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Synthesis of Tropinone & 2-CMT

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Rhodium:
What use could you have for the diethoxy which cannot be done with the dimethoxy?

Drug_Phreak:
Since they are so similar it seemed like they where interchangeable, but I wasn't 100% sure. I'm glad I can use it though... as its OTC. SWIDP is getting really close to an OTC Cocaine synth with the exception of a few chems. If SWIDP could just get a few pure grams it would make them so damn happy!  ;D  ;)  8)

Rhodium:
The Cocaine Diastereoisomers
A. C. Allen, D. A. Cooper, W. O. Kiser, R. C. Cottrell
J. Forensic Sci. 26(1), 12-26 (1981) (https://www.thevespiary.org/rhodium/Rhodium/chemistry/cocaine.diastereoisomers.html)

Abstract
In the past, it has been argued in court, from a theoretical basis, that the techniques available to the forensic chemist would differentiate the "cocaines". This work has moved that argument from the realm of the theoretical into that of experimental fact. The techniques of infrared spectroscopy (IR), nuclear magnetic resonance (NMR), and mass spectrometry (MS) will unequivocally identify the racemic cocaine diastereoisomer. In addition, this work shows that the enantiomeric form of cocaine can be assigned by crystal tests, IR, and melting point techniques. The pure enantiomers of allococaine and pseudoallococaine were not isolated. This does not create a problem because the techniques of NMR and MS, as performed in this study, will not differentiate enantiomers. Therefore, the logical sequence of first identifying the diastereoisomer (via IR, NMR, or MS) and then determining the chirality by crystal tests, IR, melting points, or optical rotation measurements is valid.
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The Three-dimensional Structure of the Cocaines. Part I.
Cocaine and Pseudococaine
Stephen P. Findlay
J. Am. Chem. Soc. 76, 2855-2862 (1953) (https://www.thevespiary.org/rhodium/Rhodium/pdf/cocaine.pseudococaine.pdf)

Abstract
Published experimental data on the chemistry of cocaine and its simpler derivatives are interpreted as indicating that this base is 2?-carbomethoxy-3?-benzoxytropane and pseudococaine 2?-carbomethoxy-3?-benzoyloxytropane. Pertinent data in the literature have been verified or corrected. Cocaine is readily transformed by sodium methoxide in methanol to pseudoecgonine methyl ester. Willstatter's ecgonine methylbetaine is in fact the pseudo isomer. O-Benzoylnorecgonine is convertible in the presence of base to the previously unknown N-benzoyl isomer. Sames and structures for the other two possible cocaines are proposed.
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The Three-Dimensional Structures of the Cocaines. Part II.
Racemic Allococaine and Racemic Allopseudococaine
Stephen P. Findlay
J. Org. Chem. 24, 1540-1550 (1959) (https://www.thevespiary.org/rhodium/Rhodium/pdf/allococaine.allopseudococaine-2.pdf)

Abstract
Catalytic hydrogenation of racemic 2-carbomethoxytropinone in acetic acid yields racemic alloecgonine methyl ester, which can be transformed to the racemates of alloecgonine, allococaine, allopseudoecgonine, allopseudoecgonine methyl ester, and allopseudococaine. Some limitations of a generalization concerning the course of the catalytic hydrogenation of cyclic ketones as it applies to certain keto derivatives of the tropane and morphine alkaloids are noted. The three-dimensional structures of the new cocaines are tentatively assigned. The possible utility of molecular rotation data in ascertaining the absolute configuration of transformation products of the 2-carbomethoxy derivatives of both tropinone and N-methyl-granatonine is indicated. Some other possible methods of synthesizing the new cocaine isomers and the drawbacks thereof are mentioned.
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The Synthesis of Racemic Allococaine and Racemic Allopseudococaine
Stephen P. Findlay
J. Org. Chem. 21, 711 (1956) (https://www.thevespiary.org/rhodium/Rhodium/pdf/allococaine.allopseudococaine-1.pdf)
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The Conversion of Certain Pyrroles to ?,?-Alkanedioximes
Stephen P. Findlay
J. Org. Chem. 21, 644-647 (1956) (https://www.thevespiary.org/rhodium/Rhodium/pdf/pyrrole2succindialdoxime.pdf)

Abstract
Contrary to the general report, hydroxylamine alone does not convert pyrrole to succindialdoxime. Hydroxylamine hydrochloride alone is likewise ineffective. However, equivalent amounts of these substances (Lossen’s hydroxylamine hemichloride) do effect the conversion. The action of these substances on 2,5-dimethylpyrrole is similar. An improved procedure for the preparation of succindialdoxime and certain of its properties are described.


For Tropinone Chemistry, see:

Post 482456 (Lego: "Mechanism of Robinson’s synthesis of tropinone", Serious Chemistry)
Post 433727 (Megatherium: "Robinson-Schöpf reaction: tropinone", Chemistry Discourse)
Post 338869 (Tricky: "Robinson's tropinone: improving method!", Novel Discourse)

Rhodium:
Synthesis of Cocaine
G. I. Bazilevskaya, M. S. Bainova, D. V. Gura, K. M. Dyumaev, and N. A. Preobrazhenskii
CA 53, 423h (1959) [Izvest. Vysshikh Ucheb. Zavedenii, Khim. i Khim. Tekhnol. 75-81 (1958)]

To a mixt. of 32.2 g. furan, 95 mL dry Et2O, and 145 mL anhyd. EtOH, cooled to -35°C, is added, dropwise, during 1 h with stirring a soln. of 24.2 mL Br2 in 335 mL EtOH also cooled to -35°C, while keeping the soln. below -25°C. After 30 min. standing, dry NH3 is added up to pH 6, the mass stirred at -5°C until the color disappears and again NH3 added up to pH 8 to give 2,5-diethoxy-2,5-dihydrofuran (I) (52.6 g), bp3 39-41°C, d20 1.0017, nD20 1.4310. The dimethoxy analog, bp17 69.74°C, d20 1.0730, nD20 1.4352, may be obtained in a similar manner except that the reaction is conducted in the absence of Et2O (yield: 71%).

I (47.5 g) is hydrogenated in the presence of 5 g of Raney Ni at room temp. and at atm. pressure with stirring. After the absorption of 7.2 L H2 during 2-3 h, the catalyst is filtered off and washed with 15 mL dry EtOH; 40.1 g 2,5-diethoxytetrahydrofuran (II), bp20 76-78°C, d20 0.9630, nD20 1.4193, is thus obtained. The methoxy analog, bp22 52-54°C, d20 1.0230, nD20 1.4178, is similarly obtained (yield: 85.5%).

To a mixt. of 360 g 50% KOH soln. and 138 mL MeOH, 70.5 g dimethyl ester of acetonedicarboxylic acid (III) is added with stirring at -5°C. The temp. rises immediately to 15°C, and then up to 25°C during 30 min. After 10 min. standing the mixt. is again cooled to 0°C and 65 mL Et2O is added. The ppt. is filtered off and washed with 65 mL MeOH and 150 mL Et2O (previously cooled to 0°C). The di-potassium salt (86.2 g) of III is obtained.

To 1 N HCl (322 mL) heated to 80°C is added 41.1 g II and the mixt. stirred during 20 min., rapidly cooled to 10°C, and 211 mL 1N HCl, 98.2 g III, 26.4 g AcONa, and 28.2 g CH3NH2·HCl added. The mixt. is stirred 4 h at 29-31°C, cooled to 10°C, satd. with 410 g KOH, and extracted 4 times with CHCl3 (75 mL, 15 min. stirring). The methyl ester (IV) (25.96 g), mp 106-107°C (from MeOH), bp0.2 85-86°C, of tropan-3-one-2-carboxylic acid crystallizes from the oily mixt. (2.88 g more is obtained from the mother soln.); IV·HCl, mp 172-173°C (from MeOH); IV·H2O, mp 97-100°C.

IV (28.34 g.) is dissolved in 10% H2SO4 (170 mL), cooled to -5°C, and treated with 3.63 kg 1.5% Na-Hg with vigorous stirring between -2°C and +2°C, the pH being kept at 3-3.5 by means of a 30% H2SO4 soln. The reduction is continued about ½ hr. until 3 drops of the reacting mixt. cease to give a red coloration with a 10% soln. of FeCl3. After the sepn. of Hg, the soln. is satd. with 235 g KOH below 15°C and extd. with CHCl3 (250 ml., 5 times). The extracts are dried over Na2SO4 and an oily liquid (26.5 g) is obtained, from which the Me ester of racemic pseudoecgonine (V) crystallizes upon long standing (5-7 days at 0°C).

The 2 isomeric esters of ecgonine, V and racemic ecgonine (VI), are sepd. by mixing the oily liquid (filled with crystals) with an equal volume of dry Et2O. The pptd. V (5.86 g), mp 128.5-130.5°C (from Et acetate), is filtered off. Its HCl salt mp 211-213°C. To the filtrate is added 250 ml. dry Et2O until no more ppt. forms (the ppt. rapidly melts in the air to form a resinous mass), and the filtrate is stirred 30 min. with activated coal. The solvents are evapd. and a light brown liquid (17.2 g) is obtained; it is dissolved in 17 ml. MeOH and neutralized with a 10% soln. of HCl in dry Et2O. Et2O is then evapd. in vacuo until the 2 layers disappear. Upon standing 2 hrs. at 0°C, VI·HCl crystallizes; it is filtered and washed with a mixt. 1:1 MeOH-dry Et2O cooled to 0°C. Pure VI·HCl, mp 194.5°C, is obtained upon recrystg. from MeOH and washing with small quantities of 1:1 MeOH-Et2O and then with Et2O; 1.55 g. more VI·HCl may be obtained from the mother soln. (total yield 9.85 g).

IV·HCl (9.33 g) is heated 10 h on a water bath with 18.7 g PhCOCl, the brown transparent liquid formed is poured into 250 mL Et2O, and upon rubbing, the viscous mass is converted into a friable powder which is dissolved in 35 ml. ice water and neutralized to the universal indicator by 20% NH4OH. Racemic cocaine (VII) (base) (6.81 g) mp 80-81°C (from ether), is filtered off, washed with 12 mL of ice water and dried over CaCl2. A still larger yield of VII (84% calcd. from VI) is obtained by treating the mother soln. VII·HCl, m. 186-187°C, is obtained by exactly neutralizing the soln. of the base in a sevenfold quantity of Et2O with an alc. soln. of HCl, followed by washing the crystals with 1:3 MeOH-Et2O and then with Et2O.

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