Berberine

Berberine

C20H18NO4

336.00

mp......203-204

Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants asBerberis [e.g. Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), Berberis aristata (tree turmeric)], Hydrastis canadensis (goldenseal), Xanthorhiza simplicissima (yellowroot), Phellodendron amurense^[2] (Amur cork tree), Coptis chinensis(Chinese goldthread 黄连素 or Huang Lian Su), Tinospora cordifolia, Argemone mexicana (prickly poppy), and Eschscholzia californica (Californian poppy). Berberine is usually found in the roots, rhizomes, stems, and bark.^{[citation needed]}

Due to Berberine's strong yellow color, Berberis species were used to dye wool, leather and wood. Wool is still today dyed with berberine in northern India. Under ultraviolet light, berberine shows a strong yellow fluorescence,^[3] so it is used in histology forstaining heparin in mast cells.^[4] As a natural dye, berberine has a colour index of 75160.

1H NMR

(400 MHz, CD3OD) δ: 9.75 (1H, s, H-8), 8.69 (1H, s, H-13), 8.10 (1H, d, J = 8.3 Hz, H-11), 7.98 (1H, d, J = 8.4 Hz, H-12), 7.64 (1H, s, H-1), 6.94 (1H, s, H-4),  6.09 (2H, s, OCH2O), 4.91 (2H, t, J = 6.4, H-6), 4.18 (3H, s, 9-OCH3),  4.09 (3H, s, 10-OCH3), 3.24 (2H, t, J = 6.4 Hz, H-5) 13 C NMR (100 MHz, CD3OD) δ: 151.0 (C-10), 150.8 (C-3), 148.7 (C-2),  144.6 (C-9), 145.2 (C-8), 138.5 (C-13a), 134.0 (C-12a),  130.7 (C-4a), 126.8 (C-11), 123.3 (C-12), 122.1 (C-8a),  120.7 (C-13b), 120.3 (C-13), 108.2 (C-4), 105.3 (C-1),  102.5 (OCH2O), 61.3 (C-9, OCH3), 56.4 (C-10, OCH3), 56.0 (C-6), 27.0 (C-5) [1H,13C] 2D NMR Spectrum MASShttp://scialert.net/fulltext/?doi=rjmp.2008.1.9

H. Raja Naika and V. Krishna, 2008. Micropropagation, Isolation and Characterization of Berberine from Leaves of Naravelia zeylanica(L.) DC.. Research Journal of Medicinal Plant, 2: 1-9.

DOI: 10.3923/rjmp.2008.1.9 

URL: http://scialert.net/abstract/?doi=rjmp.2008.1.9

The Soxhlet extraction of 100 g of dried leaves yielded 12 g of crude methanolic extract. Ten gram of the crude extract yielded 270.0 mg of total alkaloids from the leaves extract. The presence of the alkaloid confirmed qualitatively by Dragendorff’s, Mayer’s and Wagner’s tests. (Kokate et al., 1990) The separation of berberine was done by preparative TLC method and the yield was 70 mg from in vivo leaf extract. The constituent was characterized by subjecting it to IR, ¹H NMR and MASS spectral studies.

Spectral Characterization of Code RA 

IR (Kbr):

2820 cm-2 (C-H str) 1597 cm-2 (C = C, C = N str) 1354-1383 cm-2 (C-H deformation) 1060 cm-2 (C-O str) (Fig. 2)

1H NMR (CDCL3):

δ 1.75 (m, 2H,-CH2-) δ 2.4 (m, 2H, N+-CH3) δ 3.9 (s, 6H, 2 X OCH3) δ 6.0 (s, 2H, O-CH2-O) δ 6.6-9.4 (m, 6H, Ar-H) (Fig. 3)

Fig. 2:	IR spectrum of berberine

Fig. 3:	1H NMR spectrum of berberine

Mass spectra (EI-MS):

Molecular formula:C20H19NO4 Molecular weight:336.37 EIMS: (m/z):336 (m+, 20%), 322 (35%), 281 (50%), 267 (38%), 207 (76%), 147 (100%) (Fig. 4)

Biosynthesis of berberine

Berberine
Other names[hide] umbellatine; 5,6-dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium
Identifiers
CAS number	2086-83-1
PubChem	2353
ChemSpider	2263
UNII	0I8Y3P32UF
DrugBank	DB04115
ChEBI	CHEBI:16118
ChEMBL	CHEMBL12089
Jmol-3D images	Image 1
SMILES [show]
InChI [show]
Properties
Molecular formula	C20H18NO4+
Molar mass	336.36122 g/mol
Appearance	yellow solid
Melting point	145°C[1]
Solubility in water	slowly soluble[1]
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)

Title: Berberine

CAS Registry Number: 2086-83-1

CAS Name: 5,6-Dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium

Additional Names: 7,8,13,13a-tetradehydro-9,10-dimethoxy-2,3-(methylenedioxy)berbinium; umbellatine

Molecular Formula: [C20H18NO4]+

Literature References: Tautomeric alkaloid widely distributed in nine or more botanical familes but occurs most frequently inBerberidaceae. A component of many traditional medicines, first isolated in 1826. Structure: Perkin, Robinson, J. Chem. Soc. 97,305 (1910). Biosynthesis: J. R. Gear, I. D. Spenser, Can. J. Chem. 41, 783 (1963). Pharmacology: Fukuda et al., Chem. Pharm. Bull. 18, 1299 (1970). Total synthesis: Kametani et al., J. Chem. Soc. C 1969, 2036. NMR: G. Blasko et al., Heterocycles 27, 911 (1988). HPLC determn in biological fluids: C.-M. Chen, H.-C. Chang, J. Chromatogr. B 665, 117 (1995). Clinical evaluation in malaria: W. D. Sheng et al., East Afr. Med. J. 74, 283 (1997). Review of biological activities: F. E. Hahn, J. Ciak, in Antibioticsvol. 3, D. Gottlieb et al., Eds. (Springer-Verlag, New York, 1975) pp 577-584; of chemistry, distribution and use: R. S. Thakur, S. K. Srivastava, Curr. Res. Med. Aromat. Plants 4, 249-272 (1982). Review of antidiarrheal action: A. W. Baird et al., Adv. Drug Delivery Rev. 23, 111-120 (1997).

Properties: Yellow needles from ether, mp 145°: Gadamer, Arch. Pharm. 243, 33 (1905). uv max: 265, 343 nm. pK 2.47.

Melting point: mp 145°: Gadamer, Arch. Pharm. 243, 33 (1905)

pKa: pK 2.47

Absorption maximum: uv max: 265, 343 nm

Derivative Type: Acid sulfate

Additional Names: Berberine bisulfate

Molecular Formula: C20H19NO

.....................

http://www.google.com/patents/EP2444094A1?cl=en

Berberine is isoquinoline alkaloid. Molecular formula: [C₂₀H₁₈NO₄]⁺, molecular weight: 336.37 and its chemical structure is as follows:

1. The Merck Index, 10th Ed. (1983), p.165, Rahway: Merck & Co.
2. Jump up^ Zhang, Q; Cai, L; Zhong, G; Luo, W (2010). "Simultaneous determination of jatrorrhizine, palmatine, berberine, and obacunone in Phellodendri Amurensis Cortex by RP-HPLC". Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 35 (16): 2061–4. doi:10.4268/cjcmm20101603.PMID 21046728.
3. Jump up^ Weiß, Dieter (2008). "Fluoreszenzfarbstoffe in der Natur" (in German). Retrieved 17 July 2009.

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http://www.google.com/patents/US20100113494

Berberine, also called umbellatine, is an isoquinoline alkaloid represented by the following formula, which is a major active component in such plants as Coptidis chinensis Franch., Berberis amurensis Rupr., Berberis sargentiana Schneid andNandina domestica etc. Clinically, berberine is mainly used to treat diarrhea caused by bacteria with the most important advantage of having little side effects. Berberine has been used as a broad spectrum antibiotic for many years, and is effective on inhibition and elimination of various Gram-positive and Gram-negative bacteria, fungi, moulds, viruses, protozoa and nematode.

Structure of Berberine

Since 1950s, a large number of animal experiments and clinical trials have been carried out by some specialists, researchers and clinicians with berberine hydrochloride which is widely used in clinic, and the results showed that berberine are effective on the therapy of diabetes mellitus and their complications besides being antibiotic. Some research literatures are summarized in the following Table I:

TABLE I
Summary of animal experiments and clinical trials on treating diabetes mellitus with berberine
Authors	Results of animal studies and clinical trials	Literature
Qiming CHEN,	Berberine possesses advantages of both sulfonylureas and	Acta
Mingzhi XIE	biguanides. It can lower blood glucose levels of both normal mice	Pharmaceutica
(Institute of	and alloxan-induced diabetic mice, and antagonize the increase of	Sinica, 1986,
Materia Medica,	blood glucose levels induced by exogenous glucose or	21(6): 401-406.
Chinese Academy	epinephrine. It has powerful effect on lowering blood glucose
of Medical	levels and long action time lasting up to 5-6 hours. Berberine can
Sciences)	also improve abnormal blood coagulation and prevent
	atherosclerosis. It had a significant effect on lowering blood
	glucose at a dose of 40 mg/kg.
Yanxie NI, et. al.	60 cases of type 2 diabetic patients were treated with berberine	Journal of
(The 208th hospital	and the treatment was lasted for 1-3 months. The results showed	Integrated
of PLA)	that the fasting blood glucose decreased averagely by 5.1 mmol/L	Traditional and
	and the efficiency was 90%. It was found by pathologic	Western
	examinations that berberine could promote the regeneration and	Medicine, 1988,
	functional recovery of pancreatic beta-cells. No abnormality was	8(12): 711-713.
	observed for all patients in the hepatic and renal functions and
	hemogram during the treatment and no obvious adverse effect
	was found.
Guoying LIU	30 cases of type 2 diabetic patients were treated with berberine	New use of old
(Pengze traditional	and the efficiency was 90%. Berberine was significantly effective	drug, 1992, 1: 3-4.
Chinese medical	for the patients with light or moderate diabetes mellitus. In
hospital, Jiujiang,	addition, it also showed effects on lowering blood pressure and
Jiangxi)	blood fat, and preventing infection and the occurrence of
	complication etc.
Mianrong YU, et.	75 cases of type 2 diabetic patients were treated with berberine	Beijing Medical
al. (Builder	and the efficiency was 69.33%. Three diabetic symptoms, i.e.	Journal, 1994,
hospital of Beijing)	polyuria, polydipsia and polyphagia, disappeared for all patients	16(2): 117.
	within two weeks after administration of berberine accompanying
	the decrease of blood glucose. The diabetic patients have been
	treated with berberine and observed for 4 years, and none of them
	was observed with adverse effects or hypoglycemia regardless of
	dose. In addition, 11 patients had normal blood glucose with
	reduced dose more than 3 years.
Faguang HU, et. al.	60 cases of type 2 diabetic patients were treated with berberine	The Practical
(The Shanxuan	and the efficiency was 90%. Berberine had a mild and lasting	Journal of
people's hospital,	effect on lowering blood glucose, making the blood glucose start	Integrating of
Henan)	to lower after about 2 weeks, and achieving its maximum curative	Chinese with
	effect within 8 weeks. For all patients, berberine made the	Modern Medicine,
	diabetic symptoms disappearing or being relieved and showed	1995, 8(6):
	good effects on common diabetic complications. In addition, 4	358-359.
	patients with overweight recovered their normal weights. No
	toxic and/or adverse effects were observed.
Jiaqing ZHANG	Berberine has a certain effect on increasing insulin sensitivity and	Liaoning Journal
(Changhai hospital,	can improve insulin resistance with an insulin action index (IAI)	of Practical
the 2nd military	similar to metformin.	Diabetology,
surgeon college)		1999, 1(4): 56-57.
Changshan LIU, et	Renal failure often occurs to most of diabetic patients with the	Chinese Journal of
al. (Weifang	deterioration of conditions. Berberine, a traditional Chinese drug,	Diabetes, 1996,
medical college,	has a significant effect on reversing diabetic renal failure and	4(3): 163-166.
Shandong)	inhibiting the activities of the polyol and kidney aldose reductases
	of diabetic mice to lower urine protein.
Jinhua TONG	49 cases of type 2 diabetic patients were treated with berberine	New Journal of
(Sanitation School	and the efficiency was 63.3%. Berberine can suppress	Traditional
of Fengtai, Anhui)	glyconeogenesis and glycogenolysis, slow down insulin	Chinese Medicine,
	metabolism and promote the sensitivity of peripheral tissue cells	1997, 29(3):
	to insulin by lowering the activity of the sympathetic nerve and	33-34.
	inhibiting the adrenal cortical function. It can also promote the
	regeneration and functional recovery of pancreatic cells.
Huading YU,	The effect of berberine on treating non-insulin dependent diabetic	Medical Journal of
Laiwen YAN	patients was evaluated. The patients were divided randomly into 2	Communications,
(Shanghai seaman	groups, and each group had 30 persons. One group took berberine	1995, 9(4): 45.
hospital)	and another took Diamicron. After 4 weeks treatment, the
	variations of the concentrations of blood glucose and blood serum
	insulin were compared between the two groups, and the results
	showed that the two groups had similar curative effects and no
	severe adverse effects were observed.
Yunfei ZHANG	For 20 cases of type 2 diabetic patients, their conditions were not	Chinese Journal of
(Hangzhou	improved significantly after they took oral anti-diabetic drugs for	Integrated
sanatorium of Air	lowering blood glucose such as D860 and glibenclamide etc.	Traditional and
Force)	Then, they were treated with berberine. The fasting blood glucose	Western
	levels of all patients were lowered to normal levels 3 months	Medicine, 1999,
	later. The effect of berberine on lowering blood glucose was	19(9): 567.
	dependent on dose, and no side effects such as hypoglycemia
	were observed.
Hong ZHU, Wei	112 cases of type 2 diabetic patients were treated with berberine	Journal of Jining
DAI (Affiliated	and the efficiency was 90%, which showed that berberine had a	Medical College,
hospital of Jining	good effect on lowering blood glucose. Specifically, berberine	1999, 22(3): 67.
medical college)	had mild and lasting effect of lowering blood glucose without
	severe toxicity, side effects and damages to liver and renal
	function, and had good curative effect on common complications
	of diabetes mellitus.
Litian SHI, et al.	68 cases of type 2 diabetic patients were treated with berberine.	Shanxi Clinical
(Taiyuan	The blood glucose levels of the patients were lowered	Medicine, 2000,
commercial staff	significantly, and the total efficiency was 86.8%. The action	9(3): 181-182.
hospital)	mechanism of berberine on lowering blood sugar was multiple.
	The blood serum insulin levels of the patients increased
	significantly after the treatment.
Dongkou WANG	57 cases of type 2 diabetic patients were treated with a second	Zhejiang Journal
(Taizhou Health	generation sulfonylureas drug alone or in combination with	of Integrated
center, Jiangsu)	metformin. However, secondary failure occurred 3 years later.	Traditional
	Thus, berberine was taken additionally. The blood glucose levels	Chinese and
	of the patients were lowered more or less 1 month later, and total	Western
	efficiency was 81%.	Medicine, 2002,
		12(1): 50.
Jiandong JIANG et	Berberine can interact with insulin receptors and increase	CN01121906.8
al.	significantly the expressions of insulin receptor genes and
	peroxisome proliferator activated receptor genes. Therefore,
	berberine can be used as an insulin sensitizer to treat type 2
	diabetes mellitus alone or in combination with insulin or other
	type 2 diabetic drugs.
Kaimin WU	Highly soluble berberines such as berberine sulfate and berberine	WO03090749A1,
	phosphate etc. are easily dissolved in water, which may improve	CN1771944A
	the absorption of the drugs in organism and thus enhance
	significantly their curative effect. Thus, they can be used to treat
	and prevent diabetes mellitus or its complications.

Recently, berberine has been widely used to treat type 2 diabetes mellitus in clinic. It was found in an initial research that the antihyperglycemic activity of berberine was in association with its activities of resisting hyperglycemic hormones and promoting the regeneration and functional recovery of pancreatic beta-cells (Hongyan ZHENG, Weiren XU, Chinese herbal medicine. 2004, 35: 708-711). Such research showed that 5-100 μmol of berberine could increase the glucose consumption in HepG2 cells by 32-60%, but it did not stimulate βTC3 cells to secrete insulin. So it was concluded that the antihyperglycemic activity of berberine acted by increasing the glucose consumption of liver cells instead of stimulating to secrete insulin, i.e., the antihyperglycemic activity of berberine acted through liver cells without depending on insulin.

Juan WANG (Juan WANG, China and foreign medical Journal. 2004, 2(12): 65-66) reported that it was observed clinically that the blood glucose levels decreased and the blood serum insulin levels increased when berberine was used to treat diabetes mellitus, which indicated that berberine could promote the regeneration and functional recovery of pancreatic beta-cells besides its resistance to the hyperglycemic hormones. Berberine can also inhibit gluconeogenesis and improve glycolysis, thereby lowering the blood glucose. Thus, the antihyperglycemic activity of berberine belongs to the field of insulin sensitizer. Berberine also has positive effects on preventing diabetes mellitus complications because of its activities of anti-hypertension, anti-hyperlipidemia and anti-infection.

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Synthesis of erythro-9,10-dihydroxystearic acid, ارثرو-10،9-ثنائي هيدروحامض الستيارك, erythro-9,10-Διυδροστεατικό οξ

Erythro-9,10-Dihydroxystearic acid [3639-32-5]



Name erythro-9,10-Dihydroxystearic acid
Synonyms (9R,10S)-rel-9,10-Dihydroxyoctadecanoic acid
Name in Chemical Abstracts Octadecanoic acid, 9,10-dihydroxy-, (9R,10S)-rel-
CAS No 3639-32-5
EINECS No
Molecular formula C18H34O4
Molecular mass 330.51

KMnO4/NaOH

Literature
A. Lapworth und E. N. Mottram, J. Chem. Soc., 1925,1628-31

http://kriemhild.uft.uni-bremen.de/nop/en/instructions/pdf/3011_en.pdf

Reaction type:	addition to alkenes, oxidation, cis-hydroxylation
Substance classes:	alkene, alcohol, natural product
Techniques:	stirring with magnetic stir bar, filtering, recrystallizing, extracting

Instruction (batch scale 10 mmol) 

Equipment 

5 L beaker or Erlenmeyer flask, heatable magnetic stirrer, magnetic stir bar, suction flask, 

Buechner funnel, mortar, desiccator 

Substances 

oleic acid (techn. 90%) 3.14 g (equivalent to 10.0 mmol pure oleic acid) 

(oleic acid, pure: mp 16 °C, 

bp 193 °C/1.6 hPa) 

potassium permanganate 2.50 g (15.8 mmol) 

sodium hydroxid 3.14 g (78.5 mmol) 

hydrochloric acid (conc., 36%) 94 mL 

sodium sulfite or sodium disulfite 

petroleum ether (bp 60-80 °C) about 200 mL 

ethanol (bp 78 °C) for recrystallizing 

Reaction 

3.14 g (10.0 mmol) oleic acid (techn. 90%) are added to a solution of 3.14 g (78.5 mmol) 

NaOH in 320 mL water in a 5 L beaker with a magnetic stir bar. The mixture is heated under

stirring until a clear solution is formed. After the addition of 2.5 L ice-cold water, 250 mL 1% 

potassium permanganate solution are added within 1 minute under stirring at a temperature of 

10 °C. After 5 minutes so much solid sodium sulfite oder sodium disulfite is added, that the 

excess of potassium permanganate is reduced. Afterwards the solution is acidified with 94 mL 

conc. hydrochloric acid. The solution becomes colourless, and a colourless fluffy precipitation 

is formed. 

Work up 

The precipitation is sucked off and dried. Crude yield: 3.01 g, mp 81-88 °C 

The crude product is washed with 50 mL petroleum ether (60-80 °C) and dried under reduced 

pressure. The dried product is powdered in a mortar and digested with 100-150 mL petroleum 

ether in a beaker. Thus the sturated carboxylic acids contained in the oleic acid as impurities 

are removed. The dihydroxystearic acid is insoluble in petroleum ether. It is sucked off and 

recrystallized from ethanol. 

Yield: 2.74 g (8.70 mmol, 87%); mp 132 °C; colourless powder 

Yield71%Target product mass0.26gSum of input masses290gMass efficiency0.89mg/gMass index1100g input / g productE factor1100g waste / g product

Equipment

Batch scale:

0.0011 mol

	beaker 500 mL			heatable magnetic stirrer with magnetic stir bar
	suction flask			suction filter
	mortar			exsiccator with drying agent

TLC: crude product
TLC layer	Merck silica gel 60 F254
mobile phase	EtOAc
detection	immerse into solution of 2.7 g KMnO4, 18 g K2CO3, 216 mg NaOH in 274 mL H2O, heating with air dryer
Rf (educt)	0.87
Rf (product)	0.67

1H-NMR: erythro-9,10-Dihydroxystearic acid
250 MHz, DMSO-d6
delta [ppm]	mult.	atoms	assignment
0.86	t (3J = 6.4 Hz)	3 H	CH3
1.2-1.6	m	26 H	other CH2
2.18	t (3J = 7.3 Hz)	2 H	2-CH2
3.25	m	2 H	9-CH-OH, 10-CH-OH
2.45	s	6 H	DMSO

13C-NMR: erythro-9,10-Dihydroxystearic acid
62.5 MHz, DMSO-d6, 373°K
delta [ppm]	assignment
13.0	C18 (CH3)
21.2	C17 (CH2
23.9	CH2
24.8	CH2
27.9	CH2
28.0	CH2
28.3	CH2
28.4	CH2
28.6	CH2
30.6	CH2
31.8	CH2
33.2	C2
73.4	C9, C10 (CH-OH)
173.4	C1 (COOH)
38.5-40.5	DMSO-d6

IR: erythro-9,10-Dihydroxystearic acid
[KBr, T%, cm-1]
[cm-1]	assignment
3500-2500	O-H valence, superimposed on C-H valence
1716	C=O valence, carboxylic acid

Synthesis of 9,10-dihydro-9,10-ethanoanthracene-11,12-trans-dicarboxylic acid diethyl ester

+

Synthesis of 9,10-dihydro-9,10-ethanoanthracene-11,12-trans-dicarboxylic acid diethyl ester

Reaction type:	cycloaddition, Diels-Alder reaction
Substance classes:	alkene, aromatics, carboxylic acid ester, diene, dienophile, acid catalyst
Techniques:	working with moisture exclusion, heating under reflux, stirring with magnetic stir bar, filtering, evaporating with rotary evaporator, recrystallizing, use of an ice cooling bath, heating with oil bath

Operating scheme

Equipment

Batch scale:

0.01 mol

0.1 mol

Anthracene

	three-necked flask 100 mL			adapter with ground-glass joint and hose coupling
	protective gas piping			reflux condenser
	drying tube			bubble counter
	powder funnel			heatable magnetic stirrer with magnetic stir bar
	rotary evaporator			ice bath
	exsiccator with drying agent			oil bath

1H-NMR: 9,10-Dihydro-9,10-ethanoanthracene-11,12-trans-dicarboxylic acid diethyl ester
250 MHz, CDCl3
delta [ppm]	mult.	atoms	assignment
1.23	t (3J = 7.2 Hz)	6 H	CH3 ethyl
3.45	m	2 H	11-H, 12-H (-CH-COO-)
4.08	m	4 H	CH2 ethyl
4.75	m	2 H	9-H, 10-H
7.09-7.38	m	8 H	CH (arom.)
>7.4			CH (arom., educt)

13C-NMR: 9,10-Dihydro-9,10-ethanoanthracene-11,12-trans-dicarboxylic acid diethyl ester
62.5 MHz, CDCl3
delta [ppm]	assignment
14.2	CH3 (ethyl ester)
46.7	C9, C10 (CH)
47.7	C11, C12 (CH-COO)
60.9	CH2 (ethyl ester)
123.8	CH arom.
124.5	CH arom.
126.2	CH arom.
126.3	CH arom.
140.3	C quart. arom.
142.0	C quart. arom.
172.3	C(=O)O-
76.5-77.5	CDCl3

IR: 9,10-Dihydro-9,10-ethanoanthracene-11,12-trans-dicarboxylic acid diethyl ester
[KBr, T%, cm-1]
[cm-1]	assignment
3074, 3026	arom. C-H valence
2981	aliph. C-H valence
2935, 2897	aliph. C-H valence
1739	C=O valence, ester
1467	arom. C=C valence

http://kriemhild.uft.uni-bremen.de/nop/en/instructions/pdf/3010_en.pdf

Instruction (batch scale 100 mmol) 

Equipment 

1000 mL three-neck flask, adapter with ground glass joint and hose coupling, protective gas 

supply, reflux condenser, drying tube, bubble counter, powder funnel, heatable magnetic 

stirrer, magnetic stir bar, rotary evaporator , ice bath, desiccator, oil bath 

Substances 

anthracene (mp 215-217 °C9 17.8 g (100 mmol) 

fumaric acid diethyl ester (bp 219 °C) 17.2 g (16.4 mL, 100 mmol) 

aluminium chloride (water free) 13.3 g (100 mmol) 

cyclohexane (water free) (bp 81 °C) 500 mL 

cyclohexane (bp 81 °C) 200 mL 

sodium carbonate decahydrate 24.9 g (150 mmol) 

sodium carbonate (water free) 25.0 g (236 mmol) 

ethanol (bp 78 °C) 150 mL 

Reaction 

The reaction apparatus consists of a thoroughly dried 1000 mL three-neck flask with reflux 

condenser, drying tube and magnetic stir bar. On one opening of the flask is placed an adapter 

with ground glass joint and hose coupling as inlet for nitrogen. This adapter is replaced 

through a glass stopper after the addition of aluminium chloride to the flask. The reaction 

apparatus is flushed with nitrogen. Then under stirring 17.8 g (100 mmol) anthracene and 

17.2 g (16.4 mL, 100 mmol) fumaric acid diethyl ester are dissolved in the flask in 500 mL 

absolute cyclohexane. After cooling down in the ice bath 13.3 g (100 mmol) water-free 

aluminium chloride are added in one portion over a powder funnel under nitrogen counter 

flow. The reaction mixture is heated under stirring for four hours under reflux. 

Work up 

The reaction mixture is cooled down to room temperature, then 24.9 g (150 mmol) sodium 

carbonate decahydrate are added. The drying tube is replaced through a bubble counter filled 

with paraffin oil and the mixture is stirred until no more gas is formed. Then 25 g (236 mmol) 

sodium carbonate (water free) are added. The mixture is stirred for 10 minutes. The solid is 

filtered off and washed in portions with a total of 200 mL cyclohexane. The solvent is 

evaporated from the filtrate at a rotary evaporator. A solid residue remains as crude product, 

which is dried in the desiccator. Crude yield: 32.6 g 

The crude product is recrystallized from about 150 mL ethanol. 

Yield: 30.8 g (87.9 mmol, 88%); colourless crystals, mp 103 °C