TIMOLOL

(S)-1-[(1,1-dimethylethyl)amino]-3-{[4-morpholinyl)-1,2,5-thiadiazol-3yl]oxy}-2-propanol.

(S)-1-(tert-butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol

Timolol maleate

The structural formula

UV - spectrum

Conditions : Concentration - 3 mg / 100 ml
Solvent designation schedule	Methanol	Water	0.1 M HCl	0.1M NaOH
The absorption maximum	299 nm	-	295 nm	296 nm
	210	-	197	206
ε	9070	-	8540	8920

IR - spectrum

Wavelength (μm)
Wavenumber (cm -1 )

Mass Spectrum

Spectrum (for the base)
The 10 largest peaks:
Peak	30	41	56	57	70	74	86	114	128	130
Meaning	376	85	107	168	72	144	999	102	83	214

SEE FULL CHAPTER AT

http://books.google.co.in/books?id=tQiZCwMb2jAC&pg=PA641&source=gbs_toc_r&cad=4#v=onepage&q&f=false

OR CLICK

Chapter 15 Timolol Maleate

Profiles of Drug Substances, Excipients and Related ...
books.google.com › Science › Chemistry › Organic



Front Cover. Klaus Florey. Academic Press, Sep 4, 1987 - Science - 770 pages ... Chapter 15 Timolol Maleate. 641. 

http://www.google.com/patents/US5231095

The crystal structure for S-timolol hemihydrate (single crystals from water-methylene chloride) was measured with a Enraf-Nonius CAD-4 diffractometer using graphite-monochromatized MoK.sub.α (0.71073 Å) and ω-2θ method at 21° C. The cell parameters and orientation matrix were determined from 18 reflections (6<θ<10°). The measuring rate (° min^-1) was 0.87-16.5, width (θ) 0.5+0.344tan θ and area (θ) 2-25. The following crystal data were obtained: spaced group monoclinic, C2 (No. 5); a=23.435(3) Å, b=6.384(8) Å, c=11.591(1) Å, α=90.00, β=103.081(1), γ=90.00, V=1687(3) Å, Z=2, d=1.281 gcm^-3.

The results obtained with a NMR spectrometer support the above obtained X-ray diffraction results (Instrument Bruker AC 250/Aspect 3000). ¹ H-NMR (solvent CDCl₃) δ (ppm): 1.09 (s, 9H), 2.0 (b, appr. 2.5H), 2.57 (d+d, 1H; 12.0 and 8.0 Hz), 2.80 (d+d, 1H; 12.0 and 4.0 Hz), 3.52 (m, 4H), 3.79 (m, 4H), 3.91 (m, 1H), 4.36 (d+d, 1H; 11.1 and 5.8 Hz), 4.47 (d+d, 1H; 11.1 and 4.1 Hz).

¹³ C NMR (solvent CDCl₃) 6 (ppm): 28.91 (g), 50.24 (s), 44.33 (t), 66.10 (d), 72.76 (t), 153.66 (s), 149.78 (s), 47.78 (t), 66.33 (t).

S-timol hemihydrate has also been analyzed thermogravimetrically (Perkin Elmer, TGS-2 thermogravimetric analyzer and attached differential scanning DSC 4 calorimeter). The TG graph indicates splitting off of the hydrate water at about 50° C., the DSC gives a melting point of 53.3° C.

Markku Per alampi, “S-timolol hemihydrate composition and method of preparation therefor.” U.S. Patent US5574035, issued October, 1986.

US5574035 

Patents

US 6174524, US 5231095

Links

• UV and IR Spectra. H.-W. Dibbern, RM Muller, E. Wirbitzki, 2002 ECV
• NIST / EPA / NIH Mass Spectral Library 2008
• Handbook of Organic Compounds. NIR, IR, Raman, and UV-Vis Spectra Featuring Polymers and Surfactants, Jr., Jerry Workman.Academic Press, 2000.
• Handbook of ultraviolet and visible absorption spectra of organic compounds, K. Hirayama. Plenum Press Data Division, 1967.

Timolol

Systematic (IUPAC) name
(S)-1-(tert-butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol
Clinical data
Trade names	Timoptic
AHFS/Drugs.com	monograph
MedlinePlus	a602022
Pregnancy cat.	C (AU) C (US)
Legal status	℞ Prescription only
Routes	oral, Ophthalmic
Pharmacokinetic data
Bioavailability	60%
Metabolism	Hepatic: 80%
Half-life	2.5-5 hours
Excretion	Renal
Identifiers
CAS number	26839-75-8
ATC code	C07AA06 S01ED01
PubChem	CID 33624
IUPHAR ligand	565
DrugBank	DB00373
ChemSpider	31013
UNII	5JKY92S7BR
KEGG	D08600
ChEBI	CHEBI:9599
ChEMBL	CHEMBL499
Chemical data
Formula	C13H24N4O3S
Mol. mass	316.421 g/mol

SYNTHESIS

 doi:10.1021/jo00881a011.

AZERBAIJAN

http://www.baldhiker.com/wp-content/uploads/PC180077azerbaijan-food.jpg

Caucasus Mountains in northern Azerbaijan.

Justice for Khojaly

Bibi Heybat Mosque

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sindh, pakistan,INSTITUTE OF CHEMISTRY UNIVERSITY OF SINDH JAMSHORO











INSTITUTE OF CHEMISTRY UNIVERSITY OF SINDH JAMSHORO















jAMSHORO



















Food Festival organized by Institute of English Language and Literature UoS , Jamshoro.

ACARBOSE

ACARBOSE

The structural formula

Brief background information

MF C 25 H 43 NO 18

MW 645.61 g / mol

cas   56180-94-0

Acarbose, Bay-g-5421, Prandase, Glucor, Precose, Glucobay

O-4,6-Dideoxy-4-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]-alpha-D-glucopyranosyl-(1--4)-O-alpha-D-glucopyranosyl-(1--4)-D-glucose; O-4,6-Dideoxy-4-[[[1S-(1alpha,4alpha,5beta,6alpha)]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-c

Acarbose is an anti-diabetic drug used to treat type 2 diabetes mellitus and, in some countries, prediabetes. It is an inhibitor of alpha glucosidase, an enteric enzyme that releases glucose from larger carbohydrates. 

The total synthesis of acarbose has been reported. Condensation 1,6-di-O-acetyl-2,3,4-tri-O-benzyl-D-glucopyranose (I) with the protected 1,6-anhydromaltose (II) in the presence of trimethylsilyl triflate gave trisaccharide (III) as a mixture of 
epimers at position 1". Hydrogenolysis of the desired isomer using Pd/C furnished the debenzylated trisaccharide (IV). After conversion of (IV) to the corresponding 
nona-acetate and chromatographic purification, deacetylation with sodium methoxide in MeOH afforded 1,6-anhydromaltotriose (V).

http://www.chemdrug.com/databases/8_0_pcrgfloeixammedx.html

Application

• antidiabetic
• an inhibitor of α-glucosidase
• hypoglycemic

Classes of substances

• Carbohydrates, amino derivatives

Synthesis pathway

Synthesis a)
Produced by fermentation of Actinoplanes SE50 / 110

Trade Names

Country	Trade name	Manufacturer
Germany	Glucobay	Bayer
France	Glyukor	- "-
United Kingdom	Glucobay	- "-
Italy	Glikobaz	- "-
Japan	Glucobay	- "-
USA	Prekoz	- "-
Ukraine	Glucobay	Helsker Bayer AG, Germany  Bayer AG, Germany
	Alumina	ABDI IBRAHIM Ilach Sanayi ve Ticaret AS, Turkey

Formulations

• Tablets of 50 mg, 100 mg

UV - spectrum

Conditions : Concentration - 5 mg / 100 ml
Solvent designation schedule	Methanol	Water	0.1 M HCl	0.1M NaOH
The absorption maximum	-	-	-	-
	-	-	-	-
ε	-	-	-	-

IR - spectrum

Wavelength (μm)
Wavenumber (cm -1 )

NMR Spectrum

WILL BE ADDED

Links

• US 4,062,950 (Bayer; 13.12.1977; D-prior. 22.9.1973).
• DOS 2,347,782 (Bayer; appl. 21.9.1973).
• Schmidt, DD et al .: Naturwissenschaften (NATWAY) 64, 535 (1977).

• UV and IR Spectra. H.-W. Dibbern, RM Muller, E. Wirbitzki, 2002 ECV
• NIST / EPA / NIH Mass Spectral Library 2008
• Handbook of Organic Compounds. NIR, IR, Raman, and UV-Vis Spectra Featuring Polymers and Surfactants, Jr., Jerry Workman.Academic Press, 2000.
• Handbook of ultraviolet and visible absorption spectra of organic compounds, K. Hirayama. Plenum Press Data Division, 1967.

ATENOLOL SPECTRAL DATA

Atenolol 

In order for one to appreciate the spectroscopy for ATENOLOL, one must initially consider its full molecular structure. The simplest means to explore and trace the ATENOLOL's spectroscopic characteristics is to look at its 2D arrangement :

On the outset it is clear that ATENOLOL possesses a multitude of component substituents. The main "bulk" on the molecule is attached to a bulky structure itself, namely the benzene ring.  

such a molecule can be described as a benzeneacetamide by virtue of the O=C-NH2 amide group extruding from a benzene ring. As well as the amide functional group, the conjugating C=C bond in the benzene ring, the methine (CH), methylene (CH2), methyl (CH3) and -OH functional group should be distinctive on the IR spectra (amide circa 1650cm-1 ;CH circa 2880-2900cm-1 ; CH2 circa 2916-2936 cm-1 ; CH3 circa 2850 cm-1 ; conjugating C=Ccirca 1640-1610 ; -OH circa 3200-3550cm-1). 

The mass spectra should theoretically present the molecular ion at 266, being the relative molecular mass of the drug. In relation toATENOLOL's 13-Carbon and 1-Hydrogen nmr, the splitting patterns would be vast, likely to have one pronounced broad peak due to the -OH group. 
The effect of the electronegative oxygen leads to neighbouring hydrogen nuclei being deshielded, moving the coupling peaks downfield whilst also possibly giving rise to hydrogen bonding. The predictions will now be tested, utilising the 2D structure above to explain the various observations which prevail...

The structural formula

UV - spectrum

Conditions : Concentration - 2.4 mg / 100 ml; 12 mg / 100 ml
Solvent designation schedule	Methanol	Water	0.1 M HCl	0.1M NaOH
The absorption maximum	275 nm  227 nm	-	274 nm  225 nm	275 nm
	54  375	-	47.5  349	49
ε	1430  10000	-	One thousand two hundred sixty  9290	1300

IR - spectrum

Wavelength (μm)
Wavenumber (cm -1 )

IR SPECTRA

INFRA RED SPECTRA OF ATENOLOL CONDUCTED ON A KBR DISC

IR FREQUENCY BAND (cm-1)	GROUP RESPONSIBLE
3368	-OH
3198-3071	H-N
2966	C-CH3
2924	CH2
2870	C-H
1666	C=O
1649	O=C-NH2
1614	Conjugated C=C (aromatic)
886	C=CH2

A key observation which is raised in the IR spectrum of ATENOLOL is the level of hydrogen bonding. By virtue of the electronegative Nitrogen atom and the even more electronegative Oxygen atom, the IR spectra indicates that intermolecular H-bonding may be present. This is demonstrated by the IR frequency bands of the -OH and H-N and groups having stretched at 3368cm-1 and 3198-3071 cm-1 respectively. Theoretical values indicate the following ; (a "free" group representing a non H-bonded group) :

IR FREQUENCY BAND (cm-1)	GROUP RESPONSIBLE
3610-3645 (sharp)	Free -OH
3200-3550 (broad)	H bonded -OH
3300-3500	Free -NH
3070-3350	H bonded NH

By simply cross referencing these figures with those obtained from the IR spectrum one is able to establish that hydrogen-bonding is present, as hypothesised in our prediction at the beginning of the section.

MASS Spectrum

Spectrum
The 10 largest peaks:
Peak	30	32	41	43	44	56	57	72	73	107
Meaning	568	61	73	100	52	92	64	999	53	57

Source Temperature: 160 C
Sample Temperature: 140 C
Direct, 75 eV

A TABLE OF THE RESPONSIBLE STRUCTURAL FRAGMETS

m/z	Structural Fragment
266
251
222
134
72
58
44
28

The molecular ion was determined at 266, as predicted. The array of fragments tabulated above encapsulate the diversity of component constituents which structure the ATENOLOLmolecule.

NMR SPECTRUM

1-HYDROGEN NMR

1-H NMR OF ATENOLOL

CONDUCTED @ 399.65 MHz
0.039 g : 0.5 ml CDCl3

Proton	Chemical Shift (ppm)
a	7.41
b	7.158
c	6.855
d	3.84
e	5.00
f	3.91
g	2.539
h	1.50
i	2.68
j	0.970
k	0.975
l	6.85
m	3.285

There are a few key inferences that can be made from the data acquired. Proton a is bonded to Nitrogen, a fairly potent electronegative atom (3.04 Pauling units). The N-H bond is thus slightly polarised with the Nitrogen atom drawing the hydrogen's electron towards it. The nature of this bond means that Proton a becomes deshielded thereby making it extremely acidic. The net effect is that the 1-H nmr displays the proton vastly downfield in relation to its counterparts. 
For comparative purposes, it is clear that Proton's j and k are shielded rather well by virtue of their extreme upfield positions. They exhibit integration, being in the same environment shown as the largest peak on the spectra. As well as Proton a, Proton c experiences deshielding even though not being directly bonded to the electronegative species. The atom responsible is now the extremely electronegative Oxygen atom (3.44 Pauling units). Despite its distance, the pair of protons experience deshielding by virtue of oxygen's potent electron withdrawing affect. 
As predicted, Proton e is isolated as a single broad peak not coupling with neighbouring atoms, being attached to the electronegative Oxygen atom. Coupling is displayed, pronounced forProtons i whereby it is able to couple with Protons k and j, evolving a doublet of quartets.

13-CARBON NMR

13-C NMR OF ATENOLOL

CONDUCTED @ 22.53 MHz
0.039 g : 0.5 ml DMSO-d6

Carbon	Chemical Shift (ppm)	Intensity
1	172.52	366
2	157.27	440
3	129.88	967
4	128.31	477
5	114.17	946
6	70.81	361
7	68.35	478
8	49.96	394
9	48.09	553
10	41.31	285
11	22.88	1000

Similar inferences can be made for the 13-Carbon nmr, with the electronegative oxygen showing obvious electronegative potency with Carbon 1 being shifted extremely downfield this time being assisted with the largely electronegative Nitrogen atom as well. The net effect is a highly polarised delta positive carbon atom.


[1H,13C] 2D NMR Spectrum





MORE OF 1H NMR

Links

• UV and IR Spectra. H.-W. Dibbern, RM Muller, E. Wirbitzki, 2002 ECV
• NIST / EPA / NIH Mass Spectral Library 2008
• Handbook of Organic Compounds. NIR, IR, Raman, and UV-Vis Spectra Featuring Polymers and Surfactants, Jr., Jerry Workman.Academic Press, 2000.
• Handbook of ultraviolet and visible absorption spectra of organic compounds, K. Hirayama. Plenum Press Data Division, 1967.
•