First Synthesis

Taking into account the experimental conditions, a fairly large variety of thiazoles, variously substituted at the 2-position can be obtained from a-thiocyanatoketones. This method, more widely known as Tcherniac s synthesis, is a variation of the first synthesis group. 

Urea [57-13-6] was discovered ia urine by Rouelle ia 1773 and first synthesized from ammonia (qv) and cyanic acid by Woehler ia 1828. This was the first synthesis of an organic compound from an inorganic compound, and it dealt a deathblow to the vital-force theory. In 1870, urea was produced by heating ammonium carbamate ia a sealed tube. 

Prostacyclin. The total syntheses of PGI2 (4) have been extensively reviewed (58,103). The first synthesis of PGI2 as its methyl ester and... 

The first synthesis of sorbic acid was from crotonaldehyde [4170-30-3] and malonic acid [141-82-2] in pyridine in 32% yield (2,17,18)- The yield can be improved with the use of malonic acid salts (19). One of the first commercial methods involved the reaction of ketene and crotonaldehyde in the presence of boron trifluoride in ether at 0°C (20,21). A P-lactone (4) forms and then reacts with acid, giving a 70% yield. 

Cyclic Acetals. One of the most significant developments in the chemistry of sucrose was the synthesis of cycHc acetals which, despite many attempts, were not synthesized until 1974. The first synthesis of 4,6-0-benzyhdenesucrose was achieved from the reaction of sucrose with a, a-dibromotoluene in pyridine (29). Since then, many new acetalating reagents have been used to give a variety of sucrose acetals, generally by transacetalation reactions. 

The first synthesis of amphiphilic porphyrin molecules involved replacement of the phenyl rings in TPP with pyridine rings, quaternized with C2QH 2Br to produce tetra(3-eicosylpyridinium)porphyrin bromide (3) (36). The pyridinium nitrogen is highly hydrophilic the long C2Q hydrocarbon serves as the hydrophobic part. Tetra[4-oxy(2-docosanoic acid)]phenyl-porphyrin (4) has also been used for films (37). 

In the first synthesis of T, the diphenyl ether was formed from -methoxyphenol and 3,4,5-triiodonitrobenzene. The nitro group was replaced by a nitril which was then built up into the alanyl side chain by a series of steps (10). 

Chemical Synthesis. The first synthesis of ascorbic acid was reported ia 1933 by Reichsteia and co-workers (14,39—42) (Fig. 4). Similar, iadependent reports pubHshed by Haworth and co-workers followed shordy after this work (13,43—45). L-Xylose (16) was converted by way of its osazone (17) iato L-xylosone (18), which reacted with hydrogen cyanide forming L-xylonitfile (19). L-Xylonitfile cyclized under mild conditions to the cycloimine of L-ascorbic acid. Hydrolysis of the cycloimine yielded L-ascorbic acid. The yield for the conversion of L-xylosone to L-ascorbic acid was ca 40%. 

All known commercial syntheses are based on this approach with improvements in preparations of the three components (23). Shordy after the first synthesis, similar methods were pubUshed employing other C -halo compounds, such as l,l,3-tribromo-2-propanone, 2,2,3-tribromopropanal (24), 2,2,3-trichloropropanal, and l,l,3-trichloro-2-propanone (23). 

The core of the first synthesis of vitamin involved condensation of the A—D ting fragment (10) with the B—C fragment (11). The former... 

The first synthesis of vitamin IQ was reported by several workers ia the late 1930s and the synthetic approaches have been reviewed (22). Vitamin IQ was prepared by the reaction of menadione with phytyl bromide ia the preseace of 2iac (23). 

A large number of PBIs have been investigated since their first synthesis in 1961 (35) the particular polymer used in many commercial and developmental appHcations is poly(2,2 -y -phenylene)-5,5 -diben2imida2ole). 

Industrial ethyl alcohol can be produced synthetically from ethylene [74-85-17, as a by-product of certain industrial operations, or by the fermentation of sugar, starch, or cellulose. The synthetic route suppHes most of the industrial market in the United States. The first synthesis of ethanol from ethylene occurred in 1828 in Michael Faraday s lab in Cambridge (40). 

With Water. Wurtz was the first to obtain ethylene glycol by heating ethylene oxide and water in a sealed tube (1). Later, it was noted that by-products, namely diethjlene and triethylene glycol, were also formed in this reaction (50). This was the first synthesis of polymeric compounds of well-defined stmcture. Hydration is slow at ambient temperatures and neutral conditions, but is much faster with either acid or base catalysis (Table 8). The type of anion in the catalyzing acid is relatively unimportant (58) (see Glycols). 

In 1959 Clinton and coworkers reported the first synthesis of some pyrazole fused androstane derivatives and described their biological activity (B-76MI40404). Stanazolol (695) or 17-methyl-2iT-5o -androst-2-eno[3,2-c]pyrazol-17/3-ol was 10 times as active as 17a -methyltestosterone in improving nitrogen retention in rats (B-80MI40406), and its myotrophic activity was only twice that of 17a-methyltestosterone. It is used as an anabolic steroid with no lasting adverse side effects. 

The first synthesis of 4-isoxazolidinones (540) resulted from the reaction of 2,4-dibromo-2,4-dimethyl-3-pentanone with hydroxylamine (81H(16)1855>. 

The procedure described here serves to illustrate a new, general method for effecting the < -arylation of g-dicarbonyl compounds by means of an aryllead triacetate under very mild conditions. Although the first synthesis of an aryllead triacetate was reported relatively recently, a wide range of these compounds can now be readily prepared. The most direct route to these compounds is plumbation of an aromatic compound with lead tetraacetate, and in the procedure reported here p-methoxyphenyllead triacetate has been prepared in this way. It may also be obtained by reaction of the diarylmercury with lead tetraacetate, a longer, but more general method of synthesis of aryllead triacetates. 

The first synthesis of p-methoxyphenyllead triacetate by direct plumbation was reported by Harvey and Morman, who obtained the compound in 2418 yield by heating anisole and lead tetraacetate in acetic acid at SO C for 4... 

The first synthesis of enterobactin, a microbial chelator and transporter of environmental iron, was accomplished by the coupling of three protected L-serine units and macrocyclization by the double activation method. 

The first synthesis of the potent antitumor agent maytansine was carried out by the elaboration of aldehyde D, an intermediate in the enantioselective synthesis of (-)-A/-methylmaysenine (Ref. 1,2), using enantioselective and diastereoselective steps. 

Methoxatin, now known as coenzyme PQQ, was originally obtained from methylotrophic bacteria but is now known to be a mammalian cofactor, for example, for lysyl oxidase and dopamine p-hydroxylase. The first synthesis of this rare compound was accomplished by the route outlined below. In the retrosynthetic analysis both of the heterocyclic rings were disconnected using directly keyed transforms. 

The first synthesis of trisubstituted olefins from acetylenes was applied to the total synthesis of several natural products as outlined on the next page. 

The first synthesis of a P-amyrin derivative was accomplished by a convergent route which depended on cation-olefin cyclization to form the critical central ring. The plan of synthesis was largely guided by the selection of SM goals for the A/B and E ring portions of the target. 

The fourth of Pedersen s general methods is expressed as method Y. In this approach, a single unit may be both nucleophile and electrophile and react with the corresponding portions of its counterpart to yield a macrocycle. This is illustrated in Eq. (3.6). Note that there are really two possibilities here. The first of these is that two units will react as illustrated, but the other possibility is that the single unit will cyelize to afford a crown of half the size. It is precisely this approach which Pedersen used in the first synthesis of 18-crown-6 (see Sect. 3.2). 

The first synthesis of 18-crown-6 was reported by Pedersen in his first full paper on erowns . The method used was potassium r-butoxide catalyzed cyclization of hexa-ethlyene glycol monochloride in 1,2-dimethox ye thane, as shown in Eq. (3.7), below. Unfortunately, the yield by this approach was only 1.8%. ... 

In Cram s first synthesis of a chiral bis-binaphthyl system, optically pure binaph-thol and diethylene glycol ditosylate were heated at reflux in tetrahydrofuran solution for 15 h with potassium f-butoxide, two products were obtained. The 1 + 1 product (mp 230—231°) was isolated in 5% and the 2 + 2 product (mp 123—126°) was obtained in 31% yield. The reaction is shown in Eq. (3.51). 

First synthesis of aji organo-P comp iund by J. L. Lassaigne who made alkyl phosphites from H P04 + ROH. T. Graham (who later became the Hrst President of the Chemical Society) classiHed phosphates as ortho, pyro or meta, following J. J. Berzelius s preparation of pyrophosphoric acid by heat. 

V. du Vigneaud (New York) biochemically important sulfur compounds, especially the first synthesis of a polypeptide hormone. 

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