Essay Morphine

5. Synthesis
a. General Schemes of Incorporating Arsonate Groups
Arsonate dyes can be prepared starting from commercially available arylarsonic acids, which can be subsequently assembled into dye compounds. This approach can be illustrated by a synthesis of arsonic acid carbocyanine dyes according to Scheme 1.
In particular, arsanilic acid (A2) can be converted into corresponding diazonium salt (A3) by treatment with sodium nitrite in hydrochloric acid according to a known literature method [Bart Justus Liebigs Ann. Chem. 429, 100, 1922.] The diazonium salt can be reduced into corresponding hydrazine (A4) using tin(II) chloride by analogy to known procedure [Zhang, Peng; Meng, Jiben; Li, Xiaoliu; Matsuura, Teruo; Wang, Yongmei J. Heterocycl. Chem. 39, 1, pp 179-184, 2002.] Fisher cyclization of the hydrazine A4 provides the corresponding indole (A5) and indolinium salts (A6) analogously to the methods reported for synthesizing similar sulfonyl indoles [Mujumdar R. B., Ernst L. A., Mujumdar S. R., Lewis C. J. and Waggoner A. S.Bioconjugate Chem., 4(2), pp 105-111, 1993]. These publications further describe methods for making sulfonyl carbocyanine dyes from the sulfonyl indoles, which methods can be used to assemble the arsonate carbocyanine dyes of the present invention. Likewise, the methods described in these publications for preparing different N-substitutions can be equally applied to the preparation of arsonate dyes (A1) with diverse N-substituents. Typically, the N-substituent provides linkers with reactive groups (the -L-Rx moiety) for introducing the dyes into nucleic acids, proteins and other biomolecules.

Alternatively, aryl arsonate dyes can be prepared by directly introducing arsonic groups into a dye molecule according to any of the two approaches illustrated in Scheme 2.
In one approach, an arsonate group is directly introduced to an aromatic component of a dye molecule (B2) via electrophilic substitution by reacting the dye with arsenic electrophilic reagents, such as arsenic acid [Ehrlich, Bertheim Chem Ber., 40, p. 3293, 1907; Benda, Kahn Chem. Ber., 41, pp 1674-1676, 1908] or arsenic trichloride [Varma, Raman, J. Indian Chem Soc., 16, pp 515-516, 1939] to provide an arsenite intermediate B3. A subsequent oxidation converts the arsenite intermediate B3 to arsonate B1 [Gough, King J. Chem. Soc., pp 669-683, 1930]. Arsonates B1 can be converted back to dichloroarsenites B3 by treatment with PCl3 [Ehrlich, Bertheim, Chem. Ber., 43, p 918, 1910; Chem. Ber., 44, p 1264, 1911] or SO2—I2—HCl reagent [Gavrilov V. I., Khusnutdinova F. M., Gornova N. N J. Gen. Chem. USSR (Engl. Transl.), 57, pp 300-303, 1987; Zh. Obshch. Khim., 57, 2, pp 350-354, 1987].
In a second approach, the arsonate group can be introduced into a dye molecule by displacing an amino group of an amino dye B4. Specifically, the amino group is first converted to a diazonium salt B5, which undergoes copper-catalyzed replacement of arsenite (Bart's reaction) followed by oxidation into arsonic substituent to yield B1 [Bardos, T. J. et al. J. Med. Chem., 9, pp 221-227, 1966].

Aliphatic arsonates (C1) can be obtained according to Scheme 3. In this approach, an aromatic component of a dye (C2) is first alkylated. The alkylation includes, but not limited to, chloromethylation [Dacka, Stanislaw Pol. J. Chem., 57, 10-12, pp 1345-1352, 1983], bromomethylation [Gibson, S. et al., Tetrahedron, 25, pp 5047-5057, 1969] or iodomethylation [Sandin, Fieser J. Am. Chem. Soc. 62, pp 3098-3103, 1940]. The alkylated dye (C3) is then converted to an inorganic arsenite (C4) followed by an oxidation step to provide C1 [Quick; Adams J. Am. Chem. Soc. 44, p 811, 1922; Chernokal'skii, B. D. et al. J. Gen. Chem. USSR (Engl. Transl.), 36, pp 1674-1675, 1966; Zh. Obshch. Khim. 36, 1677-1679, 1966; Dehn, Mc Grath J. Am. Chem. Soc. 28, p 352, 1906].

b. Protection and Deprotection of Arsonate Dyes.
Polar arsonic acid dyes, Dye-As(═O)(OH)2, can be transformed into

Show More

Morphine and Euphoria Mental Clouding Essay

Morphine and 20th Century Cannabis Essay

Drugs: Morphine and Regular Street Drugs Essay

Morphine Research Paper

To Kill A Mockingbird Conscience Analysis

Therapeutic Practitioner Formative Assessment

Character Analysis Of Atticus Finch In 'To Kill A Mockingbird'

To Kill a Mockingbird and Body Paragraphs Essay

Atticus Courage

Crazy Women Essay