Dulcin

Dulcin is an artificial sweetener about 250 times sweeter than sugar, discovered in 1883 by the Polish chemist Józef (Joseph) Berlinerblau (27 August 1859 – 1935).^[1]^[2]^[3]^[4] It was first mass-produced about seven years later. Although it was discovered only five years after saccharin, it never enjoyed the latter compound's market success. Nevertheless, it was an important sweetener of the early 20th century and had an advantage over saccharin in that it did not possess a bitter aftertaste.

Quick facts Names, Identifiers ...

Dulcin
Names

IUPAC name (4-Ethoxyphenyl)urea
Other names Sucrol; Valzin; Dulcine
Identifiers
CAS Number	150-69-6^Y
3D model (JSmol)	Interactive image
ChemSpider	8663^N
ECHA InfoCard	100.005.244
EC Number	205-767-7
KEGG	C19415^Y
PubChem CID	9013
RTECS number	YT2275000
UNII	8U78KF577Z^Y
CompTox Dashboard (EPA)	DTXSID9020580
InChI InChI=1S/C9H12N2O2/c1-2-13-8-5-3-7(4-6-8)11-9(10)12/h3-6H,2H2,1H3,(H3,10,11,12)^N Key: GGLIEWRLXDLBBF-UHFFFAOYSA-N^N InChI=1/C9H12N2O2/c1-2-13-8-5-3-7(4-6-8)11-9(10)12/h3-6H,2H2,1H3,(H3,10,11,12) Key: GGLIEWRLXDLBBF-UHFFFAOYAA
SMILES CCOC1=CC=C(C=C1)NC(=O)N
Properties
Chemical formula	C₉H₁₂N₂O₂
Molar mass	180.207 g·mol⁻¹
Appearance	White needles
Melting point	173.5 °C (344.3 °F; 446.6 K)
Boiling point	Decomposes
Solubility in water	1.25 g/L (25 °C)
Solubility	Soluble in alcohol
log P	1.28
Hazards
Lethal dose or concentration (LD, LC):
LD₅₀ (median dose)	1900 mg/kg (rat, oral)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is ^YN ?) Infobox references

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Early medical tests marked the substance as safe for human consumption, and it was considered ideal for diabetics. However, an FDA study in 1951 raised many questions about its safety, resulting in its removal from the market in 1954 after animal testing revealed chronic toxicity.^[5] The FDA has also said that "the Federal Security Administrator regards these chemicals as poisonous substances which have no place in any food."^[6] In Japan, poisoning accidents by dulcin occurred frequently, and use of dulcin was forbidden in 1969.^[7]

Dulcin is also known by the names sucrol and valzin.^[8]

Preparation

Dulcin can be produced by the addition of potassium cyanate to p-phenetidine hydrochloride in an aqueous solution at room temperature.^[9]

An alternate way to make dulcin is by mixing urea and p-phenetidine hydrochloride to a mixture of hydrochloric acid and glacial acetic acid.^[10]

Toxicity

Dulcin is toxic to rats at 0.1% of the diet and above. At 0.1%, it causes a slight slowdown in growth; at 1.0%, the slowdown is evident alongside an increase in mortality and noticeable histological changes in liver, kidney, spleen, and heart.^[11]

References

[1]
Berlinerblau, Joseph (1884). "Ueber die Einwirkung von Chlorcyan auf Ortho- und auf Para-Amidophenetol" [On the reaction of cyanogen chloride with ortho- and para-ethoxyaniline]. Journal für praktische Chemie. 2nd series (in German). 30: 97–115. doi:10.1002/prac.18840300110. ; see pp. 103–105. From p. 104: "Der Para-Aethoxyphenylharnstoff hat einen sehr süssen Geschmack." (Para-ethoxyphenylurea has a very sweet taste.)
[2]
Hess, Ludwig (1921). Über den Süßstoff Dulcin: seine Darstellung und Eigenschaften [On the sweetener Dulcin: its preparation and properties] (in German) (2nd ed.). Berlin & Heidelberg, Germany: Springer Verlag. pp. 5–6. ISBN 9783642993923. {{cite book}}: ISBN / Date incompatibility (help)
[3]
Goldsmith, R.H. (1987). "A tale of two sweeteners". Journal of Chemical Education. 64 (11): 954–955. Bibcode:1987JChEd..64..954G. doi:10.1021/ed064p954.
[4]
For a biography of Joseph Berlinerblau (with photographs), see:
Balasiewicz, Michał S. (2013). "Józef Berlinerblau i Jan Prot-Berlinerblau – współtwórcy polskiego przemysłu Polski niepodległej" [Józef Berlinerblau and Jan Prot-Berlinerblau – co-founders of Polish industry in independent Poland [i.e., the Second Polish Republic (1918–1939)]]. Przemysł Chemiczny (Chemical Industry) (in Polish). 92 (9): 1692–1700.

Reprinted in: "Józef Berlinerblau" in ewamaria2013 (2014) (in Polish)

Reprinted in: "Josef Berlinerblau" in Reunion 69 (2014) (in Polish)
[5]
"15FR321 Title 21" (PDF). FDA Federal Register. FDA. January 18, 1950. Retrieved January 11, 2021. ... Notice to manufacturers and distributors of foods and drugs containing artificial sweeteners. Chronic-toxicity studies conducted by the Food and Drug Administration show/ that the artificial sweeteners dulcin (also known as sucrol, or 4-ethoxy-phenylurea, or paraphenetolcarbamide) and P-4000 (also known as l-n-propoxy amino4-nitrobenzene) cause injury to rats when fed at relatively low levels for approximately 2 years ...'
[6]
Food and Drug Administration- Title 21 chapter 1 Federal Register Archive
[7]
ズルチン標準品-Dulcin Standard (Japanese), Wako Pure Chemical Industries
[8]
Bender, David A. (2005). A Dictionary of Food and Nutrition. Oxford University Press.
[9]
Youssef, Khairia M.; Al-Abdullah, Ebtihal; El-Khamees, Hamad (2003). "Synthesis of sulofenur analogs as antitumour agents: Part II". Medicinal Chemistry Research. 11 (9): 481–503.
[10]
"ARYLUREAS II. UREA METHOD p-ETHOXYPHENYLUREA". Org. Synth. 31 (11): 11. 1951. doi:10.15227/orgsyn.031.0011.
[11]
Ikeda, Yoshio; Omori, Yoshihito; Oka, Shigenori; Shinoda, Mitsuo; Tsuzi, Kiyo (1960). "Studies on Chronic Toxicity of Dulcin". Food Hygiene and Safety Science (Shokuhin Eiseigaku Zasshi). 1 (1): 62–69. doi:10.3358/shokueishi.1.62.

Preparation

Toxicity

See also

References

Further reading

External links

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