Author Topic: Novel Gabriel Reagents  (Read 1970 times)

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psychokitty

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Novel Gabriel Reagents
« on: October 04, 2004, 08:19:00 PM »
For those wondering if bromosafrole can be used to any advantage, my guess is that this review of the most recent advances in the Gabriel synthesis proves that the answer is an emphatic YES!

Ritters bromosafrole synth:

Post 243189

(Ritter: "Re: Notes on bromination of safrole", Methods Discourse)


and some more details are found on the following page:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mda.azide.html




Novel Gabriel Reagents
ULF RAGNARSSON* and LEIF GREHN
Acc. Chem. Res., Vol. 24, No. 10, 1991; pp. 285-289



As demonstrated in this review, during the last two decades a considerable number of compounds have been investigated as substitutes for phthalimide or its potassium salt in the Mitsunobu and Gabriel reactions. Their major advantages are 2-fold: Much milder and rather specific conditions can be used for the final deprotection than are required for phthaloyl, and alkylation can, if required, be carried out twice, in which case also secondary amines are obtained. Several of the novel reagents are easily made, and they can be alkylated in the same way as phthalimide or its potassium salt, but neither strong acid or base nor hydrazine is needed to cleave off the protecting group(s). Besides, the approaches described above to prepare imidodicarbonates and acylcarbamates are in principle rather flexible and should, if necessary, allow additional, selectively protected compounds to be made in the same way. Thus, the imide concept as such has withstood the ravages of time since its introduction a century ago. In parallel, much work aimed at the direct alkylation of amides has recently been performed, and in many cases it is now possible to obtain specific, relatively simple amides from which the corresponding amines can be regenerated. Many acyl groups used in this context require, however, cleavage conditions which occasionally cannot be tolerated, and the application of carbamates would probably be a better alternative in such cases.

psychokitty

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Interesting . . .
« Reply #1 on: October 05, 2004, 12:41:00 PM »
It would appear that the potassium salt of saccharin could very possibly substitute fully for the potassium salt of phthalimide in the Gabriel synthesis of amines. 

Anybee think that he/she can obtain a copy of the articles or abstracts listed at the bottom of this page/post?  Hopefully they're printed in English.

Acc. Chem. Res., Vol. 24, No. 10, 2991

Taken from page 288:

Saccharin.

Sugasawa and Abe have introduced saccharin (1 1) as a replacement for phthalimide in the synthesis of amines by "the saccharin method" (ref 59) particularly to obtain secondary amines. The potassium salt is first monoalkylated, whereupon the imide ring is opened by alkaline hydrolysis to give an N-substituted sulfonamide. After acidification, the product is alkylated a second time. In this step actually 2 equivalents of the reagent are consumed, since the carboxylic group in the 2-position also reacts, and this ester is saponified. To isolate the secondary amine, heating with strong acid is required, normally giving products in good yields. The ring opening, second alkylation, and saponification can be performed consecutively without isolation of intermediates. The authors stress that the final hydrolysis takes place much more easily than in ordinary sulfonamides. The saccharin method has later been used by Abe for the synthesis also of diamines (ref 60), amino alcohols (ref 60), and less accessible secondary amines (refs 61 & 62).  The mechanism of the reaction has also been discussed (ref 63).

(59) Sugasawa, S.; Abe, K. J. Pharm. SOC. Jpn. 1952, 72,270; Chem. Abstr. 1953, 47, 1626c.
(60) Abe, K. J. Pharm. SOC. Jpn. 1955,75,153; Chem. Abstr. 1956, 50, 1778b
(61) Abe, K. J. Pharm. SOC. Jpn. 1955, 75,159; Chem. Abstr. 1956, 50, 1779a
(62) Abe, K. J. Pharm. SOC. Jpn. 1955, 75,164; Chem. Abstr. 1956, 50, 1779d
(63) Abe, K. J. Pharm. SOC. Jpn. 1955, 75,168; Chem. Abstr. 1956, 50, 1779g

psychokitty

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An example of "the saccharin method"
« Reply #2 on: October 05, 2004, 06:07:00 PM »
The Gabriel-Colman Rearrangement in Biological Systems: Design, Synthesis and Biological Evaluation of Phthalimide and Saccharin Derivatives as Potential Mechanism-Based Inhibitors of Human Leukocyte Elastase, Cathepsin G and Proteinase 3
William C. Groutas, Lee S. Chong, Radhika Venkataraman, Jeffrey B. Epp, Rongze Kuang, Nadene Houser-Archield, and John R. Hoidal
Bioorganic & Medicinal Chemistry, Vol. 3, No. 2, pp. 187-193, 1995



Here are two experimental examples (taken from page 191 of the above citation) of the use of potassium phthalimide and sodium saccharin in the same type of reaction:

2-(1, 3- D i o xo- l,3-dihydro-isoindol-2-ylmethyl)-acrylic acid methyl ester 11
Potassium phthalimide (54 mmol) was added to a solution of ~-(bromomethyl)acrylate (50 mmol) in 50 mL dry DMF. The reaction mixture was stirred at room temperature overnight, poured into 200 mL ice-cold water and extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate. The mixture was filtered and the filtrate was evaporated in vacuo, leaving a crude product which was purified by flash chromatography (8.7 g, 71% yield).

2-(1,1,3- Trio xo- l ,3-dihydro-benzo[ d ] isothiazol- 2- ylmethyl)-acrylic acid methyl ester 13
Sodium saccharin (3.0 g, 14.4 mmol) was added to a stirred solution of ¢t-(bromomethyl)acrylate (1.41 g, 7.9 mmol) in 10 mL dry DMF at 0 *C. The reaction mixture was stirred for 10 min at 0 °C, 2 h at room temperature and then poured into ice-cold water. The resulting precipitate was collected and washed with hexane (1.80 g, 81% yield).

The yield from the sodium saccharin example seems to be higher than that of the one using potassium phthalimide; furthermore, the reaction proceeds much quicker with the apparent need of a lower reaction temperature. I wonder why?

lugh

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The Requested Abstracts
« Reply #3 on: October 06, 2004, 05:40:00 PM »
The requested abstracts; Chem. Abstr 1953, 47, 1626c, Chem. Abstr 1956, 50, 1778b, Chem Abstr 1956, 50, 1779a, Chem. Abstr 1956, 50, 1779d & Chem Abstr 1956, 50, 1779g :

A new method for the preparation of secondary amines.
I. Synthesis of aliphatic secondary amines. Shigehiko Sugasawa and Kyuji Abe (Univ. Tokyo). J.  Pharm. Soc. Japan 72, 270-3(1952)(in English).--,Saccharin (11 g.), .11.4 g. PhCH2Cl, and 5 g.  K2CO3 are mixed well, heated on an oil bath 6 hrs. at 130-90°, the excess PhCH2Cl removed by  steam distn., the residue poured in cold water, and the product filtered and recrystd. from MeOH  give 13.2 g. (80.5%) N-benzylsaccharin (I), m. 112-13°; 13.2 g. I and 44 g. 10% NaOH  heated on a steam bath 10 min., acidified with HCl, and recrystd. from dil. alc. give 14 g.  ortho-C6H4­(CO2H)SO2NHCH2Ph (U), m. 134-5°; 9.7 g. II in 30 g. 10% NaOH methylated with 10  g. Me2SO4 2 hrs. at 45-50° and 30 min. at 80-90°, extd. with ether, and the ext, distil. give  10.6 g. ortho-CaH4(CO2Me)SO2N(CH2Ph)Me (III), b9-4 190--200°; 10.6 g. III  hydrolyzed with 124 g. 20% NaOH 30 min. on a steam bath, and acidified with HCl gives 10 g.  ortho-C6H4(CO2H)SO2N(CH2Ph)Me (IV), m. 69-71°; 10 g. IV heated 1 hr. at 120-30* with 20  ml. 20% HCl, made alk. with NaOH, and steam-distd. into HCl gives 4.3 g. (83%) PhCH2NHMe.HCI (V),  m. 177-8°. The process without isolating intermediate products is carried out as follows: 9.1 g.  I and 30 g. 10% NaOH are heated on a steam bath 10' min., cooled, heated with 10.3 g. Me2SO4 2  firs. at 40-50*, and 30 min. at 80-90°, 5 g. NaOH is added, and the mixt. heated on a steam bath  30 min. and acidified, giving a theoretical yield of IV, decompd., with HCl to V; the name  saccharin method is proposed for this procedure.
K. Kitsuta
A new method for preparation of secondary amines.
IV. Syntheses of ethylenediamine, ethanolamine, trimethylene­diamine, and. propanolamine  derivatives. Kyuji Abe (Gohei Tanabe & Co., Tokyo). J. Pharm. Soc. Japan 75, 153-9(1955); cf. .  C.A. 49, 177b -K salt (Ia) (33 g.) of saccharin (I) and 56 g. BrCH2CH2Br (II) heated 12 hrs. at  220-30°, unreacted II disH. off, the residue poured in water, and extd. with hot EtOH gave 22 g.  N-(R-bromoethyl)saccharin (III), needles, m. 95-6°; the residue gives 14.5 g.  alpha,beta-disaccharinoethane (IV), columns, m. 2467° (from AcOH). Similarly, 11 g.  Ia, 19 g. II, and 40 ml. H CONMe2 heated 1 hr. on a water bath and 1 hr. at 130­40° give 13 g.  II, or 22 g. Ia, 4.7 g. II, and 60 ml. HCONMe2 gave 7.3 g. IV. III (14.5 g. ), 7.4 g. o-C6H4(CO  )2NH, and 3.5 g. K2C03 heated 1.5 hrs. at 150-60°, the product poured in water and recrystd. from  di1. AcOH gave 13 g. alpha-saccharino-1-phthalimidoethane (V), columns, m. 185-6°; 29 g.  III, 18 g. AcOK, and 25 g. glacial AcOH heated 7 hrs, at 180-90°, one-half of the AcOH distd.  off, the residue heated 4 hrs., cooled, and water added yielded 22.6 g. N  ((beta-acetoxyethyl)saccharin (VI),leaves, m. 85-6° (from MeOH). Ia (11 g.) and 12 g.  ClCH2CH2OH heated 5 hrs. at 160-70°, and the product treated as above give 9.7 g.  N-(beta-hydroxy­ethyl)saccharin (VII), columns, m. 104-5° (from MeOH); or 2.7 g. VI and 20  ml. 10% H Cl heated 1 hr. on a water bath gave a quant. yield of VII; 11 g. Ia, 14 g.  para-MeCeH4SO3­CH2CH2Cl, and 8 g. xylene heated 3 hrs. at 150-60°, the solvent removed,  the residue heated 3 Jars., water added, extd. with CHCl3, and the ext. distd. gave 9g.  N-(beta-chloroethyl)saccharin (VIII), b3 180-5°, columns, m. 80-1° (from MeOH). Ia  (12.1 g.) and 10 g. BrCH2CH2OPh heated 1 hr. at 230­40° gave 12.5 g.  N-((3-phenoxyethyl)saccharin (IX), columns, m. 81-2° (from EtOH ); 2 g. IV, treated as  previously (ef. Sugasawa and Abe, C.A. 47,1626c), yielded 0.5 5g. (CH2NH­Me)2.2HCl, leaves, m.  235-7°; 7.8 g. IV treated as in the prepn. of EtNHCH2CH2Ph (C.A. 49, 178b) gave 1.9  g.(CH2NHEt)2.2HC1, leaves, m. 255-9°. Other compds. were prepd. similarly: MeNHCH2CH2NH2.2HC1, m.  130-1°; EtNHCH2CH2NH2.2HCl, m. 165-7°; MeNHCH2CH2OH (X), sirup (picrate, m. 147-9°); EtNH  CH2CH2OH, sirup (picrate, m. 125-6°); MeNHCH2CH2OPh.HCl, m. 174-5°; EtNHCH2CH2OPh.HCl, m. 171-2°.  MeNHCH2CH2Cl.­ HCl (13 g.), 20 m1. water, and 25% aq. soln. of amine, H NR'R2, in a pressure  bottle heated 10 hrs. at 1000, cooled, made alk. with solid NaOH, the upper amine layer and Et20  ext. of lower layer combined and distd. gave MeNH­CH2CH2NR.iR2 (XI) (RI, R2, % yield, b.p., and  mp of salts given): H, Et, 68.6, 130-3°, dipicrate-H20 175--7 , Me, Me, 53, 135_400, dipicrate  206-7°; Et, Et, 40, 150-5°, d i­picrate-H20 145-7°; H, Me, 53, 110-3°, di-HC1 salt 235-­7°; H, H,  50, 105-10°, di-HC1 salt 130-1°. CH2: CHCH2Br (12 g.), 26.5 g. Ia, and 100 ml. HCONMe2 heated 2  hrs. on a water bath and the product treated as usual gave 19.6 g. 2-allylsaccharin (XI),  columns, m. 88-9°; 7.5g. XI yielded 2.1 g. MeNHCH2CH: CH2, b. 61-6° [picrolonate, columns, m.  227-30° (decompn.)j . Ia (27.5 g.), 10 g. Br(CH2 )3Br, and 80 ml. HCONMe2 treated as in IV  yielded 16.4 g. a, gamma-disaccharinopropane, columns, m. 197°; 22 g. Ia, 50.5 g.  Br(CH2)3Br, and 80 ml. HCONMe2 yielded 25.5 g. 2-(gamma-bromopropyl)saccharin (XII),  sirup; 30.4 g. XII treated as in VI yielded 25.5 g. 2-(gamma-acetoxypropyl)saccharin  (XIII), columns, m. 128-9°. XIII (14 g.) and 30 ml. 10% H CI heated 1 hr. on a water bath yielded  -11..4 g. (gamma-hydroxy­propyl)saccharin, sirup; 16.6 g. Ia, 13.4 g. C6H4(CO)2N­(CH2)3Br,  and 60 ml. HCONMe2 heated 4 hrs. on a water bath and 1 hr. at 130-40° gave 15 g.  alpha-saccharine-y-phthalimidopropane (XIV), columns, m. 202°, or 6 g. XII, 3.3  g.o-C6H4(CO)2NH, and 20 ml. H CO NMe2 gave 4.3 g. XIV. Ia, Br(CH2)3OPh, and HCONMe2 yielded 80%  2-{gamma-phenoxypropyl )saccharin, columns, in. 87-8°.
V. Syntheses of aliphatic secondary amines. Ibid. 159-64.-Ia (0.03 mole), 0.02 mole RX, and 30  ml. HCONMe2 heated 3-4 hrs. on a water bath, the product poured in ail. Na2CO3, extd. with CHC13i  and the CHCl3 removed gave 2-alkylsaceharin (XV), and XV treated as usual gave secondary amine  (XVI) (RX,% yield of XV, m .p . of XV, XVI, % yield of XVI, and m . p XVI.HC1 given): MeI, 95,  129-30°, Me2NH, 78.8, 169­of 70°; EtI, 95, 93-4°, EtNHMe, 72, 126-8°; PrBr, 90, 66--8°, PrNHMe,  67.4, 145--7°; BuBr, 90.3, 38-9°, BuNH­Me, 66, 170-1°; n-C6H13Br, 90.8, sirup, n-C6H13NHMe, 43.3,  180-1°; n-C3H17Br, 91.4, sirup, n-C3H17NHMe, 43, 179-80°; n-C10H21Br, 94.2,  sirup, n-Cl4H21NHMe, 42, 179­80°; n-C12H25Br, 96, 49-50°, n-C12H25NHMe, 45, 175-6°;  PhCH2Cl, 91,112-13°, PhCH2NHMe, 75.5, 177-8°. Ia (22.1 g. ), 18.3 g. iso-PrBr, and 60 ml. HCONMe2  heated 8 hrs. on a water bath and the product treated as usual gave 20.2 g. of a neutral  substance, which treated with MeOH gave 8.5 g. easily sol..N-isopropylsaccharin (XVII), m.  62-4°, and 9.5 g. diffxcultly sol. ortho-C5H4.S02.N: COR (XVIII, R =iso-Pr ), m. 138°;  similarly were prepd. easily sot. N-(sec­butyl)saccharin (XIX), m. 80-3°, and diffxcultly  sol. XVIII (R = sec-Bu) (XX), m. 62-4°, in the ratio of 25.8% and 31.9%, resp. XVII yielded 65%  MeNHCHMe2; picrate, m. 133-5°. XIX yielded 75% MeNHCHMeEt; Ia, iso-BuBr and HCONMe2 yielded 84.9%  2-isobutylsaccharin (XXI), sirup, which yielded 69% MeNHCH2CHMe2 (HCl salt, m. 178-9°). Infrared  absorption spectra of XVIX-XXI, inclusive., are given.
VI. Syntheses of beta
methylamino alpha phenylpropane and  gamma-methylammo-a-phenylbutane. Ibid. 164-7. PhCH2CHMeOH (XXII) (16.3 g.) at 0 ° treated  with 13.5 g. PBr3 dropwise in 1.5 hrs., let stand overnight at room mp., the product poured in  ice water, washed with 5% NaOH and water, shaken with 1 ml. coned. H2SO4, and distil. gave 12.6  g..PhCH2CHMeBr (XVIII), b4 88-9°; 13.6 g. XXII in 60 ml. C5H5N at below 10° treated with 23.7 g.  p­MeC6H4SO2Cl, stirred 5 hrs. at 10-15°, the product poured in ice water, and the ester washed  with petr. yielded 27.5 g. PhCH2CHMeO3SC6H4Me-p (XXIV), m. 91-3°. XVIII (10 g.), 13.2 g. Ia, and  50 ml. H CO NMe2 heated 5 hrs. at 100° and 2 hrs. at 130-40°, the HCONMe2 removed in vacuo, and  the residue extd. with Et20 gave 10.7g. of a neutral oil (A) consisting of a mixt. of  N-(beta-phenylisopropyl)saccharin (XXV)nd XVIII (R = Ph CH2 CHMe) (XXVI), sirup; 6 g. A  boiled 2 hrs. on a water bath with 2 g. NaOH, 2 ml. water, and 20 ml. McOH, the McOH removed in  vacuo, the residue with water poured in HCl at Q ° gave 5.3 g. rapidly sepg. o-HO2  CC6H4SO2NHCHMeCH2Ph (XXVII), sirup, and 0.4 g. slowly crystg o-H02­CC6H4SO2NH2, m. 154-6°. XVVII  (5.3 g.) in 20 ml. 10% NaOH was treated with 1 g. NaHCO3 and 6 g. Me2SO4, kept 30 min. at 0°, 1  hr. at 50-60° and 30 min . at 70-80°, the ester on the bottom washed with di1. NaOH, boiled 2,  hrs. with 1.6 g. NaOH, 2 m1. water and 10 ml. EtOH­acidifled with HCI, the EtOH removed in vacuo,  the residue (4 g.) boiled 10 hrs. at 130-40° with 100 ml. coned. HCl, made alk. and the product  steam distil. in ail. HCl to obtain 1.2 g. (30% from XXIII) MeNHCHMeCH2Ph.HCl, leaves, m. 131-3°;  picrate, needles, m. 122°. Similarly, PhCH2CH2CHMeBr yielded 28.5% McNHCHMe CH2 CH2­Ph.HCI,  leaves, m. 97-8°; picrolondte, m. 164-6°. VII. Mechanism of the saccharin method. Ibid. 168-71.­  The characteristics of the saccharin method is that the final step of acid hydrolysis proceeds  with marked ease. The presence of a CO2H group in the ortho-position makes it extremely  facile, compared to the aryl sulfonamide process. The reasons given for it are that the electron  d. of the S atom is decreased by the E effect and ortho-effect of the pos. CO2H group,  making it more easily attacked by the water mol., and that the H2O-soly. of the mol. is increased  by the OH group present.
K. Kitsuta

8)


psychokitty

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Is this a newly discovered synthesis of Meth?
« Reply #4 on: October 07, 2004, 12:40:00 AM »
Check this out:

Syntheses of 3-methylamino-a-phenyl­propane and y-methylamino-a-phenylbutane.

Actually, "3-methylamino-a-phenylpropane" is listed as "B-methylamino-a-phenylpropane" in the abstract.  Lugh:  What makes you think that the "B" = "3"?

Ibid. 164-7. -PhCH2CHMeOH

Notice the middle carbon atom with one hydrogen atom attached.  Carbon has the ability to create four bonds. No more. The carbon atom bonded directly to the phenyl group is also bonded to two hydrogen atoms and to the second carbon atom, which for the second carbon atom also represents one bond.  The second carbon atom is bonded to one hydrogen atom, and also to the two carbon atoms--the first and third, to be exact--located on either side of it.  THE SECOND CARBON ATOM IS THE ONLY ONE IN THE PROPANE SIDE CHAIN THAT CANNOT ACCOUNT FOR ONE OF ITS BONDS.  Furthermore, the "OH" group cannot belong to the "Me" group (methyl group) as the  Me group already has three hydrogen atoms along with the second carbon atom accounting for its four available bonds.

(XXII) (16.3 g.) at 0° treated with 13.5 g. PBr3 dropwise in 1.5 hrs., let stand overnight at room temp., the product poured in ice water, washed with 5% NaOH and water, shaken with 1 ml. coned. H2SO4, and distd. gave 12.6 g. PhCH2CHMeBr

Same thing here.  The Br atom must be connected to the second carbon atom as it is the only carbon atom that cannot account for one of its available bonds.

(XXIII), b4 88-9°; 13.6 g.­XXII in 60 ml. C5H5N at below 10° treated with 23.7 g. p­McC6H4S02C1, stirred 5 hrs. at 10-15°, the product poured in ice water, and the ester washed with petr. yielded 27.5 g. PhCH2CHMeO3SC6H4Me-p

Here it just looks as if the authors used toluenesulfonylchloride to create an ester from the phenylisopropanol.

(XXIV), m. 91-3°. XXIII (10 g.), 13.2 g. la, and 50 ml. HCONMe2 heated 5 hrs. at , 100° and 2 hrs. at 130-40°, the HCONMe2 removed in vacuo, and the residue extd. with Et20 gave 10.7 g. of a neu­tral oil (A) consisting of a mixt. of N-(9-phenylisopropyl)sac­charin (XXV) and XVIII (R = PhCH2CHMe) (XXVI), sirup;

This part was typical of the advanced Gabriel synthesis using DMF as the solvent.  Apparantly, the DMF helps to increase the reaction rate (probably via an SN2 reaction) and lower the reaction temperature, thus minimizing the formation of byproducts. Also, in the abstract, the saccharin intermediate is written as "N-(B-phenylisopropyl)saccharin" which seems very similar to B-phenylisopropylamine.  Furthermore, why use "phenylisopropyl" prefix if not to indicate that the saccharin molecule is attached to the second central carbon atom on the propane side chain?

6 g. A boiled 2 hrs. on a water bath with 2 g. - NaOH, 2 ml. water, and 20 ml. MeOH, the McOH re­moved in vacuo, the residue with water poured in HCl at 0° gave 5.3 g. rapidly sepg. o-HO2CC6fI4SO2NHCHMe­CH2Ph (XXVII), sirup, and 0.4 g. slowly crystg o-H02­CC6H4S02NH2, m. 154-6°.

Apparently, aqueous NaOH hydrolysis of the alkylated saccharin intermediate allows for the cleavage of part of the saccharin molecule, protecting one side of the nitrogen atom, while leaving the other side available for further alkylation.

XXVH (5.3 g.) in 20 ml. 10% NaOH was treated with 1 g. NaHCO3 and 6 g. Me2SO4, kept 30 min. at 0°, 1 hr. at 50-60° and 30 min. at 70-80°,

This step adds a methyl group to the nitrogen atom, thus making it the precursor to the methylamino-phenylpropane.

the ester on the bottom washed with dil. NaOH, boiled 2, hrs. with 1.6 g. NaOH, 2 ml. water and 10 ml. EtOH acidified with HCl, the EtOH removed in vacuo, the res­idue (4 g.) boiled 10 hrs. at 130-40° with 100 ml. coned. HCI,

This part describes the hydrolysis of the final alkylated saccharin artifact to yield the desired monomethylated alkylated secondary amine; namely, B-methylamino-a-phenylpropane, better known as methamphetamine(?).

made alk. and the product steam distd. in dil. HC1 to obtain 1.2 g. (30% from XXIII) MeNHCHMeCH2Ph.HCI,

This part is definitely confusing because the way the atoms are all arranged, I really can't make heads or tails of the molecule's structure.

leaves, m. 131-3°; picrate, needles, m. 122°.

This is where I pretty much determined that the product of this reaction--of "the saccharin method"--was actually methamphetamine.

The m.p. of d,l-methamphetamine-HCl is about 132-135 C.; the m.p. reported for the product above is 131-133 C.  Almost right on the money.  As for methamphetamine picrate, it's listed as 128 C.  Only six degrees away from what is reported above, 122 C.

Final comments.

It would appear that in order to resolve this mystery, the actual Journal of the Pharmaceutical Society of Japan articles will have to be fetched by someone who has access to them.  No doubt, somewhere within the pages of the original articles--likely along with valuable and useful references to past Gabriel syntheses--will be found diagrams of the molecules in question that will help determine once and for all whether or not "B-methylamino-a-phenylpropane" is indeed synonymous with "methamphetamine".

Offline somebird

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Re: Novel Gabriel Reagents
« Reply #5 on: January 19, 2016, 03:13:54 PM »
why i can't download pdf attachment? is too many years ago.....?