up your data at the point where you are ready to publish can be a big job.
Organic compounds decompose
The work accumulates.
Get the spectra solvent-free and clean early in the game.
Save your spectra electronically
•
If you can
•
Not pdf, graphic or other white paper,
Save the actual data.
•
You might have missed something the first time.
Back Up Your DATA!

Unknowns: Working with fraction composition problems
Data generated by elemental analysis
Researchers used a combustion method to analyze a compound used as an antiknock additive in gasoline. A 9.394-mg sample yielded
31.154 mg CO
2 and 7.977 mg H
2
O from combustion.
•
Calculate the % composition of the compound.
•
Determine the empirical formula.
31.154 mg CO
2
/ 44.0098 mg/mmol CO
2
= 0.70788 mmol C
7.977 mg H
2
O/ 18.0153 mg/mmol H
2
O * 2 H/H
2
O = 0.8856 mmol H
C:H = 1: 1.25 = 4: 5 .
C
4
H
5
, DU=2.5, probably C
8
H
10
, DU=4

Unknowns: From Formula to Structure
Degrees of Unsaturation/ Double Bond Equivalents / Index of
Hydrogen Deficiency
Apply the following formula to spin paired neutral species only!
DU = ring a double or a triple bond.
•
DU = #B4 + #B3/2 - #B1/2 +1
•
Where #B4 = an element in the formula that bonds 4 times
•
Has a valence of 4. example: chloropyrole C
4
H
4
NCl
Counter example: C
4
H
5
NCl
What happens to the DU if we protonate this compound?

Unknowns:
Consider unknown substance with MW = 94.
•
94/13=7.231, 0.231x13=3 so 7 and 3/13.
•
Thus part of the formula is 7XCH. A guess at the full formula might be C
7
H
10
.
Be careful !
Consider MW = 278.35 g/mol
278.35/ 13 = 21.4118 = 21 and 5/13
C
21
H
26
? 21-13+1=9 DU. MW=278.43
But I was thinking of the following formula:
C
22
H
14
, DU = 22-7+1=16=11DB + 5 rings
•
The problem is that the C:H ratio > 1:1
•
Applying the rule of 13 is more difficult in these cases. etc.

Unknowns: Rule of 13 dealing with MS data.
What if you had the DUs and the mass you knew that the unknown was a simple hydrocarbon?
•
DU = 16 so . . . Define M and N as C
•
(1) N-M/2+1=16 and (2) N*12+M=278
N
H
M
•
(3) (278-M)/12 = N
•
(4) (278-M)/12 – M/2 +1 = 16 substituting (3) ─► (1)
•
23.17-M/12-M/2=15
•
7/12M = 8.17, M=14 solving (4) for M
•
N*12+14=278 -> 12N=264 -> N=22
•
Therefore formula = C
14
H
22
Don’t be afraid to bust out the math.

•
Give formula, calculate MW, and percent composition.
•
Calculate MW give formula
•
Give formula, choose exact mass or average mass
•
Calculate MW give formula