Phenethylamine, reaction with

Finally, attachment of a rather complex side chain to the para position of the benzene ring on the sulfonamide leads to the very potent, long-acting oral antidiabetic agent, glyburide (215). Preparation of this compound starts with the chlorosul-fonation of the acetamide of 3-phenethylamine (209). The resulting sulfonyl chloride (210) is then converted to the sulfonamide (211) and deacylated (212). Reaction with the salicylic acid derivative, 213, in the presence of carbodiimide affords the amide, 214. Condensation of that with cyclohexylisocyanate affords glyburide (215). ... 

Amino acid synthesis (cf. 12,15). The reaction of 1 with chiral a-imino esters provides an enantio- and diastereoselective synthesis of amino acid derivatives. The imine (2), prepared from (S)-phenethylamine, reacts with 1 to give 3, which... 

As AL is one of the most potent 3,4,5-trisubstituted phenethylamines yet described, and since the corresponding amphetamines are of yet greater potency, it would be a good guess that 4-allyloxy-3,5-dimethoxyamphetamine (3C-AL) would be an interesting compound to explore. It could be made from syringaldehyde in reaction with allyl iodide, followed by the formation of a nitrostyrene with nitroethane, followed by reduction with aluminum hydride. It is, as of the present time, both unsynthesized and unexplored. 

The lithiated dimethoxybenzene reaction with 2,2-dipyridyl disulfide produced 2,5-dimethoxyphenyl 2-pyridyl sulfide which distilled at 135-150 °C at 0.4 mm/Hg and could be recrystallized from cyclohexane containing 2% EtOH to give aproduct thatmelted at 66-67.5 °C. Anal. (CnHnNO,S) C,H. This would have produced 2,5-dimethoxy-4-(2-pyridylthio)phenethylamine (2C-T-10) but it was never pursued. 

The same reaction with di-(4-bromophenyl) disulfide produced 2,5-dimethoxyphenyl 4-bromophenyl sulfide which distilled at 150-170 °C at0.5 mm/ Hg and could be recrystallized from MeOH to give a product that melted at 72-73 °C. Anal. (C14H 3Br02S) C,H. This was being directed towards 2,5-dimethoxy-4-(4-bromophenylthio)phenethylamine (2C-T-11) but it also was abandoned. 

This procedure required but one resolution of the acetylenic alcohol 40 which then served to resolve the remaining chiral portion of the molecule. The resolution of octyn-3-ol 40 therefore was the start of the synthesis of the optically active 7-oxaprostanoids. Reaction of the racemic octyn-3-ol 40 with phthalic anhydride gave the phthalyl acid 41 which formed the crystalline salt 42 by reaction with ( )-o -phenethylamine with the absolute configuration shown. 

The structures of all currently approved gastric acid secretion inhibitors that act as inhibitors of the sodium-potassium pump consists of variously substituted pyiidylsulfonyl-benzimidazoles. A structurally very distinct compound based on a pyrimidine moiety has much the same activity as the benzimidazole-based drugs. In yet another convergent synthesis, reaction of (3-phenethylamine (53) with acetic anhydride affords amide 54. Treatment with polyphosphoric acid (PPA) then leads to ring closure to form the dihydroisoquinoline (55). Sodium borohydride then reduces the enamine function to afford fragment 56. 

Chen et al. reported a more environmentally friendly version of the Pictet-Spengler reaction <06H1651>. In this report, a series of 2-phenylsulfonyl-l,2,3,4-tetrahydroisoquinoline-1-carboxylic acid ethyl ester derivatives 114 were synthesized in good yields through the cyclization of A-phenylsulfonyl-P-phenethylamines 115 with a-acyl sulfide 116 using phenyliodine(III) bis(trifluoroacetate) (PIFA) in ionic liquid ([bminjPFJ. The use of the ionic liquid allows for a simple purification and [bmin]PF can conveniently be recycled. 

Beke et al. (115) have reported the preparation of the 19-type alkaloids from secologanin (132) by Pictet-Spengler reaction with phenethylamine derivatives. They have also reviewed the regio- and stereoselectivity in the formation of the ipecosane alkaloids (22). 

Related work not directly dealing with total synthesis of proaporphine, aporphine, or homoproaporphine alkaloids has appeared. A series of homopro-aporphine-type compounds (110) have been prepared, as shown in Scheme 9.12 7 Compound (106), readily prepared from 3,4-dimethoxy-/ -phenethylamine and the appropriate keto-acid derivative, was transformed by reduction and acetylation to (107). Acetylation effectively blocked any complications from the cyclohexane oxygen function during the subsequent Bischler-Napieralski cyclization. Consecutive reduction, alkylation, and hydrolysis gave the key intermediate (109) which was transformed into the tetracyclic spiro-system (110) by reaction with polyphosphate ester under strictly defined conditions. Other conditions and... 

Condensation of 2-azido-P-phenethylamine with 4-chloro- or 4-nitrobenzaldehyde followed by reaction with diphenylketene in refluxing toluene gives the ketenimine 59 which undergoes an intramolecular [2tc + 27t] cyclisation to the azeto[2,l-6][l,3]benzodiazepines 60 <97T13449>. The method may be used also to synthesise azeto[2,l- )]quinazolines, the main thrust of the publication, but the tether cannot be increased further as the respective 8- and 9-membered ring systems could not be formed. UV irradiation of 4,6-diazido-3-methylisoxazolo[4,5-c]pyridine gives two products which have been identified and isoxazolo-... 

In another example, variation in one of the starting components by using the carboxylic salt of a-epoxide in reaction with P-phenethylamine (dopamine) under the Pictet-Spengler conditions was used for the synthesis of trimethoquinol. This compound is one of a small group of compounds devoid of an aminoalcohol moiety that acts as a P-adrenergic agonist investigated as a potent bronchodilator. ... 

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