Hoffmann product

Consider the elimination reaction below, which uses a strong, sterically hindered base (LDA). The product will be a double bond. This reaction will produce the Hoffmann product. Draw this product. 

Dehydrohalogenation.1 This lithium dialkylamide shows a greater preference for the Hoffmann product in the dehydrohalogenation of 2-bromobutane than less hindered bases of this type. The preference is increased by addition of 12-crown-4 (equation I). 

So, if we look back at the reaction above, we find that the two possible products are monosubstituted and disubstituted double bonds. Whenever you have an elimination reaction where more them one possible double bond can be formed, we have names for the different products based on which one is more substituted and w hich one is less substituted. The more substituted product is called the Zaitsev product, and the less substituted product is called the Hoffmann product. Usually you get the Zaitsev product, but under special circumstances you can get the Hoffman product. If you use a strong, sterically hindered base, you can form the Hoffman product. 

PROBLEM 10.28 Search through your textbook, find the section that covers formation of Hoffmann products, and then draw the structures of the sterically hindered bases that your textbook show s you. 

Stereochemistry = if there are cis/trans isomers, you will get the one determined by the H and LG being antiperiplanar (draw Newman projections) Regiochemistry = form the more substituted double bond (Zaitsev product). If you are using a strong, sterically hindered base, then form the less substituted double bond (Hoffmann product)... 

We have seen (Section I) that there are two types of loops that are phase inverting upon completing a round hip an i one and an ip one. A schematic representation of these loops is shown in Figure 10. The other two options, p and i p loops do not contain a conical intersection. Let us assume that A is the reactant, B the desired product, and C the third anchor. In an ip loop, any one of the three reaction may be the phase-inverting one, including the B C one. Thus, the A B reaction may be phase preserving, and still B may be attainable by a photochemical reaction. This is in apparent contradiction with predictions based on the Woodward-Hoffmann rules (see Section Vni). The different options are summarized in Figure 11. 

Only one exception to the clean production of two monomer molecules from the pyrolysis of dimer has been noted. When a-hydroxydi-Zvxyljlene (9) is subjected to the Gorham process, no polymer is formed, and the 16-carbon aldehyde (10) is the principal product in its stead, isolated in greater than 90% yield. This transformation indicates that, at least in this case, the cleavage of dimer proceeds in stepwise fashion rather than by a concerted process in which both methylene—methylene bonds are broken at the same time. This is consistent with the predictions of Woodward and Hoffmann from orbital symmetry considerations for such [6 + 6] cycloreversion reactions in the ground state (5). 

Fine chemical companies are generally either small and privately held or divisions of larger companies, such as Eastman Fine Chemicals (United States) and Lonza (Switzerland). Examples of large public fife science companies, which market fine chemicals as a subsidiary activity to their production for captive use, are Hoffmann-La Roche, Sandoz, and Boehringer Ingelheim, which produce and market bulk vitamins and liquid crystal intermediates, dyestuff intermediates, and bulk active ingredients, respectively. Table 3 fists some representative companies having an important fine chemical business. 

Even though form amide was synthesized as early as 1863 by W. A. Hoffmann from ethyl formate [109-94-4] and ammonia, it only became accessible on a large scale, and thus iadustrially important, after development of high pressure production technology. In the 1990s, form amide is mainly manufactured either by direct synthesis from carbon monoxide and ammonia, or more importandy ia a two-stage process by reaction of methyl formate (from carbon monoxide and methanol) with ammonia. 

The biotin market is divided between agricultural and human use, with —90% of biotin used in the animal health care market and —10% for the human nutritional market. The major producers of biotin are Hoffmann-La Roche, Lon2a, E. Merck-Darmstadt, Rhc ne-Poulenc, Sumitomo Pharmaceutical, E. Sung, and Tanabe Seiyaku (100). Worldwide production of biotin in 1994 was approximately 60 metric tons. The Hst price for pure biotin in 1995 was — 7.00/g whereas, the Hst price for technical feed-grade biotin was — 5.50/g. Biotin is used in various pharmaceutical, food, and special dietary products, including multivitamin preparations in Hquid, tablet, capsule, or powder forms. One of the commercially available products of i7-biotin is Britrit-1, which is a 1% biotin trituration used in food premixes. 

The major producers of the calcium salt of pantothenic acid and panthenol are Hoffmann-La Roche, Daiichi, BASF, and Alps. Racemic panthenol is used mainly in hair care products, whereas (R)-panthenol is exclusively used in top-of-the-line, more expensive skin and hair care products. The current (ca 1997) price of (R,3)-panthenol varies between 12 and 18 per kg, that of D-panthenol varies between 30 and 45 per kg, and that of D-calcium pantothenate (Calpan) varies between 22 and 30 per kg. 

For the industrial production of riboflavin as pharmaceuticals, the traditional methodology comprising the dkect condensation of (13) with (14) in an acidic medium with continuous optimisation of the reaction conditions is stiU used (28). A great part of riboflavin manufactured by fermentative methods is used for feeds in the form of concentrates. The present world demand of riboflavin may be about 2500 t per year. Of this amount, 60%, 25%, and 15% are used for feeds, pharmaceuticals, and foodstuffs, respectively. The main producers are Hoffmann-La Roche, BASF, Merck Co., and others. 

Worldwide production of thiamine was estimated at 3300 t in 1995. The principal suppHers were Hoffmann-La Roche, Takeda, and several Chinese factories. Prices in the United States were in the range of 20— 28/kg in 1995. 

As practiced by Hoffmann-La Roche, the commercial synthesis of vitamin is outlined ia Figure 1. Oxidation of 2-methylnaphthalene (4) yields menadione (3). Catalytic reduction to the naphthohydroquinone (5) is followed by reaction with a ben2oating reagent to yield the bis-benzoate (6). Selective deprotection yields the less hindered ben2oate (7). Condensation of isophytol (8) (see Vitamins, vitamins) with (7) under acid-cataly2ed conditions yields the coupled product (9). Saponification followed by an air oxidation yields vitamin (1) (29). 

Because feed comprises over 80% of the cost of producing and fattening cattle, the maximum utilization of ever increasingly expensive rations is of upmost importance (179). Monensin under the trade name of Rumen sin (Elanco Products) was introduced in 1976 at a recommended level of 30 ppm in cattle feed. Lasalocid having the trade name Bovatec (Hoffmann-LaRoche, Inc.) was marketed some years later. 

Hoffmann and Schiittler (75CB844) attempted to generate methanoylcarbene by high-temperature chelotropic extrusion from a bicycloheptadiene derivative, but the only identified product was a very low yield of benzene. 

Wackerhage, H., Mneller, K., Hoffmann, U., et al., 1996. Glycolytic ATP production estimated from "" P magnetic resonance spectroscopy measurements during ischemic exercise in vivo. 4 151-155. 

Woodward and Hoffmann pointed out that the Diels-Alder reaction involved bonding overlap of the highest-occupied molecular orbital (HOMO) on the diene and the lowest-unoccupied molecular orbital (LUMO) on the dienophile. Display the HOMO for 2-methoxybutadiene. Where is it localized Display the LUMO for acrylonitrile. Where is it localized Orient the two fragments such that the HOMO and LUMO best overlap (A clearer picture is provided by examining-the HOMO map for 2-methoxybutadiene and the LUMO map for acrylonitrile.) Which product should result ... 

UV irradiation. Indeed, thermal reaction of 1-phenyl-3,4-dimethylphosphole with (C5HloNH)Mo(CO)4 leads to 155 (M = Mo) and not to 154 (M = Mo, R = Ph). Complex 155 (M = Mo) converts into 154 (M = Mo, R = Ph) under UV irradiation. This route was confirmed by a photochemical reaction between 3,4-dimethyl-l-phenylphosphole and Mo(CO)6 when both 146 (M = Mo, R = Ph, R = R = H, R = R" = Me) and 155 (M = Mo) resulted (89IC4536). In excess phosphole, the product was 156. A similar chromium complex is known [82JCS(CC)667]. Complex 146 (M = Mo, R = Ph, r2 = R = H, R = R = Me) enters [4 -H 2] Diels-Alder cycloaddition with diphenylvinylphosphine to give 157. However, from the viewpoint of Woodward-Hoffmann rules and on the basis of the study of UV irradiation of 1,2,5-trimethylphosphole, it is highly probable that [2 - - 2] dimers are the initial products of dimerization, and [4 - - 2] dimers are the final results of thermally allowed intramolecular rearrangement of [2 - - 2] dimers. This hypothesis was confirmed by the data obtained from the reaction of 1-phenylphosphole with molybdenum hexacarbonyl under UV irradiation the head-to-tail structure of the complex 158. 

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